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Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P = .021), age >35 years (HR, 1.55; P = .025), and disease status at HCT (HR, 1.98; P = .005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure.

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration–approved immune checkpoint inhibitors—pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)—demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma.

Despite its FDA approval and incorporation into the National Comprehensive Cancer Network (NCCN) treatment guidelines, ramucirumab (RAM) is associated with a drug acquisition cost that is substantially higher than other approved options. Given its substantial cost, the presence of a viable alternative treatment option, and its minimal survival improvement, the usefulness of RAM in clinical practice has been called into question. Areas covered: In this paper, we outline the cost, benefits, and economic implications of RAM from a US perspective, as it is used in the treatment of mCRC. We also dissect its use in other tumor types and in other healthcare systems around the world, and briefly compare it with similar drugs targeting the vascular endothelial growth factor pathway. We used the search engine PubMed using the following as search terms: cost-effectiveness; ramucirumab; metastatic colon cancer; angiogenesis; and value-based medicine. Expert commentary: The use of ramucirumab in the treatment of mCRC serves as a microcosm of the worsening healthcare crisis within the US and the ongoing controversy regarding oncology drug costs, benefits, and value. Therefore, there must be a joint effort in moving towards value based pricing models.

Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results.The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy.Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.

Five-year survival rates have improved over the past 40 years for nearly all types of cancer, partially thanks to early detection and prevention. Since patients typically present to their primary care physician with initial symptoms, it is vital for primary care physicians to accurately diagnose common cancers and to recognize unusual presentations of highly curable cancers such as Hodgkin lymphoma and testicular cancers, for which the 5-year overall survival rates are greater than 85%. This paper reviews these cancers and provides clinically relevant pearls from an oncologic perspective for physicians who are the first point of contact.

Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ ERK pathway. We performed a retrospective review of patients who received VD supplementation during neoadjuvant chemotherapy (n [ 134) and those who did not (n [ 112). In our final multivariate model, VD use was associated with improved disease-free survival (DFS) (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88); P [ .026). To the best of our knowledge, our study is the first to report a significant improvement in DFS for patients who received VD supplementation concurrently with trastuzumab-based chemotherapy for HER2-positive (HER2 D ) nonmetastatic breast cancer. Background: Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER þ ) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes. Patients and Methods: We performed a retrospective review of all patients (n ¼ 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison—those who received VD supplementation during neoadjuvant chemotherapy (n ¼ 134) and those who did not (n ¼ 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS). Results: More than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having aV D deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P ¼ .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P ¼ .04). There were no differences in OS based on any of

The number of patients with breast cancer diagnosed with sleep disturbance has grown substantially within the United States over the past 20 years. Meanwhile, there have been significant improvements in the psychological treatment of sleep disturbance in patients with breast cancer. More specifically, cognitive behavioral therapy for insomnia (CBT-I), mindfulness, and yoga have shown to be 3 promising treatments with varying degrees of benefit, supporting data, and inherent limitations. In this article, we will outline the treatment approach for sleep disturbance in patients with breast cancer and conduct a comprehensive review of CBT-I, mindfulness, and yoga as they pertain to this patient population.

Over the past 20 years, with the incorporation of genetic sequencing and improved understanding regarding the mechanisms of cancer growth/metastasis, novel targets and their associated treatments have emerged in oncology and are now regularly incorporated into the clinical care of patients in the US. Novel, more tumor-specific, non-chemotherapy agents, including agents that are commonly used in the treatment of patients with gastric adenocarcinoma (GA) and gastrointestinal stromal tumor (GIST), fall under a broader treatment strategy, termed “precision medicine”. While diagnostic testing and associated treatments in metastatic GA (mGA) are costly and may produce marginal benefit, those associated with GIST, despite being costly, produce significant improvements in patient outcomes. Despite the significant difference in impact, the agents associated with these cancers have similar acquisition costs. In this paper, we will review the current literature regarding cost and cost-effectiveness associated with precision medicine diagnosis and treatment strategies for GA and GIST.

