MammoSite excision volume as a predictor for residual disease

BACKGROUND: The MammoSite catheter is a brachytherapy device used for accelerated partial breast irradiation. Currently, it is available as 2 spherically shaped balloons meant to fill 70-cc and 120-cc cavity volumes. This study was designed to define the relation of these excision volumes to the likelihood of microscopically detectable, residual disease based on tumor size, margin status, patient age, and histology. METHODS: The study data base was comprised of 531 patients with Stage 0, I, and II breast carcinoma (using American Joint Committee on Cancer staging criteria) who received breast-conserving therapy and underwent surgical reexcision. Patients in the data base were stratified based on the volume of their initial excision: < or = 70 cc versus > 70 cc and < or = 120 cc versus > 120 cc. RESULTS: Surgical margin size was found to be a strong predictor of residual disease both for patients with smaller excision volumes (P = 0.0014) and patients with larger excision volumes (P = 0.0003); histology (extensive intraductal component [EIC] or pure ductal carcinoma in situ [DCIS]) also was a strong predictor. Tumor size was significant only for the larger volume group (P = 0.029). On multivariate analysis, only histology and initial margin status were significant correlates with residual disease. The adjusted odds ratio for residual disease with pure DCIS was 0.79, and the adjusted odds ratio for invasive ductal or lobular carcinoma (IDC/ILC) without EIC was 0.44 relative to IDC/ILC with EIC (P = 0.008). The adjusted odds ratio for residual disease with a positive initial margin versus a negative initial margin was 2.65 (P < or = 0.0001). CONCLUSIONS: For excisions amenable to use of the MammoSite catheter, a margin > or = 1.0 mm appeared to afford at most a 35% risk of microscopically detectable residual tumor. Evidence of EIC on excision of IDC/ILC connoted a significantly higher risk. Age did not appear to be predictive for residual disease.     

Gemcitabine,paclitaxel, and radiation for locally advanced pancreatic cancer: a Phase I trial

PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of gemcitabine, paclitaxel, and concurrent radiation for pancreatic cancer. METHODS AND MATERIALS: Twenty patients with locally unresectable pancreatic cancer were studied. The initial dose level was gemcitabine 75 mg/m(2) and paclitaxel 40 mg/m(2) weekly for 6 weeks. Concurrent radiation to 50.4 Gy was delivered in 1.8 Gy fractions. The radiation fields included the primary tumor, plus the regional peripancreatic, celiac, and porta hepatis lymph nodes. RESULTS: Dose-limiting toxicities of diarrhea, dehydration, nausea, and anorexia occurred in 3 of 3 patients at the second dose level of gemcitabine, 150 mg/m(2)/week. An intermediate dose level of gemcitabine, 110 mg/m(2)/week, was added, but gastrointestinal toxicity and pulmonary pneumonitis were encountered. The MTD therefore was gemcitabine 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and concurrent radiation. Two of 11 patients treated at the MTD had Grade 3/4 toxicity. Four of 10 assessable patients treated at the MTD responded (40%), including one pathologic complete response. CONCLUSION: The maximum tolerated dosage of gemcitabine is 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and conventional 50.4 Gy radiation fields. A Phase II Radiation Therapy Oncology Group study is under way.     

High dose radiation therapy and chemotherapy as induction treatment for stage III nonsmall cell lung carcinoma

BACKGROUND: The current study was conducted to review the authors' experience in treating consecutive patients with American Joint Committee on Cancer (1997 revision) Stage III nonsmall cell lung carcinoma with aggressive preoperative chemoradiation followed by surgical resection. METHODS: The records of all patients who received preoperative chemoradiation were evaluated. Patients received 2 cycles of concurrent cisplatin and etoposide with 5940 centigrays of radiation therapy. They then were reevaluated to determine whether they were surgical candidates. If so, resection of the primary tumor with mediastinal lymph node dissection was performed 4-6 weeks after the completion of preoperative treatment. After adequate healing, an additional four cycles of cisplatin/etoposide or carboplatin/paclitaxel was given. RESULTS: Forty-two patients received preoperative chemoradiation, 33 of whom underwent surgical resection (79%), including 9 patients who underwent pneumonectomies. Complete pathologic responses were observed in 27% of these patients. Postoperative complications were noted in 21% of the patients and included persistent air leak, supraventricular arrhythmia, and empyema. There were no reported treatment-related deaths. The median follow-up was 26 months. The overall 5-year survival rate for all patients was 36.5% and was 45. 3% for patients who underwent resection. A trend toward increased 5-year survival was observed in patients who had a complete pathologic response (57.1%). Univariate analysis revealed the N stage classification to be significant for predicting a complete response. Patterns of failure revealed the brain to be the most common site of first recurrence (50%) and the only site of recurrence in 36% of patients. There was only one case of local failure. CONCLUSIONS: Preoperative chemoradiation using high radiation doses is feasible with acceptable toxicity. The results of the current study suggest an increased complete pathologic response rate and increased overall survival rate compared with reports in the published literature.     

