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Purpose: The purpose of this study was to evaluate the impact of elapsed treatment time in external-beam radiation therapy for localized prostate carcinoma., Materials and Methods: The medical records of 1083 patients with localized prostate carcinoma treated between 1970 and December 1999 with external irradiation alone were reviewed. Median follow-up was 6 years (range, 4-24 years). Since 1987, prostate-specific antigen levels were obtained in 687 patients before the initiation of radiation therapy, and all patients seen in follow-up had prostate-specific antigen determinations. There were 344 patients with T1c, 496 with T2, and 243 with T3 tumors. The elapsed treatment time was divided into < or = 7, 7.1-9, or > 9 weeks. Local tumor control was determined by rectal examination and cause-specific survival or prostate-specific antigen failure according to American Society of Therapeutic Radiology and Oncology consensus criteria. Because of dose-escalation studies, tumor dose levels ranged from 66-73.8 Gy, given in 1.8- to 2-Gy fractions., Results: In patients with stage T1c, local failure ranged from 0% to 10% with doses < or = 72 Gy with; elapsed treatment time had no impact. No pelvic failures were detected in 88 patients receiving doses > 72 Gy. In patients with T2 who received < or = 70 Gy, overall pelvic failure rate was 4% (12/306) in those with an elapsed treatment time of < or = 9 weeks, in contrast to 27% (12/44) for those with an elapsed treatment time > 9 weeks; at 10 years, patients with T2 tumors treated in > 9 weeks had a higher actuarial pelvic failure rate (35%), in contrast to 5% to 18% with shorter treatment times. For patients with T2 tumors who received 70-72 Gy, pelvic failure rate ranged from 0% to 32%, and there were no failures in 37 patients treated to higher doses. In patients with prostate-specific antigen values whose tumors were stage T1c, the chemical failure rate was 41% (60/147) with a tumor dose < 70 Gy, compared with 17% (4/24) in those who received higher doses. In patients with stage 2 disease who were treated with < 70 Gy, the chemical failure rate was 31%, and the rate was 12%-18% in those who received higher doses. In stage T3, the clinical pelvic failure rate ranged from 25% to 32% in the three elapsed time groups, and the chemical failure rate ranged from 48% to 69%, and there was no significant correlation with elapsed time or total irradiation dose. Cause-specific survival without chemical failure in patients with stage T1c disease at 10 years was 85%-90% in the three elapsed treatment time groups. In patients with stage T2 disease, the corresponding values were 80% and 90% for elapsed treatment times < 9 weeks, in contrast to 65% for patients treated > 9 weeks. In patients with stage T3 disease, cause-specific survival was about 60% in all elapsed treatment groups. There was no significant correlation of elapsed treatment time with urinary or rectal morbidity., Conclusions: Patients treated with radiation therapy for stage T2 localized prostate carcinoma showed a greater incidence of pelvic and chemical failures and a lower cause-specific survival when elapsed treatment time was > 9 weeks in comparison with the failure and survival rates occurring with shorter times. Higher doses of irradiation (> 72 Gy) eliminate the influence of prolongation of treatment time on outcome.

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.

Purpose: Several reports document a negative impact of prolongation of overall treatment time in a course of irradiation on tumor control and survival. A correlation has been documented of incidence of significant treatment sequelae with increasing doses of irradiation, volume of the specific organ, and dose per fraction. However, no data were found on the potential correlation of overall irradiation treatment time with significant sequelae., Methods and Materials: Records were reviewed of 1,269 patients with carcinoma of the cervix (Stage IB to HI) treated with definitive irradiation (combination of external beam and two intracavitary insertions). Follow-up was obtained in 97% of patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationships between overall treatment time and time of brachytherapy and incidence of treatment sequelae were analyzed for each stage., Results: Overall incidence of Grades 2 (moderate) sequelae was 7% and of Grade 3 (severe) sequelae, 11%. There was no significant correlation of various incidences of Grade 2 and 3 sequelae with overall treatment times (8% in patients treated in less than 7 weeks, 9% in 7.1 to 9 weeks, and 12% when treatment time was longer than 9 weeks) (p = 0.08). In patients with Stage IB and IIA tumors, incidence of rectal toxicity (mostly proctitis) was comparable in patients treated in less than 7 or 7.1 to 9 weeks (4.1 and 6%, respectively) and slightly higher in those treated in longer periods (11.5%) (p = 0.24). In patients with Stage IIB and III, the incidence of Grade 2 and 3 small bowel morbidity was 2% in those treated in less than 7 weeks, 6% for 7.1 to 9 weeks, and 4.9% for longer times (p < or = 0.01). This increased morbidity was also correlated with total dose of irradiation to the lateral pelvic wall: 5 of 257 (2%) for less than 60 Gy and 21 of 438 (4.8%) for higher doses (p < or = 0.01). There was no significant correlation between the timing of brachytherapy (usually two low dose rate intracavitary insertions performed within 4.5 to 6.5 weeks of initiation of external beam therapy) and significant treatment sequelae., Conclusions: We observed a varied average incidence of Grade 2 and 3 morbidity in the bladder, rectum, and small intestine with different overall treatment times, without a definite pattern to suggest an impact of prolongation of treatment time on morbidity. Likewise, there was no significant correlation with the timing of intracavitary insertions and morbidity of therapy. Because prolongation of the overall treatment time has a well-documented detrimental effect on pelvic tumor control and survival in carcinoma of the cervix with no significant impact on morbidity, it is imperative to deliver radiation therapy in the shortest possible time and without schedule interruptions.

