Late Gastrointestinal Morbidity Research Articles

Severity and Persistency of Late Gastrointestinal Morbidity in Locally Advanced Cervical Cancer: Lessons Learned From EMBRACE-I and Implications for the Future

The purpose was to evaluate patient- and treatment-related risk factors for physician-assessed and patient-reported gastrointestinal (GI) symptoms after radio(chemo)therapy and image guided adaptive brachytherapy in locally advanced cervical cancer. Of 1416 patients from the EMBRACE-I study, 1199 and 1002 were prospectively evaluated using physician-assessed (Common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported (European Organization for Research and Treatment of Cancer [EORTC]) GI symptoms, respectively. CTCAE severe grade (grade [G] ≥3) events were pooled according to the location in the GI tract (anus/rectum, sigmoid, and colon/small bowel). CTCAE G ≥2 and EORTC "very much" and "quite a bit" plus "very much" scores (≥ "quite a bit") were analyzed for individual symptoms with Cox regression. Logistic regression was used for persistent G ≥1 and EORTC ≥ "quite a bit" symptoms, defined if present in at least half of follow-ups. The incidence of G ≥3 events was 2.8%, 1.8%, and 2.3% for G ≥3 anus/rectum, sigmoid, and colon/small bowel events, respectively. Among G ≥2 symptoms, diarrhea and flatulence were the most prevalent (8.5% and 9.9%, respectively). Among patient-related factors, baseline morbidity, increasing age, smoking status, and low body mass index were associated with GI symptoms tovarying degrees. Among treatment-related factors, rectum D2cm3 and the International Commission on Radiation Units and Measurements recto-vaginal reference point (ICRU RV-RP) correlated with G ≥3 anus/rectum events and moderate/persistent diarrhea, proctitis, bleeding, abdominal cramps, and difficulty in bowel control. Bowel D2cm3 correlated with G ≥3 sigmoid and colon/small bowel events and moderate/persistent diarrhea and flatulence. For external beam radiation therapy (EBRT), prescription dose correlated with G ≥3 anus/rectum, diarrhea, and difficulty in bowel control. Patients with large lymph-node boost (V57Gy) were at higher risk for G ≥3 sigmoid events, moderate/persistent diarrhea, proctitis, and cramps. The analysis showed that both EBRT and image guided adaptive brachytherapy contribute to GI symptoms after locally advanced cervical cancer treatment. Rectum D2cm3, ICRU RV-RP , and bowel D2cm3 are risk factors for GI morbidity. The risk for various symptoms was lower with an EBRT prescription of 45 Gy than 50 Gy and increased with larger V57Gy.

A phase I/II study of acute and late physician assessed and patient-reported morbidity following whole pelvic radiation in high-risk prostate cancer patients

Background The aim of this study was to assess acute and late morbidity measured by the physician and patient-reported outcomes (PROs) in high-risk prostate cancer (PC) patients receiving whole pelvic intensity-modulated radiotherapy (IMRT) in the setting of a national clinical trial. Material and methods A total of 88 patients with adenocarcinoma of the prostate and high-risk parameters were enrolled from 2011 to 2013. All patients received 78 Gy in 39 fractions of IMRT delivering simultaneous 78 Gy to the prostate and 56 Gy to the seminal vesicles and lymph nodes. Physician-reported morbidity was assessed by CTCAE v.4.0. PROs were registered for gastro-intestinal (GI) by the RT-ARD score, genito-urinary (GU) by DAN-PSS, sexual and hormonal by EPIC-26, and quality of life (QoL) by EORTC QLQ-C30. Results Median follow-up (FU) time was 4.6 years. No persistent late CTCAE grade 3+ morbidity was observed. Prevalence of CTCAE grade 2+ GI morbidities varied from 0 to 6% at baseline throughout FU time, except for diarrhea, which was reported in 19% of the patients post-RT. PROs revealed increased GI morbidity (≥1 monthly episode) for "rectal urgency", "use of pads", "incomplete evacuation", "mucus in stool" and "bowel function impact on QoL" all remained significantly different (p < .05) at 60 months compared to baseline. CTCAE grade 2+ GU and sexual morbidity were unchanged. GU PROs on obstructive and irritative GU items (≥daily episode) increased during RT and normalized at 24 months. No clinically significant differences were found in sexual, hormonal, and QoL scores compared to baseline. Conclusions Whole pelvic RT resulted in a mild to the moderate burden of late GI morbidities demonstrated by a relatively high prevalence of PROs. Whereas, physician-assessed morbidity revealed a low prevalence of late GI morbidity scores. This emphasizes the importance of using both PROs and physician-reported scoring scales when reporting late morbidity in clinical trials.

