- Email: [email protected]
Boron neutron capture therapy; Porphyrin distribution in various tumors
1450
Radiation Oncology 0 Biology 0 Physics
October 1980, Volume 6, Number IO
a radiotherapist selects an array of normal and tumor anatomical points of A point source calinterest, localized accurately by radiographic means. cultational procedure or tabulated data look-up method is used to approximate the dose rate to each point of interest from the brachytherapy source array. Presently, in our clinic, a computer method is followed which incorporates a maximization - minimization approach to the optimization procedure. The source loading is altered sequentially to achieve the maximum dose rate differentials between normal and tumor tissues. With this method the the loading of the ovoids, the number of sources in therapist specifies: the tandem, and the tolerance doses to several points. Given a geometric arrangement of the applicator, the computer finds the optimum arrangement of sources within the tandem. The computer program output displays a variable number of best source loadings (10 - 20) and the following judge1) R - the maximization index, 2) the rads/mg-hr to ment criteria: point A, and 3) the dose rates and total doses to anatomical reference Then with therapist input, the best plan is chosen points of interest. based upon the clinical problem and stage of disease. An isodose distribution is then printed to verify the clinically chosen best loading. Using a minicomputer, POP-8, the required computer memory storage is small and the computation time is short. Research supported in part by National Cancer Institute PO1 CA 17786.
BORON NEUTRON CAPTURE THERAPY; PORPHYRIN DISTRIBUTION IN VARIOUS TUMORS* R.G. Fairchild, Ph.D., K. Watts, B.S., 0. Greenberg, B.S., S. Packer, M.D., P. Som, D.V.M. and S.J. Hannon, Ph.D. Medical and Chemistry Departments Brookhaven National Laboratory Upton, New York 11973 The recent development of various borated compounds, and the utilization of one of these (Na2B 2HIISH) in the treatment of patients with tumors in Japan, has renewed in#.erest in Neutron Capture Therapy (NCT). In this procedure, thermal neutrons interact with "B in boron-containing cells through the"B(n,a) Li reaction. The charged particles (EToT = 2.3 MeV) have a maximum range of s 10~ in tissue. Poor results in clinical trials before 1961 were attributed to poor thermal neutron penetration in tissue, and high levels of "B in blood. The development of an epithermal nuetron beam at the Brookhaven Medical Research Reactor provides deeper neutron penetration. New compounds provide better blood clearance. Chlorpromazine (CPZ) has been synthesized in Japan, with 'L 25% by weight boron. CPZ is known to combine with pigment (melanin) in melanoma, with a clearance half-time in the order of days, thus allowing clearance from other tissues, including blood. Further, porphyrins are known to be taken up by tumors. In particular, we have studied the distribution of tetraphenylporphinesulfonate (TPPS) in several tumors, including melanotic and amelanotic melanoma, carcinoma, and sarcoma. Animals given 50 mg/kg TPPS show tumor uptakes of 'L 150 ug TPPS/g tumor. Accumulations in tumor are generally above those in other tissues, with the exception of kidney. A borated analog of TPPS has been reported in the literature. Given a distribution similar to TPPS, extrapolated boron concentrations exceed 50 pg/g. This should be more than adequate for therapy, particularly with brain tumors, where the blood-brain barrier limits penetration into normal tissue. * Work supported by National Cancer Institute, Grant No. ROl-CA22749 and in part by United States Department of Energy Contract No. DE-AC02-76CH00016.
1451
Proceedings of the 22nd Annual ASTR Meeting DEPENDENCE
OF THE CT NUMBER - ELECTRON DENSITY RELATIONSHIP
SIZE AND X-RAY BEAM FILTRATION
M.E. Masterson,
C.L. Thomason,
ON PATIENT
FOR FAN BEAM CT SCANNERS
S.C. Hsi, R. McGary,
L.D. Simpson,
D.W. Miller, J,S. Laughlin Memorial
Sloan-Kettering
Cancer Center
The applicability of information contained in CT scans to the treatment planning heterogeneity problem has been recognized by members of the Determination of the radiological community and by manufacturers. relationship between electron density and CT number is important for Results of experimental investigations using radiotherapy applications. tissue-equivalent phantoms of different cross sectional shapes and areas on the Ohio Nuclear Delta 2020 and the G.E. CT/T8800 are presented. A variation in the CT number-electron density relationship is demonstrated on these fan beam geometry scanners for phantoms of different sizes. An Investigations also cover the explanation of this effect is included. effect of "shaped" and "flat" x-ray beam filters on electron density Differences on the order of 20% in determination of tissue determination. A family of curves electron density relative to water are reported. (electron density vs. CT number) is presented for different patient cross sectional areas and different scanner settings.
EVALUATION
OF AN ECCENTRIC
R.D. Larsen,
X-RAY COLLIMATOR
K.R. Kase, B.E. Bjarngard
Joint Center for Radiation Therapy and Department of Radiation Therapy Harvard Medical School, Boston, Massachusetts Normally, the beam-defining assembly in modern x-ray producing accelerators consists of four shielding blocks, coupled together in pairs as the inner and outer collimators. The blocks define a variable rectangular field, the center of which lies on the rotational axis of the collimator assembly, which, in its turn, intersects the rotational axis of the gantry at the "isocenter". We have obtained a Siemens Mevatron XII linear accelerator, producing 8 MV x-rays, in which the four collimator blocks operate independently. This allows the shaping of rectangular fields that are eccentric with respect to the collimator rotational axis. In the system, two opposing collimator blocks can move up to the centerline, while each of the other two opposing blocks can cross the centerline to a distance of 11 cm beyond it. Since the flattening filter in this machine normally oroduces a nonuniform distribution of primary photons, special dosimetric problems may arise for eccentrically placed fields. Other problems might occur because of the difference in filtration at various parts of the field and oblique incidence of the beam. The purpose of this study has been to evaluate these potential problems. The dose delivered per monitor unit as measured in air increases as the field position moves away from the centerline. The increase reaches 4% in a 5 cm x 71cm field cantered 12 cm off the centerline and is somewhat less for larger fields. This ix'.rease disappears when the measurements are made at a depth of 10 cm in water, probably because of a balance between the variation
1452
Radiation Oncology ??Biology ??Physics
October 1980. Volume 6, Number 10
in primary intensity and the changes in beam quality as distance from the cente!*'ine increases. Half value layer studies have indicated substantial changes in beam quality as one moves away from the centerline. Isodose distributions measured for eccentrically placed fields are influenced by these changes in beam quality and in addition show a tilting of the curves caused by the variation of the primary x-ray intensity. Dose buildup measurements indicate an increase of surface dose as the field is more eccentrically placed. Modification of the flattening filter to change the primary x-ray distribution and the filtration of the beam can help to overcome the differences in isodose distributions and dose buildup for eccentrically placed fields. Independentl,y moveable collimators are useful in conventional radiotherapy for producing half-blocked fields, for matching fields, and for producing donutor shell-shaped dose distributions by gantry rotation. If the movement of the blocks can be controlled during rotation, significant advantages result for "conformation therapy".
PERINEAL
FIELD OOSIMETRY FOR THE TREATMENT OF PROSTATIC CARCINOMA Michael T. Gillin, Ph.D.*, Robert W. Michael T. Gillin, Ph.D.*, Robert W. Kline, Ph.D.*, James D. Cox, M.D.* Nalinakshi Rangala, M.D*, R. Judith Reavis, B.S.*, and W. Dennis Foley, M.D.+ Division of Radiation Therapy*, Division of Diagnostic Radiology+ Medical College of Wisconsin/Milwaukee County Medical Complex, 8700 W. Wisconsin Avenue, Milwaukee, Wisconsin 53326 Perineal fields have been an important component in the external beam irradiation of patients with prostatic carcinoma at the Medical College of Wisconsin and other centers. Many institutions, however, have been hesitant to use this technique because of concern about the homogeneity of the dose to It is difficult the prostate as well as the dose to the adjacent lymph nodes. to visualize the relative location of the prostate and surrounding anatomy, including lymph nodes, covered by the perineal field when the patient is placed in the lithotomy position. A GE 8800 CT scanner has been used to study the anatomy in the region In the normal patient, the aperature of the surrounding the prostate gland. CT unit severly limits the ability of the patient to be placed in the lithWe have scanned a patient who has had one leg amputated otomy position. above the knee and the other leg amputated immediately below the femoral head. This patient was scanned in both supine and lithotomy positions. The transverse axial images were reformatted to display anatomy in saggital midplane and planes parallel to it. Dose distributions representing typical treatment plans for patients with prostatic carcinoma have been superimposed upon the CT images in both the axial and sagittal planes. An estimation of the relative dose delivered by the anterior field, the posterior field, and the perineal field to the prostate, bladder, rectum, rectosigmoid, small bowel, hypogastric nodes, external iliac nodes, and common iliac nodes has been made. A comparison of the dose delivered to these same structures using a rotational boost technique has also been made. Suggestions will be made for CT assisted treatment planning techniques for the normal patient who will be treated utilizing the perineal field.
Proceedings of the 22nd Annual ASTR Meeting RADIUM NEEDLES IMPLANT AND DOSIMETRIC ANALYSIS CERVICAL CANCER WITH EXTENSIVE VAGINAL
1453 IN THE MANAGEMENT INVOLVEMENT
Wilfred Swechand, Sc.D., Vinita Patanaphan, M.D. Thongbliew Prempree, M.D., Ph.D., Thavinsakdi Viravathana, and Ralph M. Scott, M.D.
University
of Maryland
Departmetn of Radiation Therapy Hospital, School of Medicine, Baltimore,
OF
M.D.
Maryland
Brachytherapy is regarded as an integral part of the approach to radiaVariations range from the usual Fletchertion management of cervical cancer. Suit applicator for early cancer to protruding tandem with parametrial implant Local failures in the vagina from routine radium therapy for the late disease. have been seen in many cases of Stage IIA, IIIA and IIIB (FIGO) with extenReviews of local failures have prompted sive involvement of the vaginal canal. us to modify our radium therapy by using radium needles implant in conjuction with routine vaginal cylinder or ovoid, to boost the dose to the region of interest. Prior to radium implant, our patients are given whole pelvis radiation 4,000-5,000 rads/4-5 weeks with appropriate parametrial boost, if needed to 5,000 rads/5$ weeks. Criteria for the implant are: a) Cancer in the vagina still present after whole pelvis irradiation. b) the lesion is thicker than 0.5cm. The following table gives a typical example and pertinent dosimetry from an implant to the anterior vaginal wall, in conjunction with a protruding Our data also show an increase in dose rate of = 7.6% intrauterine tabdem. produced by radium implant for posterior vaginal wall involvement treated with a Bloedorn applicator. Further details and additional examples typical of this implant booster approach, including vaginal volume implant, will be presented. Anterior Vaginal Wall Patient A.B. (57 Y.o.) Stage IVA, with extensive anterior vaginal wall involvement, was treated by whole pelvis irradiation and parametrial boost. This was followed by radium therapy, including needle implant, and local control was achieved. Tandem
loading:
Site of Interest
15-10-10-20 mg.; Radium Needles:
Dose rate from Tandem+Needles (rads/hr)
Urethra Anterior Vaginal Wall (Mid-Radium implant) Point A Point B Bladder Rectum
6x1.5 mg.