Purpose: Definitive radiation therapy alone or combined with surgery in carcinoma of the uterine cervix yields comparable tumor control and survival in Stages I and IIA when patients are adequately treated with either modality. Our 30-year institutional experience is described., Methods and Materials: This is a nonrandomized comparison of treatment results of 415 patients with Stage IB, 137 with Stage IIA, and 340 with Stage IIB carcinoma of the uterine cervix treated with irradiation alone and 197 with Stage IB, 44 with Stage IIA, and 65 with limited Stage IIB treated with pre- or postoperative irradiation and surgery. Irradiation alone consisted of a combination of external beam therapy and intracavitary insertions to deliver doses of 70 to 85 Gy to point A for patients with Stages IB and IIA disease and 80 to 90 Gy for patients with bulky or Stage IIB tumors. For patients treated with irradiation and surgery, various combinations of external beam and intracavitary therapy were used to deliver 60 to 75 Gy to point A. Surgical procedures consisted of radical hysterectomy with or without lymph node dissection in 130 patients with Stage IB, 28 patients with Stage IIA, and 10 patients with limited Stage IIB. Fifty-seven patients had total abdominal or conservative hysterectomy with or without lymph node dissection, and 3 had vaginal hysterectomy. In addition, 51 patients with Stage IIB tumors underwent pelvic lymphadenectomy after definitive irradiation., Results: The 5-year cause-specific survival (CSS) rates for patients with Stage IB nonbulky tumors treated with irradiation alone or irradiation combined with surgery were 90 and 85%, respectively, and the 10-year survival rate was 84% with either modality. In patients with bulky tumors (> 5 cm), the 5-year CSS rates were 61% with irradiation alone and 63% with irradiation plus surgery; at 10 years the rates were 61 and 68%, respectively (p = 0.5). For those with Stage IIA nonbulky tumors, the 5-year CSS rates were 75% with irradiation alone and 83% with combined irradiation and surgery, and 10-year CSS rates were 66 and 71%, respectively. In patients with Stage IIA bulky tumors, the 5-year CSS rates were 69% with irradiation alone and 60% with irradiation plus surgery, and at 10 years, 69 and 44%, respectively (p = 0.05). In patients with Stage IIB nonbulky tumors treated with irradiation alone or combined with surgery, the 5- and 10-year CCS rates were 72 and 65%, respectively; the corresponding survival rates with bulky tumors or bilateral parametrial involvement were 56 and 50%. Incidence of pelvic failures, alone or with distant metastasis, for Stage IB was 10% (43 out of 415) with irradiation alone and 14% (28 of 197) with irradiation plus surgery; for Stage IIA, 17% (23 out of 137) with irradiation alone and 20% (9 our of 44) with irradiation plus surgery; and for Stage IIB, 23% (88 out of 391) with irradiation alone and 29% (4 out of 14) with irradiation plus surgery. Grade 3 sequelae were comparable in both groups (irradiation alone, 5% to 11%; irradiation combined with surgery, 8% to 12%); the differences are not statistically significant. The most frequent major sequelae in 892 patients receiving irradiation only were rectovaginal fistula (13 cases, 1.5%), proctitis (10, 1.1%), small bowel obstruction (16, 1.8%), ureteral stricture (16, 1.8%), and vesicovaginal fistula (8, 0.9%). In 306 patients treated with irradiation plus surgery, the most commonly recorded major sequelae were small bowel obstruction/perforation (13 cases, 4.2%), ureteral stricture (8, 2.6%), vesicovaginal fistula (5, 1.6%), and rectovaginal fistula (4, 1.3%)., Conclusion: Irradiation alone or combined with surgery yields comparable pelvic tumor control, survival, and morbidity in patients with Stage IB, IIA, and limited IIB carcinoma of the uterine cervix.

Purpose: The current study was conducted to investigate the incidence and risk factors for medical complications associated with low dose rate brachytherapy in patients with medically inoperable Stage I endometrial cancer treated with irradiation alone., Methods and Materials: From 1965 through 1991 at Mallinckrodt Institute of Radiology, 150 implants were performed on 96 patients who were deemed medically unfit for hysterectomy because of advanced age, obesity, and various medical problems. The records of these patients were examined retrospectively to determine the incidence of medical complications that occurred in the first 30 days following the initiation of brachytherapy. The association of risk factors that precluded major surgery and the occurrence of brachytherapy-related complications was examined by logistic regression., Results: Of these 96 patients, 40 patients were older than 75 years, and 31 patients were deemed morbidly obese. Medical problems included hypertension in 45 patients, and diabetes in 37; there was a history of congestive heart failure in 23, stroke in 11, myocardial infarction in 10, and thromboembolism in 8. There were concurrent malignancies in five patients. Implants were performed using intrauterine Simon-Heyman capsules, tandems, and vaginal ovoids in all patients. General anesthesia was used for 98 implants, spinal anesthesia for 26, local anesthesia for 25, and epidural anesthesia for 1. The duration of anesthesia ranged from 30 to 120 min (median, 60 min). The duration of radioisotope application ranged from 11 to 96 h (median, 46 h). Preventive measures included low dose subcutaneous heparin in 55 patients (since 1978), and intermittent pneumatic compression boots in 29 (since 1985). Four patients developed life-threatening complications including myocardial infarction (two patients), congestive heart failure (one patient), and pulmonary embolism (one patient). Two of these four patients died; one with a myocardial infarction and the other with pulmonary embolism. The morbidity rate was thus 4.2% (4 out of 96), and the mortality was 2.1% (2 out of 96). Although the four serious complications occurred within 30 days of the procedure, only one complication and one death occurred during treatment. There was no correlation between occurrence of complications and medical risk factors, type and duration of anesthesia, or type and duration of implant., Conclusions: There is a low incidence of complications associated with conventional low dose rate brachytherapy. The procedure is well tolerated in patients with medically inoperable Stage I endometrial cancer. In comparison to the predicted serious complication rate of surgery in these patients, the number of life-threatening complications from brachytherapy appears to be quite acceptable.

Background: The treatment of patients with locally advanced noninflammatory breast cancer has evolved substantially over the past 30 years. From 1968 to 1989, 281 women were treated at Mallinckrodt Radiation Oncology Center with four different treatment methods. Median follow-up was 6.2 years (range 3-22 years); no patient was lost to follow-up., Methods: Retrospective review of records and analysis of data on a computer file were carried out. Thirty-five patients were treated with irradiation alone, 33 with irradiation and adjuvant chemotherapy, 81 with mastectomy and irradiation, and 132 with mastectomy, irradiation, and chemotherapy (triple-modality)., Results: Actuarial 5- and 10-year disease free survival (DFS) rates were 45% and 36%, respectively, with triple-modality therapy, 31% and 10% with irradiation and chemotherapy, 32% and 19% with irradiation and mastectomy, and 19% and 11% with irradiation alone. Cause specific survival (CSS) paralleled DFS in the four groups. Locoregional tumor control at 5 years was 91% for irradiation, mastectomy, and chemotherapy, 80% for irradiation and mastectomy, 54% for irradiation and chemotherapy, and 31% for irradiation alone. Systemic therapy and/or irradiation given before mastectomy yielded better locoregional tumor control, DFS, and CSS (not statistically significant). No difference in results was noted with radical, modified radical, or total mastectomy. In the triple-modality group, no chest wall failures occurred with chest wall doses greater than 5040 cGy. Grade 2 or higher treatment sequelae were noted in 10-42% of patients, depending on treatment modality., Conclusions: Triple-modality therapy yielded improved locoregional tumor control, DFS, and CSS compared with other modalities. Patients treated with surgery had better locoregional tumor control than those who received irradiation alone or in combination with chemotherapy, but the impact on DFS and CSS was less impressive. Additional clinical trials are needed to define further the role and optimal use of the various therapeutic modalities in the management of locally advanced breast cancer.

