A Case Report on Solitary Extramedullary Plasmacytoma of the Pleura.

Solitary plasmacytoma is an extremely rare form of plasma cell malignancy that presents as a single mass of monoclonal plasma cells located either intraosseous or extramedullary (extraosseous). Extramedullary plasmacytoma can affect any part of the body, but the most common sites of origin are the head and neck region. The involvement of pleura is very rare. Here, we are enlightening this rare presentation and making readers aware of the clinical presentation and management of this rare malignancy.

Single-Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment.

PURPOSE: Improving our understanding of the immunologic response to cancer cells within the sentinel lymph nodes (SLN) of primary tumors is expected to identify new approaches to stimulate clinically meaningful cancer immunity. EXPERIMENTAL DESIGN: We used mass cytometry by time-of-flight (CyTOF), flow cytometry, and T-cell receptor immunosequencing to conduct simultaneous single-cell analyses of immune cells in the SLNs of patients with melanoma. RESULTS: We found increased effector-memory αß T cells, TCR clonality, and γδ T cells selectively in the melanoma-bearing SLNs relative to non-melanoma-bearing SLNs, consistent with possible activation of an antitumor immune response. However, we also observed a markedly immunotolerant environment in the melanoma-bearing SLNs indicated by reduced and impaired NK cells and increased levels of CD8+CD57+PD-1+ cells, which are known to display low melanoma killing capabilities. Other changes observed in melanoma-bearing SLNs when compared with non-melanoma-bearing SLNs include (i) reduced CD8+CD69+ T cell/T regulatory cell ratio, (ii) high PD-1 expression on CD4+ and CD8+ T cells, and (iii) high CTLA-4 expression on γδ T cells. CONCLUSIONS: Our data suggest that these immunologic changes compromise antimelanoma immunity and contribute to a high relapse rate. We propose the development of clinical trials to test the neo-adjuvant administration of anti-PD-1 antibodies prior to SLN resection in patients with stage III melanoma. See related commentary by Lund, p. 1996.

Incidence and Survival Outcomes in Patients with Lung Neuroendocrine Neoplasms in the United States.

BACKGROUND: The incidence and prevalence of neuroendocrine neoplasms (NENs) are rapidly rising. Epidemiologic trends have been reported for common NENs, but specific data for lung NENs are lacking. METHODS: We conducted a retrospective analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Associated population data were utilized to report the annual age-adjusted incidence and overall survival (OS) trends. Trends for large-cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC) were reported from 2000-2015, while those for typical carcinoid (TC) and small cell lung cancer (SCLC) were reported from 1988-2015. RESULTS: We examined a total of 124,969 lung NENs [103,890-SCLC; 3303-LCNEC; 8146-TC; 656-AC; 8974-Other]. The age-adjusted incidence rate revealed a decline in SCLC from 8.6 in 1988 to 5.3 in 2015 per 100,000; while other NENs showed an increase: TC increased from 0.57 in 1988 to 0.77 in 2015, AC increased from 0.17 in 2001 to 0.22 in 2015, and LCNEC increased from 0.16 in 2000 to 0.41 in 2015. The 5-year OS rate among SCLC, LCNEC, AC, and TC patients was 5%, 17%, 64%, and 84%, respectively. On multivariable analyses, OS and disease-specific survival (DSS) varied significantly by stage, sex, histological type, insurance type, marital status, and race, with a better survival noted in earlier stages, females, married, insured, Hispanic and other races, and urban population. Similarly, TC and AC had better survival compared to SCLC and LCNEC. CONCLUSION: The incidence of lung NENs is rising, possibly in part because of advanced radiological techniques. However, the incidence of SCLCs is waning, likely because of declining smoking habits. Such population-based studies are essential for resource allocation and to prioritize future research directions.

5-(3,3-Dimethyle-1-Triazeno) Imidazole-4-Carboxamide and Interleukin-2 Adjuvant Therapy in Resected High-Risk Primary and Regionally Metastatic Melanoma.

