Faculty Bibliography

We have previously demonstrated high pathologic response rates after neoadjuvant concurrent chemoradiation in patients with locally advanced breast cancer (LABC). We now report disease-free survival (DFS) and overall survival (OS) in the context of pathologic response. 105 LABC patients (White 46%, Non-White 54%) were treated with paclitaxel (30 mg/m(2) intravenously twice a week) for 10-12 weeks. Daily radiotherapy was delivered to breast, axillary, and supraclavicular lymph nodes during weeks 2-7 of paclitaxel treatment, at 1.8 Gy per fraction to a total dose of 45 Gy with a tumor boost of 14 Gy at 2 Gy/fraction. Pathological complete response (pCR) was defined as the absence of invasive cancer in breast and lymph nodes and pathological partial response (pPR) as the persistence of <10 microscopic foci of invasive carcinoma in breast or lymph nodes. Pathologic response (pCR and pPR) after neoadjuvant chemoradiation was achieved in 36/105 patients (34%) and was associated with significantly better DFS and OS. Pathological responders had a lower risk of recurrence or death (HR = 0.35, P = 0.01) and a longer OS (HR = 4.27, P = 0.01) compared with non-responders. Median DFS and OS were 57 and 84 months for non-responders, respectively, and have not yet been reached for responders. Importantly, pathologic response was achieved in 54% of patients with HR negative tumors (26/48). In conclusion, pathologic response to concurrent paclitaxel-radiation translated into superior DFS and OS. Half of the patients with HR negative tumors achieved a pathologic response

Purpose: To determine optimal (prone vs. supine) treatment positions for breast radiotherapy by classifying geometric features extracted from prone CT scans. Method and Materials: CT scans from patients enrolled in NYU 05‐181 Protocol were studied to discern predicting factors for optimizing treatment positions for breast radiotherapy. Each of the 400 patients accrued for this protocol underwent CT simulation and planning in both supine and prone positions. The treatment set up was chosen based on maximum sparing of heart and lung. Since the results demonstrated that most patients were best treated prone, we studied whether a support vector machine (SVM) classifier could successfully predict optimal position based on a single prone CT scan and limit a second supine CT only to the minority of women best treated supine. To build this classifier, prone CT scans of NYU 05‐181 were de‐identified and exported in DICOM RT format. Three‐dimensional shape and distance features were computed from organs at risk and the planning target volume in the CT scans. We used a k‐fold cross validation procedure to test the performance of the SVM classifier. Results: Images of 36 patients (23 prone‐treated and 13 supine‐treated) were used. Preliminary results indicate that breast volume, heart and lung involvement in the treatment field are significant predicting factors. A weighting of 1:5 (prone‐treated: supine‐treated) was used when determining the soft margin hyper plane of the SVM classifier. The purpose is to increase the specificity [true‐supine/ (true‐supine+false‐prone)] of the classifier since patients classified as prone will not receive a validation supine CT scan. A sensitivity [true‐prone/(true‐prone+false‐supine)] of 87% and a specificity of 92% was achieved using 11 geometric features and the SVM classifier. Conclusion: Preliminary data support the use of a feature‐based classification to predict the optimal treatment position from prone CT scans

PURPOSE: Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. METHODS AND MATERIALS: After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab. RESULTS: Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%. DISCUSSION: Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma