In situ psycho-cognitive assessments support self-determined urban green exercise time.

Prescribed nature walks frequently yield improvements to mood and cognition as observed in experimental studies. Research that uses real life settings such as self-determined time exercising outdoors for restorative health benefits may more accurately elicit effects than time-specified study protocols. This study examined in situ psycho-cognitive outcomes of routine walks in urban greenspace to test the concept that self-set exposure duration and not context alone is related to magnitude of psycho-cognitive benefit. Pre-post measurements taken on a diverse participant pool of individuals walking in urban parks and recruited on random days over a two-week period found significant associations between outdoor activity duration and cognitive and mood improvements. Greater outdoor walking duration linearly predicted stronger processing speeds but non-linearly in tests of other cognitive domains. Results of fixed effects model for mean mood change following green exercise show outdoor walking influenced mood change at highest levels of significance, even after accounting for individual level variability in duration. Mood improved for all durations of outdoor walking under a random effects model with high significance. Untethering fixed intervals of outdoor exercise from formal study design revealed briefer but more frequent nature engagement aligned with nature affinity. The influence of unmeasured factors, e.g., nature affinity or restorative conditioning, for prescriptive durations of urban green exercise merits further investigation toward designing wellbeing interventions directed at specific urban populations.

Assessing ablation margins of FDG-avid liver tumors during PET/CT-guided thermal ablation procedures: a retrospective study.

BACKGROUND: To retrospectively assess liver tumor ablation margins using intraprocedural PET/CT images from FDG PET/CT-guided microwave or cryoablation procedures and to correlate minimum margin measurements with local progression outcomes. METHODS: Fifty-six patients (ages 36 to 85, median 62; 32 females) with 77 FDG-avid liver tumors underwent 60 FDG PET/CT guided, percutaneous microwave, or cryoablation procedures. Single breath-hold PET/CT images were used for intraprocedural assessment of the tumor ablation margin: liver tumors remained visible on PET immediately following ablation; microwave ablation zones were visible using contrast-enhanced CT; cryoablation zones (ice balls) were visible using unenhanced CT. Two readers retrospectively determined ablation margin assessability and measured the minimum ablation margin on intraprocedural PET/CT (n = 77) and postprocedural MRI (n = 56). Local tumor progression was assessed on all available follow-up imaging (1-49 months, mean 15). Local tumor progression was correlated with PET/CT minimum margin measurements using clustered survival models for 61 tumors. RESULTS: Minimum ablation margins were more often assessable using intraprocedural PET/CT (≥ 73/77 tumors, 95%) than postprocedural MRI (≤ 35/56 tumors, 63%). In 61 tumors with PET/CT-assessable margins (excluding tumors with overlapping ablations after PET/CT), there was a 6-fold increased risk of local tumor progression [hazard ratio (HR) 6.05; P = 0.004] for minimum ablation margins < 5 mm. CONCLUSION: Breath-hold PET/CT scans, during PET/CT-guided microwave or cryoablation procedures for FDG-avid liver tumors, enable reliable intraprocedural assessment of the entire tumor ablation margin; a minimum PET/CT ablation margin threshold of 5 mm correlates well with local tumor progression outcomes.

Response rate and local recurrence after concurrent immune checkpoint therapy and radiotherapy for non-small cell lung cancer and melanoma brain metastases.

BACKGROUND: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear. METHODS: A total of 199 patients with melanoma and non-small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per-metastasis basis, using a sandwich estimator to account for intrapatient correlation. RESULTS: The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P < .001), with correspondingly lower rates of progressive disease (5% vs 26%; P < .001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18-2.63 [P = .006]) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23-0.78 [P = .006]). This effect appeared to be greater for melanoma than for non-small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression. CONCLUSIONS: Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted.

The Influence of Heat on Daily Police, Medical, and Fire Dispatches in Boston, Massachusetts: Relative Risk and Time-Series Analyses.