Dose rate from Tandem only (rads/hr)
% Increase from Implant
71.6
28.7
149.5
109.2 52.2 13.7 95.8 34.5
47.6 50.6 12.8 38.9 32.7
129.4 z 146:3 5.5
1454
Radiation Oncology 0 Biology 0 Physics
October
1980,
Volume 6. Number 10
A RANDOMIZED TRIAL TO ASSESS THE EFFICACY OF THE COMBINATION OF HORMONAL THERAPY PLUS CHEMOTHERAPY GIVEN TOGETHER TO THE EFFICACY OF SEQUENTIAL HORMONE THERAPY AND CHEMOTHERAPY IN DISSEMINATED MAMMARY CARCINOMA WITH POSITIVE OESTROGEN RECEPTORS Nora G. de Moor, M.B., B.Ch., O.M.R. (Professor)* Werner R. Bezwoda, F.C.P. (SA) ' Dennis 0. Oerman, F.C.P. (SA) ' M. Lange, M.B., B.Ch., (CT) F.R.C. (Edinbrugh)' Department of Therapeutic Radiology* Department of Medicine, Oncology Unit+ Department of Surgerya University of the Witwatersrand, Johannesburg, Republic of South Africa Patients eligible for the trial were females with Stage 4 (MI) carcinoma of the breast, with positive oestrogen receptor (ER) test on either primary or metastatic tumour tissue, and those with local recurrence on chest wall occurring within 2 years of primary treatment. Hormonal therapy consisted of Tamoxifen 20 mgms. b.d. p.o. in Group A and Tamoxifen 20 mgms. b.d. p.o. plus standard CMF therapy in Group B There were 47 cases entered with a median survival of 14 months. Both groups showed an identical survival curve and further addition of patient numbers would be unlikely to alter this. The trial has been closed and indicates there is no advantage to the addition of chemotherapy initially to hormone therapy in ER positive patients, unless patients are severely ill with disseminated visceral metastases, (these cases were excluded from the Tables and graphs will be shown trial) and urgent treatment is mandatory. noting the sites of metastases, side effects of therapy and survival. CARCINOEMBRYONIC
ANTIGEN THERAPY
(CEA) AS A MARKER OF RADIATION
IN LUNG CANCER
Noah C.H. Choi, M.D.*+ and Kurt J. Bloch, M.D.
**
*
Department of Radiation Medicine*, Department of Medicine**, Massachusetts General Hospital, Department of Radiation Therapy+, Department of Medicine*, Harvard Medical School, Eoston, MA Preoperative plasma CEA level and its changes after surgery have been reported to be a useful prognostic indicator for patients with resectable lung cancer. However, its significance relative to radiation therapy has not been adequately studied. Plasma CEA levels were measured prior to radiation therapy by radioimmunoassay in 144 patients with bronchogenic carcinoma. Elevated CEA (26 ng/ml) was observed in 3% (56/144) of all patients. Its frequencies relative to tumor stages were 14% (3/21), 43% (42/97) and 46% (12/26) for stages II, III and IV tumors, respectively. Relative frequencies of elevated CEA ('6 ng/ml) in relation to tumor histologies in stage III tumors were 334: (11/337 for squamous cell carcinoma, 65% (15/23) for adenocarcinoma, 22": (5/22) for oat cell carcinoma, 56% (g/16) for large cell carcinoma and 67X (2/3) for poorly differentiated carcinoma. For 42 patients with elevated CEA (>6 ng/ml) in stage III group, median CEA was 16 ng/ml with a range 6.6 - 63b ng/ml . Serial measurements of CEA 2 2 times were obtained in 557: (23/42) of these patients who had elevated CEA prior to radiation therapy. A very good correlation between the clinical course of the patients and the serial changes of CEA values (return to normal level or increase) was observed in all 23 patients.
Proceedings of the 22nd Annual ASTR Meeting The initial CEA values prior to radiation therapy are very closely related Survival rates > 6 months without tumors. to patients' survival in stage III relapse were ohserved in 46'; (17/37) and 58" (17/29) of patTents with the However, only initial CEA values 1 - 5.8 ng/ml and 6-20 ng/ml, respectively. 14:: (2/14) of patients with CEA > 21 ng/ml (21-630 ng/ml) survived 2 6 months without relapse, P < 0.05. This Study indicates that plasma CEA levels prior to radiation therapy and its serial changes after radiation therapy are of prognostic importance for patients with stage III lung cancer. COMPARISON OF DOSE-TIME-FRACTIONATION SCHEMES IN NON-OAT-CELL LUNG CANCER Kamla Shah, M.D.", Marvin H. Olson, M.D., and Ann E. Wright, Ph.D. Division of Radiation Oncology Department of Radiology The University of Texas Medical Branch Galveston, Texas 77550 The optimal radiation dose and fractionation schemes for inoperable nonSeventy-five percent of all oat-cell carcinoma of the lung is not known. lung cancers are referred for radiotherapy because they are inoperable. The remaining 25% are referred for palliation at some stage. A series of 205 patients with inoperable non-oat-cell carcinoma of the lung were treated with three different dose fractionation schedules. Fiftysix patients received 5000 rads in 25 fractions over five weeks (continuous A); 79 patients received 2000 rads in five fractions over five days, with two weeks rest, followed by 2030 rads in five fractions over five days (splitcourse B); 73 patients received 3000 rads in 10 fractions over two weeks, followed by three weeks rest and another 3000 rads (split-course C). A shrinking field technique was used with the split-course. The histologic distribution of the tumors treated was: squamous cell carcinoma 103 (50.3%), adenocarcinoma 25 (12.22), large cell 24 (11.7%), and undifferentiated carcinoma 46 (22.4%). The stage distribution (AJCCS) was 5.4% stage I, 22% stage II, and 72.6% stage III. The 24-month survival was analyzed by a number of factors including the stage of the disease, the histologic type and the treatment regimen. The local response of tumors was analyzed for each treatment regimen by means of a chest x-ray, taken one month after completion. Radiation fibrosis occurred in all treatient schemes and was dose related. In our experience, the results of 4000 rads split-course was poor. The median survival for continuous 5000 rads and 6000 rads split-course was the same, but the split-course was better tolerated. The above results, tolerance and complications will be presented. MANAGEMENT OF HIGH RISK BREAST CARCINOMA WITH PRIMARY IRRADIATION AND ADJUVANT CHEMOTHERAPY Leo E. Orr, M.D.* A.M. Nisar Syed, M.D., FRCS, DMRT (Eng.)** Ajmel A. Puthawala, M.D. Department of Medical Oncology* and Department of Radiation Medicine** Southern California Cancer Center - California Hospital Medical Center and Los Angeles County - University of Southern California Medical Center Los Angeles, California Fifty-three women with Stage II and III breast cancer underwent a combined modality treatment of primary irradiation and chemotherapy at Southern
1455
1456
Radiation Oncology 0 Biology 0 Physics
October 1980, Volume 6, Number 10
California Cancer Center - California Hospital Medical Center, Los Angeles, California from 1975 to 1979. All patients were staged retrospectively, according to the American Joint Commission for Cancer Staging and End Result Reporting 1977. There were 12, 15, 24 and 2 patients with T4, T3, T2 and TI primary lesions, respectively. Thirty patients had a minimum of 10 positive axillary lymph nodes. Two patients had ipsilateral chest wall metastases. Estrogen receptor studies were performed on 27 women, of which 14 indicated positive results. The primary treatment consisted of a combination of external irradiation (CO'O or 4 MeV linear accelerator), to an average tumor dose of 5000 rad in 5 to 6 weeks, followed by a booster dos f 2500 rad to 4000 rad delivered by an interstitial afterloading Iridium f9? implant. Approximately 4 weeks later all patients were started on chemotherapy usin j a combination of Cytoxan intravenously cycled 600 mg/m2, Methotrexate 50 mg/m2, 5 Fluoruracil mg/m every 21 days. Forty patients are surviving free of recurrent disease with a maximum follow-up period of 54 months (mean survival period of 26.5 months). The remaining 13 patients developed distant metastases with an average remission period of 22.6 months. One of these patients also had a local recurrence. Relapses occured in 1 out of 14 ER (+) patients and 5 out of 13 ER (-) patients The average remission for ER(+), ER(-) and ER(X). patients was 39, 18.5 and Comparable figures for patients with T2, T3_4 and 27 months, respectively. N(+) lesions were 40, 14 and 31 months. Our data suggests that irradiation-chemotherapy modality outlined here offers significant remission and survival benefits for locally advanced breast cancer patients who have substantial risk for recurrences. This treatment also appears to represent an acceptable alternative to debulking surgery and adjunctive systemic anti-tumor treatment. RADIATION THERAPY
IN THE MANAGEMENT OF SUBCLINICAL DISEASE NODES (NO) FROM HEAD AND NECK CANCERS
IN CERVICAL
Rao V.P. Mantravadi, M.D., D.M.R. David Sabato, M.D. Richard E. Haas, B.A. Edwin J. Liebner, M.D. University of Illinois Hospital/ALSM Department of Radiology and Otolaryngology This report deals with a detailed analysis of 187 patients who were initially seen with clinically negative neck and treated by radiotherapy with curative intent. Of these 57 had primary tumor in oral cavity, 38 in oropharynx, 53 in larynx, 16 in hypopharynx and 23 in nasopharynx. The T-Stage distribution for the study population was 21 Tl, 52 T2, 83 T3, and 24 T4. Lateral opposed or multiple fields were used to encompass the primary and upper and mid cervical lymph nodes. Whole neck irradiation including lower cervical and supraclavicular regions was done only during A minimum dose of 4000 rads was given to lymph node bearing recent years. areas with lymph nodes adjacent to the primary receiving the same tumoricida1 dose as that of primary. Computer analysis of the data revealed the following: 1) There were 28 failures (15%) in the neck nodes within the treatment field. Of these concomitant recurrence at the site of primary was present in 26 (93%). 2) The two in-field failures with primary controlled received less than 5000 rads and were in patients with T3 tumors. 3) Recurrent disease outside the treatment ports occured in 7 patients (4%), of whom four were in supraclavicular and lower cervical regions and three were in the posterior cervical chain.
Proceedings of the 22nd Annual ASTR Meeting
1457
We conclude from these results that: 1) A radiation dose of 5000 rad or more can sterilize 99% of the occult disease in lymph nodes. 2) Whole neck irradiation is not indicated in patients with ND disease. 3) Surgical resection of primary alone without added neck dissection is adequate, when postoperative irradiation is planned. Data comparing these results with that of 402 NO patients treated with surgery alone will be presented.
RISK OF BRAIN METASTASIS FROM SMALL CELL CARCINOMA OF THE LUNG RELATED TO LENGTH OF SURVIVAL AND PROPHYLACTIC IRRADIATION Ritsuko Komaki, M. D., James D. Cox, M. D., William Whitson,
M. S.
Division of Therapeutic Radiology Medical College of Wisconsin Affiliated Hospitals Milwaukee, Wisconsin 53226 From 1974 through 1979, 131 patients presented to the Division of Therapeutic Radiology of the Medical College of Wisconsin Affiliated Hospitals with small cell carcinoma of the lung and normal radionuclide or comFrom 1974 through 1977. 74 patients received puted tomography brain scans. no prophylactic cranial irradiation (NPCI) and from 1976 to 1979 57 received prophylactic treatment (PCI). Of the NPCI group. 50% had limited disease; 46% were treated with chest irradiation alone, and 53% had chest irradiation Of the plus simultaneous chemotherapy; the median survival was 30 weeks. PC1 group, 49% had limited disease; 40% received chemotherapy alone and 60:; received chest irradiation and chemotherapy; the median survival was 35 weeks. The NPCI patients experienced a persistent increase in the actuarial probability of clinical brain metastases which reached 28% at 12 months and 58% at 24 months. The PC1 patients had an actuarial rate of ll? at 12 and at 24 months. The difference in brain metastasis between the NPCI and PC1 Prophylactic cranial irradiation groups is highly significant (P<.OOl). eliminates the progressive increase in the risk of brain metastases that accompanies increased survival and is essential for cure of these patients.
