Faculty Bibliography

BACKGROUND: The extreme elderly (EE; >84years) are among the fastest growing segments of the population and bear a substantial cancer burden. We examined cancer incidence and cancer specific mortality changes among the EE during the implementation of cancer screening from the 1980s to 2000s. METHODS: We examined incidence and mortality rates for breast, colon, prostate, and lung cancer by age group between 1973 and 2009 in the SEER database. We compared incidence/mortality between EE and middle aged (MA; age 50-69) patients. RESULTS: Prostate cancer incidence and mortality rose and then, in the early 1990s, declined (-3.61%/year and -2.91%/year, respectively) among EE. Prostate cancer incidence rose steadily throughout the study period for MA. Breast cancer incidence rose and then declined for both MA and EE, with the decline starting in 1990 for EE (-1.34%/year), and 1998 for MA (-1.24%/year). Both age groups experienced an increase and then decrease in colon cancer incidence. The decrease in colon cancer mortality over the last decade was profound for all patients (-2.88%/year MA, and -3.29%/year EE). Lung cancer incidence (+2.35%/year to 2005) and mortality (+1.25%/year from 1995) increased for EE. Lung cancer incidence and mortality increased and then decreased (-2.54%/year for mortality from 1990) for MA. CONCLUSION: Recent trends in incidence and mortality for screened cancers (breast, colon, prostate) show substantial gains for the extreme elderly, likely due in part to the effect of screening. Incidence and mortality from lung cancer, with no recommended screening during the study period, have continued to worsen for the extreme elderly, despite improvements in younger patient populations.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of classical Hodgkin lymphoma. It is characterized histologically by presence of lymphohistiocytic cells which have B-cell phenotype, are positive for CD19, CD20, CD45, CD79a, BOB.1, Oct.2, and negative for CD15 and CD30. Patients often present with early stage of disease and do not have classical B symptoms. The clinical behavior appears to mimic that of an indolent non-Hodgkin lymphoma more than that of classical Hodgkin disease. The purpose of the present report is to define the biology of NLPHL, review its clinical presentation, and summarize the available clinical data regarding treatment.

Peripheral T-cell lymphomas are a heterogeneous group of lymphoid malignancies. Among these, hepatosplenic gammadelta T-cell lymphoma (HTCL) represents an aggressive and treatment-resistant subgroup for which new avenues of treatment are critically needed. HTCL is characterized by primary extranodal distribution of the malignant cells with typical intrasinusoidal infiltration of the liver, spleen, and bone marrow, which results in hepatosplenomegaly and peripheral blood cytopenias. Another characteristic feature is the expression of gammadelta T-cell receptors. HTCL exhibits a rapid progressive course and an extremely poor response to currently known therapeutic strategies, with a 5-year overall survival rate of only 7%. In this review, we discuss the clinical, pathologic, and molecular characteristics of this disease, along with the challenges that are associated with its diagnosis and treatment.

PURPOSE: Cancer drug shortages have increased considerably over the past 5 years, but quantitative analyses of the scope and effects are limited. We assessed the effects of drug shortages on outpatient medication use in a single New York City university hospital. METHODS: We examined pharmacy records for drug shortages, as defined by the American Society of Health-System Pharmacists. We assessed outpatient records for all patients with cancer treated with infusional antineoplastic medications from April 2010 to September 2010 and April 2011 to September 2011. RESULTS: Twelve medications were in shortage in 2010 and 22 in 2011. Drugs in shortage were used for 170 patients (50.8%) in 2010 and 241 patients (63.6%) in 2011 (P < .001). Of 235 patients treated in August-September 2011, there were 23(9.8%) documented therapy changes due to shortages, compared with zero changes in August-September 2010 (P < .001). Among patients treated in August-September 2010, 24 (11.4%) received paclitaxel and 19 (9.0%) received docetaxel. Among patients treated in August-September 2011, 11 (4.7%) received paclitaxel and 38 (16.2%) received docetaxel, a 69% decrease for paclitaxel and 80% increase for docetaxel from 1 year prior (P = .009, and P = .024, respectively). The estimated cost of a single treatment with paclitaxel for one patient with body-surface area 1.75 was $47.59 versus $858.39 for docetaxel, a 1,704% increase. Surveyed physicians frequently reported lower level evidence (30.4%) and increased risk of toxicity (34.8%) with alternative therapy in drug shortage cases. CONCLUSION: Oncology drug shortages affected the majority of patients in our center and increased at an alarming rate. Drug shortages have substantial economic costs and mandate treatment changes that may affect efficacy and toxicity.

PURPOSE: The aims of this study were to establish the maximum tolerated dose (MTD) of oxaliplatin in combination with fixed doses of gemcitabine, irinotecan, and 5-fluorouracil/leucovorin (G-FLIE) in solid tumors, including advanced pancreatic cancer, and to evaluate the toxicity of the regimen. METHODS: Patients with metastatic solid tumors were treated with a regimen consisting of gemcitabine (500 mg/m(2) by fixed-dose-rate infusion), irinotecan (120 mg/m(2)), leucovorin 300 mg, bolus/infusion 5-fluorouracil (400 and 1,500 mg/m2, respectively), and oxaliplatin at doses from 50 to 85 mg/m(2) according to the escalation schema. Treatment was repeated every 14 days. RESULTS: The study enrolled 25 patients with a median age of 64 years and median Karnofsky performance score of 80. Patients had metastatic adenocarcinomas of pancreas (n = 9), as well as gastroesointestinal, hepatobiliary, or unknown primary tumors. With only one dose limiting toxicity (neutropenia and constipation), the MTD of oxaliplatin was not reached up to the pre-specified maximum level of 85 mg/m(2). Other toxicities predictably included cytopenias, fatigue, sensory neuropathy, nausea/vomiting, diarrhea, and constipation. Four partial responses and ten disease stabilizations were observed. The overall median time to disease progression was 17 weeks (2-110 weeks) with median overall survival of 31.5 weeks (7-139 weeks). CONCLUSIONS: G-FLIE is a tolerable multi-agent chemotherapy regimen with the oxaliplatin dose up to 85 mg/m(2). The combination of full-dose oxaliplatin with gemcitabine, irinotecan, and 5-fluorouracil is feasible with attenuated doses of the drugs, but further optimization is necessary before assessment of efficacy.

