A prospective evaluation of the timing of postoperative radiotherapy for preventing heterotopic ossification following traumatic acetabular fractures.

PURPOSE: Preoperative and immediate postoperative irradiation of traumatic acetabular fractures (TAF), although known to reduce heterotopic ossification (HO), can cause significant organizational and logistic difficulties. We sought to determine an acceptable time interval between surgery and radiation without compromising control, as well as to update our large experience and to further validate our treatment philosophy. METHODS AND MATERIALS: Beginning in June 1995, we began a prospective study, irradiating 152 patients on postoperative days 1, 2, or 3. There were also 17 patients delayed further secondary to medical difficulties. RESULTS: All patients treated since June 1995 received 700 cGy/1 fx. Fifty-eight patients received radiation within 24 hours of surgery, 41 within 2 days, 53 within 3 days, 13 within 4 days, and 4 were delayed further. Delaying irradiation for up to 4 days postoperatively caused no statistical increase in HO (p = 0.625). Of 263 patients in our retrospective cohort, HO occurred in 5.3% of patients who received irradiation versus 60% of patients who did not. CONCLUSION: In our prospective study, we noted no perceptible increase in HO with up to a 3-day interval between surgery and radiotherapy. This allows a more structured treatment schedule and allows the patient more time to heal and recover. Updated results from our overall series continue to demonstrate that adjuvant radiation decreases the incidence and severity of HO after TAF.

A phase I study of combined UFT plus leucovorin and radiotherapy for pancreatic cancer.

PURPOSE: This Phase I study combines tegafur and uracil (UFT) with leucovorin and conventional radiation for the treatment of pancreatic cancer. The design seeks to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of this regimen as well as to define a future Phase II dose level. METHODS: Patients with locally advanced and unresectable pancreatic cancer were treated with 45 Gy of radiation therapy. The initial UFT dose was 150 mg/m(2)/day given with leucovorin 90 mg/day, both divided into 3 daily doses for 35 days concurrent with radiation. UFT doses were escalated at increments of 50 mg/m(2)/day. Dose-limiting toxicity (DLT) was defined as Grade 3 or greater nausea, vomiting or diarrhea despite medical intervention; or Grade 3 or greater neutropenia/thrombocytopenia; or Grade 3 or greater hepatic toxicity; or inability of the patient to take 75% or more of the planned UFT/leucovorin; or radiotherapy interruption of greater than 1 week. The MTD for UFT/leucovorin was exceeded by one dose level when a certain dose caused DLT in 2 or more patients of 6. RESULTS: Five evaluable patients had Stage I resectable disease but had pathologic adenopathy. Seven had Stage II unresectable disease. Compliance with therapy was excellent. At a daily dose of 300 mg/m(2) of UFT, we noticed minimal diarrhea and hematologic toxicity with mild-moderate nausea, anorexia, and fatigue. Three patients had Grade 4 toxicity: 1 had neutropenia on Day 38, 1 had diarrhea on Day 55, and 1 had vomiting on Day 15. CONCLUSION: Oral UFT/leucovorin and radiation therapy offers patients a viable treatment option for pancreatic cancer. The major known toxicity of diarrhea was tolerable. The MTD was not reached in this study. Our current plan is to expand this into a Phase I/II trial beginning at a UFT dose of 300 mg/m(2) and correlate this with clinical pharmacologic parameters. The potential benefit of long bioavailability and oral delivery of UFT compares favorably with continuous infusion regimens without the added morbidity of a catheter and pump.

Radiation response of Rosai-Dorfman disease presenting with involvement of the orbits.

The purpose of this study was to review an interesting case of recurrent orbital sinus histiocytosis. The patient initially failed surgery, chemotherapy, and steroid therapy, only to have a durable response to low-dose radiation therapy of the orbits, lasting 6 and 11 years, respectively. Because there are few documented responses to radiotherapy, we present a case report in conjunction with the clinical, radiographic, and histopathologic information as well as a literature review of similar cases.

Phase I/IIa study of concurrent paclitaxel and cisplatin with radiation therapy in locally advanced non-small cell lung cancer: analysis of early and late pulmonary morbidity.

Recent efforts to improve survival outcome in patients with locally advanced non-small cell lung cancer have focused on the use of chemoradiotherapy regimens containing vinblastine/cisplatin or etoposide/cisplatin. However, the overall treatment outcome with these regimens remains poor, emphasizing the need for new therapeutic options. Based on the activity of paclitaxel in advanced non-small cell lung cancer, its additive cytotoxicity with cisplatin, and the radiation-sensitizing effect of both agents, a phase I/IIa study was designed to examine the feasibility of paclitaxel/cisplatin concurrently with conventional thoracic irradiation in patients with locally advanced tumors. One major concern regarding combined modality therapy has been the enhancement of pulmonary toxicity. This report describes the incidence and severity of pulmonary toxicities observed in this trial according to the Radiation Therapy Oncology Group scoring criteria. A literature-based review was performed in an attempt to determine the impact of paclitaxel-based versus non-paclitaxel-based chemoradiotherapy regimens on the early and late pulmonary morbidity. Twenty-four evaluable patients died and 14 (37%) are still alive without evidence of disease. The 1- and 2-year survival rates are 62% and 40%, respectively, with a median survival of 17 months. Pulmonary toxicity >/=grade 2 was more frequently manifested as late toxicity in approximately 70% of the patients. In most, prompt symptomatic and radiologic improvement was observed with the early administration of corticosteroids. There were three late grade 5 toxicities characterized by diffuse (bilateral) rapidly progressive interstitial infiltrates. Protracted lymphocytopenia was noted in the great majority of patients, and its role in the pathogenesis of this complication remains to be determined. There were minor changes in pulmonary function parameters, except in the forced vital capacity and diffusion capacity to carbon monoxide. In a univariate analysis, no relationship was noted between paclitaxel dose level, degree of lymphocytopenia, changes in pulmonary function indices, and incidence of pulmonary toxicity. However, there was a significant dose-volume relationship (using conventional dose-volume histograms) with late pulmonary toxicity at radiation doses between 15 Gy and 30 Gy. Based on a literature review, paclitaxel-based chemotherapy regimens seem to be associated with a slightly higher risk of pulmonary toxicity; however, comparison of such toxicity between trials has many limitations that require that the conclusion reached be viewed with caution.