Late gastrointestinal morbidity in patients with stage I–II testicular seminoma treated with radiotherapy

ObjectivesTo define the incidence and risk factors for late gastrointestinal (GI) morbidity in patients with testicular seminoma treated with radiotherapy (RT). Methods and materialsA retrospective review was conducted of 251 patients with stage I or II testicular seminoma treated with curative-intent RT at our institution from 1974 to 2009. All patients underwent orchiectomy and postoperative external beam RT to the involved nodal basin or at-risk nodal basin or both. Potential late GI morbidities that were assessed included endoscopically confirmed peptic ulcer disease (PUD), small bowel obstruction (SBO), and biopsy-confirmed malignancy of the GI tract. The probabilities of these GI morbidities were estimated with the Kaplan-Meier method. Univariate analyses were performed to examine for associated predictive factors using the Cox proportional hazards model. ResultsMedian age at diagnosis was 36 years (range 18–80). Clinical stage was I (n = 199) or II (n = 52). Median abdominopelvic RT dose was 26Gy (interquartile range = 25–30). Median follow-up was 15 years (range = 0.1–38). PUD risk at 10, 20, and 30 years was 4%, 7%, and 9%, respectively. Age at diagnosis (per y, HR = 1.05, 95% CI 1.00–1.09, P = 0.04) and RT dose (per Gy, HR = 1.20, 95% CI 1.09–1.31, P<0.01) were associated with risk of PUD. SBO risk at 10, 20, and 30 years was 2%, 2%, and 3%, respectively. History of inflammatory bowel disease was associated with risk of SBO (HR = 43, 95% CI 7–325, P<0.01). GI second malignancy risk at 10, 20, and 30 years was 0.5%, 3% and 16%, respectively. Age at RT was associated with risk of GI malignancy (per y, HR = 1.07, 95% CI 1.02–1.14, P = 0.01). ConclusionsIn this patient population, late GI morbidity was relatively uncommon, but clinically significant. Refinements of treatment strategies may reduce this risk.

Intraoperative Radiotherapy for Pancreatic Cancer: 30-Year Experience in a Single Institution in Japan

To analyze retrospectively the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (± EBRT) for localized pancreatic cancer in the past three decades and to analyze prognostic factors by multivariate analysis. Records for 322 patients with pancreatic cancer treated by IORT ± EBRT in Tohoku University Hospital between 1980 and 2009 were reviewed. One hundred ninety-two patients who had no distant organ metastases or dissemination at the time of laparotomy were enrolled in the present study. Eighty-three patients underwent gross total resection (R0: 48 patients, R1: 35 patients), and 109 patients underwent only biopsy or palliative resection. Fifty-five patients underwent adjuvant EBRT, and 124 underwent adjuvant chemotherapy. The median doses of IORT and EBRT were 25 and 40 Gy, respectively. The median follow-up period was 37.5 months. At the time of the analysis, 166 patients had disease recurrence, and 35 patients had local failure. The 2-year local control (LC) and overall survival (OS) rates were 71.0% and 16.9%, respectively. Comparison of the results for each decade showed that OS was significantly improved decade by decade (2-year: 25.0% vs. 18.8% vs. 4.2%, p < 0.001). Multivariate analysis showed that degree of resection (R0-1 vs. R2, hazard ratio = 1.97, p = 0.001) and adjuvant chemotherapy (yes vs. no, hazard ratio = 1.54, p = 0.028) had significant impacts on OS. Late gastrointestinal morbidity of Common Terminology Criteria for Adverse Events version 3.0 grade 4 or 5 was observed in four patients. Excellent local control for pancreatic cancer with few cases of severe late toxicity was achieved by using IORT. OS of patients with pancreatic cancer treated by IORT ± EBRT improved significantly decade by decade. Multivariate analysis showed that degree of resection and adjuvant chemotherapy had significant impacts on OS.