A REVIEW OF SEVENTEEN
CASES WITH OVARIAN DYSGERMINOMA
H.H. Tewfik, M.D.*, F.A. Tewfik, M.D. and H.B. Latourette, University
of Iowa Hospitals & Clinics: Department and Radiation Research Laboratory
M.D.*
of Radiology*
This is a retrospective evaluation of 17 patients with the diagnosis of ovarian dysgerminoma who were seen & treated at the University of Iowa Hospitals from January of 1938 to December of 1976. Age ranged from 11 to 54 years. The commonest age was in the 2nd and 3rd decades. Not a single patient was lost for follow-up. Seven patients died with disease - 3 during the 1st year, 3 during the 2nd year and 1 during the 4th year after diagnosis. Two were stage Ia but there was rupture of the tumor during the unilateral salpingoophorectomy (SO). These 2 patients received no postoperative radiation therapy (RT), both recurred in the pelvis and both are dead with disease. Two were Stage IV, both had total abdominal hysterectomy and bilateral salpingoophorectomy (TAH-BSO), 1 was treated with palliative RT and chemotherapy and the other was treated with chemotherapy and both died with disease. Three patients were unstaged. Two were treated with unilateral SO & 1 with TAH-BSO, 2 received postoperative RT and recurred in the abdomen.
1458
Radiation Oncology 0 Biology ??Physics
October 1980. Volume 6, Number 10
We have 10 patients with no evidence of disease (NED); 1 died 37 years after diagnosis from other causes and the other 9 patients are living NED. The duration of follow-up of that group is from 39 to 444 months with a median of 90 months. Two patients with Stage Ia were treated with TAH-BSO & postoperative RT; 1 patient was treated in the form of external RT to the pelvis (4500 rad) and the 2nd patient had intraperitoneal instillation of radioactive gold. A 3rd patient with Stage Ia was treated with TAH-EGO with no postoperative RT. The 4th and 5th patients with Stage Ia were treated with unilateral SO and unilateral pelvic plus paraaortic lymphadenectomy and no postoperative RT. A 6th patient with Stage Ia was treated with unilateral SO only. Four patients with Stage IIb disease were treated, 3 patients with unilateral SO and postoperative RT - 2 of which had RT to the whole abdomen (2000 rad) with a boost dose to the pelvis and paraaortic lymph nodes (PALN) (1500-2100 rad). The 3rd patient received postoperative RT to the pelvic cavity and PALN's with inverted-Y field to 3000 rad. In these 3 patients, prophylactic mediastinum and left supraclavicular RT was delivered (2550 rad). The 4th patient with Stage IIb disease was treated with TAH-BSO and postoperative RT to the pelvis (3575 rad) and to the PALN's (2575 rad). Our results suggest that in Stage Ia dysgerminoma, unilateral SO may be enough with no need for postoperative RT. In Stage II disease, there is indication for postoperative RT to the pelvis and PALN. In Stage III disease, postoperative RT to the whole abdomen with a boost dose to the pelvis and In Stage II and III disease, treatment should be PALN's is recommended. followed by prophylactic mediastinal and supraclavicular RT.
COMPUTERIZED
DOSIMETRY IN CARCINOMA OF THE CERVIX, IS IT NECESSARY?
Young, J.J., Blumberg, A.L., Lambert, B.,
Littman,
P.
The University of Pennsylvania School of Medicine and The Fox Chase Cancer Center Philadelphia, Pa. A review (1972-1977) was conducted of 110 cases of Stage I and II carcinoma of the cervix treated with radiation therapy alone at the Hospital of the University of Pennsylvania and the Fox Chase Cancer Center. Particular attention was focused on the usefulness of the isodose distribution surrounding the intracavitary radium or cesium applicators (Fletcher-Suit). The relationships between local tumor control, complications and the following parameters were analyzed: miligram hours; total dose in rads, rets and TDF; relative proportions of external and intracavitary dose; Point A and Point B; the bladder; and the rectum. The treatment regimens used resulted in the actuarial disease free and overall survival at 5 years in excess of 90 percent. Severe complications occurred in only 6:: of the entire group. While the dose prescribed for brachytherapy varied within a relatively circumscribed range, there was considerable variation from patient to patient in the bladder (4780 to 9760 rads) and rectal doses (4620 to 7870 rads). Since the percentage, of local tumor control was quite high in this series, the Contumoricidal abilities of doses in common usage seems well established. versely, since severe bladder and rectal damage was infrequent, even within wide fluctuations of dose, the threshhold for these effects remains uncertain. The value of computer determined isodose distributions in assessing the potential for both cure and normal tissue injury appears limited. Patient management decisions may be made on the external irradiation based on rads and on the intracavitary component based on milligram hours, provided that a stan(At a time when interest in the dard applicator and loadings are utilized. surgical approach for Stage I and II carcinoma of the cervix is increasing, a reminder of the simple safe and effective role of radiation therapy is appropriate).
1459
Proceedings of the 22nd Annual ASTR Meeting EFFECTIVENESS, RECURRENCES AND COMPLICATIONS OF THERAPY WHEN COMBINING WHOLE PELVIS IRRADIATION AND INTRACAVITARY RADIUM APPLICATIONS IN STAGE IA TO IIB CARCINOMA OF THE CERVIX PATIENTS Bharati
Kharkar, M.D. and Ned B. Hornback, M.D.
Department of Radiation Oncology Indiana University School of Medicine 1100 West Michigan Street Indianapolis, Indiana 46223 A retrospective study of 98 patients ranging from 16 to 80 years of age (mean age of 50 to 55 years) was undertaken to evaluate the effectiveness, recurrences and complications of therapy with a full course of radiation treatments combining whole pelvis irradiation and intracavitary radium application, for patients with stage IA to IIB carcinoma of the cervix with intact uterus from January of 1968 to December of 1973. The average followup period The uncorrected overall five-year survival ranges between five to ten years. 19 of 98 patients were lost to followup. Eight out of 79 patients was 79.5%. developed pelvic recurrence (10%). The majority of the recurrences were withFour out of 79 patients dein the first two years of radiation treatments. veloped distant metastasis (5%), three out of four had pulmonary metastasis, and two out of four had bony metastasis in two to eight years post-radiation Four patients developed second primaries within five to seven years therapy. post-radiation treatments, three out of four developed breast cancer, and one out of four had medullary thyroid carcinoma. The occurrence of minor GI and GU tract complications of nausea, vomitPercentage of major ing, proctitis, sigmoiditis, and cystitis was minimal. complications including persistent diarrhea, haemorrhagic cystitis, sigmoid fibrosis, recta-vaginal, vesico-vaginal fistula was 13%. The most cornROn complication was vaginal vault necrosis (26%) which was corrected with conservative methods, no surgery was required.
MANAGEMENT OF ADENOID CYSTICCARCINOMA OF THE CERVIX UTERI (CYLINDROMA) Thongbleiw
University
Prempree,
M.D., Ph.D.*, Umberto VillaSanta, and Chik-Kwun Tang, M.D.***
M.D., F.A.C.O,G.**
Department of Radiation Therapy* Department of Obstetric and Gynecology** Department of Pathology*** of Maryland Hospital, School of Medicine, Baltimore,
Maryland
21201
Adenoid cysteic carcinoma (Cylindroma) of the cervix is a very rare disease and probably accounts for 0.2% or less of all invasive cervical cancer. To date, there have been only 38 cases of invasive adenoid cystic carcinoma of the cervix reported in world literature. Because of its rarity, the methods of treatment have not been uniform and the results are far from being satisfactory. We have identified and reviewed six cases of adenoid cystic carcinoma of the cervix treated at the University of Maryland Hospital from 1963 to 1978. The outstanding features of these six cases will be discussed in details with respect to clinical course, histopathologic uniqueness and treatment along with results. Including the present series, a total of 43 cases (from several series) of adenoid cystic carcinoma of the cervix are being analyzed and summarized in the following table:
1460
Radiation Oncology 0 Biology 0 Physics
October 1980, Volume 6. Number 10
Adenoid Cystic Carcinoma of the Cervix Cumulative Patients Data S-Year Survival NED*
Stage
No. Patients
I
16
8
4(50%)
7
5(71.4%)
1
O(O%)
-
g/16(56.2%)
II
11
_
_
8
3(38%)
2
O(O%)
1
3/11(27.3%)
III
4
_
-
4
O(O%)
-
-
-
O/4(0%)
IV
1
_
_
1
O(O%)
-
-
-
O/1(0%)
11
5
1(20%)
6
1(17%)
-
-
-
2/11(20%)
All Stages 43
13
Unknown
NB -1.
Surqery Cases NED*
Radiation Cases NED*
4
5(38.5%) 26 9(34.6%)
NED* - No evidence of Disease
POSSIBLE ENHANCEMENT
R;ise; Su;zerr
3
0(0x)
No
Total
14/43(32.5%)
(Cancer)
OF RADIATION-INDUCED
HEPATITIS
BY PRIOR CHEMOTHERAPY
Sabina R. Wallach, M.D. Raymond Taetle, M.D. Stephen L. Seagren, M.D. Divisions of Hematology/Oncology and Radiation Oncology University of California, San Diego
The syndrome of acute radiation hepatitis is characterized by the onset of right upper quadrant pain, hepatomegaly, jaundice and ascites, in association with abnormal liver function, and occurs within weeks of radiation to the organ. It appears to be dose related, with a significantly increased incidence at doses greater than 3,500 rads delivered in standard fractions -of 100-200 rads. We wish to report a case which occurred following the delivery of only 2400 rads to the liver of a patient who had previously received chemotherapy This radiation dose is the lowincluding cyclophosphamide and vincristine. est reported in association with fatal radiation hepatitis. The patient was a 50 year old man with a two year history of localized gastric lymphoma of the nodular mixed lymphocytic-histiocytic type. He had received COP combinat'on chemotherapy (cyclophosphamide 1 gm/m2 IV da 1, vincristine 1.4 mgm/m $ (maximum 2 mgms) IV day 1, prednisone 100 mg/m 3 P.O. days 1-5, q 3 weeks) intermittently during this period. Because of radiological and biopsy evidence of residual disease, and persistent symptoms, he received abdominal bath irradiation of 2400 rads in 16 fractions (150 rads per fraction) over a 3 week period, with an additional 1300 rad boost to the stomach, with the left hepatic lobe shielded. Most of the liver received a total dose of 2400 rads. His last dose of chemotherapy was administered more than one month prior to the commencement of radiation. Three weeks following the completion of radiation, he was admitted to the hospital with mild orthostatic hypotension and jaundice. His liver and spleen were normal in size. He was thrombocytopenic and had abnormal liver function with moderate elevation of hepatic transaminases and alkaline phosphatase, and markedly elevated bilirubin levels; however, prothrombin time Despite supportive therapy, he developed progresand albumin were normal. Histosive jaundice and ascites, and died of hepatic failure 19 days later.
Proceedings of the 22nd Annual ASTR Meeting
1461
pathology of the liver at autopsy revealed diffuse centrilobular veno-occlusive changes characteristic of radiation hepatitis. Several drugs, including actinomycin D and vincristine, are known to enhance the toxicity of hepatic irradiation. However, emphasis has previously been placed on the close temporal relationship between drug administration and hepatic irradiation required for development of the syndrome. Our patient suggests that this temporal relationship may not be critical to the development of radiation hepatitis. Accordingly, we recommend that a reduction in the total dose of hepatic irradiation be considered in patients with prior vincristine or cyclophosphamide exposure, irrespective of the interval between drug administration and radiotherapy.
PRE-OPERATIVE
VS. POST-OPERATIVE
C.K. Chung, M.D.,
J.A.
RADIOTHERAPY
FOR STAGE I ENDOMETRIAL
CARCINOMA
Stryker, M.D., W.A. Nahhas, M.D. & R. Mortel, M.D.
M.S. Hershey Medical Center The Pennsylvania State University Hershey, Pennsylvania One hundred eighty-five patients with endometrial carcinoma were treated at Hershey Medical Center between July, 1971, and June, 1978. Eighty-five Most of the patients (81%) patients (50%) had clinical stage I (FIGO) disease. received either pre-op or post-op RT and surgery (TAH and BSO) except those patients with stage IA - grade I patients without myometrial invasion were usually treated with surgery alone (13 patients). Thirty-three patients received pre-op RT: 6 intracavitary, 26 external, and 11 external plus intracavitary. Thirty-six patients had post-op RT: 2 intracavitary, 9 external, and 25 external plus intracavitary. Three patients were treated with RT alone. The incidence of deep myometrial invasion (>2/3 thickness) was 5% for grade 1, 17% for grade 2, and 71% for grade 3. The risk of extra-uterine disease was 0% for grade 1, 9% for grade 2, and 16% for grade 3. All 11 patients with failures (2 pelvic, 3 pelvic and D.M., and 6 D.M.) were either grade 2 or 3. Distant metastasis developed only in stage IB patients. Treatment failures and survivals were presented by histologic type and grade, clinical and surgical-pathologic stages, depth of myometrial invasion, treatment modality, and radiotherapy technique. The reasons for failure were discussed. The overall 5 year survival, pelvic failures, and complication rate were 83%, 7% and 3% respectively: these results were comparable between pre-op and post-op RT groups. However, post-op RT offers the advantages of accurate surgical-pathologic staging and optimal individualization of adjuvant therapy.
“iloW -IRI-1A FOUNDATION.. .?".4 SECOND LOOK AT SOME OBSERVAfIONS Donald E. Herbert, University
of South Alabama,
Deoartment
ON Ro07-0582.
Jr., Ph. cl.
of Radiology,
Mobile,
Alabama
36688
A significant part of the received wisdom on both the toxicitv and efficau of tne radiation sensitizer Ro07-0582 in satients seems -been derived by tne aoplication of some inaporopriate computations to clinical data. As a result, the conventional representations of these two effects of this drug are likely to be incorrect. Yoreover, it aopears that the more serious of the ap-
Radiation Oncology 0 Biology 0 Physics
1462
October 1980, Volume 6, Number 10
oarent misrepresentations of these two effects of this drug derives not so much from tne misaoolication of standard statistical methods but rather from the a~ol:cation of methods which seem to be oriainal, ad hoc, inventions. This paper describes these deficienc:es in scme detail. It also describes the application of the standard statistical methods of bioassay to some published data on this drug in order to illustrate the correct representations of these two properties. These alternative descriptions show that the true values of the location and shape of the dose-response curves, both for enhancement of radiation effects and for concommitant neuropathy, may be considerably different from those which are regularly described for 5007-0582. The uncertainty of the estimates of the true values which are orovided by these data (0.95 confidence limits on curves) are also considerably greater than the conventional representations would suggest. The paper presents an argument for the wider use of simole, statistical methods in the design and evaluation of both laboratory and clinical exberiments with such toxic substances. The correct representations of the dependence uoon serum levels of Ro070582 of enhancement of radiation effect and of incidence of neuropathy are shown in Figures 1. and 2, respectively
Figure 1
MEDULLOELASTOMA THE RESULTS OF RADIOTHERAPY AT THE UNIVERSITY OF KENTUCKY MEDICAL CENTER H. W. Chin, M.D. and Y. Maruyama, M.D. University of Kentucky Medical Center Lexington, Kertucky A review of patients treated for cerebellar medulloblastoma in the past 12 years is presented. A total of 22 patients were treated in this series. A correlation of radiation dose and survival time was carefully analyzed.
Proceedings of the 22nd Annual ASTR Meeting With uniform radiotherapy using tumor doses of 5000 rad or more, a S-year survival rate of 80% was obtained. In contrast only 33% of patients survived five years with tumor doses less than 4600 rad even when using the whole Treatment failure were due crania-spinal axis radiation treatment method. to local recurrence and occurred in more than 80X of cases with low dose irradiation. The development of hydrocephalus indicated a poor prognosis. There were no 5-year survivors in this group. Ten per cent of patients Our experience suggested a dose-dependent showed extracranial metastases. survival rate wher effective irradiation technique and a variety of tumor doses were used. The data suggests that one important factor in tumor control and long term survival is tumor dose. Available data and a review of the literature and time-dose relationship will be carried out. Literature data also indicates that such a relationship holds for this brain tumor. Supported
in part by NC1 grant POl-CA 17786.
RADIATION THERAPY FOR PITUITARY ADENOMAS ANALYSIS OF TREATMENT AND RESULT OF 59 PATIENTS WITH REVIEW OF THE CLINICAL PRESENTATION AS RELATED TO THE MICROSCOPIC DIAGNOSIS.
Eitan Medini, M.D., Chung K.K. Lee, M.D., Yashoda Rao, M.D., Roger Potish, M.D., Robert E. Haselow, M.D., Taehwan Kim, M.D., Thomas K. Jones, Jr. M.D. Seymour H. Levitt, M.D. Department of Therapeutic Radiology, University of Minnesota and Veterans Administration Medical Center, Minneapolis, Minnesota 55477
Clinical presentation, variety of laboratory and radiological methods and findings of 59 patients with pituitary adenomas, treated in the Departments of Radiation Therapy of the University of Minnesota and Veterans Administration Medical Center, Minneapolis, Minnesota, from 1966 to 1975, are being presented. Of this group: 4 patients had Cushing's syndrome; 12 had growth hormone secreting tumors; and 43 had hormone nonsecreting tumors. The clinical presentation is being discussed as related to the microscopic diagnosis. In 85% of the patients, chromophobe adenoma was found. The vast majority of the patients were referred for radiation after undergoing hypophysectomy, adenomectomy, or biopsy. No correlation was noted between the microscopic findings and the variety of the clinical presentation of Cushing's syndrome, Nelson syndrome, acromegaly, gigantism, hormonal deficiency, and mechanical pressure related symptans. Chromophobe adenoma was found in 2 out of 4 patients with Cushing's syndrome, and in 5 out of 12 with growth hormone secreting adenoma. Forty-three patients had nonfunctioning chromophobe adenoma. Special stains will be reviewed. 4500-5000 rads tumor dose by 175-200 rads/fraction, 5 fractions/week, were given postoperatively using bilateral 6 x 6 cm opposing ports isocentrically. Few patients had additional frontal port. Megavoltage units were used. The overall control rate of hormonally nonfunctioning adenomas, and that of growth hormone secreting adenomas was 85% in 5 years and 75% in 10 years. The treatment of the 4 patients with Cushing's syndrome and of those who developed Nelson syndrome was not uniform and will be reviewed accordingly. Multiinstitutional cooperation will be offered.
1463
1464
Radiation
Oncology
0
EFFECT DXE
OF
RESPONSE Timothy
Eastern
Dept. Virginia
Biology
of
0
Physics
SURVIVAL
OF
Norfolk,
Ph.
Oncology School/Medical
6, Number
10
ON
NORMAL
Schultheiss,
Radiation Medical
1980. Volume
STATISTICS
FUNCTIONS E.
October
TISSUES D.
8 Biophysics Center
Hospitals,
Virginia
When calculating survival statistics for a group going treatment for a specific disease, it is desirable rections to account -for the effect norma I morta I i ty . must be applied when analyzing clinical data to obtain
of
patients
under-
to apply age corSimi lar corrections the dose response
of
normal tissues if the average survival time is not long compared to the average latent period for the expression of the injury under study. It will be demonstrated that ignoring these corrections can result in serious errors in determining the shape of the dose will be presented by which these errors can demonstrated that these new methods consistently bioassay techniques when applied to clinical to properly analyze a group of patients for was required in order to be included in the
response curve. Two methods be eliminated. It will be out perform conventional data. One method is designed which a minimum survival time analysis. The second method
designed to allow the relaxation of the minimum survival order to allow the use of all patients in the study. It the second method is independent of the survival functions
requirement
is
in
wi I I be shown that for the treated
requiring rather a knowledge of the distribution of latent periods group, for the injury under study. One may therefore use this method to group together for analysis all patients at risk for a particualr injury no matter from what disease they suffer. These methods of analysis, validity tests of the procedures, and an application to the analysis of the dose response of spinal cord will be presented,
OF MOUSE BONE MARROW HEMOPOIETIC AND STROMAL CELLS: RADIATION SENSITIVITY EVIDENCE FOR SUBPOPULATIONS WITH DENSITY DEPENDENT SURVIVAL CHARACTERISTICS
Joel S. Greenberger, M.D., Ralph R. Weichselbaum, M.D. Annie Schmidt, B.S., Maryann Sakakeeny, M.S., and John 8. Little, M.D. Joint Center for Radiation Therapy, Department of Radiation Therapy, Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts 02115 Fresh bone marrow from NIH Swiss and NZB mice and was studied for the in vitro radiation sensitivity of clonagenic granulocyte-macrophage progenitor Cells were irradiated in suspension inMcCo;+s 5A supplemented cells (GM-CFUC). medium (Greenberger, et.al., Blood, 53:587-1001, 1979) in air or in the preCells were plated in 0.3% agar with sence of high concentrations of oxygen. McCoy's 5A medium, 10% L-cell colony stimulating factor (CSF) and 10% fetal Hemopoietic stem cells free calf serum at several different plating densities. of marrow stromal cells were obtained by harvest of nonadherent cell fractions These cells were depleted of of 16-week-old long-term bone marrow cultures. marrow stromal cells including adipocytes, fibroblasts, macrophages, and endothelial cells which are present in fresh bone marrow. The radiation survival curve of GM-CFUc from fresh bone marrow and of purified GM-CFUc from long-term bone marrow cultures revealed that both populations had a Do which5increased from 100 to 210 Rad as the plating density increased from 1.0 x 10 to 5.0 x 105 cells per mL. Although a small radioresistant cell population was also observed at low cell densities in NIH Swiss marrow cultures, NZB cultures did not reveal a resistant cell population even at low cell densities (D,=104). The radioresistance at hiqh density could not be attributed to hypoxia at the
Proceedings of the 22nd Annual ASTR Meeting
1465
higher cell plating densities since identical results were obtained with cells irradiated in the presence of oxygen. Morphologic examination of colonies revealed predominantly macrophage colonies induced by L-cell CSF. This resistant tail was not observed with nonadherent cells from long-term NIH Swiss bone marrow cultures (D,=lOO). The data suggest that a stromal-adherent cell population in bone marrow demonstrates radiation survival characteristics similar to that of embryo or skin fibroblast cells. Furthermore, subpopulations of hemopoietic cells at high density may protect other cells from radiation damage by indirect effects including induction of repair functions.
ExposingA Phantom
Back tn1960 ourchtef medlcal physlclst developed the radiotherapy phantom In general use today. The world was satisfied, but we weren’t, So we developed a new phantom of greater ftnesse, fuller fldellty We named him RT-Humanoid. His secrets: A higher standard of skeletal symmetry More completelmpreanation of marrow cavities with tissue equivalent matenal Improved water-equivalence (within ‘i percent) More sophisticated vacuum molding to reduce residual arr We Improved techniques for transecttng the phantom, using a thinner coating material (0.5 to 1 mm.) to mtnimrze bone and lung discontinuities at the Interfaces We developed new lung-equivalent plugs for greater accuracy. And we improved and stmplifled sectlonal assembly methods with skillfully deslgned aluminum plates and nylon rods Result. greater ease In patient-like posltlonlng. There you have It our Phantom, exposed. Send for COmDlete information.
Humanoid Systems 17022 Montanero Street Carson, California 90746 (213) 537-7851 Telex 69-l 186 International Division 2200 Shames Drive Wesrbury Long Island. N.Y 11590 (516) 344-3303 Telex 94-l 474 or 12-5391
Radiation Oncology 0 Biology 0 Physics
October 1980, Volume 6, Number IO
a radiotherapist selects an array of normal and tumor anatomical points of A point source calinterest, localized accurately by radiographic means. cultational procedure or tabulated data look-up method is used to approximate the dose rate to each point of interest from the brachytherapy source array. Presently, in our clinic, a computer method is followed which incorporates a maximization - minimization approach to the optimization procedure. The source loading is altered sequentially to achieve the maximum dose rate differentials between normal and tumor tissues. With this method the the loading of the ovoids, the number of sources in therapist specifies: the tandem, and the tolerance doses to several points. Given a geometric arrangement of the applicator, the computer finds the optimum arrangement of sources within the tandem. The computer program output displays a variable number of best source loadings (10 - 20) and the following judge1) R - the maximization index, 2) the rads/mg-hr to ment criteria: point A, and 3) the dose rates and total doses to anatomical reference Then with therapist input, the best plan is chosen points of interest. based upon the clinical problem and stage of disease. An isodose distribution is then printed to verify the clinically chosen best loading. Using a minicomputer, POP-8, the required computer memory storage is small and the computation time is short. Research supported in part by National Cancer Institute PO1 CA 17786.
BORON NEUTRON CAPTURE THERAPY; PORPHYRIN DISTRIBUTION IN VARIOUS TUMORS* R.G. Fairchild, Ph.D., K. Watts, B.S., 0. Greenberg, B.S., S. Packer, M.D., P. Som, D.V.M. and S.J. Hannon, Ph.D. Medical and Chemistry Departments Brookhaven National Laboratory Upton, New York 11973 The recent development of various borated compounds, and the utilization of one of these (Na2B 2HIISH) in the treatment of patients with tumors in Japan, has renewed in#.erest in Neutron Capture Therapy (NCT). In this procedure, thermal neutrons interact with "B in boron-containing cells through the"B(n,a) Li reaction. The charged particles (EToT = 2.3 MeV) have a maximum range of s 10~ in tissue. Poor results in clinical trials before 1961 were attributed to poor thermal neutron penetration in tissue, and high levels of "B in blood. The development of an epithermal nuetron beam at the Brookhaven Medical Research Reactor provides deeper neutron penetration. New compounds provide better blood clearance. Chlorpromazine (CPZ) has been synthesized in Japan, with 'L 25% by weight boron. CPZ is known to combine with pigment (melanin) in melanoma, with a clearance half-time in the order of days, thus allowing clearance from other tissues, including blood. Further, porphyrins are known to be taken up by tumors. In particular, we have studied the distribution of tetraphenylporphinesulfonate (TPPS) in several tumors, including melanotic and amelanotic melanoma, carcinoma, and sarcoma. Animals given 50 mg/kg TPPS show tumor uptakes of 'L 150 ug TPPS/g tumor. Accumulations in tumor are generally above those in other tissues, with the exception of kidney. A borated analog of TPPS has been reported in the literature. Given a distribution similar to TPPS, extrapolated boron concentrations exceed 50 pg/g. This should be more than adequate for therapy, particularly with brain tumors, where the blood-brain barrier limits penetration into normal tissue. * Work supported by National Cancer Institute, Grant No. ROl-CA22749 and in part by United States Department of Energy Contract No. DE-AC02-76CH00016.
1451
Proceedings of the 22nd Annual ASTR Meeting DEPENDENCE
OF THE CT NUMBER - ELECTRON DENSITY RELATIONSHIP
SIZE AND X-RAY BEAM FILTRATION
M.E. Masterson,
C.L. Thomason,
ON PATIENT
FOR FAN BEAM CT SCANNERS
S.C. Hsi, R. McGary,
L.D. Simpson,
D.W. Miller, J,S. Laughlin Memorial
Sloan-Kettering
Cancer Center
The applicability of information contained in CT scans to the treatment planning heterogeneity problem has been recognized by members of the Determination of the radiological community and by manufacturers. relationship between electron density and CT number is important for Results of experimental investigations using radiotherapy applications. tissue-equivalent phantoms of different cross sectional shapes and areas on the Ohio Nuclear Delta 2020 and the G.E. CT/T8800 are presented. A variation in the CT number-electron density relationship is demonstrated on these fan beam geometry scanners for phantoms of different sizes. An Investigations also cover the explanation of this effect is included. effect of "shaped" and "flat" x-ray beam filters on electron density Differences on the order of 20% in determination of tissue determination. A family of curves electron density relative to water are reported. (electron density vs. CT number) is presented for different patient cross sectional areas and different scanner settings.
EVALUATION
OF AN ECCENTRIC
R.D. Larsen,
X-RAY COLLIMATOR
K.R. Kase, B.E. Bjarngard
Joint Center for Radiation Therapy and Department of Radiation Therapy Harvard Medical School, Boston, Massachusetts Normally, the beam-defining assembly in modern x-ray producing accelerators consists of four shielding blocks, coupled together in pairs as the inner and outer collimators. The blocks define a variable rectangular field, the center of which lies on the rotational axis of the collimator assembly, which, in its turn, intersects the rotational axis of the gantry at the "isocenter". We have obtained a Siemens Mevatron XII linear accelerator, producing 8 MV x-rays, in which the four collimator blocks operate independently. This allows the shaping of rectangular fields that are eccentric with respect to the collimator rotational axis. In the system, two opposing collimator blocks can move up to the centerline, while each of the other two opposing blocks can cross the centerline to a distance of 11 cm beyond it. Since the flattening filter in this machine normally oroduces a nonuniform distribution of primary photons, special dosimetric problems may arise for eccentrically placed fields. Other problems might occur because of the difference in filtration at various parts of the field and oblique incidence of the beam. The purpose of this study has been to evaluate these potential problems. The dose delivered per monitor unit as measured in air increases as the field position moves away from the centerline. The increase reaches 4% in a 5 cm x 71cm field cantered 12 cm off the centerline and is somewhat less for larger fields. This ix'.rease disappears when the measurements are made at a depth of 10 cm in water, probably because of a balance between the variation
1452
Radiation Oncology ??Biology ??Physics
October 1980. Volume 6, Number 10
in primary intensity and the changes in beam quality as distance from the cente!*'ine increases. Half value layer studies have indicated substantial changes in beam quality as one moves away from the centerline. Isodose distributions measured for eccentrically placed fields are influenced by these changes in beam quality and in addition show a tilting of the curves caused by the variation of the primary x-ray intensity. Dose buildup measurements indicate an increase of surface dose as the field is more eccentrically placed. Modification of the flattening filter to change the primary x-ray distribution and the filtration of the beam can help to overcome the differences in isodose distributions and dose buildup for eccentrically placed fields. Independentl,y moveable collimators are useful in conventional radiotherapy for producing half-blocked fields, for matching fields, and for producing donutor shell-shaped dose distributions by gantry rotation. If the movement of the blocks can be controlled during rotation, significant advantages result for "conformation therapy".
PERINEAL
FIELD OOSIMETRY FOR THE TREATMENT OF PROSTATIC CARCINOMA Michael T. Gillin, Ph.D.*, Robert W. Michael T. Gillin, Ph.D.*, Robert W. Kline, Ph.D.*, James D. Cox, M.D.* Nalinakshi Rangala, M.D*, R. Judith Reavis, B.S.*, and W. Dennis Foley, M.D.+ Division of Radiation Therapy*, Division of Diagnostic Radiology+ Medical College of Wisconsin/Milwaukee County Medical Complex, 8700 W. Wisconsin Avenue, Milwaukee, Wisconsin 53326 Perineal fields have been an important component in the external beam irradiation of patients with prostatic carcinoma at the Medical College of Wisconsin and other centers. Many institutions, however, have been hesitant to use this technique because of concern about the homogeneity of the dose to It is difficult the prostate as well as the dose to the adjacent lymph nodes. to visualize the relative location of the prostate and surrounding anatomy, including lymph nodes, covered by the perineal field when the patient is placed in the lithotomy position. A GE 8800 CT scanner has been used to study the anatomy in the region In the normal patient, the aperature of the surrounding the prostate gland. CT unit severly limits the ability of the patient to be placed in the lithWe have scanned a patient who has had one leg amputated otomy position. above the knee and the other leg amputated immediately below the femoral head. This patient was scanned in both supine and lithotomy positions. The transverse axial images were reformatted to display anatomy in saggital midplane and planes parallel to it. Dose distributions representing typical treatment plans for patients with prostatic carcinoma have been superimposed upon the CT images in both the axial and sagittal planes. An estimation of the relative dose delivered by the anterior field, the posterior field, and the perineal field to the prostate, bladder, rectum, rectosigmoid, small bowel, hypogastric nodes, external iliac nodes, and common iliac nodes has been made. A comparison of the dose delivered to these same structures using a rotational boost technique has also been made. Suggestions will be made for CT assisted treatment planning techniques for the normal patient who will be treated utilizing the perineal field.
Proceedings of the 22nd Annual ASTR Meeting RADIUM NEEDLES IMPLANT AND DOSIMETRIC ANALYSIS CERVICAL CANCER WITH EXTENSIVE VAGINAL
1453 IN THE MANAGEMENT INVOLVEMENT
Wilfred Swechand, Sc.D., Vinita Patanaphan, M.D. Thongbliew Prempree, M.D., Ph.D., Thavinsakdi Viravathana, and Ralph M. Scott, M.D.
University
of Maryland
Departmetn of Radiation Therapy Hospital, School of Medicine, Baltimore,
OF
M.D.
Maryland
Brachytherapy is regarded as an integral part of the approach to radiaVariations range from the usual Fletchertion management of cervical cancer. Suit applicator for early cancer to protruding tandem with parametrial implant Local failures in the vagina from routine radium therapy for the late disease. have been seen in many cases of Stage IIA, IIIA and IIIB (FIGO) with extenReviews of local failures have prompted sive involvement of the vaginal canal. us to modify our radium therapy by using radium needles implant in conjuction with routine vaginal cylinder or ovoid, to boost the dose to the region of interest. Prior to radium implant, our patients are given whole pelvis radiation 4,000-5,000 rads/4-5 weeks with appropriate parametrial boost, if needed to 5,000 rads/5$ weeks. Criteria for the implant are: a) Cancer in the vagina still present after whole pelvis irradiation. b) the lesion is thicker than 0.5cm. The following table gives a typical example and pertinent dosimetry from an implant to the anterior vaginal wall, in conjunction with a protruding Our data also show an increase in dose rate of = 7.6% intrauterine tabdem. produced by radium implant for posterior vaginal wall involvement treated with a Bloedorn applicator. Further details and additional examples typical of this implant booster approach, including vaginal volume implant, will be presented. Anterior Vaginal Wall Patient A.B. (57 Y.o.) Stage IVA, with extensive anterior vaginal wall involvement, was treated by whole pelvis irradiation and parametrial boost. This was followed by radium therapy, including needle implant, and local control was achieved. Tandem
loading:
Site of Interest
15-10-10-20 mg.; Radium Needles:
Dose rate from Tandem+Needles (rads/hr)
Urethra Anterior Vaginal Wall (Mid-Radium implant) Point A Point B Bladder Rectum
6x1.5 mg.
