Mary Ann Lockett

CLINICAL DOSE-VOLUME HISTOGRAM ANALYSIS FOR PNEUMONITIS AFTER 3D TREATMENT FOR NON-SMALL CELL LUNG CANCER (NSCLC)

PURPOSE To identify a clinically relevant and available parameter upon which to identify non-small cell lung cancer (NSCLC) patients at risk for pneumonitis when treated with three-dimensional (3D) radiation therapy. METHODS AND MATERIALS Between January 1991 and October 1995, 99 patients were treated definitively for inoperable NSCLC. Patients were selected for good performance status (96%) and absence of weight loss (82%). All patients had full 3D treatment planning (including total lung dose-volume histograms [DVHs]) prior to treatment delivery. The total lung DVH parameters were compared with the incidence and grade of pneumonitis after treatment. RESULTS Univariate analysis revealed the percent of the total lung volume exceeding 20 Gy (V20), the effective volume (Veff) and the total lung volume mean dose, and location of the tumor primary (upper versus lower lobes) to be statistically significant relative to the development of > or = Grade 2 pneumonitis. Multivariate analysis revealed the V20 to be the single independent predictor of pneumonitis. CONCLUSIONS The V20 from the total lung DVH is a useful parameter easily obtained from most 3D treatment planning systems. The V20 may be useful in comparing competing treatment plans to evaluate the risk of pneumonitis for our individual patient treatment and may also be a useful parameter upon which to stratify patients or prospective dose escalation trials.

Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy

PURPOSE Some studies have described decreased pelvic tumor control and survival rates in invasive carcinoma of uterine cervix when the overall time in a course of definitive irradiation is prolonged. We attempt to confirm or deny these observations and evaluate the impact of timing of brachytherapy on outcome. We also explore the hypothesis that more extensive tumors technically require prolongation of the course of irradiation; thus, decreased tumor control and survival in these patients may not necessarily be the result of time/dose factor. METHODS AND MATERIALS Records of 1,224 patients (Stage IB to III) treated with definitive irradiation (combination of external beam and two intracavitary insertions to deliver doses of 70 to 90 Gy to point A) were reviewed. Follow-up was obtained in 97% of the patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationship between outcome and overall treatment time and time of intracavitary insertions was analyzed in each stage and according to tumor size/extent. RESULTS There was strong correlation between overall treatment time (OTT) and tumor stage (< or = 7 weeks: 81% for Stage IB; 74% for Stage IIA; 52% for Stage IIB; and 47% for Stage III). Interruptions of therapy accounting for prolongation of treatment time occurred in 25-30% of patients, most frequently because of holidays and weekends and side effects of therapy. Overall treatment time had a major impact on pelvic tumor control in Stages IB, IIA, and IIB; in Stage IB 10-year actuarial pelvic failure rates were 7% with OTT < or = 7 weeks, 22% with 7.1 to 9 weeks, and 36% with > 9 weeks (p < or = 0.01). For Stage IIA the corresponding values were 14%, 27%, and 36% (p = 0.08), and in Stage IIB pelvic failure rates were 20%, 28%, and 34%, respectively (p = 0.09). In Stage III, pelvic failure was 30%, 40%, and 50%, respectively (p = 0.08). There was also a strong correlation between OTT and 10-year cause-specific survival (CSS); in Stage IB rates were 86% with OTT of < or = 7 weeks, 78% for 7.1 to 9 weeks, and 55% for > or = 9 weeks (p < 0.01). The corresponding rates in Stage IIA were 73%, 41%, and 48% (p < or = 0.01). For patients with Stage IIB, CSS rates were 72% for OTT < or = 7 weeks, 60% for 7.1 to 9 weeks, and 70% for > 9 weeks (p = 0.01). Patients with Stage III disease had 45% 10-year CSS when treatment was delivered in 9 weeks or less and 36% for longer overall times (p = 0.16). In multivariate analysis of patients with Stage IB and IIA, OTT and clinical stage were the most important prognostic factors for pelvic tumor control, disease-free survival, and CSS. Tumor size was a prognostic factor for CSS. In Stages IIB and III, OTT, clinical stage, unilateral or bilateral parametrial invasion, and dose to point A were significant prognostic factors for pelvic tumor control, disease-free survival, and CSS. Prolongation of time had a significant impact on pelvic tumor control and CSS regardless of tumor size, except in Stage IB tumors < or = 3 cm. Regression analysis confirms previous reports that prolongation of OTT results in decreased pelvic tumor control rate of 0.85% per day for all patients, 0.37% per day in Stages IB and IIA, 0.68% per day in Stage IIB, and 0.54% for Stage III patients treated with > or = 85 Gy to point A. Performance of all intracavitary insertions within 4.5 weeks from initiation of irradiation yielded decreased pelvic failure rates in some groups of patients (8.8 vs. 18% in Stage IB and IIA tumors < or = 4 cm and 12.3 vs. 35% in Stage IIB) (p < or = 0.01). CONCLUSIONS Prolongation of treatment time in patients with Stage IB, IIA, IIB, and III carcinoma of the uterine cervix has a significant impact on pelvic tumor control and CSS. The effect of OTT was present regardless of tumor size except in Stage IB tumors < or = 3 cm.

Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone

The authors conducted a retrospective analysis of 1178 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. The minimum follow‐up time was 3 years. The 10‐year actuarial pelvic failure rate in Stage IB was 6% for tumors less than 3 cm, 15% for tumors 3 to 5 cm, and 30% for tumors more than 5 cm (P = 0.0018). The 10‐year actuarial pelvic failure rate in Stage IIA was 10% for tumors less than 3 cm, 28% for tumors 3 to 5 cm, and 20% for tumors more than 5 cm (P = 0.09). Stage IIB unilateral nonbulky tumors (less than 5 cm) had a 20% pelvic failure rate compared with 28% for bilateral lesions and 35% for unilateral bulky tumors (more than 5 cm) (P = 0.35). In Stage IIB, pelvic failures were greater when disease extended into the lateral parametrium (30%) compared with medial parametrial involvement only (17%) (P = 0.01). In Stage III unilateral nonbulky tumors, the pelvic failure rate was 28% compared with 45% to 50% for unilateral bulky lesions (P = 0.002). Bilateral parametrial disease in Stage IIB did not increase the pelvic failure rate (21% in both subgroups) (P = 0.83), whereas in Stage III, bilateral parametrial involvement was associated with a 48% pelvic failure rate versus 28% for unilateral extension (P ≤ 0.01). Five‐year disease‐free survival (DFS) rates for IB tumors less than or equal to 3 cm was 90% versus 67% for tumors more than 3 cm (P = 0.01). In Stage IIA tumors less than or equal to 3 cm, 5‐year DFS was 70% versus 45% for tumors more than 3 cm. Patients with Stage IIB nonbulky tumors (less than or equal to 5 cm in diameter) had better 10‐year DFS (65% to 70%) compared with those with bilateral bulky tumors (45% to 55%) (P = 0.10). Stage I11 patients with unilateral nonbulky tumors had a 55% 10‐year DFS compared with 35% to 40% for bulky tumors or bilateral parametrial involvement (P = 0.002). The authors concluded that clinical stage and size of tumor are critical factors in the prognosis, therapy selection, and evaluation of results in carcinoma of the uterine cervix.

Tumor Size, Irradiation Dose, and Long-Term Outcome of Carcinoma of Uterine Cervix