Intraoperative Radiotherapy for Unresectable Pancreatic Cancer: A Multi-Institutional Retrospective Analysis of 144 Patients

To retrospectively analyze the results of intraoperative radiotherapy (IORT) + external beam radiotherapy (EBRT) for unresectable pancreatic cancer. The records of 144 patients treated with IORT, with or without, EBRT were reviewed. One hundred and thirteen patients (78.5%) were treated with IORT + EBRT and 114 patients (79.2%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy and 45 Gy, respectively. The median follow-up of all 144 patients was 9.6 months (range, 0.5-69.7 months). At the time of this analysis, 131 of 144 patients (91.0%) had disease recurrences. Local progression was observed in 60 patients (41.7%), and the 2-year local control (LC) rate in all patients was 44.6%. Patients treated with IORT, with or without, EBRT had significantly more favorable LC (2-year LC, 50.9%) than those treated with IORT without EBRT (p = 0.0004). The 2-year overall survival (OS) rate and the median survival time in all 144 patients were 14.7% and 10.5 months, respectively. Patients treated with chemotherapy had a significantly favorable OS than those treated without chemotherapy (p < 0.0001). On univariate analysis, chemotherapy use alone had a significant impact on OS and on multivariate analysis; chemotherapy use was a significant prognostic factor. Late gastrointestinal morbidity of National Cancer Institute-Common Terminology Criteria Grade 3 was observed in 2 patients (1.4%). IORT + EBRT yields a relatively favorable LC rate for unresectable pancreatic cancer with low frequency of severe late toxicity, and IORT combined with chemotherapy conferred a survival benefit compared with IORT without chemotherapy.

Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose–Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V(70)), 65 Gy (V(65)), and 40 Gy (V(40)). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V(70) ≤ 10%, V(65) ≤ 20%, and V(40) ≤ 40%; 92% for men with rectal V(70) ≤ 20%, V(65) ≤ 40%, and V(40) ≤ 80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.

Late morbidity and oncological outcome after radical hypofractionated radiotherapy in men with prostate cancer

To test the hypothesis that three-dimensional hypofractionated radiotherapy (3D-HFRT) is well tolerated and not worse than 3-D conventional RT (3D-CRT) for oncological outcome. In all, 162 men with hystologically confirmed prostate adenocarcinoma were included in the analysis. In all, 82 men were treated with 3D-HFRT (15 fractions of 3.62 Gy delivered 3 times/week; a total dose of 54.3 Gy). This group was retrospectively compared with 80 men who met the same inclusion criteria and who were treated with 3D-CRT (39 fractions of 2 Gy delivered daily; a total dose of 78 Gy). A short course of hormone therapy was administered concomitantly with the RT. Only one (1.7%) patient in the 3D-CRT group and two (4.0%) in the 3D-HFRT group had Grade 3 genitourinary toxicity. There was late gastrointestinal morbidity of ≥ grade 3 in only 5.1% of men treated with 3D-HFRT and in 4.0% of men treated with 3D-CRT. In both groups there was no Grade 4 toxicity. At the median (range) follow-up of 45 (39.4-51) months for the 3D-HFRT group and 57.5 (54.9-59.1) months for 3D-CRT group the progression rate was 18/82 (21.9%) and 20/80 (25.0%), respectively, with no significant worsening in the risk of biochemical failure (BCF; log-rank test, P= 0.222). In the present study, men with clinically localized prostate cancer had similar levels of morbidity irrespective of whether they received HFRT or CRT without any worsening in the early risk of BCF. Thus, the present data provide some clinical evidence to justify trends already emerging toward HF regimens for treating clinically localised prostate cancer.