Dose rate from Tandem only (rads/hr)
% Increase from Implant
71.6
28.7
149.5
109.2 52.2 13.7 95.8 34.5
47.6 50.6 12.8 38.9 32.7
129.4 z 146:3 5.5
1454
Radiation Oncology 0 Biology 0 Physics
October
1980,
Volume 6. Number 10
A RANDOMIZED TRIAL TO ASSESS THE EFFICACY OF THE COMBINATION OF HORMONAL THERAPY PLUS CHEMOTHERAPY GIVEN TOGETHER TO THE EFFICACY OF SEQUENTIAL HORMONE THERAPY AND CHEMOTHERAPY IN DISSEMINATED MAMMARY CARCINOMA WITH POSITIVE OESTROGEN RECEPTORS Nora G. de Moor, M.B., B.Ch., O.M.R. (Professor)* Werner R. Bezwoda, F.C.P. (SA) ' Dennis 0. Oerman, F.C.P. (SA) ' M. Lange, M.B., B.Ch., (CT) F.R.C. (Edinbrugh)' Department of Therapeutic Radiology* Department of Medicine, Oncology Unit+ Department of Surgerya University of the Witwatersrand, Johannesburg, Republic of South Africa Patients eligible for the trial were females with Stage 4 (MI) carcinoma of the breast, with positive oestrogen receptor (ER) test on either primary or metastatic tumour tissue, and those with local recurrence on chest wall occurring within 2 years of primary treatment. Hormonal therapy consisted of Tamoxifen 20 mgms. b.d. p.o. in Group A and Tamoxifen 20 mgms. b.d. p.o. plus standard CMF therapy in Group B There were 47 cases entered with a median survival of 14 months. Both groups showed an identical survival curve and further addition of patient numbers would be unlikely to alter this. The trial has been closed and indicates there is no advantage to the addition of chemotherapy initially to hormone therapy in ER positive patients, unless patients are severely ill with disseminated visceral metastases, (these cases were excluded from the Tables and graphs will be shown trial) and urgent treatment is mandatory. noting the sites of metastases, side effects of therapy and survival. CARCINOEMBRYONIC
ANTIGEN THERAPY
(CEA) AS A MARKER OF RADIATION
IN LUNG CANCER
Noah C.H. Choi, M.D.*+ and Kurt J. Bloch, M.D.
**
*
Department of Radiation Medicine*, Department of Medicine**, Massachusetts General Hospital, Department of Radiation Therapy+, Department of Medicine*, Harvard Medical School, Eoston, MA Preoperative plasma CEA level and its changes after surgery have been reported to be a useful prognostic indicator for patients with resectable lung cancer. However, its significance relative to radiation therapy has not been adequately studied. Plasma CEA levels were measured prior to radiation therapy by radioimmunoassay in 144 patients with bronchogenic carcinoma. Elevated CEA (26 ng/ml) was observed in 3% (56/144) of all patients. Its frequencies relative to tumor stages were 14% (3/21), 43% (42/97) and 46% (12/26) for stages II, III and IV tumors, respectively. Relative frequencies of elevated CEA ('6 ng/ml) in relation to tumor histologies in stage III tumors were 334: (11/337 for squamous cell carcinoma, 65% (15/23) for adenocarcinoma, 22": (5/22) for oat cell carcinoma, 56% (g/16) for large cell carcinoma and 67X (2/3) for poorly differentiated carcinoma. For 42 patients with elevated CEA (>6 ng/ml) in stage III group, median CEA was 16 ng/ml with a range 6.6 - 63b ng/ml . Serial measurements of CEA 2 2 times were obtained in 557: (23/42) of these patients who had elevated CEA prior to radiation therapy. A very good correlation between the clinical course of the patients and the serial changes of CEA values (return to normal level or increase) was observed in all 23 patients.
Proceedings of the 22nd Annual ASTR Meeting The initial CEA values prior to radiation therapy are very closely related Survival rates > 6 months without tumors. to patients' survival in stage III relapse were ohserved in 46'; (17/37) and 58" (17/29) of patTents with the However, only initial CEA values 1 - 5.8 ng/ml and 6-20 ng/ml, respectively. 14:: (2/14) of patients with CEA > 21 ng/ml (21-630 ng/ml) survived 2 6 months without relapse, P < 0.05. This Study indicates that plasma CEA levels prior to radiation therapy and its serial changes after radiation therapy are of prognostic importance for patients with stage III lung cancer. COMPARISON OF DOSE-TIME-FRACTIONATION SCHEMES IN NON-OAT-CELL LUNG CANCER Kamla Shah, M.D.", Marvin H. Olson, M.D., and Ann E. Wright, Ph.D. Division of Radiation Oncology Department of Radiology The University of Texas Medical Branch Galveston, Texas 77550 The optimal radiation dose and fractionation schemes for inoperable nonSeventy-five percent of all oat-cell carcinoma of the lung is not known. lung cancers are referred for radiotherapy because they are inoperable. The remaining 25% are referred for palliation at some stage. A series of 205 patients with inoperable non-oat-cell carcinoma of the lung were treated with three different dose fractionation schedules. Fiftysix patients received 5000 rads in 25 fractions over five weeks (continuous A); 79 patients received 2000 rads in five fractions over five days, with two weeks rest, followed by 2030 rads in five fractions over five days (splitcourse B); 73 patients received 3000 rads in 10 fractions over two weeks, followed by three weeks rest and another 3000 rads (split-course C). A shrinking field technique was used with the split-course. The histologic distribution of the tumors treated was: squamous cell carcinoma 103 (50.3%), adenocarcinoma 25 (12.22), large cell 24 (11.7%), and undifferentiated carcinoma 46 (22.4%). The stage distribution (AJCCS) was 5.4% stage I, 22% stage II, and 72.6% stage III. The 24-month survival was analyzed by a number of factors including the stage of the disease, the histologic type and the treatment regimen. The local response of tumors was analyzed for each treatment regimen by means of a chest x-ray, taken one month after completion. Radiation fibrosis occurred in all treatient schemes and was dose related. In our experience, the results of 4000 rads split-course was poor. The median survival for continuous 5000 rads and 6000 rads split-course was the same, but the split-course was better tolerated. The above results, tolerance and complications will be presented. MANAGEMENT OF HIGH RISK BREAST CARCINOMA WITH PRIMARY IRRADIATION AND ADJUVANT CHEMOTHERAPY Leo E. Orr, M.D.* A.M. Nisar Syed, M.D., FRCS, DMRT (Eng.)** Ajmel A. Puthawala, M.D. Department of Medical Oncology* and Department of Radiation Medicine** Southern California Cancer Center - California Hospital Medical Center and Los Angeles County - University of Southern California Medical Center Los Angeles, California Fifty-three women with Stage II and III breast cancer underwent a combined modality treatment of primary irradiation and chemotherapy at Southern
1455
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Radiation Oncology 0 Biology 0 Physics
October 1980, Volume 6, Number 10
California Cancer Center - California Hospital Medical Center, Los Angeles, California from 1975 to 1979. All patients were staged retrospectively, according to the American Joint Commission for Cancer Staging and End Result Reporting 1977. There were 12, 15, 24 and 2 patients with T4, T3, T2 and TI primary lesions, respectively. Thirty patients had a minimum of 10 positive axillary lymph nodes. Two patients had ipsilateral chest wall metastases. Estrogen receptor studies were performed on 27 women, of which 14 indicated positive results. The primary treatment consisted of a combination of external irradiation (CO'O or 4 MeV linear accelerator), to an average tumor dose of 5000 rad in 5 to 6 weeks, followed by a booster dos f 2500 rad to 4000 rad delivered by an interstitial afterloading Iridium f9? implant. Approximately 4 weeks later all patients were started on chemotherapy usin j a combination of Cytoxan intravenously cycled 600 mg/m2, Methotrexate 50 mg/m2, 5 Fluoruracil mg/m every 21 days. Forty patients are surviving free of recurrent disease with a maximum follow-up period of 54 months (mean survival period of 26.5 months). The remaining 13 patients developed distant metastases with an average remission period of 22.6 months. One of these patients also had a local recurrence. Relapses occured in 1 out of 14 ER (+) patients and 5 out of 13 ER (-) patients The average remission for ER(+), ER(-) and ER(X). patients was 39, 18.5 and Comparable figures for patients with T2, T3_4 and 27 months, respectively. N(+) lesions were 40, 14 and 31 months. Our data suggests that irradiation-chemotherapy modality outlined here offers significant remission and survival benefits for locally advanced breast cancer patients who have substantial risk for recurrences. This treatment also appears to represent an acceptable alternative to debulking surgery and adjunctive systemic anti-tumor treatment. RADIATION THERAPY
IN THE MANAGEMENT OF SUBCLINICAL DISEASE NODES (NO) FROM HEAD AND NECK CANCERS
IN CERVICAL
Rao V.P. Mantravadi, M.D., D.M.R. David Sabato, M.D. Richard E. Haas, B.A. Edwin J. Liebner, M.D. University of Illinois Hospital/ALSM Department of Radiology and Otolaryngology This report deals with a detailed analysis of 187 patients who were initially seen with clinically negative neck and treated by radiotherapy with curative intent. Of these 57 had primary tumor in oral cavity, 38 in oropharynx, 53 in larynx, 16 in hypopharynx and 23 in nasopharynx. The T-Stage distribution for the study population was 21 Tl, 52 T2, 83 T3, and 24 T4. Lateral opposed or multiple fields were used to encompass the primary and upper and mid cervical lymph nodes. Whole neck irradiation including lower cervical and supraclavicular regions was done only during A minimum dose of 4000 rads was given to lymph node bearing recent years. areas with lymph nodes adjacent to the primary receiving the same tumoricida1 dose as that of primary. Computer analysis of the data revealed the following: 1) There were 28 failures (15%) in the neck nodes within the treatment field. Of these concomitant recurrence at the site of primary was present in 26 (93%). 2) The two in-field failures with primary controlled received less than 5000 rads and were in patients with T3 tumors. 3) Recurrent disease outside the treatment ports occured in 7 patients (4%), of whom four were in supraclavicular and lower cervical regions and three were in the posterior cervical chain.
Proceedings of the 22nd Annual ASTR Meeting
1457
We conclude from these results that: 1) A radiation dose of 5000 rad or more can sterilize 99% of the occult disease in lymph nodes. 2) Whole neck irradiation is not indicated in patients with ND disease. 3) Surgical resection of primary alone without added neck dissection is adequate, when postoperative irradiation is planned. Data comparing these results with that of 402 NO patients treated with surgery alone will be presented.
RISK OF BRAIN METASTASIS FROM SMALL CELL CARCINOMA OF THE LUNG RELATED TO LENGTH OF SURVIVAL AND PROPHYLACTIC IRRADIATION Ritsuko Komaki, M. D., James D. Cox, M. D., William Whitson,
M. S.
Division of Therapeutic Radiology Medical College of Wisconsin Affiliated Hospitals Milwaukee, Wisconsin 53226 From 1974 through 1979, 131 patients presented to the Division of Therapeutic Radiology of the Medical College of Wisconsin Affiliated Hospitals with small cell carcinoma of the lung and normal radionuclide or comFrom 1974 through 1977. 74 patients received puted tomography brain scans. no prophylactic cranial irradiation (NPCI) and from 1976 to 1979 57 received prophylactic treatment (PCI). Of the NPCI group. 50% had limited disease; 46% were treated with chest irradiation alone, and 53% had chest irradiation Of the plus simultaneous chemotherapy; the median survival was 30 weeks. PC1 group, 49% had limited disease; 40% received chemotherapy alone and 60:; received chest irradiation and chemotherapy; the median survival was 35 weeks. The NPCI patients experienced a persistent increase in the actuarial probability of clinical brain metastases which reached 28% at 12 months and 58% at 24 months. The PC1 patients had an actuarial rate of ll? at 12 and at 24 months. The difference in brain metastasis between the NPCI and PC1 Prophylactic cranial irradiation groups is highly significant (P<.OOl). eliminates the progressive increase in the risk of brain metastases that accompanies increased survival and is essential for cure of these patients.