PURPOSE To assess the impact of tumor size and extent, and dose of irradiation on pelvic tumor control, incidence of distant metastases, and disease-free survival in carcinoma of the uterine cervix. METHODS AND MATERIALS Records were reviewed of 1499 patients (Stages IA-IVA) treated with definitive irradiation (combination of external beam plus two intracavitary insertions to deliver doses of 65-95 Gy to point A, depending on stage and tumor volume). Follow-up was obtained in 98% of patients (median 11 years, minimum 3 years, maximum 30 years). The relationship between outcome and tumor size was analyzed in each stage. Pelvic tumor control was correlated with total doses to point A and to the lateral pelvic wall. RESULTS The 10-year actuarial pelvic failure rate in Stage IB was 5% for tumors <2 cm, 15% for 2.1-5 cm, and 35% for tumors >5 cm (p = 0.01); in Stage IIA, the rates were 0%, 28%, and 25%, respectively (p = 0.12). Stage IIB unilateral or bilateral nonbulky tumors <5 cm had a 23% pelvic failure rate compared with 34% for unilateral or bilateral bulky tumors >5 cm (p = 0.13). In Stage IIB, pelvic failures were 18% with medial parametrial involvement only, compared with 28% when tumor extended into the lateral parametrium (p = 0.05). In Stage III, unilateral parametrial involvement was associated with a 32% pelvic failure rate versus 50% for bilateral extension (p < 0.01). Ten-year disease-free survival rates were 90% for IB tumors <2 cm, 76% for 2.1-4 cm, 61% for 4.1-5 cm, and 47% for >5 cm (p = 0.01); in Stage IIA, the rates were 93%, 63%, 39%, and 59%, respectively (p < or = 0.01). Patients with Stage IIB medial parametrial involvement had better 10-year disease-free survival (67%) than those with lateral parametrial extension (56%) (p = 0.02). Stage III patients with unilateral tumor extension had a 48% 10-year disease-free survival rate compared with 32% for bilateral parametrial involvement (p < or = 0.01). The presence of endometrial extension or tumor only in the endometrial curettings had no significant impact on pelvic failure. However, in patients with Stage IB disease, the incidence of distant metastases was 31% with positive curettings, 15% with negative curettings, and 22% with admixture (p < or = 0.01). In Stage IIA, the corresponding values were 51%, 33%, and 18% (p = 0.05). The 10-year disease-free survival rates in Stage IB were 67% with positive curettings, 81% for negative curettings, and 77% for admixture (p = 0.02); in Stage IIA, the rates were 45%, 66%, and 67%, respectively (p = 0.14). Because this is not a prospective Phase II dose-escalation study, the correlation of doses of irradiation with pelvic tumor control in the various stages and tumor size groups is not consistent. Nevertheless, with Stage IB and IIA tumors <2 cm in diameter, the pelvic failure rate was under 10% with doses of 70-80 Gy to point A, whereas for larger lesions even doses of 85-90 Gy resulted in 25% to 37% pelvic failure rates. In Stage IIB with doses of 70 Gy to point A, the pelvic failure rate was about 50% compared with about 20% in nonbulky and 30% in bulky tumors with doses > 80 Gy. In Stage III unilateral lesions, the pelvic failure rate was about 50% with < or =70 Gy to point A versus 35% with higher doses, and in bilateral or bulky tumors it was 60% with doses <70 Gy and 50% with higher doses. CONCLUSIONS Clinical stage and size of tumor are critical factors in prognosis, therapy efficacy, and evaluation of results in carcinoma of the uterine cervix. The doses to point A suggest that for lesions <2 cm, doses of 75 Gy result in < or =10% pelvic failures, whereas in more extensive lesions, even with doses of 85 Gy, the pelvic failure rate is about 30%; and in Stage IIB-III tumors, doses of 85 Gy result in 35-50% pelvic failures. Refinements in brachytherapy techniques and/or use of agents to selectively sensitize the tumors to irradiation will be necessary to improve the present results in invasive carcinoma of t

Gross tumor volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma

PURPOSE Three-dimensional conformal radiation therapy (3D-CRT) has recently become widely available with applications for patients with non-small-cell lung cancer (NSCLC). These techniques represent a significant advance in the delivery of radiotherapy, including improved ability to delineate target contours, choose beam angles, and determine dose distributions more accurately than were previously available. The purpose of this study is to identify prognostic factors in a population of NSCLC patients treated with definitive 3D-CRT. METHODS AND MATERIALS Between March 1991 and December 1998, 207 patients with inoperable NSCLC were treated with definitive 3D-CRT. Tumor targets were contoured in multiple sections from a treatment planning computed tomography (CT) scan. Three-dimensional treatment volumes and normal structures were reconstructed. Doses to the International Commission on Radiation Units and Measurements (ICRU) reference point ranged from 60 to 83.85 Gy with a median dose of 70 Gy. The median dose inhomogeneity was +/- 5% across planning target volume. Outcome was analyzed by prognostic factors for NSCLC including pretreatment patient and tumor-related factors (age, gender, race, histology, clinical stage, tumor [T] stage, and node [N] stage), parameters from our 3D-CRT system (gross tumor volume [GTV] in cm3), irradiation dose prescribed to isocenter, volume of normal lung exceeding 20 Gy (V20), and treatment with or without chemotherapy. The median follow-up time was 24 months (range, 7.5 months to 7.5 years). RESULTS One and two-year overall survival rates for the entire group were 59% and 41%, respectively. Overall survival, cause-specific survival, and local tumor control were most highly correlated with the GTV in cm3. On multivariate analysis the independent variable most predictive of survival was the GTV. Traditional staging such as T, N, and overall clinical staging were not independent prognostic factors. Patients receiving ICRU reference doses > or =70 Gy had better local control and cause-specific survivals than those treated with lower doses (p = 0.05). Increased irradiation dose did not improve overall survival. CONCLUSIONS GTV as determined by CT and 3D-CRT planning is highly prognostic for overall and cause-specific survival and local tumor control and may be important in stratification of patients in prospective therapy trials. T, N, and overall stage were not independent prognostic factors in this population of patients treated nonsurgically. The value of dose escalation beyond 70 Gy should be tested prospectively by clinical trial.

Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation

PURPOSE To quantitate the impact of total doses of irradiation, dose rate, and ratio of doses to bladder or rectum and point A on sequelae in patients treated with irradiation alone for cervical cancer. METHODS AND MATERIALS Records were reviewed of 1456 patients (Stages IB-IVA) treated with external-beam irradiation plus two low-dose rate intracavitary insertions to deliver 70 to 90 Gy to point A. Follow-up was obtained in 98% of patients (median, 11 years; minimum, 3 years; maximum, 30 years). The relationships among various dosimetry parameters and Grade 2 or 3 sequelae were analyzed. RESULTS In Stage IB, the frequency of patients developing Grade 2 morbidity was 9%, and Grade 3 morbidity, 5%; in Stages IIA, IIB, III, and IVA, Grade 2 morbidity was 10% to 12% and Grade 3 was 10%. The most frequent Grade 2 sequelae were cystitis and proctitis (0.7% to 3%). The most common Grade 3 sequelae were vesicovaginal fistula (0.6% to 2% in patients with Stage I-III tumors), rectovaginal fistula (0.8% to 3%), and intestinal obstruction (0.8% to 4%). In the bladder, doses below 80 Gy correlated with less than 3% incidence of morbidity and 5% with higher doses (p = 0.31). In the rectosigmoid, the incidence of significant morbidity was less than 4% with doses below 75 Gy and increased to 9% with higher doses. For the small intestine, the incidence of morbidity was less than 1% with 50 Gy or less, 2% with 50 to 60 Gy, and 5% with higher doses to the lateral pelvic wall (p = 0.04). When the ratio of dose to the bladder or rectum in relation to point A was 0.8 or less, the incidence of rectal morbidity was 2.5% (8 of 320) vs. 7.3% (80 of 1095) with higher ratios (p < or = 0.01); bladder morbidity was 2.3% (7 of 305) and 5.8% (64 of 1110), respectively (p = 0.02). The incidence of Grade 2 and 3 bladder morbidity was 2.9% (10 of 336) when the dose rate was less than 0.80 Gy/h, in contrast to 6.1% (62 of 1010) with higher dose rates (p = 0.07). Rectal morbidity was 2% to 5% in Stage IB, regardless of dose rate to the rectum; in Stages IIA-B and III, morbidity was 5.2% (28 of 539) with a dose rate of 0.80 Gy or less and 10.7% (37 of 347) with higher dose rates (p < 0.01). Multivariate analysis showed that dose to the rectal point was the only factor influencing rectosigmoid sequelae, and dose to the bladder point affected bladder morbidity. CONCLUSIONS Various dosimetric parameters correlate closely with the incidence of significant morbidity in patients treated with definitive irradiation for carcinoma of the uterine cervix. Careful dosimetry and special attention to related factors will reduce morbidity to the lowest possible level without compromising pelvic tumor control.

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PURPOSE To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. RESULTS Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearsons chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fishers exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearsons chi-square test). However, the mean dose was not predictive on multivariate analysis. CONCLUSION Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

Distant metastases after irradiation alone in carcinoma of the uterine cervix

This is a retrospective analysis of 1211 patients with invasive carcinoma of the uterine cervix treated with irradiation alone from 1959 through 1986, of whom 322 developed distant metastases during the course of the disease. The 10-year actuarial incidence of distant metastases was 3% in Stage IA (34 patients), 16% in Stage IB (384 patients), 31% in Stage IIA (128 patients), 26% in Stage IIB (353 patients), 39% in Stage III (292 patients), and 75% in Stage IVA (20 patients). A multivariate analysis of factors influencing the incidence of distant metastases showed clinical stage, endometrial extension noted by dilatation and curettage (D&C) prior to therapy, and pelvic tumor control within each stage to be significant indicators of distant dissemination; histology, volume of disease, and age of patient were not significant. The frequency of metastases in all stages except IVA was greater when endometrial tumor extension was detected by D & C before to definitive irradiation (Stage IB, 28%; Stage IIA, 48%; Stage IIB, 42%; Stage III, 72%; and Stage IVA, 75%). In contrast, with normal D & C findings, the incidence of distant metastases was 15% in Stage IB, 29% in Stage IIA, 25% in Stage IIB, 45% in Stage III, and 84% in Stage IVA. The incidence of metastases in patients with pelvic tumor control was 11% in Stage IB, 22% in Stage IIA, 21% in Stage IIB, 34% in Stage III, and 50% in Stage IVA; in contrast, the corresponding incidence in patients failing in the pelvis was 76% in Stage IB, 88% in Stage IIA, 62% in Stage IIB, 87% in Stage III, and 74% in Stage IVA. The frequency of metastases per histology was comparable in squamous cell carcinoma and other histologic types. The incidence of metastases to other organs was 56%: Most frequent sites were lung, abdominal cavity, liver, and gastrointestinal tract. The incidence of clinically apparent lymph node involvement was 22%, predominantly to paraaortic, supraclavicular, and inguinal nodes. Bone metastases occurred in 16% of the patients, most commonly to the lumbar and thoracic spine. Despite aggressive local therapy with excellent local control, the incidence of distant metastases in patients with invasive carcinoma of the uterine cervix is high. The management of these patients and their response to salvage therapy are discussed. The need for effective adjuvant systemic therapy in the management of patients with invasive carcinoma of the cervix is also discussed.

