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210Prediction of normal tissue response to radiotherapy — Statistics or genetics?
$56 210 PREDICTION OF NORMAL TISSUE RESPONSE TO RADIOTHERAPY - STATISTICS OR GENETICS?
J.HPeacock, Radiotherapy Research Unit, Institute of Cancer Research, Sutton Surrey, UK, The introduction of predictive tests of tissue response to radiotherapy into routine clinical use requires the development of assays that are robust and accurate. The level of accuracy required will depend on the use of the information obtained. Dose reduction for radiosensitive patients may require less accuracy than a dose escalation protocol for resistant patients. The current basis for predictive tests of radiosensitivity comes from studies showing correlations between individual cellular sensitivity (measured by cell survival) and in situ tissue response to radiotherapy. Most assays under consideration for clinical use are based on related cellular radiation effects such as DNA and chromosome damage which have been shown to correlate with survival. The existence of a correlation between two endpoints does not necessarily prove cause and effect thus the accuracy of any test may be influenced by both experimental and biological factors. Without an understanding of these factors accuracy will depend on statistical analysis of both retrospective and prospective studies. In theory at least, current studies in molecular genetics provide the possibility of true individualization of treatment. An increasing number of genes are being identified which when defective affect individual radiosensitivity directly (e.g ATM and TPp53). Whilst in most cases such defects cause dramatic changes in radiosensitivity it is possible that the existence of leaky mutants or heterozygotic conditions of intermediate sensitivity may provide changes in sensitivity consistent with that observed in the normal patient groups. The development of a definitive test by either of these approaches still depends on a wider understanding of the mechanisms of radiation effect both in vitro and in vivo This work is funded by the Cancer Research Campaign
212 THE VIENNA EXPERIENCE IN PRIMARY TREATMENT OF ENDOMETRIAL CARCINOMA WITH HDR-BRACHYTHERAPY Knocke T.H., Kucora H., Weidinger B., H611erW., POtter R. Department of Radiotherapy and Radiobiology,University of Vienna, Austria
In order to evaluate the efficacy ofHDR brschytherapy in the primary treaunent of endomelrial carcinoma the results of 12 years of experience ( 198 I- 1992) covering 280 patients with a mean follow-up of 55 months (median 49 months) will be reported. Age distribution ranged from 46 until 95 years, mean age was 72 years (median : 73 years). Staging was based on clinical examination and fractionatedcurettage.There were 116 patientsin clinicalstage la, 119 in stage Ib, 37 in stage It and 8 in stage HI. HDR-brachytherapy was performed 4 to 5 times (8.5 Cry at 2 cm lateralthe tip of the applicator)with a one-channel intracavitaryapplicator and I to 2 times (7 Cry at 7.5 mm lateralfrom the applicatorsurface)with an intravaginalcylinder-applicator. At five years overall-survival,disease specificsurvivalend local control was 52.7% / 76.6% / 75.4`'/0,in stage la 63.9% / 84.9% / 86.0%, in stage Ib 47.3% / 73.3% 168.8%, in stage II 40.2% / 68.6°/0/ 60.5°/0,according to histopathologicgrade I: 65. t% / 83.5% / 77.7%, grade 2:44.7`'/0/ 75.4% / 75.8% and grade 3: 37.7°/`"/ 63.9"/0/ 74. I%. Eight patientsshowed progressive disease, 64 patients developed a recurrence after a median of 13 months, 45 of those a local recurrence only, 6 a local recurrence with distant metastases, 6 a lymph node recurrence only and 7 patients distant metastases only. There were 3.2% late side effects at the bladder ( 2.1% mild, 0.7% moderate, 0.4% severe), 12.1% at the rectum (7.9% mild, 3.8% moderate, 0.4% severe), 5.4% at the small bowel ( 1.9°/0mild, 1.4% moderate, 2.1% severe) and 10.0% vulvo-vaginal (7.2% mild, 2. I% moderate, 0.7% severe). At stages la, lb and 11in endomelrial carcinoma HDR-brachytherapy is a very effective ~reatment modality with acceptable local control rates and disease specific survival for those patients who are not fit for surgery. During the time frame of 12 years and on 280 patients the method has proven to have a low risk of acute complications and an accepzable risk of long tenn side effects. It is convenient for the patient for there is no need for immobilisation and it can frequently he performed on an out-patient basis.