Intraoperative Radiotherapy for Resected Pancreatic Cancer: A Multi-Institutional Retrospective Analysis of 210 Patients

To retrospectively analyze the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (EBRT) for resected pancreatic cancer. The records of 210 patients treated with gross complete resection (R0: 147 patients; R1: 63 patients) and IORT with or without EBRT were reviewed. One hundred forty-seven patients (70.0%) were treated without EBRT and 114 patients (54.3%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy (range, 20-30 Gy) and 45 Gy (range, 20-60Gy), respectively. The median follow-up of the surviving 62 patients was 26.3 months (range, 2.7-90.5 months). At the time of this analysis, 150 of 210 patients (71.4%) had disease recurrences. Local failure was observed in 31 patients (14.8%), and the 2-year local control rate in all patients was 83.7%. The median survival time and the 2-year actuarial overall survival (OS) in all 210 patients were 19.1 months and 42.1%, respectively. Patients treated with IORT and chemotherapy had a significantly more favorable OS than those treated with IORT alone (p = 0.0011). On univariate analysis, chemotherapy use, degree of resection, carbohydrate antigen 19-9, and pathological N stage had a significant impact on OS and on multivariate analysis; these four factors were significant prognostic factors. Late gastrointestinal morbidity of NCI-CTC Grade 4 was observed in 7 patients (3.3%). IORT yields an excellent local control rate for resected pancreatic cancer with few frequencies of severe late toxicity, and IORT combined with chemotherapy confers a survival benefit compared with that of IORT alone.

Morbidity and prostate-specific antigen control of external beam radiation therapy plus low-dose-rate brachytherapy boost for low, intermediate, and high-risk prostate cancer

PurposeDose escalation has been shown beneficial in prostate cancer. Brachytherapy (BT) provides an opportunity for dose escalation beyond what can be safely delivered using only teletherapy methods. The purpose of this study was to determine cancer control and morbidity of external beam radiation therapy (EBRT) plus low-dose-rate (LDR) BT boost in patients with prostate cancer treated at Duke University Health System. MethodsBetween June 1997 and August 2007, 199 patients were consecutively treated at our facility with 46Gy EBRT followed by 100Gy palladium-103 (103Pd) or 120Gy iodine-125 (125I) LDR prostate implant. Treatment characteristics and followup data were retrospectively analyzed. Intermediate risk was defined as T2b–c, Gleason score 7 (GS 7), or prostate-specific antigen (PSA) of 10.1–19.9ng/mL. High risk was defined as GS 8–10, PSA>20, T3+, or two intermediate risk factors. The Radiation Therapy Oncology Group toxicity scale was used to report morbidity for gastrointestinal (GI) and genitourinary (GU) effects. PSA recurrence was defined as nadir+2ng/mL. ResultsMedian followup was 4.2 years for all patients, 4.8 years for high-risk patients. Risk categories were as follows: 20% low risk, 47% intermediate risk, and 33% high risk. Forty five percent of patients received adjuvant androgen deprivation therapy (ADT). The median length of time since end of ADT to last followup was 2.7 years in all patients, 2.0 years for high-risk patients. Five-year biochemical relapse-free survival was 87% for all, 81% for high-risk patients. PSA control was similar at 92% for all and 86% for high-risk patients. Five-year actuarial risk of any and Grade 3 late GI morbidity was 38% and 7% respectively, and any and Grade 3 late GU morbidity was 21% and 3%, respectively. There were no significant differences in risk of Grade 2+GI or GU morbidity with choice of isotope. ConclusionsEBRT plus LDR BT has acceptable morbidity and, with 5-year followup, provides excellent cancer control even in high-risk patients.