To determine if a low fixed dosing strategy of capecitabine would produce comparable clinical activity with less adverse toxicities compared to published data with higher doses in the setting of metastatic breast cancer (mBC). We retrospectively analyzed patients treated with a low fixed dose of capecitabine (CAPE-L) at 1,000 mg twice daily for 14 days every 21 days. Outcomes included clinical benefit rate (CBR), overall response rates (ORR), time to progression (TTP), and overall survival (OS). A historical comparison group of mBC patients treated on 12 prior trials at the package-insert dose of capecitabine (n = 1,949) was utilized. Eighty-six patients were analyzed in our cohort. Positive hormone receptor status (79.1 vs. 50.6 %), and capecitabine as first-line chemotherapy (44.2 vs. 16.5 %) were more frequent in our cohort relative to the historical comparison. The median starting dose in our cohort was 633.5 mg/m(2). The CBR was similar between the CAPE-L and the standard dose cohorts (55.8 vs. 49.5 %), as was ORR (24.3 vs. 24 %), and median TTP (7 mo, 95 % CI 5.5-8.5 vs. 5.1 mo, 95 % CI 4.5-5.7). Median OS was longer in our cohort (24 mo, 95 % CI 16.8-31.2) than the historic standard dose cohort (12.1 mo, 95 % CI 9.6-14.4), a difference that was likely explained by the higher proportion of patients in the CAPE-L cohort who received capecitabine as first-line chemotherapy and who had hormone receptor positive disease. As expected, adverse events were less frequent with CAPE-L. We found that CAPE-L, which translates into a dose of 600-650 mg/m(2), appeared to have good clinical efficacy and acceptable toxicity.

Objectives: The Blood Utilization Committee implemented a standardized protocol for the preoperative blood order for cardiac patients. The aim of our study was to assess the improvement in blood utilization using the crossmatch to transfusion ratio (C:T). Methods: Four months of retrospective data were collected, which included all RBC crossmatch requests and all RBC units transfused. Similar data were gathered for the period of the intervention. The difference in C:T was calculated. Results: The retrospective group had 166 patients for whom blood products were ordered. There were 560 crossmatch requests and 237 transfused RBC units with a C:T of 2.36. The prospective group had 127 patients with 297 crossmatch requests, 190 transfused units, and a C:T of 1.56. There was a statistically significant difference in the C:T. The cost difference was $12,244.00. Conclusions: Implementing exact guidelines, with the introduction of a type-and-screen concept, allowed more efficient blood usage.

Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. Materials and Methods: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Conclusions: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.

Background: Numerous risk stratification tools exist to predict early post-pulmonary embolism (PE) mortality; however, few were specifically designed for use in patients with cancer. This study sought to evaluate the performance of 3 cancer-specific (RIETE, POMPE-C, and Font criteria) and 3 generic (Hestia, Pulmonary Embolism Severity Index [PESI], and Geneva prognostic score [GPS]) risk stratification tools for predicting 30-day post-PE mortality in patients with active cancer. Methods: We identified consecutive, adult, objectively confirmed patients with PE and active cancer presenting to our institution from November 2010 to January 2014. We calculated the proportion of patients categorized as low or high risk by each of the 6 risk stratification tools and determined each tools' accuracy for predicting 30-day all-cause mortality. Results: A total of 124 patients with PE and active cancer were included (mean age, 66.2 years; 46.0% with concurrent deep vein thrombosis; 49.2% with metastatic disease; and 46.8%, 16.9%, and 11.3% receiving chemotherapy, radiation, or both, respectively). Mortality at 30 days occurred in 25 patients (20.2%). The cancer-specific tools (POMPE-C, RIETE, and Font criteria) categorized between 32% and 43% of patients as low risk and displayed sensitivities and specificities of 88.0% to 96.0% and 38.4% to 52.5%, respectively. The generic PESI and Hestia tools had sensitivities >96.0%, but classified

In recent years, we have learned a great deal about pathogenic mutations that increase the risk of breast and ovarian cancer, particularly mutations in the BRCA1 and BRCA2 genes. Here we review current guidelines on breast and ovarian cancer screening, prophylactic surgery, and other risk-reduction strategies in patients with these mutations, and we detail the data that drive these recommendations. We also discuss guidelines on screening and management for other cancers associated with BRCA1 and BRCA2, such as male breast cancer, pancreatic cancer, and prostate cancer. Discussions about genetic testing have become more complex with the advent of panel testing, which often allows for testing of a more comprehensive panel of genes than traditional BRCA1 and BRCA2 testing, but which is also associated with a higher likelihood of obtaining results with less clear data to inform management. It is difficult to come to a consensus on how best to address the varied and potentially challenging situations that may arise from genetic testing. The complexity inherent in managing these cases makes a multidisciplinary team-including medical oncologists, surgical oncologists, genetic counselors, reproductive endocrinologists, and medical ethicists-critical to optimization of care.

