Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel.

BACKGROUND: Some chemotherapy (CT) drugs, including taxanes, may enhance the effectiveness of radiation therapy (RT). However, combining these therapies may increase the incidence of radiation pneumonitis, a lung inflammation. In a retrospective cohort study, we evaluated the incidence of radiation pneumonitis in breast cancer patients treated with RT and standard adjuvant CT by use of doxorubicin (Adriamycin) and cyclophosphamide, with and without paclitaxel. METHODS: Forty-one patients with breast cancer were treated with RT and adjuvant CT, including paclitaxel. Paclitaxel and RT (to breast-chest wall in all and lymph nodes in some) were delivered sequentially in 20 patients and concurrently in 21 patients. Paclitaxel was given weekly in some patients and every 3 weeks in other patients. The incidence of radiation pneumonitis was compared with that among patients in our database whose treatments did not include paclitaxel (n = 1286). The percentage of the lung volume irradiated was estimated. The Cox proportional hazards model was used to find covariates that may be associated with the observed outcomes. All P values were two-sided. RESULTS: Radiation pneumonitis developed in six of the 41 patients. Three patients received paclitaxel concurrently with RT, and three received it sequentially (P =.95). The mean percentage of lung volume irradiated was 20% in patients who developed radiation pneumonitis and 22% in those who did not (P =.6). For patients treated with CT including paclitaxel, the crude rate of developing radiation pneumonitis was 14.6% (95% confidence interval [CI] = 5.6% to 29.2%). For patients treated with CT without paclitaxel, the crude rate of pneumonitis was 1.1% (95% CI = 0.2% to 2.3%). The difference between the crude rates with or without paclitaxel is highly statistically significant (P<.0001). The mean time to develop radiation pneumonitis in patients treated concurrently with RT and paclitaxel was statistically significantly shorter in patients receiving paclitaxel weekly than in those receiving it every 3 weeks (P =.002). CONCLUSIONS: The use of paclitaxel and RT in the primary treatment of breast cancer should be undertaken with caution. Clinical trials with the use of combination CT, including paclitaxel plus RT, whether concurrent or sequential, must evaluate carefully the incidence of radiation pneumonitis.

Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience.

OBJECTIVE: The authors investigated the combined experience of a single institution in treating bile duct carcinoma during the modern era. SUMMARY BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with locoregional recurrence the rule, even after radical resection. Adjuvant efforts have included various radiation modalities, with limited success. Recently, charged-particle radiotherapy has also been used in these patients. METHODS: The authors performed a retrospective chart analysis of 129 patients with bile duct adenocarcinomas treated between 1977 and 1987 through the University of California at San Francisco, including 22 patients treated at Lawrence Berkeley Laboratory with the charged particles helium and neon. The minimum follow-up was 5 years. Survival, outcome, and complication results were analyzed. RESULTS: Sixty-two patients were treated with surgery alone (S), 45 patients received conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with charged particles (S + CP). The median survival times were 6.5, 11, and 14 months, respectively, for the entire group, and 16, 16, and 23 months in patients treated with curative intent. There was a survival difference in patients undergoing total resection compared with debulking (p = 0.05) and minor resections (p = 0.0001). Patients with microscopic residual disease had increased median survival times when they were treated with adjuvant irradiation, most markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109). Patients with gross residual disease had a less marked but still statistically significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP) after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was maximal surgical resection in these patients. Postoperative radiotherapy gave patients with positive microscopic margins a significant survival advantage and may be of value in selected patients with gross disease.

Definitive postoperative irradiation of bile duct carcinoma with charged particles and/or photons.

PURPOSE: To determine the rates of survival and local control in patients with bile duct adenocarcinomas treated with post-operative photons and/or charged particles. METHODS AND MATERIALS: A retrospective study was performed analyzing all patients with bile duct adenocarcinomas who received radiotherapy through the University of California San Francisco and at Lawrence Berkeley Laboratory between 1977 and 1987, a total of 62 patients. University of California San Francisco patients received photon therapy (median dose 5400 cGy), and Lawrence Berkeley Laboratory patients were treated with the charged particles helium and/or neon (median dose 6000 cGyE). Forty-eight patients were treated post-operatively with curative intent, 30 with photons and 18 with particles. Thirty-six patients in the study had gross residual disease; none had microscopically negative margins. RESULTS: The overall two-year actuarial survival was 28%: 44% for particle-treated patients and 18% for patients treated with photons (p = .048). Median actuarial survival was 23 months in particle patients and 12 months in photon patients. Local control was also improved, though less significantly, in patients treated with particles (median disease-free survival 20 months vs. 4.5 months, p = .054). A univariate and multivariate analysis was performed and revealed that only extent of residual disease predicted local failure and overall survival; no other prognostic factors were identified. CONCLUSION: Compared to conventional photon radiotherapy, treatment with post-operative charged particle irradiation at Lawrence Berkeley Laboratory appeared to offer a survival advantage in this non-randomized series. Additional investigation into protection of surrounding normal tissue with better dose localization through the use of charged particles is planned.

Charged particle irradiation of sacral chordomas.

PURPOSE: The purpose of this report is determine the impact of charged particle irradiation at Lawrence Berkeley Laboratory (LBL) in treating patients with sacral chordomas. Overall survival, local control, complications, and predictive parameters are analyzed. METHODS AND MATERIALS: Fourteen patients with sacral chordomas were treated with the charged particles helium and neon between 1977 and 1989. The median dose was 7565 cGyE and the median follow up is 5 years. All patients were treated post-operatively; ten had gross residual disease. RESULTS: Kaplan-Meier survival at 5 years is 85%. Overall 5-year local control is 55%. A trend to improved local control at 5 years was seen in patients treated with neon when compared to patients treated with helium (62% vs 34%), in patients following complete resection versus patients with gross residual tumor (75% vs 40%), and in patients who had treatment courses under 73 days (61% vs 21%). Distant metastases were seen in two patients (14%). No patient developed neurologic sequelae or pain syndromes. One previously irradiated patient required colostomy, one patient had delayed wound healing following a negative post-radiation biopsy, and one patient developed a second malignancy. There were no genitourinary complications. CONCLUSION: Our experience indicates that post-operative charged particle irradiation of sacral chordomas appears to result in reasonable local control and survival with acceptable risk, and that additional evaluation on the use of heavy charged particles is warranted.

Re-irradiation of pituitary adenoma.

Fifteen patients initially irradiated for pituitary adenoma were subsequently treated with a second course of radiotherapy at the University of California at San Francisco between 1961 and 1989. The re-irradiation followed surgery in all but two cases. The median time to recurrence was 9 years (range 2-17) and median follow-up after the second course of radiotherapy was 10 years (range 1-30). The median initial radiation dose was 4084 cGy; that at recurrence was 4200 cGy. Local control has been maintained in 12 patients. One failed locally with a benign adenoma that was surgically salvaged. Two developed pituitary carcinomas which were poorly controlled. Of the patients who presented with visual abnormalities at the time of recurrence, 50% improved and the remainder stabilized after re-irradiation. There are no long-term visual complications. Hypopituitarism was present in nine patients prior to the second course of radiotherapy and developed in the remaining six patients after re-irradiation. Temporal lobe injury was seen in two patients. Careful analysis of each patient's pituitary and temporal lobe doses, intervals between treatments, treatment volume, neurets, relative decay factors, absolute decay factors, TDF and modified LQF values, and dose-volume relationships, revealed no correlation with complication or likelihood of local control. Repeat radiotherapy for recurrent pituitary adenoma with the doses used in these patients appears to carry acceptable risk with good local control.