Developing a Predictive Model for Clinical Outcomes of Advanced Non-Small Cell Lung Cancer Patients Treated With Nivolumab.

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 < .0001). 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.

Patient with typical carcinoid initially diagnosed as high-grade neuroendocrine carcinoma.

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.

Knowledge, attitudes, and barriers to carrier screening for the Ashkenazi Jewish panel: a Florida experience : Education and Barriers assessment for Jewish Genetic Diseases.

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 < 0.0001). Concern about the possibility of being a carrier of a JGD was significantly higher after an educational session (5-point Likert scale mean difference = 0.45; p < 0.0001), as was their level of concern regarding having an affected child (mean difference = 0.20; p < 0.0001). The number of participants who agreed or strongly agreed that the test results would not have any influence on their reproductive behavior was lower after the session (17.2 vs. 20.8 %; p < 0.0001). This study demonstrates that an educational carrier screening program increased knowledge and elucidated awareness of the attitudes and barriers toward JGDs and carrier screening.

Concurrent chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy (sequential approach) in the management of head and neck cancer.

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.

Emerging causes of iron deficiency anemia refractory to oral iron supplementation.

While oral iron supplementation is commonly used throughout many clinical setting, treatment with intravenous (IV) iron has historically been reserved for specific settings, such as chronic kidney disease, gynecologic issues, and anemia associated with cancer and its treatments. However, the use of IV iron has begun to gain popularity in the treatment of iron deficiency anemia (IDA) associated with two conditions that are being seen more frequently than in years past: patients who are status post gastric bypass procedure and those with inflammatory bowel disease (IBD). The Roux-en-Y procedure involves connecting a gastric pouch to the jejunum, creating a blind loop consisting of distal stomach, duodenum, and proximal jejunum that connects to the Roux limb to form a common tract. IDA occurs in 6%-50% of patients who have undergone a gastric bypass, the etiology being multifactorial. The proximal gastric pouch, the primary site of gastric acid secretion, is bypassed, resulting in a decreased ability to metabolize molecular iron. Once metabolized, most iron is absorbed in the duodenum, which is entirely bypassed. After undergoing bypass procedures, most patients significantly limit their intake of red meat, another factor contributing to post-bypass IDA. Chronic anemia occurs in approximately 1/3 of patients who suffer from IBD, and almost half of all IBD patients are iron deficient. IBD leads to IDA through multiple mechanisms, including chronic intestinal blood loss, decreased absorption capabilities of the duodenum secondary to inflammation, and an inability of many IBD patients to tolerate the side effects of oral ferrous sulfate. In this study, we reviewed the charts of all patients who received IV iron at Sylvester Comprehensive Cancer Center/University of Miami Hospital Clinic from January 2007 to May 2012. The most common indications for IV iron were for issues related to cancer and its treatment (21.9%), IBD (20.1%), and gastric bypass (15.0%). Of the 262 patients who received IV iron, 230 received iron sucrose and 36 received iron dextran. While doses of 100, 200, 300, and 400 mg of iron sucrose were given, 100 and 200 mg were by far the most common dosages used, 122 and 120 times, respectively. The number of dosages of iron sucrose given ranged from 1 to 46, with a mean of 5.5 and a median of 4 doses. The average dose of iron dextran given was 870.5 mg, with 1000 mg being the most common dosage used. Most patients (22 of 36) who received iron dextran only received one dose. While patients with traditional indications for IV iron, such as gynecologic issues and kidney disease, still were represented in this study, we expect to see a continued increase in physicians using IV iron for emerging gastrointestinal indications, especially considering the increased safety of new low-molecular formulations.

Comparison of cancer care and outcomes between a public safety-net hospital and a private cancer center.

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.

Treating breast cancer in the 21st century: emerging biological therapies.

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.

Progressive multifocal leukoencephalopathy following treatment with bendamustine and rituximab.

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.

A retrospective study evaluating the efficacy and safety of bendamustine in the treatment of mantle cell lymphoma.

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.

High-dose glucocorticoids improve renal failure reversibility in patients with newly diagnosed multiple myeloma.

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 <160 mg (low-dose/no GC group, n = 8). There was no difference in age, baseline calcium, and creatinine levels between the two groups. Renal function was restored in seven patients in the high-dose GC group (44%) and in none of the patients in the low-dose/no GC group (P = 0.026). The only other factor found to impact the RF reversibility was the delay of GC initiation. Four and 1 patients developed a severe infection in the high- and low-dose/no GC groups, respectively. The use of higher dose GCs in the newly diagnosed MM patients who present with RF increases the likelihood of renal function restoration.