Efficacy of Second-Line Chemotherapy in Extrapulmonary Neuroendocrine Carcinoma.

OBJECTIVES: A platinum/etoposide doublet is standard first-line therapy for poorly differentiated neuroendocrine carcinoma (PD NEC); however, evidence to guide treatment beyond first-line regimens is lacking. This study aimed to evaluate the efficacy of second-line regimens in PD NEC. METHODS: We performed a retrospective analysis of patients treated with second-line chemotherapy for PD NEC. Inclusion criteria were previous first-line therapy with platinum/etoposide, extrapulmonary PD NEC, and follow-up data. The primary end points were overall survival (OS) and progression-free survival (PFS) after second-line therapy. Secondary end points included OS and PFS from first-line therapy. RESULTS: Sixty-four patients were included. The median OS from initiation of second-line therapy was 6.2 months (95% confidence interval [CI], 4.9-8.9). The median PFS was 2.3 months (95% CI, 2.0-3.2). No second-line regimen showed a statistically significant difference in OS or PFS. There was a significant increase in OS for cisplatin first-line regimens compared with carboplatin (17.0 months [95% CI, 12.5-22.6] vs 11.7 months [95% CI, 8.0-14.0]). CONCLUSIONS: The efficacy of current second-line therapy in PD NEC is poor. No second-line regimen showed statistically significant superiority. Cisplatin was associated with longer OS regardless of second-line regimen or age. However, unmeasured confounders such as performance status or comorbidities may explain this effect.

Renal Neuroendocrine Neoplasms: A Single-center Experience.

BACKGROUND: Primary neuroendocrine neoplasms (NENs) of the kidney are exceedingly rare malignancies and the available literature is very limited. The natural history and response to treatments is not well characterized. We aimed to describe the presenting features, demographics, tumor characteristics, and treatment outcomes of patients with renal NENs. PATIENTS AND METHODS: We performed a retrospective analysis of all Mayo Clinic patient records with a tissue diagnosis of a primary renal NEN. Baseline patient and surgical pathologic features and treatment modalities were collected. Time to recurrence after resection and overall survival (OS) were estimated using with survival analysis. Surveillance, Epidemiology, and End Results data were used to estimate the population-wide incidence and OS. RESULTS: A total of 17 patients were included in the present study, with a median follow-up of 62.8 months. Distant metastasis was present in 29% at diagnosis, with 76% experiencing distant metastasis at any point; 24% had a horseshoe kidney. Of the 17 patients, 14 had undergone surgical resection with no evidence of disease postoperatively. Ten of these patients had documented recurrence. The median time to recurrence was 18 months (95% confidence interval, 9-46 months). Only 1 of the 10 patients showed a radiographic response to systemic therapy. Of 9 patients, 4 had stable disease with somatostatin analogs. The median OS was 143 months (95% confidence interval, 50-143 months). CONCLUSIONS: Renal NENs are rare malignancies affecting mostly middle-age patients, with distant metastasis being common. Approximately one half of patients experience stable disease with somatostatin analogs. The OS usually exceeds 5 years.

Influence of Sociodemographic Factors on Treatment Decisions in Non-Small-Cell Lung Cancer.