Purpose. Kaposi’s sarcoma (KS) is a rare low-grade vascular tumor associated with the human herpes virus 8. By analyzing the epidemiology, staging, and treatment of KS, we hoped to improve the quality of care at our institution. Methods. Review of the Mount Sinai Medical Center tumor registry database in Miami Beach, FL, USA, identified 143 cases of KS between January 1, 1987 and December 31, 2007. Results. The majority of patients were non-Hispanic whites, non smoking males diagnosed between 1987 and 1996. Most of the patients were HIV positive, with an equal percentage diagnosed with local or distant disease. Most patients received no chemotherapy or radiation. There were no significant differences in patient survival based on sex, HIV status, or radiation received. There was a trend toward improved survival among older patients who smoked, received no chemotherapy, and had localized stage at diagnosis. Multivariate analysis revealed that non-Hispanic whites had a significant worse survival than Hispanic whites (HR = 0.55, 95% CI (0.33, 0.90), ). Patients diagnosed between 1987 and 1996 had a worse survival than those between 1997 and 2007 (HR = 0.33 (95% CI 0.19, 0.55), ). Conclusion. This large retrospective study provides further insight into KS. Ethnicity and date of diagnosis are important predictors of long-term survival.

Introduction Characterized by the development of hundreds to thousands of colonic adenomas, classic familial adenomatous polyposis (FAP) is one of the most common hereditary syndromes associated with an increased risk of colorectal cancer. Several studies have attempted to correlate specific APC mutations with clinical phenotype. 6 However, there is considerable variability in the expression of specific phenotypes within families and among individuals with identical mutations. 7 Case Presentation A 30 year-old Hispanic female presented to the emergency department with a 2-week history of persistent, worsening, left lower quadrant abdominal pain. She had no family history of malignancy. Sigmoidoscopy revealed innumerable polyps in the rectum and sigmoid colon and a large mass in the sigmoid colon. Biopsy of the mass revealed a moderately differentiated adenocarcinoma invading the subserosa. Endoscopy revealed innumerable polyps. Genetic testing of the patient via southern blot revealed a germline APC mutation 3927del5, resulting in a premature truncation of the APC protein at amino acid position 1312. Conclusion Genetic information has only recently started being incorporated into clinical care. More research and randomized clinical trials need to be conducted to definitively characterize random mutations. Once these mutations are further understood, FAP patients may be able to be risk stratified and this may ultimately improve the screening, diagnosis, and treatment of this rare condition.

The hydroxy-methyl-glutaryl-CoA reductase inhibitors (statins) are used extensively in the treatment of hyperlipidemia. They have also demonstrated a benefit in a variety of other disease processes via actions known as pleiotropic effects. Our paper serves as a focused review of pre-clinical investigations and published clinical data regarding the pleiotropic effects of statins in malignancies and emphasizes the importance of randomized, placebo-controlled trials to further elucidate this interesting phenomenon.

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.

The management of metastatic melanoma has been revolutionized in recent years with the development of both targeted therapy and immunotherapy. Although potentially extending the life expectancy for patients, these therapies also significantly increase the healthcare expenditure. In this paper, we review the monthly costs for drugs approved by the FDA since 2011. Additionally, factors that affect the cost, such as dosing strategies, biomarkers, combination therapies, and political/legislative issues, will be discussed.

To evaluate, from a US payer perspective, the cost-effectiveness of treatment strategies for metastatic colorectal cancer (mCRC), we performed a systematic review of published cost-effectiveness analyses. We identified 14 papers that fulfilled our search criteria and revealed varying levels of value among current treatment strategies. Older agents such as 5-fluorouracil, irinotecan, and oxaliplatin provide high-value treatments. More modern agents targeting the EGFR or VEGF pathways, such as bevacizumab, cetuximab, and panitumumab, do not appear to be cost-effective treatments at their current costs. The analytical methods used within the papers varied widely, and this variation likely plays a significant role in the heterogeneity in incremental cost-effectiveness ratios. The cost-effectiveness of current treatment strategies for mCRC is highly variable. Drugs recently approved by the US Food and Drug Administration for mCRC are not cost-effective, and this is primarily driven by high drug costs.

Secondary AML (s-AML) encompasses AML evolving from myelodysplasia (AML-MDS) and treatment-related AML (t-AML) after exposure to chemotherapy, radiation, or environmental toxins. S-AML has traditionally been considered a devastating disease, affecting a vulnerable population of heavily pretreated, older adults. A limited understanding of disease pathogenesis/heterogeneity and lack of effective treatments have hampered overall improvements in patient outcomes. With the recent understanding that the secondary nature of sAML does not by itself incur a poor prognosis and incorporation of cytogenetics and molecular genetics into patient care and the advancement of treatment, including improved supportive care, novel chemotherapeutics agents, and nonmyeloablative conditioning regimens as part of allogeneic hematopoietic cell transplantation (HCT), modest gains in survival and quality of life are beginning to be seen among patients with s-AML.