BACKGROUND: In the precheckpoint inhibitor era, high-dose interferon was the only approved adjuvant therapy for high-risk melanoma. In this manuscript, we analyze the recurrence-free survival, overall survival and toxicity profile of adjuvant treatment with interleukin-2 (IL-2) and 5-(3,3-dimethyle-1-triazeno) imidazole-4-carboxamide (DTIC) for resected high-risk melanoma patients. METHODS: All patients with stage IIB, IIC or stage III melanoma who were treated with DTIC/IL-2 combination therapy at a single institution from 2000 to 2010 were identified from the University of Louisville Hospital medical record. Patients received 6 months of subcutaneous IL-2 (12 × 106 units days 1-4) and intravenous DTIC (750 mg/m2 day 1 of each cycle) every 28 days for 6 cycles. Individual medical records were accessed to collect the data. RESULTS: Of the 112 patients treated, all underwent surgical resection and then received adjuvant treatment. A total of 58.7% of the patients were male, 42.2% female; 99% were Caucasian. A total of 79 (72.5%) of the patients were alive at the time of analysis and 57 (47.7%) patients were currently event free. A total of 69 (63.3%) patients completed all 6 months of adjuvant combination treatment with 13.8% of the patients requiring IL-2 and 21.1% of the patients requiring DTIC dose reduction. Five year overall survival was 75.57% with recurrence-free survival of 53.05%. CONCLUSIONS: For several decades, there has not been an ideal adjuvant treatment for patients with resected high risk melanoma. Our retrospective analysis suggests that combination therapy with DTIC/IL-2 is beneficial and relatively well tolerated as an alternative adjuvant treatment for patients with high-risk melanoma.

Treatment and outcomes of non-small-cell lung cancer patients with high comorbidity.

BACKGROUND: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC. METHODS: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic regression models were used to measure association between receiving treatment and comorbidity. Kaplan-Meier plots were constructed to estimate time-to-event outcomes. RESULTS: A total of 4014 patients were identified; of this, 94.9% were white and 55.7% were male. The proportion of patients who did not receive any treatment was 8.7%, 3.9%, 19.1%, and 23.5% for stages I, II, III, and IV, respectively (p<0.0001). In multivariate analysis, older age, higher stage, and higher comorbidity (KCI ≥3) were associated with a lower likelihood of receiving any treatment. The median overall survival (OS) for untreated and KCI=0 was 17.7 months for stages I and II, 2.3 months for stage III, and 1.3 months for stage IV. The median OS for treated and KCI=0 was 58.9 months for stages I and II, 16.8 months for stage III, and 5.8 months for stage IV (p<0.01). Treatment was an independent predictor of OS in multivariate analysis that included KCI scores. CONCLUSION: Our data suggest that lung cancer patients may derive a survival benefit from therapies, regardless of the presence of comorbidities, although the degree of benefit seems to decrease with higher KCI scores.

"Lost to Follow-up" Among Adult Cancer Survivors.

BACKGROUND: Follow-up cancer care is important for patients who have received IV chemotherapy but some patients discontinue their care and are lost to follow-up (LFU) at the cancer center where they were treated. The purpose of this study was to determine what proportion of cancer survivors are LFU at 5 years after treatment, the timing of LFU, and the characteristics of those who do not continue survivorship care. METHODS: Adult patients with cancer who were treated with chemotherapy at a large community teaching hospital in 2006 and 2007 were identified and linked with State tumor registry data. Hospital medical records were reviewed to obtain information on demographics, diagnosis, treatment, and date of last follow-up visit. Characteristics of patients with ≥5 years of follow-up care were compared with those who were LFU. RESULTS: In total, 487 patients received chemotherapy and 304 died (62%) during the 5-year follow-up period. Among the 183 cancer patients who were known to be alive at 5 years, 92 (50%) were LFU and 50% (46/92) of this LFU group were LFU within 1 year of diagnosis. At 5 years, follow-up care was continuing for 55% of women, compared with 39% of men. The highest proportion of follow-up was observed among lung cancer patients (84%), followed by patients with breast cancers (63%) and gastrointestinal cancers (40%). Patients with hematological cancers had the lowest follow-up proportion at 5 years (29%) (P<0.05). Follow-up was not significantly associated with age (P=0.48), insurance status(P=0.29), and race(P=0.06). CONCLUSIONS: It is estimated that 65% of the cancer survivors in the United States are ≥5 years beyond their diagnosis but there is little data on oncology follow-up rates. In our retrospective study of 183 patients who were treated with chemotherapy only 49.7% continue to follow-up at their treatment center. LFU has important implications in planning long-term care strategies for cancer survivors and in survivorship research.