INTRODUCTION: In stage IV non-small-cell lung cancer (NSCLC), survival has significantly improved. Despite such trends, it has been noted that patients frequently refuse treatment. Therefore, we explored the factors associated with treatment refusal in NSCLC. PATIENTS AND METHODS: Utilizing the National Cancer Data Base (NCDB), we identified all stage IV NSCLC cases from 2004 to 2014. Patients who received cancer treatment outside of the reporting facility were excluded. Multivariable logistic regression models were used to determine associations with treatment refusal. RESULTS: A total of 341,993 patients were identified; 5.4% of patients refused radiotherapy and 10.3% refused chemotherapy despite provider recommendations. The proportion of patients refusing radiotherapy and chemotherapy increased over time from 4.2% to 7.3% and 7.9% to 15%, respectively (P < .001). In multivariable analysis, men were less likely to refuse treatment compared to women (respectively, odds ratio = 0.80; 95% confidence interval, 0.76-0.84; P < .001; odds ratio = 0.82; 95% confidence interval, 0.80-0.85; P < .001, respectively). Factors associated with radiotherapy refusal included: Medicaid or Medicare as primary insurance, uninsured status, low household median income, and lower educational level. Regarding chemotherapy, uninsured patients, Medicaid patients, and patients with a high comorbidity index were more likely to refuse chemotherapy. Asians had lower rates of chemotherapy refusal relative to non-Hispanic whites. Non-Hispanic whites, Hispanics, and Asians had increasing chemotherapy refusal rates over time, while non-Hispanic blacks had less pronounced trends over time. CONCLUSION: Socioeconomic factors rather than race/ethnicity appear to influence the refusal of cancer treatment in patients with stage IV NSCLC. Assessing socioeconomic challenges should be an essential part of patient evaluation when discussing treatment options.

Clinicopathologic features and outcomes of gastrointestinal stromal tumors arising from the esophagus and gastroesophageal junction.

BACKGROUND: Our aim was to characterize the clinicopathological features and outcomes of gastrointestinal stromal tumors (GISTs) arising from the esophagus and gastroesophageal junction (GEJ) and describe the survival of patients treated at our institution as well as from a national hospital-based registry. METHODS: Twenty-eight cases were identified using the Mayo Clinic Cancer Registry from 1997 to 2016, and 1,010 cases from the National Cancer Database (NCDB) between 2004 and 2014, with analysis of TNM staging, histopathological features, mitotic index, immunohistochemical studies, and KIT mutational analysis. RESULTS: At Mayo Clinic, the tumors ranged in size from 0.3-13 cm (mean 5.40 cm). IHC results were: CD117 (KIT) in 100% (23/23 cases) and DOG1 in 100% (6/6), followed by CD34 (85.7%, 12/14), smooth muscle actin (27.8%, 5/18), desmin (18.2%, 2/11), and S-100 protein (13.3%, 2/15). Mutational analysis (performed in 10 cases) showed KIT exon 11 mutations in 8 cases; KIT mutation was not identified in 2 cases (presumed wild-type). Two-thirds of patients underwent surgery, of which 70% had an esophagectomy. Fourteen patients received adjuvant imatinib mesylate. Five patients had liver metastases at the time of diagnosis; none had lymph node metastases. A total of 38.9% of cases had recurrent or metastatic disease. Complete clinical follow-up was available for 10 patients (median follow-up duration 31.5 months; range, 10-145 months): one (male) had a local recurrence at the anastomotic site and one (female) suffered a liver metastasis; the others were either disease-free or had stable disease at the time of last follow-up. There was a significant association seen among metastatic disease and mitotic count >5/50 high-powered field (HPF) (P=0.016), with median mitotic rate 90/50 HPF (range, 7-500) for metastatic tumors versus 6/50 HPF (range, 0-100) for non-metastatic tumors. For metastatic disease, median tumor size was 7.3 cm (range, 1-66 cm) compared to 4.8 cm (range, 0.02-71 cm) for non-metastatic disease, which was also statistically significant (P≤0.0001). Two hundred and fifty-eight NCDB cases were risk stratified using the Joensuu criteria. Among 89 low risk category tumors, only 2 (2.2%) were ultimately metastatic. A total of 10.9% (15/138) of high risk category tumors were metastatic. The median overall survival (OS) from the time of diagnosis for the Mayo Clinic cohort was 129.5 months (95% CI, 55.7-not reached), with 5-year OS 85.7%. Median OS for the NCDB cohort was 135.95 months (95% CI, 104.08-not reached) with 5-year OS 68.2%. Superior OS was seen in females (HR 0.67, 95% CI, 0.49-0.89, P=0.006). CONCLUSIONS: Among esophageal and GEJ GISTs, metastatic disease was associated with increased mitotic count and increased tumor size. Men were found to have inferior OS. The Joensuu risk criteria were validated for risk stratification of esophageal and GEJ GISTs.