Anti-B4-blocked ricin (anti-B4-bR) is a potent immunotoxin directed against the CD19 antigen. Previous phase I and II studies suggested a possible role for anti-B4-bR as consolidation after high-dose chemotherapy and autologous stem cell transplant. Cancer and Leukemia Group B (CALGB) 9254 is a phase III study which randomized 157 patients with B-cell lymphoma in complete remission following autologous transplant to treatment with anti-B4-bR or observation. With a median follow-up time for patients of 5.8 years, the median event-free survival for protocol treatment and observation are 2.1 and 2.9 years, respectively (p = 0.275). The median overall survival for treatment and observation are 6.1 years and not reached, respectively (p = 0.063). Therefore, no differences were found in event-free survival and overall survival between protocol treatment and observation, although there was a trend toward improved survival with observation. These data fail to support a role for anti-B4-bR as consolidative therapy after bone marrow transplant in patients with B-cell lymphoma.

For many years, the cornerstone of treatment for non-small-cell lung cancer (NSCLC) has been third-generation platinum-based chemotherapy. Unfortunately, clinical outcomes with the use of this approach have remained poor, with median survival times of only 8-13 months. In an attempt to improve survival, several therapeutic strategies have recently been investigated, including extended-duration chemotherapy. Although historically maintenance chemotherapy in NSCLC has resulted in less-than-optimal outcomes and there has been a recent surge in interest with this treatment modality. This has been in part because of the strategy of the early delivery of a non-cross-resistant agent after platinum chemotherapy, now termed switch maintenance therapy. Results from several recent phase III trials using this strategy are shifting the treatment paradigm of patients with advanced-stage NSCLC. Despite more favorable outcomes demonstrated with this strategy, study designs and reported results have not been without critique. Here, we review all published extended-duration chemotherapy strategies in NSCLC and seek to clarify outstanding issues as they relate to more recent approaches using this strategy.

PURPOSE: The purpose of this retrospective study is to determine the results and the toxicity of concurrent chemoradiation for squamous cell carcinoma of the anal canal in HIV-positive patients treated at a single institution. PATIENTS AND METHODS: HIV-positive patients with squamous cell carcinoma of the canal treated at Continuum Cancer Centers-affiliated hospitals were identified from tumor registries. We reviewed hospital and treatment charts to gather data relating to demographics, HIV status including cluster of differentiation 4 (CD4) count and viral load, tumor stage, radiation and chemotherapy treatment, toxicity and local control, and survival. RESULTS: Thirty-four patients were identified. All patients received radiation and concurrent chemotherapy consisting of either mitomycin-C and 5-fluorouracil (5-FU; 20 patients), cisplatin and 5-FU (13 patients), or 5-FU alone (1 patient). The most frequently reported severe toxicities were dermatologic (50% grade 3 or 4 toxicity) and hematologic (36% grade 3 or 4 toxicity). Actuarial local control and overall survival (OS) at 3 years were 63% and 69%, respectively. CONCLUSION: Concurrent chemoradiation with cisplatin or mitomycin and 5-FU in HIV-positive patients provides local control and OS comparable to that observed in the HIV-negative population, with acceptable toxicity.

Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features. While the incidence of pure BAC is rare, comprising only 1% to 4% of non-small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas--and that figure may be increasing. Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies. Current options for multifocal BAC include both surgery and systemic therapies. Unfortunately, prospective data on systemic approaches are limited by study design and small patient numbers; there are only seven phase II studies involving four therapies. This article evaluates key characteristics of BAC, including the current understanding of histopathology and tumor biology. In addition, it comprehensively reviews the systemic phase II studies in an attempt to clarify the therapeutic challenges in this disease. It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.

Primary presentation of intradural non-Hodgkin lymphoma is rare. Recently, B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) have been recognized as an important pathologic subtype. When MALT lymphomas present in the central nervous system (CNS), they are distinguishable from primary high-grade CNS lymphomas. We present the clinicopathologic features of 5 patients with primary CNS MALT lymphoma treated at our institution from 1999 to 2006. Four out of 5 patients were women, and all patients presented with headaches, focal motor deficits, or cranial nerve palsy. Radiologic studies demonstrated ill-defined dural masses in 3 and well-defined masses in 2 patients. Pathology revealed small to medium-sized cells with a moderate amount of cytoplasm and irregular nuclear borders, expressing pan B-cell markers (CD19, CD20, and CD79a) but lacking CD10, CD23, and cyclin D1, confirming low-grade MALT lymphoma. Plasma cells were encountered in all the biopsies with variable reactive T-cell infiltration. wedge chain restriction was seen in 3 patients. Therapy consisted of either surgical resection, whole-brain radiation, or systemic or intrathecal chemotherapy. There was no evidence of recurrence or systemic relapse in 4 patients at 4 years of follow-up. One patient died in 2 months, unrelated to CNS lymphoma. This case series illustrates the rare occurrence of low-grade dural B-cell lymphoma and the need to consider this entity in the differential diagnosis of CNS lesions.