Background Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable. Methods Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between 1996 and 2006 after primary treatment. There were 189 patients diagnosed with metastatic disease within 2 months of being seen by our therapeutic team and 101 patients diagnosed with metastatic disease greater than 2 months. The patients were divided in order to account for lead-time bias than could potentially confound the analysis of the latter 101 patients. Results Median survival for our primary study population of 189 patients was 33 months. As expected, the median survival from first systemic relapse (MSFSR) for the 101 patients excluded because of the potential for lead-time bias was better at 46 months. Factors influencing prognosis included estrogen receptor (ER) status, disease-free interval (DFI), and dominant site of metastasis. Compared with our original series, even with elimination of local-regional recurrences in our present series, the median survival from first relapse has improved by 7 months over the past two decades. Conclusion The new benchmark for MSFSR approaches 3 years.

Everolimus in combination with exemestane significantly improved progression-free survival compared to exemestane alone in patients previously treated with non-steroidal aromatase inhibitors in the BOLERO-2 trial. As a result, this combination has been approved by the food and drug administration to treat postmenopausal women with hormone receptor positive and HER2 negative metastatic breast cancer. A cost-effectiveness analysis was conducted to determine whether everolimus represents good value for money, utilizing data from BOLERO-2. A decision-analytic model was used to estimate the incremental cost-effectiveness ratio between treatment arms of the BOLERO-2 trial. Costs were obtained from the Center for Medicare Services drug payment table and physician fee schedule. Benefits were expressed as quality-adjusted progression-free survival weeks (QAPFW) and quality-adjusted progression-free years (QAPFY), with utilities/disutilities derived from the literature. Deterministic and probabilistic sensitivity analyses were performed. A willingness to pay threshold of 1–3 times the per capita gross domestic product was adopted, as per the definition of the World Health Organization. The U.S. per capita gross domestic product in 2013 was $49,965; thus, a threshold varying between $49,965 and $149,895 was considered. Everolimus/exemestane had an incremental benefit of 11.88 QAPFW (0.22 QAPFY) compared to exemestane and an incremental cost of $60,574. This translated into an ICER of $265,498.5/QAPFY. Univariate sensitivity analyses showed important variations of the ICER, ranging between $189,836.4 and $530,947/QAPFY. A tornado analysis suggested that the key drivers of our model, by order of importance, included health utility value for stable disease, everolimus acquisition costs, and transition probabilities from the stable to the progression states. The Monte-Carlo simulation showed results that were similar to the base-case analysis. This cost-effectiveness analysis showed that everolimus plus exemestane is not cost-effective compared to exemestane alone. Further research is needed to investigate the cost-effectiveness of the drug combination within sub-groups of the population studied in BOLERO-2.

Background: Axillary lymph node status at diagnosis remains the strongest predictor of long-term survival in breast cancer. Patients with more than ten axillary lymph nodes at diagnosis have a poor long-term survival. In this single institutional study, we set out to evaluate the prognosis of this high-risk group in the era of multimodality therapy. Materials and Methods: In this retrospective study, we looked at all breast cancer patients with greater than ten axillary lymph nodes diagnosed at Mount Sinai Medical Center (MSMC) from January 1st 1990 to December 31st 2007 (n=161). In the univariate analysis, descriptive frequencies, median survival, and 5- and 10-year survival rates were estimated for common prognostic factors. A multivariate prognostic analysis for time-to-event data, using the extended Cox regression model was carried out. Results: With a median and mean follow-up of 70 and 89.9 months, respectively, the overall median survival was estimated to be 99 months. The five-year disease-free survival (DFS) was 59.3% and the ten-year DFS was 37.9%, whereas the five- and ten-year overall survival (OS) was 66.6% and 43.9%, respectively. Multivariate analysis revealed a significant improvement in DFS among black patients compared to whites (p=0.05), improved DFS and OS among young patients (ages 21-45) compared to elderly patients (age greater than 70) (p=0.00176, p=0.0034, respectively), and improved DFS and OS among patients whose tumors were ER positive (p=0.049, p=0.0034). Conclusions: In this single institution study of patients with greater than 10 positive axillary nodes, black patients had a significantly improved DFS compared with white patients. Young age and ER tumor positivity was associated with improved outcomes. Using multivariate analysis, there were no other variables associated with statistically significant improvements in DFS or OS including date of diagnosis. Further work is needed to improve breast cancer survival in this subgroup of patients.