Background: Optimal treatment for patients with localized carcinoma of the prostate is controversial. Radiation therapy is an established modality in the management of these patients, and several reports indicate the results are comparable to those achieved with radical prostatectomy. Recently effectiveness of therapy for carcinoma of the prostate is being evaluated in light of post-treatment prostate-specific antigen (PSA) determinations., Methods: A review was performed of multiple publications and data from selected institutions with large experience in the management of carcinoma of the prostate. Survival and clinical incidence of local recurrence and distant metastases were analyzed as well as preliminary data on postirradiation PSA levels. Factors that affect the outcome of therapy and relevant clinical trials are discussed., Results: Reported differences in the age of patients treated with radical prostatectomy (59-63 years), irradiation (63-69 years), or observation (69-75.5 years) were identified. The effect of surgical staging on outcome of irradiation was significant. In multiple series of patients clinically and radiographically staged, the 5-year disease-free survival (DFS) with external irradiation was 95-100% for clinical stage T1a, 80-90% for Stage T1b,c, and 50-70% for clinical Stage T3. A correlation has been identified between the initial PSA levels and the probability from freedom of chemical failure (PSA elevation) after definitive irradiation. In five series comprising 814 patients with Stage T1c and T2 tumors, the DFS (end point chemical failure) was 95%, with initial PSA of less than 4 ng/ml, 83-92% with 4.1-10 ng/ml, 35-85% with 10.1-20 ng/ml, and 10-63% with PSA higher than 20 ng/ml. In the various series, follow-up ranged from a median of 1.5 years to a minimum of 4 years. In two series of 225 and 201 patients receiving doses of 7500-8000 cGy, less morbidity has been observed with three-dimensional treatment planning conformal radiation therapy than with conventional irradiation. New directions for future clinical trials are discussed, including dose escalation studies; use of high linear energy transfer to improve locoregional tumor control; and combination of irradiation and androgen suppression to enhance local tumor control, decrease distant metastasis, and improve survival. Preliminary results of a randomized study recently reported by RTOG strongly suggest that the use of goserelin acetate and flutamide decreases the incidence of clinical local recurrence (12.4% in 225 patients) compared with a control group treated with irradiation alone (25.2% in 230 patients) and enhances disease-free survival., Conclusions: Although modern approaches to the management of patients with localized carcinoma of the prostate with irradiation are effective, investigators must continue to critically assess policies of treatment, develop appropriately designed prospective clinical trials, and define the optimal management of patients with localized carcinoma of the prostate.

Background: This report consists of a retrospective analysis of 50 patients with primary invasive and 17 with recurrent histologically confirmed vulvar carcinoma treated with radiation therapy for locoregional disease., Methods: Of the patients with primary tumors, 13 were treated with wide local excision plus radiation therapy; 13 had radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes; 8 received similar postoperative radiation therapy after partial or simple vulvectomy; 16 patients had radiation therapy alone after biopsy; and 17 had recurrent tumors treated with radiation therapy alone., Results: In patients treated with biopsy/local excision, local tumor control was 92-100% in T1-3N0 disease, 40% in similar stages with N1-3, and 27% in recurrent tumors. Among patients treated with partial/radical vulvectomy and radiation therapy, primary tumor control was 90% in those with T1-3 tumors and any nodal stage, 33% in those with any T stage and N3 lymph nodes, and 66% in patients with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for patients with T1N0 disease, 62% for those with T2-3N0 disease, 30% for those with T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 disease. Four of 17 patients treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and radiation therapy. In patients with T1-2 tumors treated with biopsy/wide tumor excision and radiation therapy with doses less than 50 Gy, the local tumor control was 75% (three of four patients), in contrast to 100% (13 of 13 patients) with 50.01-65 Gy. With T3-4 tumors treated with local excision and radiation therapy, tumor control occurred in none of three patients with doses less than 50 Gy and 66% (six of nine) with 50.01-65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and radiation therapy, local tumor control was 75% (six of eight), regardless of dose level; in T3-4 tumors, it was 67% (four of six patients) with 50-60 Gy and 86% (six of seven) with 65-70 Gy. Differences were not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes, with doses of 50 Gy being adequate for elective treatment of nonpalpable lymph nodes and 60-70 Gy controlling tumor growth in 75-80% of patients with N2-3 nodes when administered postoperatively, after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess., Conclusions: Wide local tumor excision and radiation therapy or irradiation alone in T1-2 tumors is an alternative treatment to radical vulvectomy in controlling vulvar carcinoma, with significantly less morbidity. In comparison with reported rates for surgery alone, radiation therapy after radical vulvectomy for locally advanced tumors improves tumor control at the primary site and regional lymphatics. Indications and techniques of radiation therapy are discussed.

