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.

Gynecologic cancers metastatic to bone are a rare entity, and a metastasis to the mandible at initial presentation is even more infrequently seen. We present a case of a 71-year-old woman with stage IV endometrial cancer with a metastasis to the mandible, with no other sites of distal spread apparent. The endometrial tumor was a FIGO grade III adenocarcinoma. The pathologic evaluation of the mandibular lesion revealed poorly differentiated adenocarcinoma with focal squamous differentiation. She was treated with a total abdominal hysterectomy and bilateral salpingo-oophorectomy, radiation therapy to the mandible, and chemotherapy consisting of Taxol and carboplatin for six cycles. She had a complete response, but 10 months after the original diagnosis developed spinal cord compression and progressive disease in the pelvis. Patients in good clinical condition with a single bone metastasis should be treated aggressively, as survival can be extended.

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.

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.

Records of 98 patients undergoing surgery for squamous cell carcinoma of the vulva between 1960 and 1982 were analyzed to evaluate and develop treatment policy. There were 32, 34, 26, and 6 patients in FIGO stages I-IV, respectively. Eighty-six patients underwent radical vulvectomy, 8 patients underwent less extensive procedures, and 4 underwent more extensive procedures. Eighty-seven patients underwent inguinal node dissection, and 40 underwent pelvic node dissection as well. Eight patients received external beam irradiation. Actuarial 5-year survival was 57%. Age, tumor size, FIGO (clinical) stage, surgically determined T and N stages, tumor differentiation, lymph vessel invasion, extent of surgical procedure, and adjuvant irradiation were analyzed to determine their effects on local control, freedom from distant metastases, and survival, using single variable and multivariate analysis. Local control was significantly related to FIGO stage; freedom from distant metastasis was significantly related to surgical N stage, tumor size, and surgical T stage; survival was significantly related to surgical N stage, tumor size, surgical T stage, age, and lymph vessel invasion. Metastatic involvement of inguinal lymph nodes was significantly correlated with tumor size and differentiation. Of 87 evaluable patients, 33 had inguinal node involvement, and of these, 17 developed recurrent disease. All 7 patients with pelvic node metastases had positive inguinal nodes, and all died; the cause of death could be determined in 5, of whom 4 manifested distant metastases. Pelvic lymphadenectomy conferred no survival benefit in this series, even in the presence of positive inguinal nodes. Local vulvar recurrence is a significant problem in patients with positive inguinal nodes, and postoperative irradiation should be directed to this area in these patients. Patients with vulvar recurrences, especially those occurring at least 2 years after surgery, can be successfully salvaged, and should therefore be treated aggressively.

A retrospective analysis of 252 patients with renal cell carcinoma was performed with the tumor, nodes and metastasis system of cancer staging. Each patient received a clinical and a pathological classification. Patient survival was calculated for each pT stage. All patients with stage pT1 disease (100 per cent) were alive at 5 years, as were 91 per cent of those with stage pT2 tumors. Higher T stages showed poorer survival; 58 per cent of the patients with stage pT3 and only 25 per cent with stage pT4 tumors were alive at 5 years. Invasion into the inferior vena cava (pT3c) had an adverse effect on survival, which was statistically significant compared to patients in the pT3a and pT3b subgroups. The type of surgical procedure performed had no influence on ultimate survival, nor did the use of adjuvant radiation therapy. The tumor, nodes and metastasis system clearly documents that the survival of patients with renal cell carcinoma depends on the local extent of the primary tumor, determined at the time of surgical exploration.

The management and prognosis of human chorionic gonadotropin-producing seminoma still are controversial issues. In a review of 210 patients irradiated between 1950 and 1982, 10 had elevated human chorionic gonadotropin values: 3 with stage I, 6 with stage II and 1 with stage IV disease. All human chorionic gonadotropin values became negative: 4 postoperatively and 6 following radiotherapy. All patients are well with a mean followup of 6 years. One patient who suffered liver metastases only was salvaged by chemotherapy. Based on these patients human chorionic gonadotropin production is not an unfavorable prognostic sign in cases of pure seminoma.

