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We report the case of a patient initially diagnosed with a high-grade neuroendocrine carcinoma, which 5 years later was determined to have a low-grade typical carcinoid. The patient received radiotherapy and numerous chemotherapy regimens for treatment of a high-grade metastatic mixed large and small cell neuroendocrine carcinoma, without a significant response to any treatment. Subsequent imaging revealed widely metastatic disease and computed tomography-guided biopsy demonstrated a carcinoid tumor with no necrosis. The patient was started on temozolomide + capecitabine, long-acting octreotide and denosumab, with everolimus planned upon disease progression. Findings from this case study highlight the importance of accurate histopathologic classification of thoracic neuroendocrine tumors at diagnosis, to avoid the unnecessary administration of aggressive chemotherapy to patients with low-grade tumors.

The knowledge, attitudes, and barriers to Jewish genetic diseases (JGDs) and screening and their relative importance in reproductive decision-making were assessed in a population-based sample of Ashkenazi Jewish young adults in Florida. These adults attended educational screening fairs hosted by The Victor Center for the Prevention of Jewish Genetic Diseases at the University of Miami. Parametric and nonparametric tests were used as appropriate to analyze data from a single group pretest/posttest design. Four hundred twelve individuals (mean age = 24.9; 54.7 % female, 45.3 % male) completed the questionnaires. Participants' level of knowledge increased from pre- to post-intervention (81.4 vs. 91.0 %; p

Concurrent chemoradiation is considered the standard-of-care for locally advanced head and neck cancer of the hypopharynx, oropharynx and larynx, as well as unresectable disease. This paradigm was challenged by the introduction of induction chemotherapy (IC), which demonstrated non-inferiority in regards of overall survival (OS), along with increased organ preservation, when compared to the surgery and radiotherapy. More recently, IC followed by concurrent chemoradiation, the so-called sequential approach was developed in an attempt to decrease metastatic spread and improve locoregional control (LRC) rates, with much controversy amongst experts. A careful evaluation by a multidisciplinary team is necessary to recognize which patients should be offered this therapeutic approach due to a significantly greater rate of toxicity. Herein, we analyze the most current available evidence regarding the use of sequential therapy versus concurrent chemoradiation. Different factors including toxicity profile, adherence and patient characteristics play a major role in choosing the most appropriate treatment regimen.

For many years, the medical treatment of breast cancer was reliant solely on cytotoxic chemotherapy. However, over the past twenty years, treatment has evolved to a more target-directed approach. We now employ tailored therapy based on the presence or absence of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2). We expect this trend to continue, as agents that use novel approaches to target HER2, as well as targeting different portions of the HER signaling pathway, are in various stages of development. Notably, pertuzumab, a humanized monoclonal antibody that binds to a different domain of the extracellular portion of the HER2 receptor than trastuzumab, was recently approved for use, as was lapatinib, a small-molecule tyrosine kinase inhibitor. Patients with triple negative breast cancer, particularly those with the BRCA mutation, have more limited treatment options and carry a worse prognosis than those who are hormone receptor positive. However, recent data has shown that PARP inhibitors may have significant anti-tumor effect in those with this subtype of breast cancer. Novel agents that inhibit mTOR, PI3K, the insulin-like growth factor, heat shock protein 90, and histone deacetylase have shown promise in phase I-III trials and offer exciting new possibilities for the treatment of this often fatal disease. As we are presented with an ever increasing number of treatment options, the timing and combinations of therapeutic agents used becomes ever more complex in the age of personalized care, but we are hopeful that ultimately this will lead to improved patient outcomes.

A 66-year-old female developed progressive multifocal leukoencephalopathy (PML) 17 months after treatment with bendamustine and rituximab chemoimmunotherapy. During her evaluation for PML, she was found to have a CD4 count of 176 cells/μL (reference range 492-1740). The patient demonstrated spontaneous recovery of symptoms that occurred in parallel with recovery of the CD4 counts. While PML is associated with rituximab therapy, the timing and patients' clinical course are atypical, raising the possibility of a previously unreported association with bendamustine therapy.