This retrospective analysis reports the results of therapy in 128 patients with carcinoma of the uterine cervix classified as barrel-shaped or expanded cervix (over 5 cm in diameter). Seventy-five percent of the patients were treated with irradiation alone and 25% with combinations of irradiation and surgery. The results of therapy are compared with those observed in 714 patients with non-barrel-shaped carcinoma of the uterine cervix treated with similar techniques during the same period of time. The distribution of histological type of tumor was similar in both groups (90% epidermoid carcinoma, 8% adenocarcinoma, and 2% adenosquamous carcinoma). Approximately 15% of the patients in both groups with Stage IB and 25% with Stage IIA and IIB had positive endometrial curettings (stromal invasion or replacement by tumor only). Thus, the aggressive behavior observed in the barrel-shaped tumors is not a result of endometrial involvement, but to the large volume of tumor present. The actuarial 5-year tumor free survival in Stage IB barrel-shaped cervix was 76% compared to 92% in the non-barrel-shaped lesions. In Stage IIA the 5-year NED survival for patients with barrel-shaped cervix was 60 compared to 80% for the patients with non-barrel-shaped cervix. In Stage IIB the survival rates were 58 and 70%, respectively. A noteworthy finding in this analysis is the high incidence of distant metastases in the patients with barrel-shaped cervix (32% in Stage IB, 40% in Stage IIA, and 32% in Stage IIB) in comparison with patients with non-barrel-shaped tumors (10% in Stage IB, 16% in Stage IIA, and 25% in Stage IIB). The incidence of pelvic failures was comparable in both groups. Higher doses of irradiation resulted in better tumor control, which was comparable to that observed with a combination of irradiation and surgery (conservative hysterectomy). The 5-year survival rate in Stage IB was similar in both the barrel-shaped and non-barrel-shaped tumors treated with irradiation alone or combination irradiation and surgery. In Stage IIA the non-barrel-shaped lesions had the same survival with either treatment technique. In the barrel-shape group, eight patients treated with irradiation alone or survival of 70%, compared to 45% in 24 patients treated with irradiation alone. However, these differences are not statistically significant (p = .50). In eight patients treated with definitive irradiation and a lymphadenectomy and four patients irradiated after an exploratory laparotomy, two major and three minor (grade 2) complications were noted.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation Therapy Oncology Group (RTOG) protocol 7706 was a randomized Phase III study designed to test the value of elective (prophylactic) pelvic irradiation in addition to prostatic irradiation in patients with carcinoma of the prostate with no clinical evidence of tumor extension through the capsule. Eligible patients were those who had clinical Stage T1bNOMO (A2) or T2NOMO (B), who did not have curative surgery, and who had no evidence of lymph node metastases. Assessment of the regional lymphatics was mandatory but, at the discretion of the investigator, lymphangiography (LAG) or staging lymphadenectomy (SL) could be used. A total of 445 eligible and analyzable patients were entered in the study between 1978 and 1983 when the study was closed. The median follow-up was 7 years; minimum follow-up was 5 years. There were no significant differences in survival or local control whether treatment was administered to the prostate or to the prostate and pelvic lymph nodes. The nodal status for 117 (26%) patients was assessed by staging lymphadenectomy (SL) whereas for 328 (74%) patients it was assessed by lymphangiography (LAG). Pretreatment characteristics felt to have impact on survival were evaluated and found to be free of serious imbalance between the staging lymphadenectomy and lymphangiography groups. Compared to the lymphangiography group, the staging lymphadenectomy group showed better overall survival (87% to 76% at 5 years, p = .02), better disease-free survival (76% to 63% at 5 years, p = .008) and better metastases-free survival (88% to 82% at 5 years, p = .04). There was no difference between the groups in local control. The lymphangiography evaluation of pelvic nodes was clearly inferior for demonstration of the absence of pelvic node metastasis as reflected by reduced survival and increased metastasis.

This report is a retrospective analysis of 376 patients with recurrent cervical carcinoma, following definitive radiation therapy to 1054 patients with stage IB-IVA carcinoma of the uterine cervix treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, from January 1959 through December 1982. The sites of failure after treatment by stage at initial diagnosis were classified as pelvic only (P), pelvic plus distant metastasis (P + DM), or distant metastasis only (DM). The sites of first failure were for stage IB, P = 0.8%, P + DM = 7.4%, DM = 7.9%; for stage IIA, P = 1.7%, P + DM = 14.7%, DM = 17.2%; for stage IIB, P = 10.4%, P + DM = 11.0%, DM = 14.9%; for stage III, P = 15.4%, P + DM = 23.9%, DM = 18.9%; and for stage IV, P = 16.7%, P + DM = 61.1%, DM = 16.7%. The actuarial probability of pelvic failure at 5 years from initial therapy was 8% for stage IB, 16% for stage IIA, 21% for stage IIB, 42% for stage III, and 100% for stage IV. The incidence of distant metastasis at 5 years was 14, 32, 28, 47, and 100% for stages IB, IIA, IIB, III, and IV, respectively. The therapy after failure was surgery, irradiation, irradiation plus surgery, or chemotherapy. There appeared to be no major difference in survival after recurrence by type of treatment or initial stage. The overall survival at 5 years for all untreated patients was 1%. The median survival was evaluated as a function of time to failure after initial treatment. Patients who developed disease more than 36 months after initial treatment had a median survival of 22.5 months. The median survival was 12.1, 7.6, 9.4, and 9.1 months for those failing less than 6, 6-12, 13-24, and 25-36 months after initial treatment. Severe treatment complications occurred in 3.6% (5/140).