Late gastrointestinal morbidity after three-dimensional conformal radiation therapy for prostate cancer fades with time in contrast to genitourinary morbidity

Late gastrointestinal morbidity after three-dimensional conformal radiation therapy for prostate cancer fades with time in contrast to genitourinary morbidity

Late Gastrointestinal Morbidity After Three-Dimensional Conformal Radiation Therapy for Prostate Cancer Fades With Time in Contrast to Genitourinary Morbidity

To investigate the incidence, time course, and relation to irradiated volumes of late morbidity after three-dimensional conformal radiation therapy (RT) for prostate cancer. From January 2000 to December 2001, a total of 247 patients with prostate cancer received a target dose of 70 Gy using conformal RT. Forty-eight patients (20%) received irradiation to the prostate only (Group P), 154 patients (62%) received irradiation to the prostate and seminal vesicles (Group PSV), and 45 patients (18%) received modified pelvic fields (Group MPF). Androgen deprivation was given to 86% of patients. Median follow-up was 62 months. Late gastrointestinal (GI) and genitourinary (GU) morbidity were recorded according to the Radiation Therapy Oncology Group scoring system. We observed 9%, 7%, and 25% Grade 2 or higher GI morbidity and 36%, 30%, and 21% Grade 2 or higher GU morbidity in Groups P, PSV, and MPF, respectively. In multivariate analyses, age and treatment group were independent predictors for the incidence of late Grade 2 or higher GI morbidity, whereas age and urinary symptoms before treatment were independent predictors for late Grade 2 or higher GU morbidity. Acute side effects predicted for late effects. The rectum dose-volume histogram parameters correlated with the incidence of late Grade 2 or higher GI morbidity, especially the fractional volume receiving more than 40-43 Gy. At 5 years of follow-up, the rate of Grade 2 late GI morbidity was only 1.4%, and Grade 2 or higher GU morbidity was 10.6%. The data presented here show that late GI morbidity after prostate RT is low and subsides with time.

Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy

To investigate the correlations between observed clinical morbidity and dosimetric parameters for whole pelvic radiotherapy (WPRT) for prostate cancer using either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). Between December 1996 and January 2002, 27 patients with prostate adenocarcinoma were treated with conformal WPRT as part of their definitive treatment. WPRT was delivered with 3D-CRT in 14 patients and with IMRT in 13 patients. For each of the patients treated with IMRT, optimized conventional two-dimensional (2D) and 3D-CRT plans were retrospectively generated for the whole pelvic phase of the treatment. Dose-volume histograms for the bowel, bladder, and rectum were compared for the three techniques. Acute toxicities were evaluated for all 27 patients, and late toxicities were evaluated for 25 patients with sufficient follow-up. Toxicities were scored according to the Radiation Therapy Oncology Group morbidity grading scales. Median follow-up was 30 months. Three-dimensional-CRT resulted in a 40% relative reduction (p < 0.001) in the volume of bowel receiving 45 Gy compared with 2D, and IMRT provided a further 60% reduction relative to 3D-CRT (p < 0.001). Compared with either 2D or 3D-CRT, IMRT reduced the volume of rectum receiving 45 Gy by 90% (p < 0.001). Overall, 9 patients (33%) experienced acute Grade 2 gastrointestinal (GI) toxicity, and only 1 of these patients was treated with IMRT. Antidiarrhea medication was required for 6 patients (22%). However, 5 of these 6 patients also received chemotherapy, and none were treated with IMRT. No Grade 3 or higher acute or late GI toxicities were observed. No cases of late radiation enteritis were observed. Acute and late genitourinary toxicity did not appear significantly increased by the addition of conformal WPRT. Compared to conventional 2D planning, conformal planning for WPRT resulted in significant reductions in the doses delivered to the bowel, rectum, and bladder. IMRT was superior to 3D-CRT in limiting the volume of bowel and rectum within high-dose regions. These dosimetric findings correlated with low rates of acute and late GI morbidity.

Toxicity following high-dose three-dimensional conformal and intensity-modulated radiation therapy for clinically localized prostate cancer