Dose-modeling study to compare external beam techniques from protocol NSABP B-39/RTOG 0413 for patients with highly unfavorable cardiac anatomy

PURPOSE: The aim of this study was to select patients with heart anatomy that is specifically unfavorable for tangential irradiation in whole-breast radiotherapy (WBRT), to be used as an experimental cohort to compare cardiac dosimetric and radiobiological parameters of three-dimensional conformal external beam accelerated partial breast irradiation (3D-CRT APBI) to WBRT with techniques as defined by the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 clinical trial. METHODS AND MATERIALS: A dosimetric modeling study that compared WBRT and 3D-CRT APBI was performed on CT planning data from 8 patients with left-sided breast cancer. Highly unfavorable cardiac anatomy was defined by the measured contact of the myocardium with the anterior chest wall in the axial and para-sagittal planes. Treatment plans of WBRT and 3D-CRT APBI were generated for each patient in accordance with NSABP B-39/RTOG 0413 protocol. Dose-volume relationships of the heart, including the V5min (minimum dose delivered to 5% of the cardiac volume), biological effective dose (BED) of the V5min, and normal tissue complication probability (NTCP) were analyzed and compared. RESULTS: Despite expected anatomic variation, significantly large differences were found favoring 3D-CRT APBI in cumulative dose-volume histograms (p < 0.01), dose to the entire heart (mean difference 3.85 Gy, p < 0.01), NTCP (median difference, 1.00 Gy; p < 0.01), V5min (mean difference, 24.53 Gy; p < 0.01), and proportional reduction in radiobiological effect on the V5min (85%, p < 0.01). CONCLUSIONS: Use of 3D-CRT APBI can demonstrate improved sparing of the heart in select patients with highly unfavorable cardiac anatomy for WBRT, and may result in reduced risk of cardiac morbidity and mortality.     

Paclitaxel and concurrent radiation for locally advanced pancreatic cancer

Purpose: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer.

Methods and Materials: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m² by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments.

Results: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%.

Conclusion: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.     

Emergence of increased cerebral metastasis after high-dose preoperative radiotherapy with chemotherapy in patients with locally advanced nonsmall cell lung carcinoma.

BACKGROUND: In recent years, combined modality induction therapy has defined a new standard of care in the treatment of patients with American Joint Committee on Cancer (AJCC) Stage III nonsmall cell lung carcinoma, providing improved local control and improved disease-free survival. However, the majority of Stage III patients still die of recurrent disease. METHODS: Forty-two consecutive patients with AJCC Stage IIIA/IIIB nonsmall cell lung carcinoma (NSCLC) who were undergoing induction chemoradiotherapy followed by surgical resection of the primary NSCLC tumor between December 1, 1987 and September 1, 1999 were analyzed for resectability, survival, and patterns of disease failure. These patients received cisplatin (60 mg/m(2)) on Days 1 and 22 and etoposide (100 mg/m(2)) on Days 1, 2, and 3, and Days 22, 23, and 24 together with 5940 centigrays (cGy) of radiation in 180-cGy fractions delivered over 6 weeks. RESULTS: Thirty-one of the 42 patients (74%) underwent surgical resection of the primary lung tumor and mediastinal lymph nodes after chemoradiotherapy. No surgical deaths were reported. The median survival of these 31 patients was 52 months. The 5-year survival estimate using the Kaplan-Meier method was 49.9%. The local control rate was 80%. The incidence of distant metastases other than in the brain was reduced. The most frequently involved site of isolated first recurrence was the brain. The median time to brain recurrence was 7.5 months from the time of surgical resection. All brain metastases were detected within 2 years. CONCLUSIONS: The high incidence of isolated brain metastasis after induction chemoradiotherapy and curative resection and their response to treatment suggest that routine scans of the brain may be indicated in the follow-up of patients with locally advanced NSCLC.