A retrospective analysis was carried out on 811 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. A correlation was made of the doses of irradiation delivered to the pelvic organs with external beam and intracavitary insertions. Approximately 3% of the patients exhibited grade 2 gastrointestinal complications, and 2% developed grade 2 urinary complications; 5% of the patients developed grade 3 gastrointestinal complications, and 3% developed grade 3 urinary complications. Other types of complications, primarily grade 2, such as vaginal necrosis, pelvic abscess, thrombophlebitis, etc, were seen in approximately 5% of the patients. Thus, the total percentage of patients developing grade 2 complications was 10% and grade 3 complications, approximately 8%. About 25% of the patients who had complications showed more than one sequela. The most frequently observed grade 2 complications were proctitis, cystitis, vaginal stenosis, and partial small bowel obstruction which were treated with conservative management. Grade 3 complications required surgical treatment and consisted most frequently of ureteral stricture, vesicovaginal fistula, rectovaginal fistula, sigmoid stricture, small bowel obstruction, proctitis, and large rectal ulcers. The most significant factor affecting the appearance of complications was the total dose of irradiation delivered to the pelvic organs by the whole pelvis external irradiation and intracavitary insertions. With maximum total doses up to 8000 rad the incidence of grade 2 and 3 complications was less than 5%. However, with higher doses the incidence of complications increased to 10% to 15%. In patients receiving total doses of 6000 rad to the bladder or rectum, more complications were noted when only one intracavitary insertion was performed, as compared with two or three. Eighty percent of the rectosigmoid complications occurred within 30 months of initial therapy, in contrast to 48 months for the urinary complications. Patients who developed complications had survival rates comparable to those without complications. This underscores the need to rapidly institute treatment on patients who have severe injury after radiation therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Between 1976 and 1982, 293 patients were treated for carcinoma of the uterine cervix at Washington University by definitive radiotherapy consisting of external beam therapy and two standard Fletcher-Suit applications (tandem plus vaginal colpostats). In ninety-nine patients (34%) mini-colpostats (MC) were used for one or both of their intracavitary insertions while 194 (66%) patients were treated twice with regular Fletcher-Suit colpostats (RC). The frequency of MC use was related to the age and parity of the patients. The distribution by stage of MC and RC groups was not significantly different. Pelvic failure in the MC group was similar to that of the RC group (21% vs 24%). Five-year disease-free survival was also similar between the two groups: 86% vs 80% Stage IB, 57% vs 61% Stage IIA, 47% vs 52% Stage IIB, and 27% vs 45% Stage III for MC and RC groups, respectively. The rate of major complications (grade 3) was 15% in the MC group and 8% in the RC group (p = 0.08). Careful phantom dosimetric studies in both types of colpostats and correlations of dose distributions at various points in the pelvis with frequency of rectal and bladder complications were carried out. The bladder and rectum received a 5-10% higher mean radiation dose (Gy) in the MC group than in the RC group despite lower overall exposure (milligram-hours). Thermoluminescent dosimetry in a polystyrene phantom demonstrates that approximately 10% higher doses are delivered to the bladder, rectum, and point A with an MC system as compared to an RC system, for constant exposure in mgh. Phantom measurements of a newer MC with bladder and rectal shielding demonstrate no influence on the bladder and rectal point dose at a source separation of 3 cm; midline points of the bladder and rectum are not within the full shadow of the shields even if the colpostats are flush with the tandem. Implications for therapy are discussed.

Between 1958 and 1985, 107 patients with nonmetastatic inflammatory breast cancer (IBC) received radiotherapy as all or part of initial treatment at the Mallinckrodt Institute of Radiology. For this review, the diagnosis of IBC was made on the basis of either clinical or histopathologic criteria. Fifteen factors of potential prognostic significance were evaluated, by both univariate and multivariate analysis. For relapse-free survival, univariate analysis suggested prognostic value for initial tumor size, discrete versus diffuse tumor mass, adjuvant chemotherapy, and mastectomy. In the multivariate analysis, the independent prognostic factors, in order of significance, were mastectomy, diffuse versus discrete tumor mass, and race (marginal). For survival, univariate analysis suggested prognostic value for initial tumor size, diffuse versus discrete tumor mass, nodal stage, year of treatment, adjuvant chemotherapy, and mastectomy. In the multivariate analysis, the prognostic factors in order of significance were mastectomy and chemotherapy (marginal). The diagnostic selection group showed no prognostic value, suggesting that either clinical or histopathologic criteria justify the diagnosis of IBC. Our results appear to support a role for surgery as part of the combined modality approach to this disease.

