Faculty Bibliography

Introduction: The treatment of ductal carcinoma in situ (DCIS) remains controversial, and treatment approaches include surgery, post-lumpectomy radiation therapy (RT), and/or hormonal therapy for prevention of recurrent disease. These decisions may be particularly difficult for patients with minimal disease. There is a dearth of information regarding patients who have been diagnosed with DCIS on core-needle biopsy (CNB) who have no residual disease in the area at surgery. The purpose of this study was to explore the frequency of this presentation and short-term outcomes in these patients. Methods: Our institutional Breast Cancer Database was queried for all women who were diagnosed with pure DCIS from 2010-2016. Variables included age, method of presentation, risk factors, tumor characteristics and outcomes. Statistical analyses included Pearson's Chi Square and Fisher's Exact Tests. Results: Out of a total of 548 patients with pure DCIS, 55 (10%) had DCIS on CNB alone with no residual in the surgical specimen. The median age was 55 years (range 36-83). Of the patients with DCIS on CNB alone, 6 (11%) were treated with mastectomies. 14 (25%) had lumpectomy and RT, while 35 (64%) had lumpectomy without RT. The median follow up was 4 years. There were three ipsilateral recurrences in women who were treated by lumpectomy alone. One of these recurrences was invasive carcinoma, and the other two were recurrent pure DCIS. None of the patients who recurred had taken hormonal therapy. There were no contralateral second primaries detected in the study period in this cohort. Conclusions: Despite the minimal extent of disease exhibited in these cases, 3 of 35 patients with DCIS on CNB with no residual disease at surgery and no RT had ipsilateral recurrence at a median follow up of 4 years. These data suggest that even minimal DCIS represents a significant risk of recurrence to the patient. Additional information provided by genomic analysis may better stratify the risk for recurrence in this group and help identify the population that would most benefit from post-lumpectomy RT

BACKGROUND CONTEXT: Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control. PURPOSE: To identify early MRI biomarkers to predict local control after SBRT for patients with sarcoma spine metastases. STUDY DESIGN/SETTING: Retrospective case series at a large tertiary cancer center. PATIENT SAMPLE: From 2011 to 2014, nine consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with DCE-MRI both pre- and post-SBRT. OUTCOME MEASURE: Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multi-parametric MRI (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control. METHODS: All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t-tests were used to compare groups. P<0.05 was deemed statistically significant. RESULTS: The median time from SBRT until post-treatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared to pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <0.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of "worsening," "no change," or "improvement," respectively, by both radiologists' graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2 = 0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared to the mpMRI score change post-SBRT (R2 = 0.026). CONCLUSIONS: We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at two months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control.

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is rare, comprising approximately 5% of all Hodgkin lymphoma (HL) cases. Patients with NLPHL tend to have better prognoses than those with classical HL (CHL). Our goal was to assess differences in survival between NLPHL and CHL patients, controlling for differences in patient and disease characteristics. METHODS AND MATERIALS: Using data from the population-based Surveillance, Epidemiology and End Results (SEER) cancer registry program, we identified patients diagnosed with pathologically confirmed HL between 1988 and 2010. RESULTS: We identified 1,162 patients with NLPHL and 29,083 patients with CHL. With a median follow-up of 7 years, 5- and 10-year overall survival (OS) rates were 91% and 83% for NLPHL, respectively, and 81% and 74% for CHL, respectively. After adjusting for all available characteristics, NLPHL (vs CHL) was associated with higher OS (hazard ratio [HR]: 0.62, P<.01) and disease-specific survival (DSS; HR: 0.48, P<.01). The male predominance of NLPHL, compared to CHL, as well as the more favorable prognostic features in NLPHL patients are most pronounced in NLPHL patients <20 years old. Among all NLPHL patients, younger patients were less likely to receive radiation, and radiation use has declined by 40% for all patients from 1988 to 2010. Receipt of radiation was associated with better OS (HR: 0.64, P=.03) and DSS (HR: 0.45, P=.01) in NLPHL patients after controlling for available baseline characteristics. Other factors associated with OS and DSS in NLPHL patients are younger age and early stage. CONCLUSIONS: Our results in a large population dataset demonstrated that NLPHL patients have improved prognosis compared to CHL patients, even after accounting for stage and baseline characteristics. Use of radiation is declining among NLPHL patients despite an association in this series between radiation and better DSS and OS. Unique treatment strategies for NLPHL are warranted in both early and advanced stage disease.

Brain metastases (BM) frequently develop in patients with melanoma and are associated with a poor prognosis. Whole brain radiation therapy (WBRT) is a standard intervention for intracranial disease, particularly in patients with multiple BM. Ipilimumab improves survival in patients with advanced melanoma. The purpose of this study is to investigate the safety and efficacy of concurrent WBRT and ipilimumab. A retrospective analysis was conducted of 13 consecutive patients treated with WBRT within 30 days of ipilimumab administration. Radiographic response, as measured by serial magnetic resonance imaging scans post-treatment, was graded by modified World Health Organization (mWHO) and immune-related response criteria (irRC) in the 9 patients with follow-up imaging. Treatment-related toxicity was prospectively assessed during treatment. Four of nine patients (44 %) experienced partial response or stable central nervous system (CNS) disease as measured by mWHO criteria. This number increased to 5 patients (56 %) when irRC criteria were used. Rates of treatment-related neurologic toxicity were low with only one patient experiencing grade 3-4 neurologic toxicity. There was a high rate of intratumoral hemorrhage in this patient population, with 10 of 10 patients with post-treatment imaging demonstrating new or increased intratumoral bleeding after WBRT. This retrospective study demonstrates that the primary pattern of CNS response to WBRT and ipilimumab is stable disease and not regression of BM. Furthermore, while the combination of WBRT and ipilimumab may offer promising efficacy, prospective studies are needed to further assess efficacy and toxicity.

Whole-lung irradiation (WLI) is standard of care in the treatment of patients with rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor and pulmonary metastases. However, it is not routinely utilized in the treatment of pulmonary metastases arising from other soft tissue sarcoma histologies. A patient presented with synovial sarcoma of his groin and punctate pulmonary metastases. After completion of multimodality treatment to his primary lesion, he received WLI. The patient is without evidence of disease at 3.8 years. This case demonstrates the need for further study of WLI in synovial sarcoma as it may improve outcomes in patients with this disease.

BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. METHODS: We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs. RESULTS: The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs. CONCLUSIONS: While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression.