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Intraoperative radiation therapy (IORT) in pelvic malignancies
SOCIETY OF GYNECOLOGIC will analyze false negative results obtained with both cytology and FCM and will suggest practices to maximize the usefulness of FCM. 96. Dose Intensity Study of Weekly Intramuscular Methotrexate (WZMJ for Nonmetastatic Gestational Trophoblastic Disease (NGTDJ (A Gynecologic Oncology Group (COG) Study). H. D. HOMESLEY, J.
A.
BLESSING, J. MAJOR, Bowman
B. SCHLAERTH, M. A. RETTENMAIER, AND F. J. Gray School of Medicine. Winston-Salem, North Carolina 27103 and Gynecologic Oncology Group, Philadelphia, Pennsylvania 19105. Sixty-two patients with NGTD were entered into this GOG study to determine the relationship of efficacy and toxicity to dose intensity of WIM. The treatments were initiated at 40 mg/m’ of WIM. If no major toxicity was encountered, the weekly dose was escalated by 5 mg/m’ after two doses until a maximum dose of 50 mg/m’ per week was achieved. Complete response (CR) was defined as three normal p-hCG values measured on consecutive weeks. Forty-four of 60 (73%) evaluable patients had a CR to this regimen. The duration of therapy ranged from 3 to 16 weeks with a median of 7 weeks. No major toxicity occurred. All 16 WIM failures second-line received 5 day intramuscular methotrexate (0.4 mg/kg up to 25 mg/day maximum) with only a 50% CR. Fifteen of the 16 WIM failures ultimately had a CR after treatment with subsequent chemotherapy. One patient with elevated p-hCG has refused further chemotherapy after receiving 5 day methotrexate and 5 day dactinomycin. Compared to a previous GOG study (escalating 30 mg/m’ WIM), the complete response rate is similar and the median time to response is the same. The results of second-line therapy support changing to another agent such as dactinomycin rather than dose escalating to a higher more toxic methotrexate dose intensity such as 5 day methotrexate. In the current study, the higher dose regimen of WIM therapy for NGTD does not appear to be more effective but is of similar low toxicity to a less-intense dose regimen reported earlier by the GOG. 97. Intraperitoneal Cal25 Levels at Secondary Operations for Ovarian and Tubal Cancer. R. ROME, H. KOH, M. CAUCHI,AND D. FORTUNE,
Royal Women’s Hospital, Melbourne, Australia. The level of Cal25 in peritoneal washings is considerably higher than in peripheral blood. The objectives of this study were to examine the correlation between serum Ca125, intraperitoneal (ip) Ca125, and surgical findings at 37 secondary operations for ovarian and tubal malignancy. Fifty milliliters of Hanks’ solution was instilled into the cul-de-sac at the commencement of surgery and then aspirated for cytology and ipCa125 assay. At 19 positive operations ipCa125 levels ranged from 77-16200 u/ml and were significantly higher than at 18negative operations at which levels ranged from 15-620 u/ml (P < 0.05). There was overlap between values for negative and positive operations. There was also a rough correlation between the amount of tumor and the ipCa125 level. One patient has relapsed after a negative operation-she had a high level of ipCa125 (510 u/ml) yet her serum Cal25 was within the normal range (29 u/ml). These preliminary results suggest ipCa125 assay may enhance the sensitivity of second-look surgery. High levels of ipCaI25 were also found in patients with benign pelvic disease such as fibroids and endometriosis and patients with normal pelvic viscera. These patients have not been regarded as “controls” because it is known that high levels of Cal25 can be found in secretions from tissues of Mullerian duct origin. 98. lntraoperative
Radiation
Therapy (IORTJ in Pelvic Malignancies,
E. YORDAN, M. JURADO, K. KIEL, S. REDDY, T. KRAMER, F. CALVO, D. ROSEMAN, J. GRAHAM, AND G. WILBANKS, Rush Medical College (RMC), Chicago, Illinois, and The University of Navarre (UN), Pamplona, Spain.
ONCOLOGISTS-ABSTRACTS
117
Local control of advanced pelvic malignancies, particularly when complete surgical resection is not feasible is often impeded by dosage limitations of radiation therapy (RT) and RT intolerance by normal tissues. This is a preliminary report on the feasibility of improved local control in pelvic malignancies treated by adding IORT to conventional surgical resection and external beam RT. Results of IORT from 15 gynecologic malignancies (cervix 5, uterus 5, ovary 4, vulva I) from RMC and UN, as well as from 36 other pelvic malignancies (colorectal 32, genitourinary 4) from RMC were reviewed. All tumors were advanced or recurrent, and all patients were felt to be at high risk for local failure. In addition to surgery and external beam RT, IORT was administered at a dose range between 10 and 22.5 Gy. Among the gynecologic cases, 9 show no evidence of disease (NED) with a mean disease-free survival (DFS) of 14.4 months, 5 are dead of disease (DOD) at a mean DFS of 5.2 months, and one is dead of intercurrent disease. Twenty-two percent of patients with microscopic residual after resection failed locally vs 60% of patients with gross residual. Five of 6 primary colorectal tumors are NED with a mean DFS of 31 months, while only 5 of 26 recurrent colorectal tumors are NED with a mean DFS of 14 months. Twenty-seven percent of patients with microscopic residual after resection failed locally vs 47% of patients with gross residual. One of 4 genitourinary tumors is NED at 23 months. Preliminary results suggest improvement in local control and survival in selected groups of patients. Complications are moderate but acceptable. Details of IORT technique, patterns of treatment failure, and case selection criteria will be discussed. of the Screening Interval for Cervical Smears. M. L. ROMANZI, R. FRUCHTER, AND J. BOYCE.State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203.
99. The Fallacy MAIMAN,
The American Cancer Society has recommended that Pap smears be done every three years after three consecutive negative annual smears. The justification for this recommendation is that the increased interval affords the same protection for the patient. We have examined the cervical smear histories of 118patients with cervical cancer. Fortytwo patients had no previous smear, 66 patients had a previous smear, 44 patients had previous negative smears, and 16 patients had previous abnormal smears. Of the 44 patients with a previous negative smear, 22 had a smear within an interval of 3 years with I7 having Stage I disease. Twenty-two patients had a smear with an interval exceeding 3 years with 13 having Stage I disease. Sixteen patients had previous abnormal smears, 8 with an interval less than 3 years and all had Stage I disease while 8 had an interval exceeding 3 years and 4 patients had Stage I disease. Forty percent of all Stage I patients, 20% of all Stage II patients, 10% of all Stage III patients and 0% of Stage IV patients were diagnosed using an interval of 3 years. These data focus clearly on the problem of using an invasive case as an index case for screening programs and should stimulate the use of an intraepithelial case as an index case. 100. Augmentation of Doxorubicin and 4’Epidoxorubicin in Parental and Multidrug-Resistant Chinese Hamster Ovary Cell Lines by Cyclosporin A and Its Nonimmunosuppressive Homologs. S. K.
W. N. HAIT, ANDR. E. HANDSCHUMACHER, Yale University School of Medicine, New Haven, Connecticut 06510.
CHAMBERS,
Cyclosporins have been shown to sensitize multidmg-resistant (MDR) cells to chemotherapeutic agents but, with some exceptions, have minimal effect on sensitive lines. We studied the effect of Cyclosporin A (CsA) and its nonimmunosuppressive homologs, 1I-me-leu-CsA (MLCsA) and 6-me-ala-CsA (MACsA), on the growth inhibitory action of doxorubicin (DOX) and 4’epidoxorubicin (EPI) toward sensitive (AuXB,) and MDR (CHRC,) Chinese hamster ovary cells. Cells were incubated for 72 hr
A.
BLESSING, J. MAJOR, Bowman
B. SCHLAERTH, M. A. RETTENMAIER, AND F. J. Gray School of Medicine. Winston-Salem, North Carolina 27103 and Gynecologic Oncology Group, Philadelphia, Pennsylvania 19105. Sixty-two patients with NGTD were entered into this GOG study to determine the relationship of efficacy and toxicity to dose intensity of WIM. The treatments were initiated at 40 mg/m’ of WIM. If no major toxicity was encountered, the weekly dose was escalated by 5 mg/m’ after two doses until a maximum dose of 50 mg/m’ per week was achieved. Complete response (CR) was defined as three normal p-hCG values measured on consecutive weeks. Forty-four of 60 (73%) evaluable patients had a CR to this regimen. The duration of therapy ranged from 3 to 16 weeks with a median of 7 weeks. No major toxicity occurred. All 16 WIM failures second-line received 5 day intramuscular methotrexate (0.4 mg/kg up to 25 mg/day maximum) with only a 50% CR. Fifteen of the 16 WIM failures ultimately had a CR after treatment with subsequent chemotherapy. One patient with elevated p-hCG has refused further chemotherapy after receiving 5 day methotrexate and 5 day dactinomycin. Compared to a previous GOG study (escalating 30 mg/m’ WIM), the complete response rate is similar and the median time to response is the same. The results of second-line therapy support changing to another agent such as dactinomycin rather than dose escalating to a higher more toxic methotrexate dose intensity such as 5 day methotrexate. In the current study, the higher dose regimen of WIM therapy for NGTD does not appear to be more effective but is of similar low toxicity to a less-intense dose regimen reported earlier by the GOG. 97. Intraperitoneal Cal25 Levels at Secondary Operations for Ovarian and Tubal Cancer. R. ROME, H. KOH, M. CAUCHI,AND D. FORTUNE,
Royal Women’s Hospital, Melbourne, Australia. The level of Cal25 in peritoneal washings is considerably higher than in peripheral blood. The objectives of this study were to examine the correlation between serum Ca125, intraperitoneal (ip) Ca125, and surgical findings at 37 secondary operations for ovarian and tubal malignancy. Fifty milliliters of Hanks’ solution was instilled into the cul-de-sac at the commencement of surgery and then aspirated for cytology and ipCa125 assay. At 19 positive operations ipCa125 levels ranged from 77-16200 u/ml and were significantly higher than at 18negative operations at which levels ranged from 15-620 u/ml (P < 0.05). There was overlap between values for negative and positive operations. There was also a rough correlation between the amount of tumor and the ipCa125 level. One patient has relapsed after a negative operation-she had a high level of ipCa125 (510 u/ml) yet her serum Cal25 was within the normal range (29 u/ml). These preliminary results suggest ipCa125 assay may enhance the sensitivity of second-look surgery. High levels of ipCaI25 were also found in patients with benign pelvic disease such as fibroids and endometriosis and patients with normal pelvic viscera. These patients have not been regarded as “controls” because it is known that high levels of Cal25 can be found in secretions from tissues of Mullerian duct origin. 98. lntraoperative
Radiation
Therapy (IORTJ in Pelvic Malignancies,
E. YORDAN, M. JURADO, K. KIEL, S. REDDY, T. KRAMER, F. CALVO, D. ROSEMAN, J. GRAHAM, AND G. WILBANKS, Rush Medical College (RMC), Chicago, Illinois, and The University of Navarre (UN), Pamplona, Spain.