A retrospective analysis of 165 patients with histologically confirmed carcinoma of the vagina is reported. Actuarial disease-free 10-year survival was: Stage 0 (16 patients)--94%, Stage I (50 patients)--75%, Stage IIA (49 patients)--55%, Stage IIB (26 patients)--43%, Stage III (16 patients)--32%, Stage IV (8 patients)--0%. All but one of the in situ lesions were controlled with intracavitary therapy. Of the patients with Stage I disease, 86% showed no evidence of vaginal or pelvic recurrence. Most of them received interstitial or intracavitary therapy or both; the addition of external beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) 61% of the tumors were controlled with a combination of brachytherapy and external beam irradiation. Ten of 16 Stage III tumors were controlled in the pelvis. Two of the patients with Stage IV disease had no recurrence in the pelvis with relatively high doses of irradiation. The total incidence of distant metastases was 16% in Stage I, 30.6% in Stage IIA, 46.1% in Stage IIB, 62% in Stage III, and 50% in Stage IV. The dose of irradiation delivered to the primary tumor or the parametrial extension was critical in achieving successful results. The incidence of grade 2-3 complications (12%) is correlated with the stage of the tumor and type of treatment given. More effective irradiation techniques including the optimization of dose distribution by judicious combination of external irradiation and interstitial brachytherapy will be necessary to enhance loco-regional tumor control. The high incidence of distant metastases underscores the need for earlier diagnosis and effective systemic cytotoxic agents if survival is to be significantly improved in these patients.

From 1958 to 1985, 107 patients with a clinical and/or histopathologic diagnosis of non-metastatic inflammatory breast cancer received radiotherapy as all or part of initial treatment. Therapy included definitive irradiation alone in 31 patients, irradiation with mastectomy in 16 patients, irradiation and combination chemotherapy in 23 patients, and irradiation with chemotherapy and surgery in 37 patients. Survivors have a median follow-up of 30 months. Overall median relapse-free survival (RFS) was 12 months (12% at 5 years). Local control and relapse-free survival were significantly improved for patients receiving surgery as part of initial treatment: 19% (10/52) of operated patients experienced locoregional failure vs. 70% (37/53) not operated (p less than 0.0001). The median overall actuarial survival was 24 months (17% at 5 years). Patients who received surgery showed improved survival (44 months vs. 18 months median; 37% vs. 7% at 5 years; p = 0.0004). Chemotherapy also was associated with improved relapse-free survival (18 months vs. 8 months median; 20% vs. 5% at 5 years; p = 0.02) and actuarial survival (32 months vs. 17 months median; 23% vs. 3% at 5 years; p less than 0.02). Patients treated with initial chemotherapy (usually 2-3 cycles of CAF), surgery, and postoperative irradiation followed by maintenance chemotherapy showed a 34 month median relapse-free survival (37% at 5 years RFS) and a 47 month median survival (48% at 5 years). Moderate to severe complications were seen in 25% of patients, the most frequent complication being fibrosis of the breast or chest wall. There were two fatalities secondary to Adriamycin-induced cardiomyopathy. This study suggests better local control, with fewer complications, when surgery and irradiation are combined with multiagent chemotherapy. Further prospective clinical trials are strongly recommended.

A review of 1048 patients with cancer of the cervix treated with radiation, either alone or combined with surgery, disclosed 32 cases of second primary malignancies occurring from 1 to 16 years subsequent to treatment. Using the person years approach, the incidence rate of second primaries was 5.49 per 1000 person years, which is not significantly different from population based rates. The anatomic locations of the new malignancies and the times from treatment of the cervix cancer to diagnosis of a new primary are presented; the possible carcinogenic effects of radiation are discussed. In this group of patients, it was concluded that under the period of observation irradiation administered at therapeutic doses did not increase the probability of second malignancy in the pelvis or at other sites.

Pretreatment computed tomography (CT) scanning of the pelvis was performed in 100 consecutive patients with carcinoma of the prostate treated with external irradiation (82 patients) or interstitial I125 (18 patients). Treatment plan modifications prompted by CT scan findings were most frequent in patients with (clinical) involvement of the seminal vesicles in whom the conventional treatment planning often resulted in an underestimate of tumor volume. Seventeen of 32 (53%) such patients required an enlargement of treatment fields to adequately encompass the target volume. Using skeletal landmarks as reference, the dimensions of the prostate, seminal vesicles and the detectable tumor and their topographic relationships were systematically tabulated. These measurements provide a basis for the definition of the target volume in patients with carcinoma of the prostate in whom CT scans might not be available.

Forty patients with histologically confirmed primary or recurrent vulvar carcinoma were treated with radiation therapy for loco-regional disease. Nineteen of the patients with primary tumors received postoperative radiotherapy (5000 cGy in 6 weeks). Fifteen of the 19 exhibited local tumor control. Five patients with Stage III or IV disease were managed with radiotherapy alone. Four had a complete response with two currently NED. Two patients who received preoperative radiotherapy with local excision are also currently free of disease. The 4-year NED survival for the study population is 100%, 28%, 50%, 0% and 10% for Stage I, II, III, IV and recurrent tumors respectively. The poor results obtained in Stage II tumors is likely due to selection criteria since four of seven patients developed distant metastases. Two of the 14 patients treated for recurrent disease remain NED after local excision of their tumors prior to irradiation. Even though the number of patients is small no dose response for subclinical disease could be found between 4500 and 7000 cGy. Treatment morbidity was acceptable with two patients developing severe long-term complications requiring surgical intervention.