Objectives. To examine the impact of extreme heat on emergency services in Boston, MA.Methods. We conducted relative risk and time series analyses of 911 dispatches of the Boston Police Department (BPD), Boston Emergency Medical Services (BEMS), and Boston Fire Department (BFD) from November 2010 to April 2014 to assess the impact of extreme heat on emergency services.Results. During the warm season, there were 2% (95% confidence interval [CI] = 0%, 5%) more BPD dispatches, 9% (95% CI = 7%, 12%) more BEMS dispatches, and 10% (95% CI = 5%, 15%) more BFD dispatches on days when the maximum temperature was 90°F or higher, which remained consistent when we considered multiple days of heat. A 10°F increase in daily maximum temperature, from 80° to 90°F, resulted in 1.016, 1.017, and 1.002 times the expected number of daily BPD, BEMS, and BFD dispatch calls, on average, after adjustment for other predictors.Conclusions. The burden of extreme heat on local emergency medical and police services may be agency-wide, and impacts on fire departments have not been previously documented.Public Health Implications. It is important to account for the societal burden of extreme heat impacts to most effectively inform climate change adaptation strategies and planning.

Prescription of memantine during non-stereotactic, brain-directed radiation among patients with brain metastases: a population-based study.

PURPOSE: Whole brain radiation therapy (WBRT) remains an important component of treatment for patients with multiple brain metastases (BrM) but is associated with significant neurotoxicity and memory impairment. Although RTOG 0614 demonstrated that administration of memantine to patients receiving WBRT may reduce radiation-associated cognitive decline, prior literature has suggested that radiation oncologists are hesitant to prescribe memantine. We sought to assess the frequency of memantine prescription in patients managed with non-stereotactic, brain-directed radiation for BrM. METHODS: Patients > 65 years old with newly diagnosed BrM between 2007 and 2016 receiving non-stereotactic, brain-directed radiation (including WBRT) were identified using the SEER-Medicare database. Receipt of memantine with non-stereotactic, brain-directed radiation was defined as any Part D claim for memantine 30 days before or after initiation of non-stereotactic, brain-directed radiation. Clinical and demographic variables among patients who did and did not receive memantine were compared. RESULTS: Between 2007 and 2016, we identified 6220 patients with BrM receiving non-stereotactic, brain-directed radiation. Only 2.20% of patients (n = 137) received memantine with radiation. Rates were 1.10% versus 5.14% in the period preceding (2007-2013) and following (2014-2016) the publication of RTOG 0614, respectively. Overall utilization of memantine remained low across several clinical, demographic, and prognostic variables. CONCLUSION: Despite phase 3 evidence supporting memantine utilization among patients receiving WBRT, our population-based study indicates that rates of memantine prescription are strikingly low, although memantine utilization seems to be increasing since publication of RTOG 0614. Further investigation is needed to identify provider and practice-related barriers preventing incorporation of memantine into management paradigms.

Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases.

PURPOSE: Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms. METHODS: We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Patients were stratified by subtype: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), HER2+ positive (HER2+), or triple-negative breast cancer (TNBC). A per-metastasis assessment was conducted. Time-to-event analyses were conducted using multivariable Cox regression. RESULTS: Of the 349 patients, 116 had HR+/HER2- subtype, 164 had HER2+ subtype, and 69 harbored TNBC. Relative to HR+/HER2- subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78-5.75, p < 0.001), while patients with TNBC demonstrated higher rates of new brain metastases after initial treatment (HR 3.16, 95% CI 1.99-5.02, p < 0.001) and shorter time to salvage whole brain radiation (WBRT) (HR 3.79, 95% CI 1.36-10.56, p = 0.01) and salvage stereotactic radiation (HR 1.86, 95% CI 1.11-3.10, p = 0.02). CONCLUSIONS: We identified a strong association between breast cancer subtype and intracranial recurrence patterns after brain-directed radiation, particularly local progression for HER2+ and distant progression for TNBC patients. If validated, the poorer local control in HER2+ brain metastases may support evaluation of novel local therapy-based approaches, while the increased distant recurrence in TNBC suggests the need for improved systemic therapy and earlier utilization of WBRT.