A REVIEW OF SEVENTEEN
CASES WITH OVARIAN DYSGERMINOMA
H.H. Tewfik, M.D.*, F.A. Tewfik, M.D. and H.B. Latourette, University
of Iowa Hospitals & Clinics: Department and Radiation Research Laboratory
M.D.*
of Radiology*
This is a retrospective evaluation of 17 patients with the diagnosis of ovarian dysgerminoma who were seen & treated at the University of Iowa Hospitals from January of 1938 to December of 1976. Age ranged from 11 to 54 years. The commonest age was in the 2nd and 3rd decades. Not a single patient was lost for follow-up. Seven patients died with disease - 3 during the 1st year, 3 during the 2nd year and 1 during the 4th year after diagnosis. Two were stage Ia but there was rupture of the tumor during the unilateral salpingoophorectomy (SO). These 2 patients received no postoperative radiation therapy (RT), both recurred in the pelvis and both are dead with disease. Two were Stage IV, both had total abdominal hysterectomy and bilateral salpingoophorectomy (TAH-BSO), 1 was treated with palliative RT and chemotherapy and the other was treated with chemotherapy and both died with disease. Three patients were unstaged. Two were treated with unilateral SO & 1 with TAH-BSO, 2 received postoperative RT and recurred in the abdomen.
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Radiation Oncology 0 Biology ??Physics
October 1980. Volume 6, Number 10
We have 10 patients with no evidence of disease (NED); 1 died 37 years after diagnosis from other causes and the other 9 patients are living NED. The duration of follow-up of that group is from 39 to 444 months with a median of 90 months. Two patients with Stage Ia were treated with TAH-BSO & postoperative RT; 1 patient was treated in the form of external RT to the pelvis (4500 rad) and the 2nd patient had intraperitoneal instillation of radioactive gold. A 3rd patient with Stage Ia was treated with TAH-EGO with no postoperative RT. The 4th and 5th patients with Stage Ia were treated with unilateral SO and unilateral pelvic plus paraaortic lymphadenectomy and no postoperative RT. A 6th patient with Stage Ia was treated with unilateral SO only. Four patients with Stage IIb disease were treated, 3 patients with unilateral SO and postoperative RT - 2 of which had RT to the whole abdomen (2000 rad) with a boost dose to the pelvis and paraaortic lymph nodes (PALN) (1500-2100 rad). The 3rd patient received postoperative RT to the pelvic cavity and PALN's with inverted-Y field to 3000 rad. In these 3 patients, prophylactic mediastinum and left supraclavicular RT was delivered (2550 rad). The 4th patient with Stage IIb disease was treated with TAH-BSO and postoperative RT to the pelvis (3575 rad) and to the PALN's (2575 rad). Our results suggest that in Stage Ia dysgerminoma, unilateral SO may be enough with no need for postoperative RT. In Stage II disease, there is indication for postoperative RT to the pelvis and PALN. In Stage III disease, postoperative RT to the whole abdomen with a boost dose to the pelvis and In Stage II and III disease, treatment should be PALN's is recommended. followed by prophylactic mediastinal and supraclavicular RT.
COMPUTERIZED
DOSIMETRY IN CARCINOMA OF THE CERVIX, IS IT NECESSARY?
Young, J.J., Blumberg, A.L., Lambert, B.,
Littman,
P.
The University of Pennsylvania School of Medicine and The Fox Chase Cancer Center Philadelphia, Pa. A review (1972-1977) was conducted of 110 cases of Stage I and II carcinoma of the cervix treated with radiation therapy alone at the Hospital of the University of Pennsylvania and the Fox Chase Cancer Center. Particular attention was focused on the usefulness of the isodose distribution surrounding the intracavitary radium or cesium applicators (Fletcher-Suit). The relationships between local tumor control, complications and the following parameters were analyzed: miligram hours; total dose in rads, rets and TDF; relative proportions of external and intracavitary dose; Point A and Point B; the bladder; and the rectum. The treatment regimens used resulted in the actuarial disease free and overall survival at 5 years in excess of 90 percent. Severe complications occurred in only 6:: of the entire group. While the dose prescribed for brachytherapy varied within a relatively circumscribed range, there was considerable variation from patient to patient in the bladder (4780 to 9760 rads) and rectal doses (4620 to 7870 rads). Since the percentage, of local tumor control was quite high in this series, the Contumoricidal abilities of doses in common usage seems well established. versely, since severe bladder and rectal damage was infrequent, even within wide fluctuations of dose, the threshhold for these effects remains uncertain. The value of computer determined isodose distributions in assessing the potential for both cure and normal tissue injury appears limited. Patient management decisions may be made on the external irradiation based on rads and on the intracavitary component based on milligram hours, provided that a stan(At a time when interest in the dard applicator and loadings are utilized. surgical approach for Stage I and II carcinoma of the cervix is increasing, a reminder of the simple safe and effective role of radiation therapy is appropriate).
1459
Proceedings of the 22nd Annual ASTR Meeting EFFECTIVENESS, RECURRENCES AND COMPLICATIONS OF THERAPY WHEN COMBINING WHOLE PELVIS IRRADIATION AND INTRACAVITARY RADIUM APPLICATIONS IN STAGE IA TO IIB CARCINOMA OF THE CERVIX PATIENTS Bharati
Kharkar, M.D. and Ned B. Hornback, M.D.
Department of Radiation Oncology Indiana University School of Medicine 1100 West Michigan Street Indianapolis, Indiana 46223 A retrospective study of 98 patients ranging from 16 to 80 years of age (mean age of 50 to 55 years) was undertaken to evaluate the effectiveness, recurrences and complications of therapy with a full course of radiation treatments combining whole pelvis irradiation and intracavitary radium application, for patients with stage IA to IIB carcinoma of the cervix with intact uterus from January of 1968 to December of 1973. The average followup period The uncorrected overall five-year survival ranges between five to ten years. 19 of 98 patients were lost to followup. Eight out of 79 patients was 79.5%. developed pelvic recurrence (10%). The majority of the recurrences were withFour out of 79 patients dein the first two years of radiation treatments. veloped distant metastasis (5%), three out of four had pulmonary metastasis, and two out of four had bony metastasis in two to eight years post-radiation Four patients developed second primaries within five to seven years therapy. post-radiation treatments, three out of four developed breast cancer, and one out of four had medullary thyroid carcinoma. The occurrence of minor GI and GU tract complications of nausea, vomitPercentage of major ing, proctitis, sigmoiditis, and cystitis was minimal. complications including persistent diarrhea, haemorrhagic cystitis, sigmoid fibrosis, recta-vaginal, vesico-vaginal fistula was 13%. The most cornROn complication was vaginal vault necrosis (26%) which was corrected with conservative methods, no surgery was required.
MANAGEMENT OF ADENOID CYSTICCARCINOMA OF THE CERVIX UTERI (CYLINDROMA) Thongbleiw
University
Prempree,
M.D., Ph.D.*, Umberto VillaSanta, and Chik-Kwun Tang, M.D.***
M.D., F.A.C.O,G.**
Department of Radiation Therapy* Department of Obstetric and Gynecology** Department of Pathology*** of Maryland Hospital, School of Medicine, Baltimore,
Maryland
21201
Adenoid cysteic carcinoma (Cylindroma) of the cervix is a very rare disease and probably accounts for 0.2% or less of all invasive cervical cancer. To date, there have been only 38 cases of invasive adenoid cystic carcinoma of the cervix reported in world literature. Because of its rarity, the methods of treatment have not been uniform and the results are far from being satisfactory. We have identified and reviewed six cases of adenoid cystic carcinoma of the cervix treated at the University of Maryland Hospital from 1963 to 1978. The outstanding features of these six cases will be discussed in details with respect to clinical course, histopathologic uniqueness and treatment along with results. Including the present series, a total of 43 cases (from several series) of adenoid cystic carcinoma of the cervix are being analyzed and summarized in the following table:
1460
Radiation Oncology 0 Biology 0 Physics
October 1980, Volume 6. Number 10
Adenoid Cystic Carcinoma of the Cervix Cumulative Patients Data S-Year Survival NED*
Stage
No. Patients
I
16
8
4(50%)
7
5(71.4%)
1
O(O%)
-
g/16(56.2%)
II
11
_
_
8
3(38%)
2
O(O%)
1
3/11(27.3%)
III
4
_
-
4
O(O%)
-
-
-
O/4(0%)
IV
1
_
_
1
O(O%)
-
-
-
O/1(0%)
11
5
1(20%)
6
1(17%)
-
-
-
2/11(20%)
All Stages 43
13
Unknown
NB -1.
Surqery Cases NED*
Radiation Cases NED*
4
5(38.5%) 26 9(34.6%)
NED* - No evidence of Disease
POSSIBLE ENHANCEMENT
R;ise; Su;zerr
3
0(0x)
No
Total
14/43(32.5%)
(Cancer)
OF RADIATION-INDUCED
HEPATITIS
BY PRIOR CHEMOTHERAPY
Sabina R. Wallach, M.D. Raymond Taetle, M.D. Stephen L. Seagren, M.D. Divisions of Hematology/Oncology and Radiation Oncology University of California, San Diego
The syndrome of acute radiation hepatitis is characterized by the onset of right upper quadrant pain, hepatomegaly, jaundice and ascites, in association with abnormal liver function, and occurs within weeks of radiation to the organ. It appears to be dose related, with a significantly increased incidence at doses greater than 3,500 rads delivered in standard fractions -of 100-200 rads. We wish to report a case which occurred following the delivery of only 2400 rads to the liver of a patient who had previously received chemotherapy This radiation dose is the lowincluding cyclophosphamide and vincristine. est reported in association with fatal radiation hepatitis. The patient was a 50 year old man with a two year history of localized gastric lymphoma of the nodular mixed lymphocytic-histiocytic type. He had received COP combinat'on chemotherapy (cyclophosphamide 1 gm/m2 IV da 1, vincristine 1.4 mgm/m $ (maximum 2 mgms) IV day 1, prednisone 100 mg/m 3 P.O. days 1-5, q 3 weeks) intermittently during this period. Because of radiological and biopsy evidence of residual disease, and persistent symptoms, he received abdominal bath irradiation of 2400 rads in 16 fractions (150 rads per fraction) over a 3 week period, with an additional 1300 rad boost to the stomach, with the left hepatic lobe shielded. Most of the liver received a total dose of 2400 rads. His last dose of chemotherapy was administered more than one month prior to the commencement of radiation. Three weeks following the completion of radiation, he was admitted to the hospital with mild orthostatic hypotension and jaundice. His liver and spleen were normal in size. He was thrombocytopenic and had abnormal liver function with moderate elevation of hepatic transaminases and alkaline phosphatase, and markedly elevated bilirubin levels; however, prothrombin time Despite supportive therapy, he developed progresand albumin were normal. Histosive jaundice and ascites, and died of hepatic failure 19 days later.
Proceedings of the 22nd Annual ASTR Meeting
1461
pathology of the liver at autopsy revealed diffuse centrilobular veno-occlusive changes characteristic of radiation hepatitis. Several drugs, including actinomycin D and vincristine, are known to enhance the toxicity of hepatic irradiation. However, emphasis has previously been placed on the close temporal relationship between drug administration and hepatic irradiation required for development of the syndrome. Our patient suggests that this temporal relationship may not be critical to the development of radiation hepatitis. Accordingly, we recommend that a reduction in the total dose of hepatic irradiation be considered in patients with prior vincristine or cyclophosphamide exposure, irrespective of the interval between drug administration and radiotherapy.
PRE-OPERATIVE
VS. POST-OPERATIVE
C.K. Chung, M.D.,
J.A.
RADIOTHERAPY
FOR STAGE I ENDOMETRIAL
CARCINOMA
Stryker, M.D., W.A. Nahhas, M.D. & R. Mortel, M.D.