A retrospective analysis is reported of 116 patients with Stage II carcinoma of the endometrium treated definitively with combined radiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) or irradiation alone from January 1960 through December 1981. At 5 and 10 years, the overall survival for all patients was 71 and 52% and the disease-free survival was 73 and 69%, respectively. Of 90 patients in the combined therapy group, most received a preoperative intracavitary insertion (3500 mgh to the uterus and 2000 mgh to the upper vagina) and preoperative external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria, with midline shield) followed in 4 to 6 weeks by a TAH-BSO. The 5 and 10 year disease-free survival for this group was 78 and 75%, respectively. The incidence of major complications was 7% for the combined therapy group. Twenty-six patients were treated with irradiation alone; most of them received two intracavitary insertions (5000 mgh to the uterus and 3000 mgh to the upper vagina) and external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria). The 5 and 10 year disease-free survival was 53 and 45%, respectively. The incidence of major complications was 19%. Factors found to influence the prognosis were histologic grade of tumor, clinical and histologic degree of tumor involvement of the ectocervix, presence of residual tumor in the hysterectomy specimen and the depth of myometrial invasion.

A total of 500 patients with extracapsular extension (clinical Stage C) carcinoma of the prostate received definitive radiotherapy directed to the prostate and the regional lymphatics. Pretreatment evaluation of the regional lymphatics was optional and was done in 245 patients who underwent either staging laparotomy or lymphangiography. The remaining 255 patients had no nodal evaluation. In 72 of the node-evaluated patients there was evidence of spread to the pelvic lymphatics and in 173 patients lymph nodes were negative. The three populations (lymph nodes-not evaluated, lymph nodes-involved, and lymph nodes-not involved) were analyzed as to the distribution of the recognized prognostic variables and compared as to the study end points (locoregional failure, incidence of distant metastases, disease-free survival, and survival).

A prospective randomized study in selected patients with Stage IB and IIA carcinoma of the uterine cervix was carried out at Washington University between January 1966 and December 1979. Patients were randomized to be treated with irradiation alone consisting of 1000 cGy whole pelvis, additional 4000 cGy to the parametria with a step wedge midline block, and two intracavitary insertions for 7500 mgh; or irradiation and surgery, consisting of 2000 cGy whole pelvis irradiation, one intracavitary insertion for 5000-6000 mgh followed 2 to 6 weeks later by a radical hysterectomy with pelvic lymphadenectomy. A total of 40 patients with Stage IB and 16 with Stage IIA were randomized to be treated with irradiation alone. A similar group of 48 patients with Stage IB and 14 with IIA were randomized to the preoperative radiation and surgery group. The 5-year, tumor-free actuarial survival for Stage IB patients treated with radiation was 89% and with preoperative radiation and surgery 80%. In Stage IIA, the tumor-free actuarial 5-year survival was 56% for the irradiation alone group and 79% for the patients treated with preoperative radiation and radical hysterectomy. In the patients with Stage IB treated by irradiation alone only one pelvic failure combined with distant metastasis occurred, and 3 patients developed distant metastasis. In the 48 patients treated with combined therapy, there were six pelvic failures (12.5%) all combined with distant metastases and two distant metastases alone. In the 16 patients with Stage IIA treated with radiotherapy alone, there were four pelvic failures (all parametrial), three of them combined with distant metastasis. In the 14 patients treated with irradiation and surgery, two developed a pelvic recurrence, and one distant metastasis. In the preoperative radiation group, the incidence of metastatic pelvic lymph nodes was 6.3% in Stage IB and 7.1% in Stage IIA. Major complications of therapy in the patients treated with radiation alone (10%) consisted of one rectovaginal fistula, two vesicovaginal fistulas, and one rectal stricture. In the preoperative radiation group, three ureteral strictures and two severe proctitis-rectal strictures were noted (8%). The present study shows no significant difference in therapeutic results or morbidity for invasive carcinoma of the uterine cervix Stage IB or IIA treated with irradiation alone or combined with a radical hysterectomy and lymphadenectomy.

Nine patients with metastatic carcinoma of the fallopian tube were treated with a combination of cisplatin, doxorubicin, and cyclophosphamide. Three are in complete clinical remission following surgically documented complete response, at 18-56 months following the onset of chemotherapy. Two others died of intercurrent causes without evidence of disease. The remaining four died of tumor at 12, 23, 28, and 52 months following the initiation of treatment. Four second-look laparotomies were performed upon patients who were in complete clinical remission. No disease was found in any of these patients. It is concluded that this combination is an effective treatment for adenocarcinoma of the fallopian tube, and that second-look laparotomy may be useful in assessing response to chemotherapy in this disease.