Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060

Prognostic Value of Multiple Draining Lymph Node Basins in Melanoma: A Matched-Pair Analysis Based on the John Wayne Cancer Institute Experience

BackgroundThe prognostic significance of multiple draining basins is controversial in melanoma because analyses have not adequately controlled for standard prognostic variables. We hypothesized that an analysis based on prognostically matched pairs of patients with multiple versus single drainage basins would clarify any independent role of basin number.Study designWe identified patients in our 40-year prospective database, who underwent preoperative lymphoscintigraphy, intraoperative sentinel node biopsy and wide local excision for cutaneous melanoma. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared in patients with multiple versus single drainage basins after matching by age, sex, Breslow depth, primary site, and stage at diagnosis.ResultsWe identified 274 patients with multibasin drainage and 1,413 patients with single draining lymph node basins. Matching yielded 259 pairs (226 trunk, 27 head/neck, 6 extremity). Among matched pairs, multibasin drainage did not affect rates of lymph node metastasis (p = 0.84), OS (p = 0.23), DSS (p = 0.53), overall recurrence (p = 0.65), locoregional recurrence (p = 0.58), or distant recurrence (p = 1.0). Multivariable analysis linked higher T stage, ulceration, older age, and lymph node positivity to decreased DSS (p < 0.01) and DFS (p < 0.001). Number of drainage basins was not significant on univariable or multivariable analysis.ConclusionThis analysis, the first to match for standard prognostic factors, suggests that multiplebasin drainage as identified by lymphoscintigraphy has no independent biological or prognostic significance in primary cutaneous melanoma

Determination of Factors Associated with Upstage in Atypical Ductal Hyperplasia to Identify Low-Risk Patients Where Active Surveillance May be an Alternative.

BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, regional; OR 19.28, 95% CI 3.47-106.97, p < 0.001, linear). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery

A Microcosm of Disparities in Breast Cancer: Comparison Between a Private Hospital and a Safety-Net County Hospital Within Los Angeles County.

Background: Breast cancer survival is improving due to early detection and treatment advances. However, racial/ethnic differences in tumor biology, stage, and mortality remain. The objective of this study was to analyze presumed disparities at a local level. Methods: Breast cancer patients at a county hospital and private hospital from 2010 to 2012 were retrospectively reviewed. Demographic, clinical, pathologic, and surgical data were collected. Comparisons were made between hospital cohorts and between racial/ethnic groups from both hospitals combined. Results: 754 patients were included (322 from county hospital and 432 from private hospital). All patients were female. The median age was 54 years at county hospital and 60 years at private hospital (P \u3c .0001). Racial/ethnic minorities comprised 85% of county hospital patients vs. 12% of private hospital patients (P \u3c .0001). County hospital patients had a higher grade, clinical/pathologic stage, HER2-positive rate, and mastectomy rate. Compared to other racial/ethnic groups, non-Hispanic white women were more likely to have lower grade and ER-positive tumors. Hispanic/Latina women were younger and were more likely to have HER2-positive tumors. Both Hispanic/Latina and non-Hispanic black women presented at higher clinical stages and were more likely to undergo neoadjuvant chemotherapy and mastectomy. Discussion: At county hospital compared to private hospital, the proportion of racial/ethnic minorities was higher, and patients presented at younger ages with more aggressive tumors and more advanced disease. The racial/ethnic disparities that were identified locally are largely consistent with those identified in national database studies. These marked differences at hospitals within a diverse city highlight the need for further research into the disparities. Keywords: breast; socioeconomic

Clinical Benefit from Ipilimumab Therapy in Melanoma Patients may be Associated with Serum CTLA4 Levels

Stage IV metastatic melanoma patients historically have a poor prognosis with 5-10% 5-year survival. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen 4 (CTLA4), is one of the first treatments to provide beneficial durable responses in advanced melanoma. However, less than 25% of those treated benefit, treatment is expensive, and side effects can be fatal. Since soluble (s) CTLA4 may mediate inhibitory effects previously ascribed to the membrane-bound isoform (mCTLA4), we hypothesized patients benefiting from ipilimumab have higher serum levels of sCTLA4. We found that higher sCTLA4 levels correlated both with response and improved survival in patients treated with ipilimumab in a small patient cohort (patients with (n=9) and without (n=5) clinical benefit). sCTLA4 levels were statistically higher in ipilimumab-treated patients with response to ipilimumab. In contrast, sCTLA4 levels did not correlate with survival in patients who did not receive ipilimumab (n=11). These preliminary observations provide a previously unrecognized link between serum sCTLA-4 levels and response to ipilimumab as well as to improved survival in ipilimumab-treated melanoma patients and a potential mechanism by which ipilimumab functions