M.S. Hershey Medical Center The Pennsylvania State University Hershey, Pennsylvania One hundred eighty-five patients with endometrial carcinoma were treated at Hershey Medical Center between July, 1971, and June, 1978. Eighty-five Most of the patients (81%) patients (50%) had clinical stage I (FIGO) disease. received either pre-op or post-op RT and surgery (TAH and BSO) except those patients with stage IA - grade I patients without myometrial invasion were usually treated with surgery alone (13 patients). Thirty-three patients received pre-op RT: 6 intracavitary, 26 external, and 11 external plus intracavitary. Thirty-six patients had post-op RT: 2 intracavitary, 9 external, and 25 external plus intracavitary. Three patients were treated with RT alone. The incidence of deep myometrial invasion (>2/3 thickness) was 5% for grade 1, 17% for grade 2, and 71% for grade 3. The risk of extra-uterine disease was 0% for grade 1, 9% for grade 2, and 16% for grade 3. All 11 patients with failures (2 pelvic, 3 pelvic and D.M., and 6 D.M.) were either grade 2 or 3. Distant metastasis developed only in stage IB patients. Treatment failures and survivals were presented by histologic type and grade, clinical and surgical-pathologic stages, depth of myometrial invasion, treatment modality, and radiotherapy technique. The reasons for failure were discussed. The overall 5 year survival, pelvic failures, and complication rate were 83%, 7% and 3% respectively: these results were comparable between pre-op and post-op RT groups. However, post-op RT offers the advantages of accurate surgical-pathologic staging and optimal individualization of adjuvant therapy.
“iloW -IRI-1A FOUNDATION.. .?".4 SECOND LOOK AT SOME OBSERVAfIONS Donald E. Herbert, University
of South Alabama,
Deoartment
ON Ro07-0582.
Jr., Ph. cl.
of Radiology,
Mobile,
Alabama
36688
A significant part of the received wisdom on both the toxicitv and efficau of tne radiation sensitizer Ro07-0582 in satients seems -been derived by tne aoplication of some inaporopriate computations to clinical data. As a result, the conventional representations of these two effects of this drug are likely to be incorrect. Yoreover, it aopears that the more serious of the ap-
Radiation Oncology 0 Biology 0 Physics
1462
October 1980, Volume 6, Number 10
oarent misrepresentations of these two effects of this drug derives not so much from tne misaoolication of standard statistical methods but rather from the a~ol:cation of methods which seem to be oriainal, ad hoc, inventions. This paper describes these deficienc:es in scme detail. It also describes the application of the standard statistical methods of bioassay to some published data on this drug in order to illustrate the correct representations of these two properties. These alternative descriptions show that the true values of the location and shape of the dose-response curves, both for enhancement of radiation effects and for concommitant neuropathy, may be considerably different from those which are regularly described for 5007-0582. The uncertainty of the estimates of the true values which are orovided by these data (0.95 confidence limits on curves) are also considerably greater than the conventional representations would suggest. The paper presents an argument for the wider use of simole, statistical methods in the design and evaluation of both laboratory and clinical exberiments with such toxic substances. The correct representations of the dependence uoon serum levels of Ro070582 of enhancement of radiation effect and of incidence of neuropathy are shown in Figures 1. and 2, respectively
Figure 1
MEDULLOELASTOMA THE RESULTS OF RADIOTHERAPY AT THE UNIVERSITY OF KENTUCKY MEDICAL CENTER H. W. Chin, M.D. and Y. Maruyama, M.D. University of Kentucky Medical Center Lexington, Kertucky A review of patients treated for cerebellar medulloblastoma in the past 12 years is presented. A total of 22 patients were treated in this series. A correlation of radiation dose and survival time was carefully analyzed.
Proceedings of the 22nd Annual ASTR Meeting With uniform radiotherapy using tumor doses of 5000 rad or more, a S-year survival rate of 80% was obtained. In contrast only 33% of patients survived five years with tumor doses less than 4600 rad even when using the whole Treatment failure were due crania-spinal axis radiation treatment method. to local recurrence and occurred in more than 80X of cases with low dose irradiation. The development of hydrocephalus indicated a poor prognosis. There were no 5-year survivors in this group. Ten per cent of patients Our experience suggested a dose-dependent showed extracranial metastases. survival rate wher effective irradiation technique and a variety of tumor doses were used. The data suggests that one important factor in tumor control and long term survival is tumor dose. Available data and a review of the literature and time-dose relationship will be carried out. Literature data also indicates that such a relationship holds for this brain tumor. Supported
in part by NC1 grant POl-CA 17786.
RADIATION THERAPY FOR PITUITARY ADENOMAS ANALYSIS OF TREATMENT AND RESULT OF 59 PATIENTS WITH REVIEW OF THE CLINICAL PRESENTATION AS RELATED TO THE MICROSCOPIC DIAGNOSIS.
Eitan Medini, M.D., Chung K.K. Lee, M.D., Yashoda Rao, M.D., Roger Potish, M.D., Robert E. Haselow, M.D., Taehwan Kim, M.D., Thomas K. Jones, Jr. M.D. Seymour H. Levitt, M.D. Department of Therapeutic Radiology, University of Minnesota and Veterans Administration Medical Center, Minneapolis, Minnesota 55477
Clinical presentation, variety of laboratory and radiological methods and findings of 59 patients with pituitary adenomas, treated in the Departments of Radiation Therapy of the University of Minnesota and Veterans Administration Medical Center, Minneapolis, Minnesota, from 1966 to 1975, are being presented. Of this group: 4 patients had Cushing's syndrome; 12 had growth hormone secreting tumors; and 43 had hormone nonsecreting tumors. The clinical presentation is being discussed as related to the microscopic diagnosis. In 85% of the patients, chromophobe adenoma was found. The vast majority of the patients were referred for radiation after undergoing hypophysectomy, adenomectomy, or biopsy. No correlation was noted between the microscopic findings and the variety of the clinical presentation of Cushing's syndrome, Nelson syndrome, acromegaly, gigantism, hormonal deficiency, and mechanical pressure related symptans. Chromophobe adenoma was found in 2 out of 4 patients with Cushing's syndrome, and in 5 out of 12 with growth hormone secreting adenoma. Forty-three patients had nonfunctioning chromophobe adenoma. Special stains will be reviewed. 4500-5000 rads tumor dose by 175-200 rads/fraction, 5 fractions/week, were given postoperatively using bilateral 6 x 6 cm opposing ports isocentrically. Few patients had additional frontal port. Megavoltage units were used. The overall control rate of hormonally nonfunctioning adenomas, and that of growth hormone secreting adenomas was 85% in 5 years and 75% in 10 years. The treatment of the 4 patients with Cushing's syndrome and of those who developed Nelson syndrome was not uniform and will be reviewed accordingly. Multiinstitutional cooperation will be offered.
1463
1464
Radiation
Oncology
0
EFFECT DXE
OF
RESPONSE Timothy
Eastern
Dept. Virginia
Biology
of
0
Physics
SURVIVAL
OF
Norfolk,
Ph.
Oncology School/Medical
6, Number
10
ON
NORMAL
Schultheiss,
Radiation Medical
1980. Volume
STATISTICS
FUNCTIONS E.
October
TISSUES D.
8 Biophysics Center
Hospitals,
Virginia
When calculating survival statistics for a group going treatment for a specific disease, it is desirable rections to account -for the effect norma I morta I i ty . must be applied when analyzing clinical data to obtain
of
patients
under-
to apply age corSimi lar corrections the dose response
of
normal tissues if the average survival time is not long compared to the average latent period for the expression of the injury under study. It will be demonstrated that ignoring these corrections can result in serious errors in determining the shape of the dose will be presented by which these errors can demonstrated that these new methods consistently bioassay techniques when applied to clinical to properly analyze a group of patients for was required in order to be included in the
response curve. Two methods be eliminated. It will be out perform conventional data. One method is designed which a minimum survival time analysis. The second method
designed to allow the relaxation of the minimum survival order to allow the use of all patients in the study. It the second method is independent of the survival functions
requirement
is
in
wi I I be shown that for the treated
requiring rather a knowledge of the distribution of latent periods group, for the injury under study. One may therefore use this method to group together for analysis all patients at risk for a particualr injury no matter from what disease they suffer. These methods of analysis, validity tests of the procedures, and an application to the analysis of the dose response of spinal cord will be presented,
OF MOUSE BONE MARROW HEMOPOIETIC AND STROMAL CELLS: RADIATION SENSITIVITY EVIDENCE FOR SUBPOPULATIONS WITH DENSITY DEPENDENT SURVIVAL CHARACTERISTICS
Joel S. Greenberger, M.D., Ralph R. Weichselbaum, M.D. Annie Schmidt, B.S., Maryann Sakakeeny, M.S., and John 8. Little, M.D. Joint Center for Radiation Therapy, Department of Radiation Therapy, Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts 02115 Fresh bone marrow from NIH Swiss and NZB mice and was studied for the in vitro radiation sensitivity of clonagenic granulocyte-macrophage progenitor Cells were irradiated in suspension inMcCo;+s 5A supplemented cells (GM-CFUC). medium (Greenberger, et.al., Blood, 53:587-1001, 1979) in air or in the preCells were plated in 0.3% agar with sence of high concentrations of oxygen. McCoy's 5A medium, 10% L-cell colony stimulating factor (CSF) and 10% fetal Hemopoietic stem cells free calf serum at several different plating densities. of marrow stromal cells were obtained by harvest of nonadherent cell fractions These cells were depleted of of 16-week-old long-term bone marrow cultures. marrow stromal cells including adipocytes, fibroblasts, macrophages, and endothelial cells which are present in fresh bone marrow. The radiation survival curve of GM-CFUc from fresh bone marrow and of purified GM-CFUc from long-term bone marrow cultures revealed that both populations had a Do which5increased from 100 to 210 Rad as the plating density increased from 1.0 x 10 to 5.0 x 105 cells per mL. Although a small radioresistant cell population was also observed at low cell densities in NIH Swiss marrow cultures, NZB cultures did not reveal a resistant cell population even at low cell densities (D,=104). The radioresistance at hiqh density could not be attributed to hypoxia at the
Proceedings of the 22nd Annual ASTR Meeting
1465
higher cell plating densities since identical results were obtained with cells irradiated in the presence of oxygen. Morphologic examination of colonies revealed predominantly macrophage colonies induced by L-cell CSF. This resistant tail was not observed with nonadherent cells from long-term NIH Swiss bone marrow cultures (D,=lOO). The data suggest that a stromal-adherent cell population in bone marrow demonstrates radiation survival characteristics similar to that of embryo or skin fibroblast cells. Furthermore, subpopulations of hemopoietic cells at high density may protect other cells from radiation damage by indirect effects including induction of repair functions.
ExposingA Phantom
Back tn1960 ourchtef medlcal physlclst developed the radiotherapy phantom In general use today. The world was satisfied, but we weren’t, So we developed a new phantom of greater ftnesse, fuller fldellty We named him RT-Humanoid. His secrets: A higher standard of skeletal symmetry More completelmpreanation of marrow cavities with tissue equivalent matenal Improved water-equivalence (within ‘i percent) More sophisticated vacuum molding to reduce residual arr We Improved techniques for transecttng the phantom, using a thinner coating material (0.5 to 1 mm.) to mtnimrze bone and lung discontinuities at the Interfaces We developed new lung-equivalent plugs for greater accuracy. And we improved and stmplifled sectlonal assembly methods with skillfully deslgned aluminum plates and nylon rods Result. greater ease In patient-like posltlonlng. There you have It our Phantom, exposed. Send for COmDlete information.
Humanoid Systems 17022 Montanero Street Carson, California 90746 (213) 537-7851 Telex 69-l 186 International Division 2200 Shames Drive Wesrbury Long Island. N.Y 11590 (516) 344-3303 Telex 94-l 474 or 12-5391