ONCOLOGISTS-ABSTRACTS
117
Local control of advanced pelvic malignancies, particularly when complete surgical resection is not feasible is often impeded by dosage limitations of radiation therapy (RT) and RT intolerance by normal tissues. This is a preliminary report on the feasibility of improved local control in pelvic malignancies treated by adding IORT to conventional surgical resection and external beam RT. Results of IORT from 15 gynecologic malignancies (cervix 5, uterus 5, ovary 4, vulva I) from RMC and UN, as well as from 36 other pelvic malignancies (colorectal 32, genitourinary 4) from RMC were reviewed. All tumors were advanced or recurrent, and all patients were felt to be at high risk for local failure. In addition to surgery and external beam RT, IORT was administered at a dose range between 10 and 22.5 Gy. Among the gynecologic cases, 9 show no evidence of disease (NED) with a mean disease-free survival (DFS) of 14.4 months, 5 are dead of disease (DOD) at a mean DFS of 5.2 months, and one is dead of intercurrent disease. Twenty-two percent of patients with microscopic residual after resection failed locally vs 60% of patients with gross residual. Five of 6 primary colorectal tumors are NED with a mean DFS of 31 months, while only 5 of 26 recurrent colorectal tumors are NED with a mean DFS of 14 months. Twenty-seven percent of patients with microscopic residual after resection failed locally vs 47% of patients with gross residual. One of 4 genitourinary tumors is NED at 23 months. Preliminary results suggest improvement in local control and survival in selected groups of patients. Complications are moderate but acceptable. Details of IORT technique, patterns of treatment failure, and case selection criteria will be discussed. of the Screening Interval for Cervical Smears. M. L. ROMANZI, R. FRUCHTER, AND J. BOYCE.State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203.
99. The Fallacy MAIMAN,
The American Cancer Society has recommended that Pap smears be done every three years after three consecutive negative annual smears. The justification for this recommendation is that the increased interval affords the same protection for the patient. We have examined the cervical smear histories of 118patients with cervical cancer. Fortytwo patients had no previous smear, 66 patients had a previous smear, 44 patients had previous negative smears, and 16 patients had previous abnormal smears. Of the 44 patients with a previous negative smear, 22 had a smear within an interval of 3 years with I7 having Stage I disease. Twenty-two patients had a smear with an interval exceeding 3 years with 13 having Stage I disease. Sixteen patients had previous abnormal smears, 8 with an interval less than 3 years and all had Stage I disease while 8 had an interval exceeding 3 years and 4 patients had Stage I disease. Forty percent of all Stage I patients, 20% of all Stage II patients, 10% of all Stage III patients and 0% of Stage IV patients were diagnosed using an interval of 3 years. These data focus clearly on the problem of using an invasive case as an index case for screening programs and should stimulate the use of an intraepithelial case as an index case. 100. Augmentation of Doxorubicin and 4’Epidoxorubicin in Parental and Multidrug-Resistant Chinese Hamster Ovary Cell Lines by Cyclosporin A and Its Nonimmunosuppressive Homologs. S. K.
W. N. HAIT, ANDR. E. HANDSCHUMACHER, Yale University School of Medicine, New Haven, Connecticut 06510.
CHAMBERS,
Cyclosporins have been shown to sensitize multidmg-resistant (MDR) cells to chemotherapeutic agents but, with some exceptions, have minimal effect on sensitive lines. We studied the effect of Cyclosporin A (CsA) and its nonimmunosuppressive homologs, 1I-me-leu-CsA (MLCsA) and 6-me-ala-CsA (MACsA), on the growth inhibitory action of doxorubicin (DOX) and 4’epidoxorubicin (EPI) toward sensitive (AuXB,) and MDR (CHRC,) Chinese hamster ovary cells. Cells were incubated for 72 hr