Introduction. Despite its low incidence, acquired factor VIII inhibitor is the most common autoantibody affecting the clotting cascade. The exact mechanism of acquisition remains unclear, but postpartum patients, those with autoimmune conditions or malignancies, and those with exposure to particular drugs appear most susceptible. There have been several case reports describing acquired FVIII inhibitors in patients receiving interferon alpha for HCV treatment and in patients being treated for HIV. To our knowledge, this is the first case of a patient with HCV and HIV who was not actively receiving treatment for either condition.Case Presentation. A 57-year-old Caucasian male with a history of HIV and HCV was admitted to our hospital for a several day history of progressively worsening right thigh bruising and generalized weakness. CTA of the abdominal arteries revealed large bilateral retroperitoneal hematomas. Laboratory studies revealed the presence of a high titer FVIII inhibitor.Conclusion. Our case of a very rare condition highlights the importance of recognizing and understanding the diagnosis of acquired FVIII inhibitor. Laboratory research and clinical data on the role of newer agents are needed in order to better characterize disease pathogenesis, disease associations, genetic markers, and optimal disease management.

Objective: Chronic stress is widespread, and is detrimental to immune functioning and to overall physical and emotional health. These effects may be potentiated in patients with chronic illness, as high levels of chronic stress are common in this population. Numerous studies support the efficacy of mindfulness-based stress reduction (MBSR) in improving psychological functioning. If a strong relationship is found between MBSR and immune function, then MBSR may be implemented as a strategy to improve immune functioning and overall well-being. Methods: In the present review paper, the relationship between MBSR and immune function is evaluated. Empirical studies measuring immune markers as they relate to a standard MBSR intervention were reviewed. Relevant articles primarily involved patients with cancer or HIV. Therefore, the associations of immune measures with psychological distress are discussed, with an emphasis on patients with these conditions. A psychoneuroimmunological (PNI) framework was utilized to propose a mechanism for the relationship between MBSR and immune function. Results: Overall, the findings support a positive relationship between MBSR intervention and beneficial immunological outcomes. Variability in immune measures assessed across studies precludes pooling data to develop more conclusive results. Conclusions: MBSR has been shown to consistently improve emotional functioning and quality of life, and these effects appear to facilitate immune function.

Introduction: The Hestia criteria has been established as a highly sensitive prognostic tool used by clinicians to identify newly diagnosed pulmonary embolism (PE) patients from the general population at low vs. high risk of early (30 day) mortality. Font et al. applied similar risk stratification criteria in a population restricted to PE patients with cancer. We evaluated the performance of the generic Hestia tool and cancer-specific criteria by Font et al. for predicting 30-day post-PE mortality in patients with active cancer. Methods: We identified consecutive, adult, objectively confirmed PE patients with active cancer presenting to the emergency department at our institution from 11/2010-1/2014. We calculated the proportion of patients categorized as low-risk by each set of criteria and determined the accuracy of the criteria for predicting 30-day all-cause mortality. Mortality was determined through Social Security Death Index searches. Results: A total of 124 patients with PE and active cancer (mean age 66.2 years, 46.0% with concurrent deep vein thrombosis, 49.2% with metastatic disease and 46.8%, 16.9% and 10.4% receiving chemotherapy, radiation or both, respectively) were included. Mortality at 30-days occurred in 25 (20.2%) patients. The Hestia tool had a sensitivity of 100% but classified 90% for >24 hours (n=19). Conclusion: In this external validation study, both the generic Hestia tool and cancer-specific Font et al. risk stratification criteria displayed acceptable sensitivity. Compared to Hestia, the Font et al. criteria classified two times as many patients as low-risk. Larger, prospective studies are needed to confirm our results. Disclosures Coleman: Janssen Pharmaceuticals: Consultancy, Research Funding; Bayer Pharmaceuticals AG: Consultancy, Research Funding; Boehringer-Ingelheim Pharmaceuticals, inc.: Consultancy, Research Funding.

6607Background: Patients (pts) diagnosed with unresectable stage III or IV melanoma have 5-year survival rates of 15-20%. Recent FDA approved treatment options include pembrolizumab (PEM), nivoluma...

