To determine if there is a subset of women with endometrial cancer in which post hysterectomy external beam pelvic radiation therapy (EBPRT) confers a survival advantage, we analyzed the data available from the Survival, Epidemiology, and End Results (SEER) Program. The SEER Data Base contains 14,775 women with cancer of the corpus uteri (code 54) diagnosed from 1973 to 2003. Of these, 2,189 were stage I endometrial adenocarcinoma with myometrial invasion who underwent at least a hysterectomy and had records that adequately defined the extent of disease, type of surgery, type of radiation (if any), and outcome. For our study, women were stratified as follows: low grade (LG) versus high grade (HG) and involvement of the inner half of myometrium (IH) versus the outer half (OH). We compared survival of those who received EBPRT, in addition to hysterectomy, with those who did not. The Cox proportional hazard method was used to control for potential confounding effects of age, ethnicity, and extent of surgery. For this analysis, women who received brachytherapy were excluded (this was felt to represent a separate issue) as were those who survived less than six months after diagnosis (to eliminate the lead time bias of treatment). Of the 1,460 women with LG/IH cancer, 37 received EBPRT and 1,423 did not. Of the 229 with LG/OH cancer, 76 received EBPRT and 153 did not. Of the 344 with HG/IH cancer, 95 received EBPRT and 249 did not. Of the 156 with HG/OH cancer, 71 received EBPRT and 85 did not. In the LG/IH group no difference was seen, comparing EBPRT with no EBPRT, in either overall survival (OAS), p = 0.6, or disease specific survival (DSS), p = 0.3. Likewise there was no survival effect of EBPRT in the LG/OH group, OAS p = 0.9 and DSS p = 0.7, or in the HG/IH group, OAS p = 0.7 and DSS p = 0.9. In contrast, the HG/OH group demonstrated a substantial survival advantage with EBPRT. The 5-year OAS increased from 62% to 80% with the addition of EBPRT (p = 0.001) and the 5-yr DSS increased from 65% to 82% (p = 0.001). However, no statistically significant survival advantage was seen in any group, even the HG/OH, when the analysis was limited to women who had at least 11 lymph nodes removed at the time of hysterectomy (Figures). Analysis of the SEER data base showed that women with LG/IH, LG/OH, and HG/IH stage I endometrial adenocarcinoma did not obtain a survival benefit from EBPRT. Only among those with HG/OH who underwent hysterectomy with resection of fewer than 11 lymph nodes was EBPRT associated with a survival benefit.

PURPOSE:External beam radiation therapy (EBRT) alone for early stage, medically inoperable non-small cell lung cancer (MILC) can produce local disease control and sometimes cure. We have previously reported that higher EBRT doses result in improved disease control and, for patients with tumors > or =3.0 cm, improved survival. This report describes the impact of dose escalation with endobronchial brachytherapy boost during or following EBRT upon local disease control. METHODS AND MATERIALS:Medical records of 404 patients with MILC treated with radiotherapy alone were reviewed. Thirty-nine patients received a planned endobronchial brachytherapy boost during or following a course of EBRT. A matched-pair analysis of disease control and survival was performed by matching each brachytherapy patient to 2 EBRT patients from a reference group of the remaining patients. RESULTS:Endobronchial brachytherapy boost significantly improved local disease control over EBRT alone (58% vs. 32% at 5 years). The local control benefit for brachytherapy was found to be limited to patients with T(1-2) disease or tumors < or =5.0 cm. Among these patients treated with endobronchial boost, EBRT doses of > or =6500 cGy were necessary to optimize local disease control. No overall survival differences were observed at 3 years. Excess toxicity with brachytherapy was not observed. CONCLUSION:Endobronchial brachytherapy boost enhances local disease control rates in MILC treated with EBRT. Local control outcome is optimized when radical EBRT doses are used in conjunction with brachytherapy.

PURPOSE:To reach a consensus on a set of optimal endpoint measurements for future external beam radiotherapy trials in bone metastases.METHODS:An International Bone Metastases Consensus Working Party invited principal investigators and individuals with a recognized interest in bone metastases to participate in the two surveys and a panel meeting on their preference of choice of optimal endpoints.RESULTS:Consensus has been reached on the following: (a) eligibility criteria for future trials; (b) pain and analgesic assessments; (c) radiation techniques; (d) follow-up and timing of assessments; (e) parameters at follow-up; (f) endpoints; (g) re-irradiation; and (h) statistical analysis.CONCLUSIONS:Based on the available literature and the clinical experience of the working party members, an acceptable set of endpoints has been agreed upon for future clinical trials to promote consistency in reporting. It is intended that the consensus will be re-examined every 5 years. Areas of further research were identified.