The rates of survival, tumor recurrence, and tumor progression were analyzed in 225 patients with meningioma who underwent surgery as the only treatment modality between 1962 and 1980. Patients were considered to have a recurrence if their studies verified a mass effect in spite of a complete surgical removal, whereas they were defined as having progression if, after a subtotal excision, there was clear radiological documentation of an increase in the size of their tumor. There were 168 females and 57 males (a ratio of 2.9:1), with a peak incidence of tumor occurrence in the fifth (23%), sixth (29%), and seventh (23%) decades of life. Anatomical locations were the convexity (21%), parasagittal area (17%), sphenoid ridge (16%), posterior fossa (14%), parasellar region (12%), olfactory groove (10%), spine (8%), and orbit (2%). The absolute 5-, 10-, and 15-year survival rates were 83%, 77%, and 69%, respectively. Following a total resection, the recurrence-free rate at 5, 10, and 15 years was 93%, 80%, and 68%, respectively, at all sites. In contrast, after a subtotal resection, the progression-free rate was only 63%, 45%, and 9% during the same period (p less than 0.0001). The probability of having a second operation following a total excision after 5, 10, and 15 years was 6%, 15%, and 20%, whereas after a subtotal excision the probability was 25%, 44%, and 84%, respectively (p less than 0.0001). Tumor sites associated with a high percentage of total excisions had a low recurrence/progression rate. For example, 96% of convexity meningiomas were removed in toto, and the recurrence/progression rate at 5 years was only 3%. Parasellar meningiomas, with a 57% total excision rate, had a 5-year probability of recurrence/progression of 19%. Only 28% of sphenoid ridge meningiomas a second resection, the probability of a third operation at 5 and 10 years was 42% and 56%, respectively. There was no difference in the recurrence/progression rates according to the patients' age or sex, or the duration of symptoms. Implications for the potential role of adjunctive medical therapy or radiation therapy for meningiomas are discussed.

A pilot study using low-dose preoperative radiation therapy, i.e., 10 Gy in 3 to 4 days as an adjuvant preoperative procedure for grade 2 or 3 (FIGO classification) endometrial carcinoma, was done. The concept of low-dose preoperative radiation therapy is to administer treatment, either surgical or radiotherapeutic, postoperatively according to the surgical and pathologic findings, allowing identification of those patients with previously undiagnosed extensive metastatic disease outside the pelvis found at laparotomy in whom routine pelvic radiation therapy is futile, as well as those patients with relatively low risk of recurrence who may not require further radiotherapy. Forty-four patients with clinical Stage I, grade 2 or 3 with adenocarcinoma of the endometrium were entered into the pilot study. Following surgery, 68% remained Stage I by pathologic examination, and in the remaining patients the stages were changed to II in seven, III in three, and IV in four. Postoperative treatment was administered according to extent of the disease found at surgery. The 4-year actuarial probability of survival rate for the entire group of patients with clinical Stage I disease was 80%; corresponding disease-free rate was 77%. For the Stage I disease confirmed by pathologic examination, the corresponding rate was 96%. The rates for Stages II through IV, as shown by pathologic findings at laparotomy, were 53% and 42%, respectively. In this pilot stud, a treatment policy for clinical Stage I, grade 2 or 3 adenocarcinoma of the endometrium using low-dose preoperative radiation therapy is recommended.

Pentobarbital anesthesia has been observed to increase markedly the effectiveness of respiration of oxygen at 3 atmospheres of pressure absolute to increase the response of early generation isotransplants of C3H mouse tumors to two-dose irradiation. A possible mechanism of this phenomenon is suppression of oxygen utilization by the pentobarbital and hence increasing mean pO2 and oxygen diffusion lengths. Measurements of QO2 of suspension of MCaIV and FSaII cells from freshly excised tumor tissue have been measured for cells suspended in PBS, Hank's buffered with HEPES +/- glutamate. The oxygen utilization by these tumor cells in vitro (when measured at congruent to 10 minutes after excision) is low, viz. 1 nmole/min/mg protein as compared with 6-9 nmoles/min/mg protein for established cell lines cultured in vitro. The suppression of QO2 by 2mM pentobarbital is less than 10%. This is a concentration of pentobarbital that is judged to be close to that which obtains in the tissues of the animals in the radiation response assays. Pentobarbital at .2mM did not change the cell survival characteristics of Chinese V79 cell spheroids irradiated in vitro. The results of these experiments do not indicate the suppression of oxygen utilization is an important contributor to the observed phenomenon of the increased response of tumors irradiated in mice respiring oxygen at high pressure. The role of hypothermia produced by the anesthesia is under further study.