Introduction: Although cabazitaxel was proven efficacious by a large Phase III trial and was approved for second-line treatment of metastatic castrate-resistant prostate cancer, case reports describing its efficacy and safety are lacking in the literature. More data is needed describing castrate-resistant prostate cancer cases that progress with 1st line therapy. Case Presentation: A 78-year old Hispanic male presented to the clinic in July 2011 with a 3-month history of worsening left knee pain, generalized fatigue, and a 5.4 kilogram weight loss. His past medical history was significant for metastatic prostate cancer and his laboratory results were notable for an alkaline phosphatase of 221U/L, a prostate specific antigen of 837.7ng/ml, and a creatinine of 1.94. Discussion: Metastatic prostate cancer results from the combination of lymphatic, blood, or contiguous local spread. Cabazitaxel is a novel semi-synthetic tubulin binding taxane that uses a precursor molecule extracted from yew tree needles. In the phase III TROPIC study, CRPC patients previously taking docetaxel had a significant increase in overall survival with cabazitaxel compared with mitoxantrone (15.1 vs. 12.7 months, p

Introduction: Acute myeloid leukemia (AML) is one of the most lethal types of adult cancer, with 10,460 deaths among 18,860 diagnoses in 2014. Although some patients are cured with induction and consolidation chemotherapy with or without stem cell transplantation (SCT), between 50-80% of patients will either fail to obtain a complete remission (CR; primary refractory AML) or will relapse. The median overall survival (OS) for relapsed and refractory AML patients is dismal, and there is no clear consensus on the management of relapsed/refractory AML. In this study, with extended follow-up, we set out to look at our own experience with primary refractory and relapsed AML patients in order to try to identify the best therapy and factors associated with improved outcomes. Methods: This retrospective study in AML patients seen at Emory University Hospital (EUH) was IRB approved. Descriptive statistics were used to characterize the demographic and clinical variables. Cytogenetic and molecular signatures were defined based upon the European Leukemia Network and Southwest Oncology group classifications (Döhner et al. 2010, Slovak et al. 2000). Response criteria were based upon the revised recommendations of the International Working Group (Cheson et al. 2003). The combined prognostic score was created using previously validated prognostic variables including age (< 60 vs. >/= 60), Eastern Cooperative Oncology Group Performance Status (ECOG PS; 0-1 vs. >/= 2), and cytogenetic and molecular signatures (favorable vs unfavorable). A score of 0 was termed "favorable" and a score of 1 or greater was termed "unfavorable." The Kaplan-Meier and Cox proportional hazard statistical methods were used to estimate OS. Results: Review of electronic medical records identified 67 consecutive patients between January 1st 2008 and December 31st 2012 diagnosed with primary refractory or relapsed AML. Median age was 56 (range 18-81). Cytogenetic/molecular signatures were favorable in 6%, intermediate in 60%, and unfavorable in 34%, and PS was 0-1 in 34% and 2 in 66%. The majority of patients had a combined prognostic score of unfavorable (n = 53, 79%). Among the 67 patients, 17 (25%) achieved CR with salvage therapy, with 13 (76%) of those able to undergo SCT. With an extended follow-up of approximately 5.6 years, the median OS of our refractory/relapsed AML cohort was 4 months (95% CI 2.2-5.8), with 8% of patients living at least 5 years from their date of relapse. Univariate analysis identified the following factors to be associated with a significantly worse median OS: Secondary AML at initial diagnosis (2.0 vs 5.0 months; p = 0.005), unfavorable cytogenetic/molecular signature at initial diagnosis (3.0 vs 6.0 months; p = 0.014), ECOG PS of 2 or greater at relapse (2.0 vs. 7.0 months; p< 0.001), an unfavorable combined prognostic score at relapse (3.0 vs 18.0 months; p < 0.001), lack of SCT after salvage (3.0 vs. 39.0 months; p < 0.001), lack of treatment in the refractory/relapsed setting with the combination of induction chemotherapy and hypomethylating agents (1.0 vs 8.0 months; p < 0.001), and lack of attainment of CR in the refractory/relapsed setting (3.0 vs. 40.0 months; p < 0.001). In the final multivariable model, only a favorable combined prognostic score at relapse (hazard ratio, HR 0.5; 95% CI 0-0.8; p = 0.02; Figure 1) and ECOG PS of 0-1 (HR 0.42; 95% CI 0.1-0.8; p=0.04) were associated with an improved OS, while the lack of attainment of a CR in the refractory/relapsed setting (HR 15.9; 95%CI 15.2-16.6; p < 0.001; Figure 2) was associated with a worse OS. Conclusion: In our cohort, the median OS among all patients diagnosed with primary refractory/relapsed AML was dismal. Despite the incorporation of novel agents and treatment approaches among this vulnerable patient population, there remains significant heterogeneity in patient outcomes within the first year, with only a small minority having a significantly longer OS. Similarly to patients with newly diagnosed AML, the most important prognostic variables among our refractory/relapsed AML cohort appears to be their combined prognostic score and their ability to achieve a CR in the salvage setting. It may be beneficial for future studies to focus on improving both, modifiable patient prognostic factors (i.e., PS) and treatment approaches in order to achieve CR in the refractory/relapsed setting. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Kota: Pfizer: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding.

Background The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median OS ranging from several months to more than 10 years. Age at diagnosis, performance status (PS), and karyotype expression have long been established in prognostication. Loss of TP53, a tumor suppressor gene located on the short arm of chromosome 17, is one of the most frequent genetic abnormalities in human cancer and is one of the more promising prognostic markers for AML. Studies have shown that TP53 mutations are present in 5-25% of all AML patients, in 70% of those with complex karyotypes, and are associated with old age, chemotherapy resistance, and worse OS. Single nucleotide polymorphisms (SNPs), changes in DNA seen in an appreciable amount of the population, have been examined in AML and studies have suggested a possible correlation with worse outcomes. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized TP53 mutations and SNPs would mimic the literature, occurring in a minority of patients, and conferring a worse OS. Methods We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n =10). Immunohistochemical (IHC) analysis of bone marrows and peripheral blood smears was assessed via DO-1 antibody on paraffin embedded tissue. Conventional cytogenetic analyses were performed on short-term cultured bone marrow and peripheral blood cells with the use of the GTG-banding technique. TP53 PCR sequencing was performed using DNA from bone marrow smears using the Sanger sequencing platform and resolved by capillary electrophoresis. Analysis was performed using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Descriptive frequencies and median survivals were calculated for demographic information, prognostic factors, and treatment variables. A univariate analysis was performed. Results The majority of patients in our pilot study were older than age 60 (80%), male (60%), Hispanic (60%), and had a poor PS (ECOG 2-3: 60%). Most patients had de-novo AML (50%) with an intermediate (50%) non-complex (70%) karyotype and a TP53 P72R SNP (50%). Fewer than half of these patients harbored TP53 mutations (40%). There was no significant difference in OS based on sex, AML history, risk-stratified karyotype, or TP53 mutation. There was a trend toward improved survival among patients younger than age 60 (11, 4 mo, p = 0.09), of Hispanic ethnicity (8, 1 mo, p = 0.11), and those not harboring P72R (8, 2, p = 0.10). There was a significant improvement in survival among patients with a better PS (28, 4 mo, p = 0.01) and those who did not have a complex karyotype (8, 1 mo, p = 0.03). Among patients with a TP53-mutation, there were a larger number of individuals who were younger than age 60 (25.0, 16.7%), who were male (75.0, 50.0%), had a good performance status (ECOG 0-1: 50.0, 16.7%), had de-novo AML (50.0, 66.7%), and who had an adverse karyotype (50.0, 33%). Patients with a P72R SNP were more often male (80, 40%) and had a worse PS (ECOG 2-3: 80, 40%) with AML secondary to MDS (60, 20%) and a complex karyotype (40, 0%). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Patients with more than one TP53 mutation had a worse clinical course than those with only a single mutation. Conclusion Our study demonstrated that poor PS and the presence of a complex karyotype were associated with a decreased OS. TP53 mutations were relatively uncommon, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a trend toward worse OS among patients with a specific SNP. These results suggest that different TP53 mutations and SNPs should not be treated the same, and that some may confer a worse prognosis than others. Larger studies are needed to validate these findings. Disclosures: No relevant conflicts of interest to declare.

6548 Background: Everolimus in combination with exemestane is approved for the treatment of postmenopausal women with hormone-receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). The BOLERO-2, a randomized phase 3 trial, demonstrated a significantly improved progression free survival (PFS) with everolimus plus exemestane compared to exemestane alone in patients previously treated with non-steroidal aromatase inhibitors. In order to better inform U.S. policymakers, this study aimed to assess the cost-effectiveness, from a payer perspective, of everolimus in combination with exemestane. Methods: We created decision analytical and Markov models using published data from the BOLERO-2 trial. Utilities were derived from available literature. Costs were obtained from the Center for Medicare Services drug payment table and physician fee schedule and were represented in 2012 U.S. dollars. The quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. One way and probabilistic sensitivity analyses were performed. Results: Everolimus added 0.42 years of progression-free survival (PFS) by central radiographic assessment with an incremental cost of $33,103, an overall cost of $62,751.54 per year of PFS gained, and an ICER of $79,376/QALY. By local assessment, everolimus added 0.29 years PFS years with an incremental cost of $31,873, an overall cost of $83,222 per year of PFS gained, and an ICER of $108,131/QALY. The results of the model were robust in sensitivity analyses. The primary drivers in this model were found to be: PFS duration, progression free probability on therapy, and overall everolimus cost. Conclusions: Everolimus plus exemestane appears to be cost-effective in the treatment of metastatic breast cancer. Based on efficacy and value, this newly approved combination should be considered to be a viable option in treating patients with HR+/HER2- MBC upon progression on non-steroidal aromatase inhibitors.

e11575 Background: Axillary lymph node status is one of the most important prognostic factors in patients with breast cancer, and those with more than ten metastatic lymph nodes at diagnosis have a decreased overall survival. The purpose of this study is to better characterize the clinical course of this high-risk, poorly described patient population and determine the factors associated with long-term survival. Methods: A retrospective cohort analysis of all breast cancer patients with greater than ten metastatic lymph nodes diagnosed at Mt. Sinai Medical Center from January 1990 to December 2007 (n= 175). Descriptive frequencies, overall median survival (OMS), 5- and 10-year survival were calculated for standard prognostic factors and treatment variables. Univariate statistical analysis was performed, followed by a multivariate prognostic analysis for time-to-event data, using the Cox and extended Cox regression model. Results: The majority of patients were non-Hispanic white females between the ages of 56-70, diagnosed between 1990-1999, with tumors between 2-5 cm and 10-15 metastatic lymph nodes. Most were ER/PR positive, HER2 negative, and treated with surgery, chemotherapy, radiation and hormonal therapy. The OMS was 94 months (CI = 69-114) with 5- and 10-year survival rates of 64.3 and 41.6%, respectively. Ages between 21-45 years (OMS of 187 months, p = 0.03), tumors less than 2 cm (146 months (95% CI = 85-198), p = 0.02), ER positivity (131 months (95% CI = 94-157) vs. 39 months (95% CI = 27-59), p = 0.0003) and treatment received between 2000-2003 (98 months (95% CI = 55-133), p = 0.02) were all associated with significantly improved survival. Conclusions: Over the past decade there were significant gains in the long-term survival of breast cancer patients with greater than ten positive nodes at diagnosis, possibly due to improvements in multimodality therapy, such as the introduction of taxanes, although stage migration may be another contributing factor. Our study further showed an encouraging survival for ER positive patients and a dismal one for ER negative patients, highlighting the need for new targeted therapies directed towards ER negative tumors.

Abstract 4830 Introduction Kaposi's sarcoma (KS) is a rare low-grade vascular tumor associated with the human herpes virus 8 (HHV-8). The demographics, epidemiology, diagnosis, and treatment for Kaposi's sarcoma changed significantly over the past 30 years with the spread of the HIV/AIDS epidemic in the early 1980s, the widespread introduction of combination highly active anti-retroviral treatment (HAART) in the mid 1990s, and finally the advanced aging of the United States population seen in the 2000s. Our Miami Beach community had a very unique position during this time span: It served an extensive elderly population while also serving a population that was one of the epicenters for the HIV/AIDS epidemic in the United States. Materials and Methods Upon review of the Mount Sinai Medical Center tumor registry database in Miami Beach, FL, 143 cases of KS were identified between January 1st 1987 and December 31st 2007. Descriptive statistics were used to characterize the demographic and background variables. The Kaplan-Meier and Cox proportional hazard statistical methods were used to estimate overall survival and clinical variables. A chart review was performed for confirmation of CD4 counts. Results Of the 143 KS patients identified in the database, the majority were non-Hispanic white (60.1%) non-smoking (42.7%) males (90.2%) diagnosed between 1987–1996 (57.3%). More than half of our study population was HIV positive (52.4%), with an equal percentage of patients diagnosed with local or distant disease (40.6%), and most of the patients receiving no chemotherapy (80.4%) or radiation (65%). The overall survival at 5 years was 27% with a median survival time of 24 months. No significant differences in survival were observed among patients based on sex, age at diagnosis, or treatment received. There was a trend towards improved survival among current smokers and patients presenting with local versus distant disease stage. Multivariate analysis and analysis of maximum likelihood estimates revealed that among patients with KS, Hispanic whites were significantly less likely to die than non-Hispanic whites (HR=0.47, 95% CI=(0.29, 0.78), p=0.003). Patients diagnosed between 1997–2007 had a significantly longer survival than those diagnosed between 1987–1996 (HR=0.38 (95% CI 0.24, 0.60), p Conclusion The majority of KS patients identified through our database were young, non-smoking, HIV positive, non-Hispanic white males diagnosed during the peak of the HIV epidemic between 1987 and 1996. Hispanic patients diagnosed with KS during this time period had superior outcomes when compared to non-Hispanic whites. Patients diagnosed from 1997–2007 had superior outcomes when compared to those diagnosed from 1987–1996. There was a trend toward a significance difference in survival among patients based on smoking status and tumor stage at diagnosis. There were no significant differences in survival among patients based on sex, age, or treatment received. Disclosures: No relevant conflicts of interest to declare.