Survival and Prognostic Factors in Patients With Solid Pseudopapillary Neoplasms of the Pancreas.

OBJECTIVES: Prognostic factors for solid pseudopapillary neoplasms (SPN) of the pancreas have been incompletely defined in the literature. We aimed to use the National Cancer Database to describe survival and characterize prognostic factors in patients with pancreatic pseudopapillary neoplasms. METHODS: We identified 304 patients with pancreatic SPN diagnosed between 2004 and 2012 using the National Cancer Database. All patients were included in the survival analysis. Kaplan-Meier method, χ, and log-rank tests were used for statistical analysis. Cox proportional hazard regression model was used for multivariate analysis. RESULTS: The median age at diagnosis was 36.5 years. Eighty-five percent of patients were female, 69% were white, and 25% were black. Metastases were observed in 5% of patients. Median tumor size was 5.1 cm. Ninety-two percent of patients underwent primary tumor resection. At 60 months, 98% of patients who underwent resection were alive, and 40% who did not undergo resection were alive. On multivariate analysis, female sex, resection of primary tumor, and absence of metastasis were correlated with improved survival. CONCLUSIONS: Patients with SPN who undergo resection have an excellent survival at 5 years. Surgery should be considered in all patients with this diagnosis.

Characteristics and long-term outcomes of head and neck squamous cell carcinoma after solid organ transplantation.

INTRODUCTION: Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients with post-transplant HNSCC are unknown. MATERIALS AND METHODS: We retrospectively identified patients who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and adequate follow up were included. Median overall survival and progression free survival were analyzed using the Kaplan-Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. RESULTS: Thirty-three patients met study inclusion criteria. The median time to diagnosis of HNSCC after transplant was 5.9years. The primary site was oral cavity in 15 patients, oropharynx in 10, larynx in 3, hypopharynx in 2, parotid in 2 and unknown in 1 patient. Eighty-eight percent underwent upfront surgical resection. Of those, sixty-six percent received adjuvant therapy. Six percent of patients had definitive chemoradiation. Treatment was well tolerated and did not lead to graft rejection. The 5-year overall survival rate was 45% and 37% for localized and locally advanced disease respectively. Seventy-five percent of patients with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year overall survival rate of 67%). In multivariate analysis, age ≥60years was a negative predictor of survival (HR 2.7; 95% CI, 1.1-6.5; P=0.03). CONCLUSIONS: Patients with post-transplant HNSCC have relatively poor survival and high risk of locoregional and distant recurrence. HPV- positive oropharyngeal tumors continue to have better outcomes in this population.

Presentation, Treatment, and Outcomes of Haitian Women With Breast Cancer in Miami and Haiti: Disparities in Breast Cancer-A Retrospective Cohort Study.

PURPOSE: We compared a cohort of Haitian immigrants with residents in Haiti with breast cancer (BC) to evaluate the effects of location on presentation, treatment, and outcomes. PATIENTS AND METHODS: Participants were Haitian women with BC living in Miami who presented to the University of Miami/Jackson Memorial Hospital and women with BC living in Haiti who presented to the Innovating Health International Women's Cancer Center. The primary outcome was the relationship between location, cancer characteristics, and survival. The secondary objective was to compare our results with data extracted from the SEER database. Cox regression was used to compare survival. RESULTS: One hundred two patients from University of Miami/Jackson Memorial Hospital and 94 patients from Innovating Health International were included. The patients in Haiti, compared with the patients in Miami, were younger (mean age, 50.2 v 53.7 years, respectively; P = .042), presented after a longer duration of symptoms (median, 20 v 3 months, respectively; P < .001), had more advanced stage (44.7% v 25.5% with stage III and 27.6% v 18.6% with stage IV BC, respectively), and had more estrogen receptor (ER) -negative tumors (44.9% v 26.5%, respectively; P = .024). The percentage of women who died was 31.9% in Haiti died compared with 17.6% in Miami. Median survival time was 53.7 months for women in Haiti and was not reached in Miami. The risk of death was higher for women in Haiti versus women in Miami (adjusted hazard ratio, 3.09; P = .0024). CONCLUSION: Women with BC in Haiti experience a significantly worse outcome than immigrants in Miami, which seems to be related to a more advanced stage and younger age at diagnosis, more ER-negative tumors, and lack of timely effective treatments. The differences in age and ER status are not a result of access to care and are unexplained.