211 iNTERSTITIAL BRACHY'rHERAPY IN THE SALVAGE TREATMENT OF UPPER THIRD VAGINAL RECURRENCE ( U T V R ) OF UTERINE CARCINOMA
P. ROMESTAING - C. CHARRA - P. ROY - R. COQUARD J.M ARDIET - F. MORNEX - J.P GERARD Service de Radioth6rapie-Oncologie, Centre Hospitalier LYON SUD, 69495 PIERRE BENITE CEDEX, France Introduction : Analysis of a series of 78 patients with UTVR of uterine carcinoma treated with a dedicated vaginal template and interstitial Iridium 192 brachytherapy (I.B). Patient and t r e a t m e n t : From 1978 to 1993, 78 patients with UTVR cervical (41) and endometrial (37) cancers were included. Mean age 61 years. Initial treatment was surgery alone, or associated with radiation therapy (29 pts). Tumor size was 4 cm in 21 pts and less than 4 cm in 57 pts. Treatment was performed with IB in all cases associated with pelvic extemal beam radiation therapy (EBRT) in 34 pts. A dedicated vaginal template made possible to perform a volume implant or the vaginal vault and the tumor with 6 Iridium wires of 5 cm long with homogeneous dose in the vaginal mucosa. Dose (Paris system) was 60 Gy (IB alone) and 25 Gy + 40 Gy EBRT according to the size of the tumor. Results : 5 years local control rate was 70% with 5 years overall survival of 56%. Grade 3 complications occured in 10% of cases mainly in patients with previous irradiation. Conclusion : IB with a dedicated template gives good local control and survival in UTVR with acceptable toxicity.
213 ACUTE AND LATE SIDE EFFECTS IN TI IE ADJUVANT COMBINED RADIATION THERAPY OF ENDOMETKIAL CARCINOMA E. Weiss, H. Amold-Bofinger°, N. Weidner. P. Himle°, M. Bamberg Dpt. or Radiation Therapy and Dpt. of Gyuecology and Obstetrics° at the University of Tuebingen, Germany Introduction: In a retrospective study of all adjuvantly irradiated patients (pts) with endometrial carcinoma in our department we analyse the incidence of compfications regarding early and late side effects. Material and Methods: 175 women received both radiation therapy of the pelvis and vaginal HDR-brachytherapy (BT) with Ir-192 after hysterectomy. Fractionation usually was 5x1.8 / 2 Gy per week up to 45 / 50 Cry for the pelvis and Ix7 Gy per week up to 21 Cry (at the surface of the vaginal cylinder) as BT. During BT in vivo dosimetry was performed. All side effects occurring during therapy and followup were registered. Results: Of 175 pts 29 % reported dysuria/i)ollakisuria, in 6 % treatment became necessary. 48 % suffered from Oiarrhea, in 17 % requiring treatment. Rectal bleeding uuder therapy was noticed in 3 % of pts. Erythema was seen in 9 %, dry desquamation in 5 %, moist desquamation in 6 %, ulceration in one pt, vaginal bleeding in 2 %. 7 % reported general weakness. In II % vagi,al synechiae were observed. /Ls late effects in 2 pts rectal nlcera were seen, one developing are, ctovaginal fistula. One pt had resection of the sigma due to liens. 4 pts suffered from recurrent rectal bleeding (not neces~tating any transfusion). In vivo dosimetry did not show elevated doses in pts with late side effects, yet 6 pts had severe acute problems already under therapy: partially bleeding diarrllea leading to treatment interruption in 4 pts and to a defiuitive stop at 40 Gy in 2 pts. Discussion and Conclusion: After combined radiation for endometrial carcinoma in an adjuvant setting 66 % of all women reported acute side effects, whereas late side effects were seen in only 4 % concerning mostly the rectum, in 1 % requiring surgical interventio,.
