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Purpose: Neutropenia is a serious complication of chemotherapy in patients with solid tumors. The influence of hospital volume on outcomes in patients with neutropenia has been little investigated. We hypothesized that large-volume hospitals would have reduced mortality rates for neutropenic patients compared with small-volume institutions., Methods: We used the Nationwide Inpatient Sample database of the Healthcare Cost and Utilization Project, for the years 2007-2011. All adult inpatient episodes with a diagnosis of both neutropenia and solid-tumor malignancy were included. Hospital volume was defined as the number of neutropenic cancer episodes per institution per year. Mortality was defined as death during admission. A multilevel mixed-effects logistic regression model was applied., Results: Twenty thousand three hundred and ten hospitalizations were included in the study, from 1,869 different institutions. Median age was 62 years. The overall inpatient mortality was 2.3%, and was dependent on age (age 50-59 years-1.6% and age 80-89 years-5.3%). The median number of neutropenic inpatient episodes in each institution per year was 14 (range, 1-168). Mortality was 3.3%, 2.7%, 2.2%, 2.2%, and 1.2% for each quintile of hospital volume (from lowest to highest volume, P < .001). Likewise, the proportion discharged home was 85.7%, 90.3%, 91.5%, 92.7%, and 95.4% ( P < .001). The association between hospital volume and mortality remained significant after adjustment for patient-level and hospital-level variables., Discussion: Patients with neutropenia hospitalized in large-volume institutions have a substantially lower mortality compared with those hospitalized at low-volume institutions. Further study is required to validate our findings or overcome potential biases, understand mechanism, and investigate how smaller institutions can improve outcomes., Competing Interests: Damien UrbanHonoraria: Boehringer Ingelheim, Merck Sharp & Dohme, Roche, Bristol-Myers Squibb, Takeda, AstraZenecaConsulting or Advisory Role: Merck Sharp & Dohme, Takeda, Teva, Roche IsraelTravel, Accommodations, Expenses: Boehringer Ingelheim, Takeda, Merck Sharp & Dohme Ofer MargalitEmployment: RocheResearch Funding: Checkmate PharmaceuticalsTravel, Accommodations, Expenses: Merck Serono Talia GolanHonoraria: MSD, Rafael PharmaceuticalsConsulting or Advisory Role: AbbVie, AstraZeneca, Bayer, MSD, TevaSpeakers' Bureau: AbbVie, AstraZenecaResearch Funding: AstraZeneca, MSDTravel, Accommodations, Expenses: AstraZeneca, MSD Yaacov Richard LawrenceHonoraria: Bristol-Myers SquibbConsulting or Advisory Role: Clinigen Group, Roche/GenentechResearch Funding: Karyopharm Therapeutics, Checkmate Pharmaceuticals, Bristol-Myers Squibb, Merck SeronoTravel, Accommodations, Expenses: PfizerNo other potential conflicts of interest were reported.

Background: Cancer of unknown primary (CUP) is the fourth most common cause of cancer death. With advanced diagnostics and treatments, we investigated the proportion of cancers diagnosed as CUP, treatment outcomes and association with socioeconomic disparities., Methods: We analysed trends in CUP diagnosis and outcome within the Surveillance, Epidemiology, and End Results registry between 1973 and 2008., Results: The percentage of all cancers diagnosed as CUP has decreased over time comprising <2% of cancers since 2007. A higher proportion of CUP was diagnosed in the elderly, females, blacks and residents of less affluent or less educated counties. Median survival of all CUP patients was 3 months, with no improvement over time. The 5-year survival significantly improved in those with squamous histology (squamous cell carcinoma; SCC) but only marginally in non-SCC. Factors associated with a longer survival on multivariate analysis included white race; female; <65 years old; most recent decade at diagnosis; SCC; married; a histological diagnosis; and treatment with radiotherapy (all P<0.001). Despite the improvement in survival with radiotherapy, its use was less frequent in females and blacks., Conclusion: The percentage of cancers diagnosed as CUP is decreasing but prognosis remains poor, particularly in non-SCC CUP. However, significant socioeconomic disparities exist in diagnosis and survival, suggesting inequalities in access to diagnostic investigations and treatment.

Background: Over the past 2 decades, significant progress has been made in the field of metastatic colorectal cancer (mCRC) regarding new imaging techniques, surgical interventions, and systemic therapy. It is not known whether the benefit from these interventions has extended overall survival (OS) within the general mCRC population. A population-based survival analysis of newly diagnosed patients who presented with mCRC was therefore performed., Methods: Survival statistics were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with mCRC between 1988 and 2008. Demographic variables collected included age, race, and tumor grade. Survival was analyzed using the Kaplan-Meier method and extended Cox proportional hazard model as appropriate., Results: The study population consisted of 42,347 patients diagnosed with mCRC between 1988 and 2008 (52% women; mean age, 67 years). The 1- and 2-year estimated OS rates were 44% and 22%, respectively. Prognostic variables included race, sex, age, tumor location, and year of diagnosis. Median OS improved from 8 months to 14 months between 1988 and 2008. Significant improvements in OS were seen for all disease sites, but especially for descending colon cancers. Whereas the median OS increased by 13 months in patients ≤50 years of age and by 7 months in patients 51-70 years of age, the median OS of patients >70 years of age increased by only 1 month between 1988 and 2008., Conclusions: There has been a continuous improvement in OS of patients diagnosed with mCRC between 1988 and 2008, especially for left-sided tumors. Little improvement has been seen in patients over 70 years of age., (Copyright © 2013 American Cancer Society.)

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry's diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials-acute toxicity and maximum-tolerated dose-are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II "screening" trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation.

Purpose: In light of concerns regarding the quality of radiation treatment delivery, we surveyed the practice of quality assurance peer review chart rounds at American academic institutions., Methods and Materials: An anonymous web-based survey was sent to the chief resident of each institution across the United States., Results: The response rate was 80% (57/71). The median amount of time spent per patient was 2.7 minutes (range, 0.6-14.4). The mean attendance by senior physicians and residents was 73% and 93%, respectively. A physicist was consistently present at peer review rounds in 66% of departments. There was a close association between attendance by senior physicians and departmental organization: in departments with protected time policies, good attendance was 81% vs. 31% without protected time (p = 0.001), and in departments that documented attendance, attending presence was 69% vs. 29% in departments without documentation (p < 0.05). More than 80% of institutions peer review all external beam therapy courses; however, rates were much lower for other modalities (radiosurgery 58%, brachytherapy 40%-47%). Patient history, chart documentation, and dose prescription were always peer reviewed in >75% of institutions, whereas dosimetric details (beams, wedges), isodose coverage, intensity-modulated radiation therapy constraints, and dose-volume histograms were always peer reviewed in 63%, 59%, 42%, and 50% of cases, respectively. Chart rounds led to both minor (defined as a small multileaf collimator change/repeated port film) and major (change to dose prescription or replan with dosimetry) treatment changes. Whereas at the majority of institutions changes were rare (<10% of cases), 39% and 11% of institutions reported that minor and major changes, respectively, were made to more than 10% of cases., Conclusion: The implementation of peer review chart rounds seems inconsistent across American academic institutions. Brachytherapy and radiosurgical procedures are rarely reviewed. Attendance by senior physicians is variable, but it improves when scheduling clashes are avoided. The potential effect of a more thorough quality assurance peer review on patient outcomes is not known., (Copyright © 2012 Elsevier Inc. All rights reserved.)