Helicobacter Pylori Infection in Texas Hispanic and Non-Hispanic White Men: Implications for Gastric Cancer Risk Disparities.

Chronic Helicobacter pylori ( H. pylori) infection is a major gastric adenocarcinoma (GA) risk factor. GA disproportionately affects U.S. Hispanics compared with non-Hispanic Whites (NHWs). Since H. pylori infection studies in Hispanics are few, infection rates in Hispanic and NHW men in Bexar County were compared, and relationships with ethnicity and obesity examined. Age- and zip code-matched participants from a community-dwelling cohort were randomly selected. Sera from 284 men were analyzed by enzyme immunoassay for H. pylori antibodies. Adjusted risk ratio estimation for matched data was conducted to identify differences. Hispanics had a markedly higher prevalence of infection (30.3%) than NHWs (9.2%). Matched risk ratio (mRR) analyses revealed a strong association between H. pylori seropositivity and Hispanic ethnicity (mRR = 3.31; 95% CI [1.91, 5.73], adjusted by BMI, smoking status, and family history of cancer (mRR range = 3.28-3.89). BMI mRRs (range = 1.19-1.22) were significant in all models. In this cohort, Hispanic men had higher H. pylori infection rates than NHWs, and parallel the disproportionately higher rates of GA; obesity contributes to this higher prevalence. Future studies should address country of origin, acculturation, and other factors influencing obesity to further elucidate risk of GA in Hispanic populations.

Exploring Big Data in Hematological Malignancies: Challenges and Opportunities.

Secondary analysis of large datasets has become a useful alternative to address research questions outside the reach of clinical trials. It is increasingly utilized in hematology and oncology. In this review, we provided an overview of some examples of commonly used large datasets in the USA and described common research themes that can be pursued using such a methodology. We selected a sample of 14 articles on adult hematologic malignancies published in 2015 and highlighted their contributions as well as limitations.

Novel Therapeutic Strategies in Acute Lymphoblastic Leukemia.

Chemotherapy cures only a minority of adult patients with acute lymphoblastic leukemia (ALL). In addition, relapsed ALL has a poor outcome with 5-year survival as low as 7 %. Hence, there is a need to develop effective therapies to treat relapsed disease and to combine these agents with chemotherapy to improve outcomes in newly diagnosed patients. ALL cells express several antigens amenable to target therapies including CD19, CD20, CD22, and CD52. Over the last decade, there has been a surge in the development of immune therapies which target these receptors and that have induced robust responses. In this manuscript, we review these novel immune agents in the treatment of B-ALL. As these new therapies mature, the challenge going forward will be to find safe and effective combinations of these agents with chemotherapy and to determine their place in the current treatment schema.

Biologic impact and clinical implication of mTOR inhibition in metastatic breast cancer.

ABSTRACTThe goal of therapy for patients with metastatic breast cancer (MBC) is prolonging life and palliation of symptoms. Thus the preferred approach remains to use, at least initially, non-cytotoxic drugs. In hormone receptor-positive breast cancer the sequential use of single anti-estrogen drugs, e.g. tamoxifen, aromatase inhibitors, and many others is standard, but eventually drug resistance will lead to failure of these compounds and a switch to chemotherapy will be necessary. Reversing resistance to anti-estrogen therapy in MBC is one of the strategies to avoid and delay the use of cytotoxic compounds. The mammalian target of rapamycin (mTOR) has been recently associated with in vitro reversal of drug resistance, including tamoxifen resistance. A number of early clinical studies have confirmed the concept and, more recently, everolimus was successfully tested in a randomized controlled trial in postmenopausal patients who progressed on previous anti-estrogen therapy for MBC. This manuscript will review the biology, preclinical and clinical data including the randomized controlled trial that lead to the approval of everolimus by the US FDA.