Purpose: To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma.Methods and Materials: Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were reviewed. The indications for radiation therapy, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patient's symptoms, radiographic findings, palpable mass, or CA-125 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated.Results: The median age of the patients was 67 years (range 26 to 90 years). A median of one laparotomy was performed before irradiation. Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23), obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second-look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = 1), lymphedema (n = 3), skin involvement (n = 1), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in 5. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA-125 level. Forty-five percent had a partial response. Only 11% suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months (median = 9 months). The 1-, 2-, 3-, and 5-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33%, respectively. The survival rates calculated from the completion of radiotherapy were 39%, 27%, 13%, and 10%, respectively. Five percent of patients experienced Grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced Grade 1 or 2 diarrhea, 19% experienced Grade I or 2 nausea and vomiting, and 11% had Grade 1 or 2 myelosuppression.Conclusions: In this series of radiation therapy for advanced ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy before nonplatinum and/or nonpaclitaxel chemotherapy in these patients. (C) 2001 Elsevier Science Inc.

Purpose: Little is known about the outcome of patients with prostate cancer who present with hormonal[y-resistant disease and who are treated with local radiation therapy.We reviewed our institutional experience with a cohort of such patients to determine their clinical and biochemical response.

The treatment of small-cell lung carcinoma (SCLC) requires the careful combination of chemotherapy and radiation therapy. To understand the factors involved in the outcome of these patients, the authors undertook a study of patients treated for limited stage SCLC. The charts of 194 consecutive patients treated at our facilities between 1986 and 1994 were reviewed. All patients underwent thoracic radiation therapy (TRT), 50% received prophylactic cranial irradiation (PCI), and all but one received chemotherapy. The probability of survival at 5 years was 14%, and the disease-free survival (DFS) was 17%. Patients receiving a combination of platinum and etoposide (PE) and Cytoxan (Bristol-Myers, Evansville, IN, U.S.A.), Adriamycin (Adria Laboratories, Dublin, OH, U.S.A.), and Vincristine (Eli Lilly, Indianapolis, IN, U.S.A.) (CAV) experienced a DFS at 3 years of 31%, versus 14% for CAV only and 18% for PE only (p = 0.004). In a multivariate survival analysis, only PCI (p = 0.001), having received PE and CAV (p = 0.01), and response to treatment (p = 0.001) were significant. Radiation dose and field size did not influence outcome. The combination of PE and CAV chemotherapy produced the best results in our series. Unanswered questions regarding the optimal TRT dose, field size, and timing of TRT await the results of ongoing randomized trials.

The treatment of small-cell lung carcinoma (SCLC) requires the careful combination of chemotherapy and radiation therapy. To understand the factors involved in the outcome of these patients, the authors undertook a study of patients treated for limited stage SCLC. The charts of 194 consecutive patients treated at our facilities between 1986 and 1994 were reviewed. All patients underwent thoracic radiation therapy (TRT), 50% received prophylactic cranial irradiation (PCI), and all but one received chemotherapy. The probability of survival at 5 years was 14%, and the disease-free survival (DFS) was 17%. Patients receiving a combination of platinum and etoposide (PE) and Cytoxan (Bristol-Myers, Evansville, IN, U.S.A.), Adriamycin (Adria Laboratories, Dublin, OH, U.S.A.), and Vincristine (Eli Lilly, Indianapolis, IN, U.S.A.) (CAV) experienced a DFS at 3 years of 31%, versus 14% for CAV only and 18% for PE only (p = 0.004). In a multivariate survival analysis, only PCI (p = 0.001), having received PE and CAV (p = 0.01), and response to treatment (p = 0.001) were significant. Radiation dose and field size did not influence outcome. The combination of PE and CAV chemotherapy produced the best results in our series. Unanswered questions regarding the optimal TRT dose, field size, and timing of TRT await the results of ongoing randomized trials.

Small cell anaplastic carcinoma of the prostate (SCCP) is a rare entity; a literature review disclosed fewer than 150 cases. SCCP has an aggressive course, and both local and distant failure is common. The optimal treatment method has not been clearly established. We review our experience with 7 patients, with attention paid to clinical and pathological details based on a review of the histological specimens. Three patients had mixed tumors of both SCCP and adenocarcinoma, 3 had pure adenocarcinomas that recurred as small cell, and 1 had pure small cell. Our series confirms the aggressive nature of the disease, with all patients dying of their disease < or = 42 months after diagnosis. All patients progressed locally, and at least 5 later developed distant metastases. Treatment with combination chemotherapy and/or hormones resulted in short-lived responses in most patients. We recommend use of hormonal manipulation and combination chemotherapy as well as surgery and/or radiation therapy to the prostate for local control and emphasize that histologic recognition of the entity is important for proper treatment.