RADIOTHERAPY FOR EPITHELIAL SKIN CANCER

PURPOSE To retrospectively review patterns of failure, cosmesis, and outcomes according to treatment modality of patients with histologically confirmed epithelial skin cancer. METHODS AND MATERIALS The records of 468 patients having 531 lesions were analyzed; 389 basal cell carcinomas and 142 squamous cell carcinomas were treated, 167 of which were recurrent tumors. Median follow-up was 5.8 years. Electron beam irradiation was used in 19%, superficial x-rays in 60%, a combination of electron beam and superficial x-rays in 20%, and megavoltage photons in <2%. RESULTS The overall local tumor control rate was 89%; it was 93% for previously untreated lesions and 80% for recurrent lesions. Patients with basal cell carcinoma had a 92% overall control rate; patients with squamous cell carcinoma 80%. Multivariate analysis showed that local failure was related to the daily dose fractionation. The maximal diameter of the lesion and pathologic tumor type were also significant (p 0.01). Treatment type, patient age, and treatment duration were not significant. Overall, 92% of the treated population with cosmesis data had excellent or good results. The overall complication rate was 5.8%, consisting primarily of soft-tissue necrosis. CONCLUSIONS Radiotherapy remains an excellent treatment modality for epithelial skin cancer. Local tumor control, cosmesis, and complications are related to the size of the primary lesion. Recurrent lesions fared worse, and therefore treatment at the earliest possible stage is strongly recommended.

Impact of dose in outcome of irradiation alone in carcinoma of the uterine cervix: analysis of two different methods

This is a retrospective analysis of 1211 patients with histologically proven invasive carcinoma of the uterine cervix with a minimum follow-up of 3 years treated with irradiation alone. The pelvic failure rates by stage were 9.6% for IB, 18.6% for IIA, 23% for IIB, 41% for III, and 75% for Stage IVA disease. External beam and intracavitary irradiation doses to point A and pelvic lymph nodes were calculated. In patients with Stage IB and IIA disease there was no significant correlation between doses to these points and pelvic tumor control. In Stage IIB doses of less than 6000 cGy to point A correlated with a high pelvic failure rate (8 of 12, 66.7%) in contrast to doses of 6000 to 9000 cGy (61 of 261, 23.4%) or higher than 9000 cGy (10 of 74, 13.5%) (p less than or equal to 0.01). In Stage III the pelvic failure rate with doses below 6000 cGy to point A was 72% (18 of 25) compared to 39% (71 of 180) for 6000 to 9000 cGy or 35% (27 of 77) with doses above 9000 cGy (p less than or equal to 0.01). TDF calculation of doses was carried out. In Stage IB and IIA there was no significant correlation between TDF to point A and probability of pelvic recurrence. In Stage IIB with TDF below 135, the pelvic recurrence rate was 41.6% (20 of 48) compared to 20% (61 of 305) with higher TDF (p less than or equal to 0.01). In Stage III the pelvic failure rate was 51% with TDF below 160 (70 of 136) in comparison with 29.5% (46 of 156) with higher TDF (p less than or equal to 0.01). Grade 2 sequelae of therapy were noted in about 10% of the patients and grade 3 in 4.7% of patients with Stage IB (18 of 384), 10.2% (12 of 128) with Stage IIA, 9.3% (33 of 353) with Stage IIB, and 8.2% (24 of 293) with Stage III disease. Doses from external beam and intracavitary irradiation to the rectum or the bladder neck were calculated. The actuarial incidence of major rectal or rectosigmoid sequelae was 2% to 4% with doses to the rectum of 6000 to 8000 cGy, 7% to 8% with 8000 to 9500 cGy, and 13% with doses higher than 9500 cGy (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)