J.HPeacock, Radiotherapy Research Unit, Institute of Cancer Research, Sutton Surrey, UK, The introduction of predictive tests of tissue response to radiotherapy into routine clinical use requires the development of assays that are robust and accurate. The level of accuracy required will depend on the use of the information obtained. Dose reduction for radiosensitive patients may require less accuracy than a dose escalation protocol for resistant patients. The current basis for predictive tests of radiosensitivity comes from studies showing correlations between individual cellular sensitivity (measured by cell survival) and in situ tissue response to radiotherapy. Most assays under consideration for clinical use are based on related cellular radiation effects such as DNA and chromosome damage which have been shown to correlate with survival. The existence of a correlation between two endpoints does not necessarily prove cause and effect thus the accuracy of any test may be influenced by both experimental and biological factors. Without an understanding of these factors accuracy will depend on statistical analysis of both retrospective and prospective studies. In theory at least, current studies in molecular genetics provide the possibility of true individualization of treatment. An increasing number of genes are being identified which when defective affect individual radiosensitivity directly (e.g ATM and TPp53). Whilst in most cases such defects cause dramatic changes in radiosensitivity it is possible that the existence of leaky mutants or heterozygotic conditions of intermediate sensitivity may provide changes in sensitivity consistent with that observed in the normal patient groups. The development of a definitive test by either of these approaches still depends on a wider understanding of the mechanisms of radiation effect both in vitro and in vivo This work is funded by the Cancer Research Campaign
212 THE VIENNA EXPERIENCE IN PRIMARY TREATMENT OF ENDOMETRIAL CARCINOMA WITH HDR-BRACHYTHERAPY Knocke T.H., Kucora H., Weidinger B., H611erW., POtter R. Department of Radiotherapy and Radiobiology,University of Vienna, Austria
In order to evaluate the efficacy ofHDR brschytherapy in the primary treaunent of endomelrial carcinoma the results of 12 years of experience ( 198 I- 1992) covering 280 patients with a mean follow-up of 55 months (median 49 months) will be reported. Age distribution ranged from 46 until 95 years, mean age was 72 years (median : 73 years). Staging was based on clinical examination and fractionatedcurettage.There were 116 patientsin clinicalstage la, 119 in stage Ib, 37 in stage It and 8 in stage HI. HDR-brachytherapy was performed 4 to 5 times (8.5 Cry at 2 cm lateralthe tip of the applicator)with a one-channel intracavitaryapplicator and I to 2 times (7 Cry at 7.5 mm lateralfrom the applicatorsurface)with an intravaginalcylinder-applicator. At five years overall-survival,disease specificsurvivalend local control was 52.7% / 76.6% / 75.4`'/0,in stage la 63.9% / 84.9% / 86.0%, in stage Ib 47.3% / 73.3% 168.8%, in stage II 40.2% / 68.6°/0/ 60.5°/0,according to histopathologicgrade I: 65. t% / 83.5% / 77.7%, grade 2:44.7`'/0/ 75.4% / 75.8% and grade 3: 37.7°/`"/ 63.9"/0/ 74. I%. Eight patientsshowed progressive disease, 64 patients developed a recurrence after a median of 13 months, 45 of those a local recurrence only, 6 a local recurrence with distant metastases, 6 a lymph node recurrence only and 7 patients distant metastases only. There were 3.2% late side effects at the bladder ( 2.1% mild, 0.7% moderate, 0.4% severe), 12.1% at the rectum (7.9% mild, 3.8% moderate, 0.4% severe), 5.4% at the small bowel ( 1.9°/0mild, 1.4% moderate, 2.1% severe) and 10.0% vulvo-vaginal (7.2% mild, 2. I% moderate, 0.7% severe). At stages la, lb and 11in endomelrial carcinoma HDR-brachytherapy is a very effective ~reatment modality with acceptable local control rates and disease specific survival for those patients who are not fit for surgery. During the time frame of 12 years and on 280 patients the method has proven to have a low risk of acute complications and an accepzable risk of long tenn side effects. It is convenient for the patient for there is no need for immobilisation and it can frequently he performed on an out-patient basis.
211 iNTERSTITIAL BRACHY'rHERAPY IN THE SALVAGE TREATMENT OF UPPER THIRD VAGINAL RECURRENCE ( U T V R ) OF UTERINE CARCINOMA
P. ROMESTAING - C. CHARRA - P. ROY - R. COQUARD J.M ARDIET - F. MORNEX - J.P GERARD Service de Radioth6rapie-Oncologie, Centre Hospitalier LYON SUD, 69495 PIERRE BENITE CEDEX, France Introduction : Analysis of a series of 78 patients with UTVR of uterine carcinoma treated with a dedicated vaginal template and interstitial Iridium 192 brachytherapy (I.B). Patient and t r e a t m e n t : From 1978 to 1993, 78 patients with UTVR cervical (41) and endometrial (37) cancers were included. Mean age 61 years. Initial treatment was surgery alone, or associated with radiation therapy (29 pts). Tumor size was 4 cm in 21 pts and less than 4 cm in 57 pts. Treatment was performed with IB in all cases associated with pelvic extemal beam radiation therapy (EBRT) in 34 pts. A dedicated vaginal template made possible to perform a volume implant or the vaginal vault and the tumor with 6 Iridium wires of 5 cm long with homogeneous dose in the vaginal mucosa. Dose (Paris system) was 60 Gy (IB alone) and 25 Gy + 40 Gy EBRT according to the size of the tumor. Results : 5 years local control rate was 70% with 5 years overall survival of 56%. Grade 3 complications occured in 10% of cases mainly in patients with previous irradiation. Conclusion : IB with a dedicated template gives good local control and survival in UTVR with acceptable toxicity.
213 ACUTE AND LATE SIDE EFFECTS IN TI IE ADJUVANT COMBINED RADIATION THERAPY OF ENDOMETKIAL CARCINOMA E. Weiss, H. Amold-Bofinger°, N. Weidner. P. Himle°, M. Bamberg Dpt. or Radiation Therapy and Dpt. of Gyuecology and Obstetrics° at the University of Tuebingen, Germany Introduction: In a retrospective study of all adjuvantly irradiated patients (pts) with endometrial carcinoma in our department we analyse the incidence of compfications regarding early and late side effects. Material and Methods: 175 women received both radiation therapy of the pelvis and vaginal HDR-brachytherapy (BT) with Ir-192 after hysterectomy. Fractionation usually was 5x1.8 / 2 Gy per week up to 45 / 50 Cry for the pelvis and Ix7 Gy per week up to 21 Cry (at the surface of the vaginal cylinder) as BT. During BT in vivo dosimetry was performed. All side effects occurring during therapy and followup were registered. Results: Of 175 pts 29 % reported dysuria/i)ollakisuria, in 6 % treatment became necessary. 48 % suffered from Oiarrhea, in 17 % requiring treatment. Rectal bleeding uuder therapy was noticed in 3 % of pts. Erythema was seen in 9 %, dry desquamation in 5 %, moist desquamation in 6 %, ulceration in one pt, vaginal bleeding in 2 %. 7 % reported general weakness. In II % vagi,al synechiae were observed. /Ls late effects in 2 pts rectal nlcera were seen, one developing are, ctovaginal fistula. One pt had resection of the sigma due to liens. 4 pts suffered from recurrent rectal bleeding (not neces~tating any transfusion). In vivo dosimetry did not show elevated doses in pts with late side effects, yet 6 pts had severe acute problems already under therapy: partially bleeding diarrllea leading to treatment interruption in 4 pts and to a defiuitive stop at 40 Gy in 2 pts. Discussion and Conclusion: After combined radiation for endometrial carcinoma in an adjuvant setting 66 % of all women reported acute side effects, whereas late side effects were seen in only 4 % concerning mostly the rectum, in 1 % requiring surgical interventio,.