James H. Rubenstein

Radiation therapy in the management of medically inoperable carcinoma of the lungs: Results and implications for future treatment strategies

Surgery is the treatment of choice for resectable non-small cell lung carcinoma. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. We reviewed the records of 152 patients with medically inoperable non-small cell lung carcinoma treated at our institution between 1982 and 1990. Patients with metastatic disease, mediastinal lymph node involvement or unresectable tumors were excluded. The actuarial overall survival at 2 and 5 years was 40% and 10%, respectively. The disease-free survival at 2 and 5 years was 31% and 15%. The disease-free survival for patients with T1 tumors was 55% at 2 years, versus 20 and 25% for T2 and T3 lesions, respectively (p = .0006). Increasing tumor dose was also associated with increasing disease-free survival (p = .0143). Overall, 66% percent of the patients were considered to have failed. Of these, 70% showed a component of local failure and 45% failed distantly. Patients with T1 tumors experienced a lower probability of failing locally or distantly than did patients with T2 or T3 tumors. A reduced risk of local and distant failure was seen for patients treated to doses of greater than 65 Gray, especially for T1 tumors. We conclude that radical radiation therapy is an effective treatment for small tumors when treated to doses of 65 Gray or more. Since local failure is the prominent pattern of relapse in patients with large tumors, new therapeutic strategies should be considered for this patient group.

Small cell anaplastic carcinoma of the prostate : Seven new cases, review of the literature, and discussion of a therapeutic strategy

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.

The results of radiotherapy for orbital pseudotumor

Between January 1982 and March 1987, 23 patients (26 orbits) were treated for orbital pseudotumor with radiation therapy at the Department of Radiation Oncology, Hospital of the University of Pennsylvania. The patients were referred for clinical relapse after steroid taper in 70%, no response to steroids in 17%, and no steroid treatment (refused or contraindicated) in 13%. Presenting symptoms/signs included soft tissue swelling in 92% of orbits, pain in 92%, proptosis in 85%, and extraocular muscle dysfunction or ptosis in 69%. Decreased visual acuity was seen in only 19% of orbits. Biopsy was performed in nine patients. Treatment consisted of 2000 cGy in 2 weeks in 10 fractions for all patients. Median follow-up was 41 months, with a mean of 53 months, and a range of 21-92 months. Complete response was documented in 87% of orbits with soft tissue swelling, 82% with proptosis, 78% with extraocular muscle dysfunction, and 75% with pain. Of the five patients with visual acuity defects, three experienced complete recovery. There was no difference in complete response in patients biopsied versus those not biopsied. Overall, 17 orbits have remained in complete orbital response with no further steroid requirement (66%). Three orbits suffered local relapse at some point following radiation therapy and were retreated with steroids. These three orbits had durable local control off steroids at last follow-up (11%). Therefore, 77% of orbits attained durable local control and were steroid independent with radiation therapy alone or radiation therapy followed by steroids for relapse. Only one patient developed systemic lymphoma with follow-up. No pretreatment clinical factor reached statistical significance with respect to prognosis following radiation therapy at the less than or equal to .05 level. There were no significant acute or chronic side effects secondary to treatment. Steroids should continue to be first line treatment for orbital pseudotumor, but radiation therapy has a well-defined role in cases of steroid failure or in patients unable to tolerate steroid therapy.

Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma

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 patients 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 1 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.

Quantitative lung scans for prediction of post-radiotherapy pulmonary function

Quantitative perfusion scans were used to predict the proportion of pulmonary function lost by inclusion of lung in radiotherapy fields. Nineteen patients receiving radiotherapy for carcinoma of the lung had pulmonary function evaluated by forced expiratory volume at 1 second (FEV1) prior to and following radiotherapy. FEV1 measurement followed initiation of radiotherapy from two to 18 months (mean: seven months). Prior to radiotherapy quantitative lung scans were performed with Tc-99m macroaggregated albumin. On images acquired by computer, the radiotherapy field was drawn as a region of interest (ROI) and the proportion of count within this ROI relative to total lung count was determined. The total FEV1 was apportioned by the ROI ratio of count excluded from radiation ROI to total count in lungs to predict the FEV1 expected to be remaining after radiotherapy. In only two cases was the measured post-therapy FEV1 less than predicted (and then, by only 2% and 5%, respectively). The data indicate that quantitative perfusion lung scans can be used to predict conservatively the pulmonary function that may be expected to remain post-radiotherapy. Therapy fields may be adjusted in patients with underlying compromised pulmonary function to conserve a pre-selected FEV1.

Small-cell lung carcinoma : An analysis of 194 consecutive patients

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.