Forty-nine patients with biopsy-proven Waldeyer's ring lymphoma were treated with radiation therapy between 1968 and 1979; 45 to 50 Gy were given to Waldeyer's ring structures with a 5- to 10-Gy boost to the primary site. Uninvolved low cervical nodes received 40 to 50 Gy. Chemotherapy was reserved for treatment failures. Actuarial 5-year survival was 53%, disease-free survival was 48%, and local control was 98%. Patients with Stage I disease fared better than patients with Stage II disease, and unilateral adenopathy conferred a better prognosis than bilateral adenopathy. When classified by the Rappaport system, nodular lymphomas had a better prognosis than diffuse lymphomas, and of the diffuse lymphomas, histiocytic lymphoma was a more lethal disease than lymphocytic lymphoma. Patients with diffuse undifferentiated lymphomas in the Rappaport system, or high-grade lymphomas in the Working Formulation, fared poorly. Most relapses were systemic, and actuarial 5-year survival after salvage was only 20%. A logical approach to the treatment of this disease can be based on these prognostic features.

Primary gastric lymphoma, lymphoma originating in the stomach, without involvement of peripheral or mediastinal lymph nodes, viscera, or the bloodstream, is sufficiently uncommon that the indications for radiation therapy, the dose of irradiation necessary for control of lymphoma, optimum field size, and patterns of failure have never been established. The authors identified 26 patients, and reviewed their charts and pathologic material. Their overall 5-year survival was 57%. Factors significantly influencing 5-year survival were serosal penetration (32% versus 91%), regional lymph node involvement (33% versus 81%), and location on the lesser curvature (20% versus 89%). Histologic characteristics, extent of surgery, and, provided the patient was irradiated, involvement of surgical margins did not influence survival. Overall, survival was not affected by irradiation, but in patients with poor prognostic factors there appeared to be a beneficial effect. Analysis of local control in this and other series suggests that patients should receive at least 40 Gy, and that whole abdominal irradiation is not necessary. The majority of failures were distant, indicating a need for effective systemic therapy.

A regimen of low-dose preoperative radiation therapy (RT), surgery, and elective postoperative RT for resectable carcinomas of the rectum and rectosigmoid is presented. Initial results in a group of 36 patients is discussed. In four patients clinically silent metastatic disease was discovered. Of 16 patients without indications for postoperative RT, only one died with disease. Indications for postoperative irradiation were found in 15 patients and four relapses (26%) subsequently occurred. Since the surgicopathologic stage of the tumor is the best prognostic predictor for rectal cancer, this regimen allows for the delivery of high-dose adjuvant irradiation only to those at high risk of local recurrence. Thus, this combination selects patients likely to benefit from postoperative RT while preserving the advantages of preoperative RT.

Computed tomography (CT) correctly identified extraluminal extension in carcinoma of the rectum and distal sigmoid in 20 patients who were deemed clinically inoperable because of tumor fixation. All patietns received preoperative radiation therapy and subsequent surgical resection of the tumor. The findings at surgery corroborated the presence and location of tumor extension deep to the wall of the colon. Based on this preliminary data, further investigation into the place of CT in treatment planning of colon carcinomas is indicated.

Previous reports have suggested that the immunosuppressive effects of lymphoid irradiation (LI) are related to changes in T cell peripheral blood levels. We prospectively studied 13 patients with Stages I and II Hodgkin's disease before, during, and after a course of Lt. Forty to 45Gy delivered to the mantle field in 412–5 weeks was followed by a 3–4 week break and 35–40Gy to the paraaortic field. Daily fraction size was 1.1–1.8Gy. Peripheral venous samples were drawn weekly. T cell subsets were identified by fluorescent staining of lymphocyte surface antigens using murine monoclonal antibodies OKT3, OKT4, and OKT8 (reactive with all T cells, helper/inducer cells (H/I), and cytotoxic/suppressor cells (C/S), respectively), and quantitated by flow cytometry. The absolute lymphocyte count prior to LI was 1400 ± 270/mm3. This fell to 597 ± 280/mm3 at the conclusion of LI and returned to 1490 ± 800/mm3 at 7–8 months post-LI. The percent total T cells and H/I were reduced from pre-LI values of 66 ± 8 % and 48 ± 10%, respectively, to 7–8 month post-LI values of 36 ± 16% and 19 ± 8%. The percent C/S cells was relatively unchanged by Lt: 20 ± 4% before treatment and 26 ±10 % at 7–8 months after Lt.

The records of 30 patients with primary lymphoma of bone (PLB) who were treated with radiation therapy were reviewed. The probability of NED-survival and overall survival at five-year follow-up was 53 and 63%, respectively. There were three local failures following treatment. The cumulative incidence of local recurrence was 14% at five years. No local failures were observed when tumors received doses higher than 50 Gy, or equivalent to a TDF of 70 or greater. The number of failures was too small to examine for a correlation between histologic subclassification and local control frequency if doses higher than 50 Gy were utilized. Complications of treatment occurred in four patients. Functional results were excellent in all except two patients. These data provide guidelines for determination of a clinically appropriate radiation dose level for PLB.