Breast cancer is the most common cancer affecting women worldwide, comprising approximately 20% of all cancers. Although many advances in the treatment of this disease have been made and mortality of early breast cancer improved over the past three decades, metastatic breast cancer (MBC) remains an incurable disease. Cytotoxic chemotherapy continues to play a major role in the treatment of MBC and has been recently combined with biologic agents such as monoclonal antibodies or kinase inhibitors. Over the past decade, several novel cytotoxic chemotherapies have been evaluated in clinical trials. Encouraging results have been observed with novel anti-microtubule agents, with recent US Food and Drug Administration approval of eribulin in 2010. Other novel cytotoxic agents currently under clinical development include novel anti-microtubule drugs, platinum compounds, and anti-angiogenic agents combined with chemotherapy. Here, we review all the major novel cytotoxic agents that have undergone clinical study over the past 5 years for the treatment of MBC.

Introduction Despite significant improvement of clinical outcomes of advanced non–small-cell lung cancer (NSCLC) patients treated with immunotherapy, our knowledge of optimal biomarkers is still limited. Patients and Methods We retrospectively evaluated 159 advanced NSCLC patients in our institution treated with nivolumab after disease progression during platinum-based chemotherapy. We correlated several variables with progression-free survival (PFS) to develop the immunotherapy, Sex, Eastern Cooperative Oncology Group performance status, Neutrophil-to-lymphocyte ratio (NLR), and Delta NLR (iSEND) model. We categorized patients into iSEND good, intermediate, and poor risk groups and evaluated their clinical outcomes. Performance of iSEND at 3, 6, 9, and 12 months was evaluated according to receiver operating characteristic (ROC) curves and internally validated using bootstrapping. The association of iSEND risk groups with clinical benefit was evaluated using logistic regression. Results Median follow-up was 11.5 months (95% confidence interval [CI], 9.4-13.1). There were 50 deaths and 43 with disease progression without death. PFS rates at 3, 6, 9, and 12 months were 78.4%, 63.7%, 55.3%, and 52.2% in iSEND good; 79.4%, 44.3%, 25.9%, and 19.2% in iSEND intermediate; and 65%, 25.9%, 22.8%, and 17.8% in iSEND poor. Time-dependent area under ROC curves of iSEND for PFS at 3, 6, 9, and 12 months were 0.718, 0.74, 0.746, and 0.774. The iSEND poor group was significantly associated with progressive disease at 12 ± 2 weeks (odds ratio, 9.59; 95% CI, 3.8-26.9; P Conclusion The iSEND model is an algorithmic model that can characterize clinical outcomes of advanced NSCLC patients receiving nivolumab into good, intermediate, or poor risk groups and might be useful as a predictive model if validated independently.

We compared the cancer outcomes and care-associated service defects between Jackson Memorial Hospital (ABC), a large public safety-net hospital, and Sylvester Comprehensive Cancer Center (XYZ), a private not-for-profit cancer center in patients with stage II-III colorectal cancer (CC) who received adjuvant chemotherapy (AC) and in patients with diffuse large B cell lymphoma (DLBCL). Colorectal cancer patients treated at ABC were more likely to have undergone urgent surgery. While in the CC cohort, three-year overall survival and relapse-free survival rates were significantly higher among patients treated at XYZ compared with those treated at ABC, there was no significant difference between patients treated for DLBCL in the two hospitals. Colorectal cancer patients treated at ABC were more likely to have undergone urgent surgery, to have delays before surgery or during chemotherapy, and to experience a system/patient-related service defect; whereas were less likely to complete a full course of AC.