Gemcitabine and carfilzomib induced thrombotic microangiopathy: eculizumab as a life-saving treatment.

Drug-induced aHUS is rare; however, early diagnosis is vital to reduce morbidity and mortality. With confirmation of the diagnosis, eculizumab appears to be a viable treatment option to suppress the pro-inflammatory surge. Furthermore, adverse side effects of medications such as carfilzomib and gemcitabine should be considered in the appropriate settings.

High-dose versus weekly cisplatin definitive chemoradiotherapy for HPV-related oropharyngeal squamous cell carcinoma of the head and neck.

OBJECTIVES: To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx). METHODS: All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS). RESULTS: Of the 55 patients included, 22 were patients treated with HDC at dose of 100mg/m2 on days 1 and 22; and the remaining 33 patients were treated with WC at 40mg/m2. Both cohorts received a median total dose of cisplatin of 200mg/m2. At median follow-up of 31months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p=0.04). There was no significant difference in 2-year OS (95% vs. 94%; p=0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups. CONCLUSIONS: HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar.

Age-related Disparity: Breast Cancer in the Elderly.

Aging poses an unique opportunity to study cancer biology and treatment in older adults. Breast cancer is often studied in young women; however, much investigation remains to be done on breast cancer in our expanding elderly population. Diagnostic and management strategies applicable to younger patients cannot be empirically used to manage older breast cancer patients. Lack of evidence-based data continues to be the major impediment toward delivery of personalized cancer care to elderly breast cancer patients. This article reviews the relevant literature on management of curable breast cancer in the elderly, the role of geriatric assessment, complex treatment decision making within the context of patient's expected life expectancy, comorbidities, physical function, socioeconomic status, barriers to health care delivery, goals of treatment, and therapy-related side effects. Continuing efforts for enrolling elderly breast cancer patients in contemporary clinical trials, and thus improving age-appropriate care, are emphasized.

Symptoms and symptom management in long-term cancer survivors.

It is estimated that there are 13 million cancer survivors in the United States, and more than 65% of them are 5 or more years beyond their diagnosis. The majority are "cancer-free and free of cancer," although some survivors have late or long-term effects of treatment or develop second or secondary cancers. Late and long-term effects for survivors of childhood cancers have been well studied, but less is known about the "seasons of survivorship" for adult cancer survivors. Symptoms during diagnosis, treatment, and then extending through the first several years of survivorship were reported in more than half of a large and heterogeneous group of cancer survivors. The incidence of late and/or long-term symptoms and health problems of long-term cancer survivors is less well characterized. These persistent symptoms are related to survivors' cancer diagnosis and the treatment they received, as well as age and other comorbidities. Health-related quality of life generally is stable for many years, although some cancer survivors experience a significant drop in health-related quality of life years after treatment, although the etiology is not clear yet. This article provides an overview of the natural history of cancer survivorship ("The seasons of survivorship"), disease-specific toxicities, and changes in symptoms in cancer survivors over time. Several common symptoms are used as examples including pain, fatigue, and cognitive dysfunction.