Purpose: Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses.Methods and Materials: One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI.Results: Patients receiving PCI exhibited brain failure in 15%, while 38% of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS greater than or equal to 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018).Conclusion: In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials.

Patients unable to undergo a pancreatoduodenectomy for adenocarcinoma of the pancreas are often treated with radiation therapy. A randomized trial by the Gastrointestinal Tumor Study Group has shown an advantage in combining it with chemotherapy. A similar size retrospective study at a large community radiation therapy center assessed this finding in the nonprotocol setting. The study population consisted of 86 patients treated with primary radiation therapy between 1982 and 1992; 62 of them also received chemotherapy. The overall probability of survival was 39% and 13% at 12 and 24 months respectively. Patients receiving chemotherapy had a significantly (p = .018) longer survival (44% versus 25% at 12 months). Results confirm the Study Group's findings and suggest that they be applied to the community setting.

Purpose: For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control.Methods and Materials: We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy.Results: For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with Tl tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival.Conclusion: Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial ''boost'' irradiation, and sensitizing chemotherapy agents.

Radiation therapy to control heterotopic bone formation does not appear to be commonly used in sites other than hips where effective control is evident following arthroplasty. Reported are the results in 12 sites in 10 patients including three with treatment to the elbow, humerus, and ulna. Ten sites received a radiation dose of 10.00 Gy, one 16.00 Gy, and one was treated to 20.00 Gy, all delivered in 2.00 Gy fractions. Preoperative and follow-up x-rays were reviewed and graded. There was no clinically significant regrowth of heterotopic bone. Five sites (42%) demonstrated mild regrowth or persistence following surgery with the other seven (58%) showing no evidence of heterotopic bone. No complications were seen. Radiation therapy is effective for the prevention of heterotopic bone after total hip arthroplasties as well as surgery for fractures to other areas.

This is a report of a 10-year median follow-up of a randomized, prospective study investigating the optimal sequencing of radiation therapy (RT) in relation to surgery for operable advanced head and neck cancer. In May 1973, the Radiation Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients, duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before 7 years. Loco-regional control was significantly better for 141 postoperative radiation therapy patients than for 136 preoperative radiation therapy patients (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis was restricted to supraglottic larynx primaries (60 postoperative radiation therapy patients versus 58 preoperative radiation therapy patients), the difference for loco-regional control was highly significant (p = .007), but not for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco-regional failures occurred in the first 2 years. Thirty-one percent (18/58) of preoperative patients failed locally within 2 years versus 18% (11/60) of postoperative patients. After 2 years, distant metastases and second primaries became the predominant failure pattern, especially in postoperative radiation therapy patients. This shift in the late failure pattern along with the increased number of unrelated deaths negated any advantage in absolute survival for postoperative radiation therapy patients. The rates of severe surgical and radiation therapy complications were similar between the two arms. Because of an increased incidence of late distant metastases and secondary primaries, additional therapeutic intervention is required beyond surgery and postoperative irradiation to impact significantly upon survival.

Uveal melanoma threatens life, as well as sight. To evaluate the effect of constitutional factors and UV radiation on the risk of uveal melanoma, 197 cases in New England were compared with 385 matched population controls, identified by random-digit dialing, and 337 cases residing within the United States were compared with 800 sibling controls. In the population-based comparison, estimated relative risks (RRs) of uveal melanoma, after adjustment for other factors, were elevated for the following: ancestry from more northern latitudes with a substantially elevated risk for Northern European ancestry (RR, 6.5; 95% confidence interval [CI], 1.9 to 22.4) and more than a twofold risk for British ancestry (RR, 2.4; 95% CI, 1.1 to 5.1), as compared with Southern European or other Mediterranean heritage; light skin color as compared with dark (RR, 3.8; 95% CI, 1.1 to 12.6); and 10 or more cutaneous nevi as compared with none (RR, 2.7; 95% CI, 1.5 to 4.9). There was a statistically significant trend for increasing risk with more northern heritage and more moles. Southern residence (below latitude 40 degrees N) for more than 5 years also increased risk (RR, 2.8; 95% CI, 1.1 to 6.9), as compared with none. In both comparisons, use of sunlamps was a risk determinant (RR, 3.4; 95% CI, 1.1 to 10.3 with random-digit dialed controls and RR, 2.3; 95% CI, 1.2 to 4.3 with sibling controls, comparing occasional or frequent use to never use), as was intense sun exposure (RR, 1.7; 95% CI, 0.9 to 3.0 and RR, 2.1; 95% CI, 1.4 to 3.2, respectively). However, birthplace below latitude 40 degrees N and outdoor work were associated with a lower risk.(ABSTRACT TRUNCATED AT 250 WORDS)