Bendamustine is approved in the United States for relapsed indolent lymphoma. However, it has not been widely studied in mantle cell lymphoma (MCL). We retrospectively reviewed the records of all patients with MCL who were treated with bendamustine at three centers. The primary endpoint was overall response rate (ORR). Thirty patients with MCL received bendamustine, 25 for relapsed disease. After a median follow-up of 12 months, there were 15 complete responses (CRs) with an ORR of 83% (95% confidence interval [CI] 70-97%). Factors significantly associated with longer survival were achieving a CR and classical (versus blastic) variant of MCL. Grade 3 or 4 neutropenia, anemia and thrombocytopenia occurred in 23%, 3% and 20%, respectively. There was one case of progressive multifocal leukoencephalopathy 10 months after therapy completion. Bendamustine in combination with rituximab demonstrated a high response rate in this study of patients with predominantly relapsed MCL.

One-fifth of the newly diagnosed multiple myeloma (MM) patients present with renal failure (RF) [1-3]. Glucocorticoids (GCs) may improve RF in MM by (1) rapid reduction of paraprotein production, (2) lessening inflammation and fibrosis in renal parenchyma, and (3) decreasing serum calcium level. We hypothesized that lower dose GCs may be less effective in restoring renal function and retrospectively compared the RF reversibility between the newly diagnosed MM patients who were treated with GCs equivalent to ≥160 mg DX over 4 days (high-dose GC group, n = 16) versus those who were treated with

1585 Background: Two types of adipose tissue exist: white adipose tissue (WAT) and BAT. WAT is the main energy store in humans and is associated with obesity and inflammation. BAT is thought to be protective against obesity and acts as an energy dissipating organ, which may fight obesity by reducing adipokines, inflammatory cytokines, and insulin resistance. The relationship of brown fat activation and cancer prognosis is unknown. We hypothesize that BAT may be protective to breast cancer patients by shifting glucose pool away from tumors and reducing tumor activity. Methods: Through a retrospective chart review of over 900 patients treated by the Breast Cancer Group at our institution, we identified 98 patients with BAT on PET CT scans. We collected information on patient demographics, lifestyle, staging and treatments received and response, progression of disease, overall survival, labs (lipids, hemoglobin A1C, Vitamin D, CRP), metabolic syndrome, metformin use, and antidepressants. Results: Of the 98 c...

e16001 Background: Cetuximab (Cx) + radiation therapy (RT) is well tolerated and has improved survival in patients (pts) with LA-HNSCC. However, its efficacy when compared to HD-DDP + RT has been questioned. At our institution, low-dose weekly carboplatin (Carbo) is added to Cx + RT for pts unsuitable for HD-DDP. Methods: We reviewed records of 16 pts with LA-HNSCC treated with definitive Cx + Carbo + RT at the University of Miami from 2007-2011. Median follow-up was 9.4 months (range: 1-50 months). Results: Median age: 71.5 years (range: 57-90 years); 15 male, 1 female.ECOG PS 0=15, 1=1. TNM staging was: T1= 1, T2= 5, T3=8, T4=2; N stage: N0=8, N1=5, N2a=2, N2b=1. All pts received weekly Carbo (AUC 1.5-2), Cx given conventionally and daily conventionally-fractionated RT. Median total weeks of concurrent systemic therapy= 7 (range: 3-8 weeks). RT was delivered to a median total dose of 70 Gy (range 30-74 Gy). Of the 15 evaluable pts, there were: 12 CR, 2 PR, and 1 PD. There were 2 local in-field failures, 1 regional failure, and 3 distant failures. At last follow-up, 11/16 pts remained with NED. 3-year locoregional recurrence was 29.5% (95% CI: 5.3%-45.9%). Toxicity (NCI-CTCAE v4.0): Mean percentage of weight loss was 14% (range: 6-26%). Two pts required systemic therapy dose-reduction. Three pts experienced a treatment delay and 3 did not finish RT as planned including one pt who received only 30Gy due to death secondary to MI during treatment. Conclusions: In this small retrospective series, Carbo/Cx/RT was well-tolerated and efficacious in pts unsuitable for HD-DDP having LA-HNSCC. Acute toxicities were similar to Cx + RT, likely due to the non-overlapping toxicity profiles of the two systemic agents. We hypothesize that the addition of a well-tolerated cytotoxic chemotherapy agent may improve the therapeutic ratio of Cx + RT in pts who are poor candidates for more aggressive therapies and warrants evaluation in a prospective manner. [Table: see text]

