Amol K. Narang

Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study.

BackgroundThe role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation.MethodsPatients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007) and at the Mayo Clinic (n = 130; 1977-2005) were reviewed. Patients with <60 days of follow-up, metastatic disease at surgery, or insufficient pathologic data were excluded. The final combined study consisted of 186 patients (n = 104 Johns Hopkins, n = 82 Mayo). Most patients received 5-FU based chemoradiation with conformal radiation. Cox proportional hazards models were used for survival analysis.ResultsMedian overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002), node positive status (RR = 3.18, p < 0.001), and poor histological grade (RR = 1.69, p = 0.011). Patients who received adjuvant chemoradiation (n = 66) vs. surgery alone (n = 120) showed a higher rate of T3/T4 stage disease (57.6% vs. 30.8%, P < 0.001), lymph node involvement (72.7% vs. 30.0%, P < 0.001), and close or positive margins (4.6% vs. 0.0%, P = 0.019). Five year survival rates among node negative and node positive patients were 58.7% and 18.4% respectively. When compared with surgery alone, use of adjuvant chemoradiation improved survival among node positive patients (mOS 32.1 vs. 15.7 mos, 5 yr OS: 27.5% vs. 5.9%; RR = 0.47, P = 0.004). After adjusting for adverse prognostic factors on multivariate analysis, patients treated with adjuvant chemoradiation demonstrated a significant survival benefit (RR = 0.40, P < 0.001). Disease relapse occurred in 37.1% of all patients, most commonly metastatic disease in the liver or peritoneum.ConclusionsNode-positive patients with resected ampullary adenocarcinoma may benefit from 5-FU based adjuvant chemoradiation. Since a significant proportion of patients develop metastatic disease, there is a need for more effective systemic treatment.

The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma.

Objectives:Lymphopenia is a common consequence of chemoradiation therapy yet is seldom addressed clinically. This study was conducted to determine if patients with locally advanced pancreatic cancer (LAPC) treated with definitive chemoradiation develop significant lymphopenia and if this affects clinical outcomes. Methods:A retrospective analysis of patients with LAPC treated with chemoradiation at a single institution from 1997 to 2011 was performed. Total lymphocyte counts (TLCs) were recorded at baseline and then monthly during and after chemoradiation. The correlation between treatment-induced lymphopenia, established prognostic factors, and overall survival was analyzed using univariate Cox regression analysis. Important factors identified by univariate analysis were selected as covariates to construct a multivariate proportional hazards model for survival. Results:A total of 101 patients met eligibility criteria. TLCs were normal in 86% before chemoradiation. The mean reduction in TLC per patient was 50.6% (SD, 40.6%) 2 months after starting chemoradiation (P<0.00001), and 46% had TLC<500 cells/mm3. Patients with TLC<500 cells/mm3 2 months after starting chemoradiation had inferior median survival (8.7 vs. 13.3 mo, P=0.03) and PFS (4.9 vs. 9.0 mo, P=0.15). Multivariate analysis revealed TLC<500 cells/mm3 to be an independent predictor of inferior survival (HR=2.879, P=0.001) along with baseline serum albumin (HR=3.584, P=0.0002), BUN (HR=1.060, P=0.02), platelet count (HR=1.004, P=0.005), and radiation planning target volume (HR=1.003, P=0.0006). Conclusions:Severe treatment-related lymphopenia occurs frequently after chemoradiation for LAPC and is an independent predictor of inferior survival.

Out-of-pocket spending and financial burden among medicare beneficiaries with cancer

Importance Medicare beneficiaries with cancer are at risk for financial hardship given increasingly expensive cancer care and significant cost sharing by beneficiaries. Objectives To measure out-of-pocket (OOP) costs incurred by Medicare beneficiaries with cancer and identify which factors and services contribute to high OOP costs. Design, Setting, and Participants We prospectively collected survey data from 18 166 community-dwelling Medicare beneficiaries, including 1409 individuals who were diagnosed with cancer during the study period, who participated in the January 1, 2002, to December 31, 2012, waves of the Health and Retirement Study, a nationally representative panel study of US residents older than 50 years. Data analysis was performed from July 1, 2014, to June 30, 2015. Main Outcomes and Measures Out-of-pocket medical spending and financial burden (OOP expenditures divided by total household income). Results Among the 1409 participants (median age, 73 years [interquartile range, 69-79 years]; 46.4% female and 53.6% male) diagnosed with cancer during the study period, the type of supplementary insurance was significantly associated with mean annual OOP costs incurred after a cancer diagnosis (

Molecularly Targeted Agents as Radiosensitizers in Cancer Therapy—Focus on Prostate Cancer

2116 among those insured by Medicaid,

Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer

2367 among those insured by the Veterans Health Administration,

Socioeconomic factors affect the selection of proton radiation therapy for children

5976 among those insured by a Medicare health maintenance organization,

Development of an evidence-based strategy to assess and manage substance use in oncology patients

5492 among those with employer-sponsored insurance,

Long-term analysis of 2 prospective studies that incorporate mitomycin C into an adjuvant chemoradiation regimen for pancreatic and periampullary cancers

5670 among those with Medigap insurance coverage, and

Prostate cancer: Case volume and improved outcomes across cancer care

8115 among those insured by traditional fee-for-service Medicare but without supplemental insurance coverage). A new diagnosis of cancer or common chronic noncancer condition was associated with increased odds of incurring costs in the highest decile of OOP expenditures (cancer: adjusted odds ratio, 1.86; 95% CI, 1.55-2.23; P < .001; chronic noncancer condition: adjusted odds ratio, 1.82; 95% CI, 1.69-1.97; P < .001). Beneficiaries with a new cancer diagnosis and Medicare alone incurred OOP expenditures that were a mean of 23.7% of their household income; 10% of these beneficiaries incurred OOP expenditures that were 63.1% of their household income. Among the 10% of beneficiaries with cancer who incurred the highest OOP costs, hospitalization contributed to 41.6% of total OOP costs. Conclusions and Relevance Medicare beneficiaries without supplemental insurance incur significant OOP costs following a diagnosis of cancer. Costs associated with hospitalization may be a primary contributor to these high OOP costs. Medicare reform proposals that restructure the benefit design for hospital-based services and incorporate an OOP maximum may help alleviate financial burden, as can interventions that reduce hospitalization in this population.

Dosimetric predictors of sexual function decline following LDR brachytherapy for prostate cancer (PCa).

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.