Objectives. To report the toxicity profile of patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) receiving doses of 82 Gy or more to portions of their prostate. Methods. Forty-four patients treated with radiation therapy for prostate cancer between June 1992 and August 1998 at the University of California, San Francisco received a maximal dose within the target volume (Dmax) of 82 Gy or more. Eighteen patients were boosted selectively to a limited portion of their prostate using IMRT, whereas 26 patients were treated with 3D-CRT and had unselected “hot spots” within their prostate. The Radiation Therapy Oncology Group (RTOG) acute and late toxicity scales were used to score gastrointestinal (GI) and genitourinary (GU) morbidity. Results. Median follow-up and Dmax were 23.1 months (range 10.0 to 84.7) and 84.5 Gy (range 82.0 to 96.7), respectively. Of the patients, 59.1% and 34.1% developed some level of acute GU and GI toxicity, respectively. One patient experienced grade 3 acute GI toxicity. No other grade 3 or greater acute toxicity was observed. The 2-year actuarial rates for freedom from late GI and GU morbidity were 77.1% (95% confidence interval [CI] 60.4% to 87.5%) and 79.5% (95% CI 62.7% to 89.3%), respectively. Although no grade 3 or greater late GU morbidity has been observed to date, 3 patients experienced grade 3 late GI morbidity. However, these cases involved rectal bleeding and were effectively managed with laser coagulation/fulguration. Conclusions. Doses of 82 Gy or more to a portion of the prostate gland can be tolerated with acceptable morbidity. This observation supports the continued investigation of IMRT as a means for improving disease control in prostate cancer.

Chemotherapy, early surgical reassessment, and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: Results of a gynecologic oncology group study

Purpose : To determine outcomes and treatment toxicities in patients with optimal (⩽1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdonimal irradiation (WAI). Methods and Materials : Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32–76 years (median 58); Stage IIIA ( n = 1, 2%), IIIB ( n = 2, 5%), IIIC ( n = 39, 93%); histology-serous papillary ( n = 21, 50%); other ( n = 21, 50%); Grade 1 ( n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. Results : Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity ( p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Condisering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. Conclusions : (a) Disease progression occurred within three cycles of cisplating and cyclophosphamide chemotherapy in 40% of patients with optimal (⩽1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease: Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.

Incidence of and factors related to late complications in conformal and conventional radiation treatment of cancer of the prostate

The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of late Grade 3 and 4 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. Six hundred sixteen consecutive patients treated with conformal or standard techniques between 1986 and 1994 to doses greater than 65 Gy and with more than 3 months follow-up were analyzed. No patients treated with prostatectomies were included in the analysis. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using a retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Multivariate analysis using a proportional hazards model compares differences in the incidence of Radiation Therapy Oncology Group/European Organization for Research and Center Treatment (RTOG/EORTC) Grade 3 and 4 late gastrointestinal (GI) and genitourinary (GU) morbidity by technique, T-stage, grade, age, hormonal treatment, irradiated volume, dose, and comorbid conditions. Grade 3 rectal bleeding was defined as requiring three or more cautery procedures. The overall actuarial incidence of genitourinary (GU) toxicities at 5 years was 3.4%, with the crude incidence being six cases in 616 patients satisfying the selection criteria; for gastrointestinal (GI) toxicities, the overall actuarial incidence was 2.7%, with the crude incidence being 13 cases out of 616 patients. The average time to complication for our patients was 12.8 months for GI toxicity and 32.9 months for GU toxicity (p < 0.001). No factors were found that were predictive for GU morbidity. The only factors significantly related to incidence of late GI morbidity on multivariate analysis of our data were dose and age. The central axis dose was a more significant variable than the dose prescribed to the Treated Volume. Age was negatively correlated with late GI morbidity, with older patients having a reduced incidence of toxicity. The median tolerance dose for GI complications was estimated to be 92.8 Gy, and the dose for 10% incidence was estimated to be 80.2 Gy. Treating the pelvis to 45 Gy did not increase the incidence of late morbidity. Late GI and GU toxicities were not correlated. The conformal technique has been associated with fewer acute Grade 2 toxicities (6). The use of conformal fields did not decrease the incidence of late GI morbidity; however, patients with this technique invariably had higher doses. Because of the dose response for this complication and the correlation between the dose and the use of conformal fields, one would not expect to demonstrate an advantage to conformal fields in this data set. On the other hand, no dose effect was observed for late GU morbidity. In this case, there appears to be an advantage for conformal treatment that has not reached statistical significance because the follow-up time is shorter than for the patients treated with conventional fields and the latency for GU morbidity is long.