From April 1983 through December 1989, 42 consecutive patients with diagnosis of epithelial ovarian carcinoma were initially managed by aggressive surgery and three courses of endoperitoneal ...cis-platinum-based chemotherapy followed by an alternating combination chemotherapy and second-look laparotomy. Patients with residual tumor less than or equal to 2 cm subsequently received whole abdominal radiation therapy (WAR). Twenty-eight patients (42% with no residual disease, 21% with microscopic disease, and 36% with residual disease less than 2 cm) were eligible for WAR. WAR was delivered using an open-field technique up to 22 Gy in 20 fractions followed by a pelvic boost of 18 Gy in 10 fractions. The kidneys were shielded posteriorly at 1100 cGy; hepatic shields were not added. One patient did not complete WAR for lung metastases after 5 radiotherapy fractions. The complete treatment program lasted 8 months (range, 6.8-11). The median follow-up of the 28 patients entered into the study was 50 months. Eight patients are alive and disease-free at 5 years. The overall and disease-free survival rates at 5 years are 45 and 30%, respectively. All but 2 patients relapsed within the abdominopelvic cavity and 3 developed brain metastases. Toxic effects, during WAR, required treatment interruption in all but 4 patients: 3 developed a small bowel obstruction requiring surgery and 1 died of surgical complications in complete remission. The poor disease-free survival and the severe toxicity encountered have been valid indications that WAR should be discontinued as a treatment modality in advanced ovarian cancer at our department.
Experience with a multiple fractions per day radiation therapy program for inoperable esophageal cancer is reported. The treatment program consisted of 3 daily fractions of 1.6 Gy, with a 4 hr ...interval between fractions, for 5 consecutive days (24 Gy). After a rest period of 2 weeks, a second course of radiation was given with the same dose and fractionation for a total dose of 48 Gy in an overall treatment time of 4 weeks. Thirty-four patients were treated between February 1981 and July 1983. Acute reactions consisted of mild esophagitis noted in 30% of patients. No treatment related complications were reported. Median survival was 7 months and the 2- and 5-year survival rates were 12 and 9%, respectively. Tumor size and Karnofsky performance status were found to be the most important prognostic indicators for prolonged survival. Prompt palliation of symptoms was noted. Thirty-three per cent of patients had complete resolution and 41% had partial improvement of symptoms after completion of treatment. Four patients (12%) obtained complete tumor regression with negative biopsy at endoscopic examination and 2 of them are free of disease at 58 and 64 months. A partial response was reported in 12 patients (35%) for a median duration of 5 months (3-26). Treatment with multiple fractions per day was feasible in patients with esophageal cancer and could be preferred to more conventional fractionations for promptness of palliation and the shorter treatment time. The expected therapeutic gain is discussed.
Combined total body irradiation (TBI) and Prednimustine were prospectively evaluated in 30 patients affected either with chronic lymphocytic leukemia (CLL) or with low-grade non-Hodgkin's lymphoma ...(NHL) eleven patients were previously treated. Between January 1984 and May 1987, 20 evaluable patients with CLL, median age 66 years (range 43-82), classified according to Rai (4 in stage I, 10 in stage II, 4 in stage III, 2 in stage IV) and 10 evaluable patients with NHL low-grade malignancy according to the Working Formulation, Stages III and IV, median age 54 years (range 32-71) were treated using a 6 MeV Linear Accelerator, applying two opposite alternating fields including total body, with a fraction of 15 cGy, 2 fractions weekly (3-day interval) for a total dose of 150 cGy given over 5 weeks. Prednimustine (100 mg/m2, orally, for 5 consecutive days, every 3-4 weeks, for 6-9 courses) was administered 2 months after TBI treatment, as consolidation therapy. By May 1989, a total of 85% hematological responses (defined as normalization of the differential white cell count, of the total blood cell count and of bone marrow infiltration) were obtained after combined treatment in CLL patients; moreover 3 CR (according to the WHO criteria), 75% with splenomegaly reduction and 40% with lymphadenopathy reduction were seen. Ninety percent objective responses (5 CR and 4 PR) were observed in the NHL patients, with 50% having splenomegaly reduction and 67% lymphadenopathy reduction. The median response time in the two groups was, respectively, 14 and 23 months. The overall toxicity (WHO grades 1,2,3,4) after combined treatment was 65% and 70% in the two patient groups. WHO grade III toxicity, completely reversible, was verified in only 16.6% of the cases; all cases, except one, were previously treated. Additionally, 1 toxic death (grade IV thrombocytopenia and leukopenia) was observed in a heavily pretreated patient affected with CLL after TBI alone. Prednimustine regimen was generally well tolerated. The high response rate and acceptable toxicity, confirms the feasibility and the usefulness of TBI in the context of a combined treatment for CLL and low-grade NHL patients. However in order to further reduce the severe toxic side effects, observed in one patient, white blood cells and platelet count should be plotted and monitored carefully, particularly in pretreated patients.
Between July 1981 and December 1983, 63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy ...each (with 4-h interval between the fractions), for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1 (48 males and 15 females). Median age was 58 years (range 24 to 75). The most frequent site of primary tumor was lung (squamous cell carcinoma in 33 patients and oat cell carcinoma in 8 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. In 33 patients (52.3%), metastases were present in other sites outside the central nervous system. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. We obtained complete remission (CR) in 4 patients and partial remission (PR) in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results we obtained are similar to those reported by other studies; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required.
Sixty-four consecutive patients with inoperable epidermoid bronchogenic carcinoma (limited disease) were treated with radiotherapy to the primary and nodal areas and combination chemotherapy with ...cyclophosphamide, adriamycin, methotrexate and procarbazine. The overall response rate (CR + PR) to combined treatment was 62%. The median survival time was 12.7 months. The toxicity was acceptable and no treatment-related death occurred.
From October 1978 to June 1981, 35 consecutive patients with grade III-IV malignant glioma were treated with a concentrated course of radiotherapy (two cycles of 17 Gy in two sessions over a 3-day ...period) with a cobalt unit, followed by chemotherapy with vincristine and BCNU. In the 30 evaluable patients, no complete remission, seven partial remissions, 23 stable disease, and no progression were encountered. Median duration of response was 6 months (range 4-11+). Median survival time was 9 months (range 7-19); radically resected patients survived longer than those with inoperable tumor. Toxicity of treatment was acceptable; however, two patients with brain stem tumors had acute neurologic toxicity following the first radiotherapy session.
Twelve consecutive patients with advanced lymphoepithelioma and no previous chemotherapy or radiotherapy were observed in our Division between January 1975 and December 1980. Primary treatment of 11 ...evaluable patients with doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) for at least three cycles resulted in complete remission (CR) in four patients; partial remission with a less than 50% reduction of tumor volume in four; partial remission with a greater than 50% reduction of tumor volume in one; and no response in two. With the addition of radiotherapy in doses of 4500-6000 rad to the primary tumor and the bilateral laterocervical lymph node chains, the combined treatment resulted in CR in eight patients. At 27 months the median duration of CR in these patients has not been achieved, and the median survival has not been achieved at 32 months.