Abstract 4940 Background: Bendamustine has evolved as an increasingly used chemotherapeutic agent for diverse lymphomas in the United States (US) and Europe. It is an alkylating agent that was approved in the US for use as a first line therapy for chronic lymphocytic leukemia and relapsed indolent B-cell non-Hodgkin's Lymphoma (NHL) in 2008. However, the two pivotal studies that established bendamustine for this indication included only few patients with mantle cell lymphoma (MCL). The goal of this retrospective study was to evaluate efficacy of bendamustine in MCL. Patients and Methods: We retrospectively reviewed the records of all MCL patients who were treated with bendamustine at Jackson Memorial Hospital and the Sylvester Comprehensive Cancer Center (both in Miami, FL) and the Stanford Cancer Center (in Stanford, CA). The primary endpoint was overall response rate (ORR) and secondary endpoints were overall survival (OS), time to treatment failure (TTF), and safety. Results: Thirty MCL patients received bendamustine, 28 in combination with rituximab and 2 as monotherapy. Nineteen of these patients were treated at the University of Miami and 11 at Stanford. The median age at diagnosis was 58 years and 77% of the patients were male. The most common extranodal site of involvement at diagnosis was the bone marrow (57%), followed by the GI tract (33%). Most patients presented with advanced disease, with 69% and 28% of the patients having stage IV and III disease at diagnosis, respectively. Seven patients (23%) were diagnosed with the blastic variant of MCL. Five patients received bendamustine as initial therapy and 25 for relapsed disease. Five of these patients had relapsed MCL after an autologous HSCT The most common schedule was bendamustine 100mg/m2 on days one and two and rituximab 375mg/m2 on day one of a 28 day cycle, for a median of six cycles. Of the 30 patients, there were fifteen complete responses (CR) and ten partial responses (PR), for an ORR of 83% (95% confidence interval [CI] 70–97%). With a median follow-up of 8 months (range 0.3–29.5 months), the median overall survival (OS) was not reached; the one-year OS rate was 73%; the two year OS rate was 67%. When OS and time to treatment failure (TTF) were stratified by response (using a 2-month landmark as the starting point for analysis), patients achieving a CR had a significantly longer OS and TTF compared to patients who did not achieve a CR (log rank p < 0.001). The TTF and OS were significantly worse for patients with the blastic variant versus the diffuse variant. In 5 patients with relapse post autologous HSCT, bendamustine induced a CR in three and a PR in one other patient. The majority of serious adverse events associated with bendamustine were hematological. Grade 3 or 4 neutropenia, anemia, and thrombocytopenia occurred in 23%, 3%, and 20%, respectively. Common non-hematologic grade 1 or 2 toxicities were fatigue (27%), edema (20%), erythematous rash (20%), and nausea (13%). Two patients developed neurological sequelae during or after treatment with bendamustine. The first patient developed left sided weakness and dysmetria ten months after completing therapy. A brain biopsy revealed progressive multifocal leukoencephalopathy. A second patient developed ataxia and incontinence while on rituximab plus bendamustine therapy and expired before a definitive diagnosis could be established. Conclusions: Bendamustine appears to have a favorable profile as a second-line agent for patients with relapsed MCL. The response rate is at least comparable to other therapies, especially when examined in light of the toxicity profile seen with other regimens. This study supports the need for continued investigation of bendamustine as a therapy for MCL patients both in the frontline and relapsed settings in prospective clinical trials, some of which are presently ongoing. Disclosures: No relevant conflicts of interest to declare.

e18562 Background: BDM is approved in the United States for relapsed indolent lymphoma. However, the prospective study establishing the BDM monotherapy indication did not include any MCL pts (Fried...