Local control after brain-directed radiation in patients with cystic versus solid brain metastases.

PURPOSE: Brain metastases can be radiographically cystic or solid. Cystic metastases are associated with a greater intracranial disease burden and poorer oncologic outcomes, but the impact of cystic versus solid appearance on local control after radiation remains unknown. We investigated whether cystic versus solid nature is predictive of local control after management with stereotactic or whole brain radiation (WBRT) and whether the radiation modality utilized is an effect modifier. METHODS: We identified 859 patients with 2211 newly-diagnosed brain metastases managed with upfront stereotactic radiation or WBRT without preceding resection/aspiration at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Multivariable Cox regression with an interaction term and sandwich covariance matrix was used to quantify local failure. RESULTS: Cystic lesions were more likely to recur than solid ones when managed with stereotactic radiation (HR 2.33, 95% CI 1.32-4.10, p = 0.004) but not WBRT (HR 0.92, 95% CI 0.62-1.36, p = 0.67), p-interaction = 0.007. 1 year local control rates for cystic versus solid metastases treated with stereotactic radiation were 75% versus 88%, respectively; estimates with WBRT were 76% versus 76%, respectively. However, no significant differences were noted between the two cohorts in post-radiation outcomes including all-cause mortality and neurologic death (p > 0.05). CONCLUSIONS: Among patients with brain metastases, stereotactic radiation yields improved local control and less morbidity than WBRT, and consequently for many patients the cystic versus solid designation does not impact treatment selection. However, our results suggest that in patients with a large number of cystic brain metastases, a lower threshold to consider WBRT, as opposed to stereotactic radiation, should be employed. If our results can be confirmed, further investigation into the underlying mechanism(s) would be warranted.

Effects of biophilic interventions in office on stress reaction and cognitive function: A randomized crossover study in virtual reality.

Biophilia hypothesis suggests humans have an innate connection to nature which may affect our health and productivity. Yet we currently live in a world that is rapidly urbanizing with people spending most of their time indoors. We designed a randomized crossover study to let 30 participants experience three versions of biophilic design in simulated open and enclosed office spaces in virtual reality (VR). Throughout the VR session, we measured blood pressure, heart rate, heart rate variability, and skin conductance level and administered cognitive tests to measure their reaction time and creativity. Compared to the base case, participants in three spaces with biophilic elements had consistently lower level of physiological stress indicators and higher creativity scores. In addition, we captured the variation in the intensity of virtual exposure to biophilic elements by using eye-tracking technology. These results suggest that biophilic interventions could help reduce stress and improve creativity. Moreover, those effects are related to both the types of biophilic elements and may be different based on the workspace type (open vs enclosed). This research demonstrates that VR-simulated office spaces are useful in differentiating responses to two configurations and among biophilic elements.

Phase 2 study of treatment selection based on tumor thymidylate synthase expression in previously untreated patients with metastatic colorectal cancer: A trial of the ECOG-ACRIN Cancer Research Group (E4203).

BACKGROUND: The authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS-L) expression would have a higher response rate to combined 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS-H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS-H tumors. METHODS: TS protein expression was determined in mCRC tissue. Patients who had TS-L tumors received FOLFOX/Bev, and those who had TS-H tumors were randomly assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the response rate (complete plus partial responses). RESULTS: In total, 211 of 247 patients (70% TS-H) were registered to the treatment phase. Efficacy analyses included eligible patients who had started treatment (N = 186). The response rates for patients who received IROX/Bev (TS-H), FOLFOX/Bev (TS-H), and FOLFOX/Bev (TS-L) were 33%, 38%, and 49%, respectively (P = nonsignificant). The median progression-free survival (PFS) was 10 months (95% confidence interval [CI], 9-12 months; 10 months in the IROX/Bev TS-H group, 9 months in the FOLFOX/Bev TS-H group, and 13 months in the FOLFOX/Bev TS-L group). The TS-L group had improved PFS compared with the TS-H group that received FOLFOX/Bev (hazard ratio, 1.6; 95% CI, 1.0%-2.4%; P = .04; Cox regression). The median overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the IROX/Bev TS-H group, 21 months in the FOLFOX/Bev TS-H group, and 32 months in the TS-L group). OS comparisons for the 2 TS-H arms and for the FOLFOX/Bev TS-H versus TS-L arms were not significantly different. CONCLUSIONS: TS expression was prognostic: Patients with TS-L tumors who received FOLFOX/Bev had a longer PFS than those with TS-H tumors, along with a trend toward longer OS. Patients with TS-H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev. Cancer 2018;124:688-97. © 2017 American Cancer Society.

Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.

BACKGROUND: This study sought to determine the efficacy and safety profile of cabozantinib in patients with advanced Merkel cell carcinoma (MCC). EXPERIMENTAL DESIGN: This prospective, phase II, single-institution trial enrolled patients with platinum-failure, recurrent/metastatic MCC to receive cabozantinib 60 mg orally daily until disease progression, withdrawal from study, or severe toxicity. The primary endpoint was disease control rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity. Immunohistochemistry for VEGFR-2, MET, and HGF expression and next-generation sequencing of tumor tissue were performed and correlated with outcome. RESULTS: Eight patients were accrued from January 24, 2014, to June 8, 2016. The study was closed prematurely because of toxicity and lack of responses. The most frequent adverse events were grades 1 and 2 and included anorexia, fatigue, nausea, hypothyroidism, and dysgeusia. Two patients developed nonhealing, painful ulcers and tumor-skin fistula. One patient had stable disease for 8 months. One patient withdrew from the study after 2 weeks of therapy because of adverse events. Three patients required dose reduction because of toxicity. Median PFS and OS were 2.1 and 11.2 months, respectively. No expression of MET, HGF, or VEGFR-2 was identified in tumor cells by immunohistochemistry of patients' tissue samples. CONCLUSION: Cabozantinib was poorly tolerated and did not demonstrate activity in patients with recurrent/metastatic, platinum-failure MCC. It is unclear whether preselection of patients with the specific upregulation or genetic alteration in the targets for cabozantinib would have changed the results of this study. (Clinical trial identification number: NCT02036476) IMPLICATIONS FOR PRACTICE: This phase II study demonstrated poor tolerability and lack of activity of cabozantinib in an unselected group of patients with advanced Merkel cell carcinoma. Although it is unclear whether preselection of patients with the specific upregulation and genetic alterations in targets for cabozantinib would have changed the results of this study, this would have likely led to an extremely rare patient population that would take many years to accrue.

The need for preoperative baseline arm measurement to accurately quantify breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) is a feared outcome of breast cancer treatment, yet the push for early screening is hampered by a lack of standardized quantification. We sought to determine the necessity of preoperative baseline in accounting for temporal changes of upper extremity volume. 1028 women with unilateral breast cancer were prospectively screened for lymphedema by perometry. Thresholds were defined: relative volume change (RVC) ≥10 % for clinically significant lymphedema and ≥5 % including subclinical lymphedema. The first postoperative measurement (pseudo-baseline) simulated the case of no baseline. McNemar's test and binomial logistic regression models were used to analyze BCRL misdiagnoses. Preoperatively, 28.3 and 2.9 % of patients had arm asymmetry of ≥5 and 10 %, respectively. Without baseline, 41.6 % of patients were underdiagnosed and 40.1 % overdiagnosed at RVC ≥ 5 %, increasing to 50.0 and 54.8 % at RVC ≥ 10 %. Increased pseudo-baseline asymmetry, increased weight change between baselines, hormonal therapy, dominant use of contralateral arm, and not receiving axillary lymph node dissection (ALND) were associated with increased risk of underdiagnosis at RVC ≥ 5 %; not receiving regional lymph node radiation was significant at RVC ≥ 10 %. Increased pseudo-baseline asymmetry, not receiving ALND, and dominant use of ipsilateral arm were associated with overdiagnosis at RVC ≥ 5 %; increased pseudo-baseline asymmetry and not receiving ALND were significant at RVC ≥ 10 %. The use of a postoperative proxy even early after treatment results in poor sensitivity for identifying BCRL. Providers with access to patients before surgery should consider the consequent need for proper baseline, with specific strategy tailored by institution.

Body Mass Index and Locoregional Recurrence in Women with Early-Stage Breast Cancer.

BACKGROUND: Higher body mass index (BMI) has been associated with increased distant recurrence and decreased survival for women with breast cancer. However, the relationship between BMI and locoregional recurrence (LRR) has been less well studied and was therefore the subject of this investigation. METHODS: The study identified 878 women with early-stage invasive breast cancer who underwent breast-conservation therapy (BCT) between June 1997 and October 2007. Time from diagnosis to LRR was calculated using a competing risk analysis with contralateral breast cancer (CBC), distant metastases (DM), and death as the competing risks. Gray's competing risks analysis, which included an interaction term between menopausal status and BMI, was used to identify significant risk factors for the development of LRR. RESULTS: After a median follow-up period of 10.8 years, LRR was diagnosed as a first event for 45 women. In a multivariable analysis, BMI was positively associated with LRR but only in premenopausal women. Specifically, when these women were compared with normal- and underweight women, both the overweight women (hazard ratio (HR), 2.97; 95 % confidence interval (CI) 1.04-8.46; p = 0.04) and the obese women (HR, 3.36; 95 % CI 1.07-10.63; p = 0.04) showed a higher risk of LRR. A similar association between BMI and disease-free survival was noted for premenopausal but not postmenopausal women. CONCLUSION: For premenopausal women with invasive breast cancer who undergo BCT, BMI is an independent prognostic factor for LRR. If confirmed, these findings suggest that more aggressive treatment strategies may be warranted for these women.

Variation in National Use of Long-Term ADT by Disease Aggressiveness Among Men With Unfavorable-Risk Prostate Cancer.

BACKGROUND: The current NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer recommend long-term androgen deprivation therapy (ADT) for all men with high-risk prostate cancer treated with external-beam radiation therapy (EBRT). We determined whether the use of long-term ADT varied by the recently defined subcategories of high-risk disease (favorable, other, and very high) versus unfavorable intermediate-risk disease. METHODS: We identified 5,524 patients with unfavorable-risk prostate cancer diagnosed from 2004 to 2007 and managed with EBRT using the SEER-Medicare linked database. Patients were stratified by risk group: unfavorable intermediate-risk, favorable high-risk (previously defined and validated as clinical stage T1c, Gleason score of 4 + 4 = 8, and prostate-specific antigen [PSA] level <10 ng/mL, or clinical stage T1c, Gleason score of 6, and PSA level >20 ng/mL), very-high-risk (clinical stage T3b-T4 or primary Gleason pattern 5), or other high risk (ie, neither favorable nor very high). We used multivariable competing risks regression to estimate the rates of long-term (≥2 years) ADT by group. RESULTS: Men with favorable high-risk prostate cancer were significantly less likely to receive long-term ADT than those with other high-risk disease (15.4% vs 24.6%, adjusted hazard ratio [AHR], 0.68; 95% CI, 0.60-0.76;P<.001), and similarly likely as those with unfavorable intermediate-risk disease (AHR, 1.10; 95% CI, 0.99-1.23;P=.087). Other high-risk disease was less likely to receive long-term ADT than very high-risk cancer (24.6% vs 30.8%; AHR, 0.83; 95% CI, 0.74-0.93;P=.002). CONCLUSIONS: Despite current guidelines, patients with EBRT-managed high-risk prostate cancer received significantly different rates of long-course ADT based on subclassification. Our results suggest that oncologists view these patients as a heterogeneous group with favorable high-risk cancer warranting less aggressive therapy than other high-risk or very high-risk disease.

Hepatic Microwave Ablation Zone Size: Correlation with Total Energy, Net Energy, and Manufacturer-Provided Chart Predictions.

PURPOSE: To determine whether total energy (TE) reaching the microwave (MW) applicator or net energy (NE) exiting the applicator (after correcting for reflectivity) correlates better with hepatic MW ablation zone dimensions than manufacturer-provided chart predictions. MATERIALS AND METHODS: Single-applicator, nonoverlapping ablations of 93 liver tumors (0.7-5.9 cm) were performed in 52 adult patients. TE and NE were recorded for each ablation. Long axis diameter (LAD), short axis diameter (SAD), and volume (V) of each ablation zone were measured on magnetic resonance imaging or computed tomography after the procedure and retrospectively compared with TE; NE; and manufacturer-provided chart predictions of LAD, SAD, and V using correlation and regression analyses. RESULTS: For treated tumors, mean (± SD) TE and NE were 49.8 kJ (± 22.7) and 36.4 kJ (± 19.4). Mean LAD, SAD, and V were 5.8 cm (± 1.3), 3.7 cm (± 0.8), and 44.1 cm(3) (± 25.4). Correlation coefficients (95% confidence interval) with LAD, SAD, and V were 0.46 (0.28, 0.61), 0.52 (0.36, 0.66), and 0.52 (0.36, 0.66) for TE; 0.42 (0.24, 0.58), 0.55 (0.39, 0.68), and 0.53 (0.36, 0.66) for NE; and 0.51 (0.34, 0.65), 0.63 (0.49, 0.74), and 0.60 (0.45, 0.73) for chart predictions. Using regression analysis and controlling for TE, SAD was 0.34 cm larger in patients with cirrhosis than in patients without cirrhosis. CONCLUSIONS: Correcting for reflectivity did not substantially improve correlation of energy values with MW ablation zone size parameters and did not outperform manufacturer-provided chart predictions. Correlations were moderate and variable using all methods. The results suggest a disproportionate influence of tissue factors on MW ablation results.

Changing prognostic significance of tumor stage and nodal stage in patients with squamous cell carcinoma of the oropharynx in the human papillomavirus era.

BACKGROUND: Although human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) tends to present at an advanced nodal stage (N stage), the prognosis is generally better than that for HPV-negative OPSCC. Prior work has demonstrated the increasing incidence of HPV-related OPSCC in the United States. This study was designed to determine whether the changing epidemiology of OPSCC is reflected in changes in the prognostic significance of the tumor stage (T stage) and the N stage in a population-based cohort. METHODS: The Surveillance, Epidemiology, and End Results program was used to identify 13,328 patients who were 18 years old or older and were diagnosed with OPSCC from 1997 to 2008. The Kaplan-Meier method was used to estimate head and neck cancer-specific survival. Cox proportional hazards models were used to evaluate the associations between head and neck cancer-specific mortality (HNCSM) and T and N stages and the interaction of variables with the year of diagnosis. RESULTS: With a median follow-up of 67 months, there were 4099 head and neck cancer deaths. There was a significant interaction between the T stage and time (P for interaction = .01), with the effect of the T stage on HNCSM increasing from 1997 to 2008. The T stage retained a linear relationship with HNCSM. The effect of the N stage on HNCSM declined over time (P for interaction = .0004). The current American Joint Committee on Cancer (AJCC) staging system did not subdivide distinct prognostic subgroups for HNCSM by overall stage. CONCLUSIONS: In this population-based study of OPSCC, the effect of the N stage on cancer-specific mortality decreased over time as the impact of the T stage increased. The current AJCC staging system did not distinguish prognostic subgroups. These changes may reflect the increasing prevalence of HPV-related OPSCC. Further study in HPV-defined cohorts is needed to tailor the AJCC staging system to better reflect HNCSM risk. Cancer 2015;121:2594-2602. © 2015 American Cancer Society.

Minimally invasive esophagectomy: results of a prospective phase II multicenter trial-the eastern cooperative oncology group (E2202) study.

OBJECTIVE: The primary aim of this trial was to assess the feasibility of minimally invasive esophagectomy (MIE) in a multi-institutional setting. BACKGROUND: Esophagectomy is an important, potentially curative treatment for localized esophageal cancer, but is a complex operation. MIE may decrease the morbidity and mortality of resection, and single-institution studies have demonstrated successful outcomes with MIE. METHODS: We conducted a multicenter, phase II, prospective, cooperative group study (coordinated by the Eastern Cooperative Oncology Group) to evaluate the feasibility of MIE. Patients with biopsy-proven high-grade dysplasia or esophageal cancer were enrolled at 17 credentialed sites. Protocol surgery consisted of either 3-stage MIE or Ivor Lewis MIE. The primary end point was 30-day mortality. Secondary end points included adverse events, duration of hospital-stay, and 3-year outcomes. RESULTS: Protocol surgery was completed in 95 of the 104 patients eligible for the primary analysis (91.3%). The 30-day mortality in eligible patients who underwent MIE was 2.1%; perioperative mortality in all registered patients eligible for primary analysis was 2.9%. Median intensive care unit and hospital stay were 2 and 9 days, respectively. Grade 3 or higher adverse events included anastomotic leak (8.6%), acute respiratory distress syndrome (5.7%), pneumonitis (3.8%), and atrial fibrillation (2.9%). At a median follow-up of 35.8 months, the estimated 3-year overall survival was 58.4% (95% confidence interval: 47.7%-67.6%). Locoregional recurrence occurred in only 7 patients (6.7%). CONCLUSIONS: This prospective multicenter study demonstrated that MIE is feasible and safe with low perioperative morbidity and mortality and good oncological results. This approach can be adopted by other centers with appropriate expertise in open esophagectomy and minimally invasive surgery.

Patients' expectations about effects of chemotherapy for advanced cancer.

BACKGROUND: Chemotherapy for metastatic lung or colorectal cancer can prolong life by weeks or months and may provide palliation, but it is not curative. METHODS: We studied 1193 patients participating in the Cancer Care Outcomes Research and Surveillance (CanCORS) study (a national, prospective, observational cohort study) who were alive 4 months after diagnosis and received chemotherapy for newly diagnosed metastatic (stage IV) lung or colorectal cancer. We sought to characterize the prevalence of the expectation that chemotherapy might be curative and to identify the clinical, sociodemographic, and health-system factors associated with this expectation. Data were obtained from a patient survey by professional interviewers in addition to a comprehensive review of medical records. RESULTS: Overall, 69% of patients with lung cancer and 81% of those with colorectal cancer did not report understanding that chemotherapy was not at all likely to cure their cancer. In multivariable logistic regression, the risk of reporting inaccurate beliefs about chemotherapy was higher among patients with colorectal cancer, as compared with those with lung cancer (odds ratio, 1.75; 95% confidence interval [CI], 1.29 to 2.37); among nonwhite and Hispanic patients, as compared with non-Hispanic white patients (odds ratio for Hispanic patients, 2.82; 95% CI, 1.51 to 5.27; odds ratio for black patients, 2.93; 95% CI, 1.80 to 4.78); and among patients who rated their communication with their physician very favorably, as compared with less favorably (odds ratio for highest third vs. lowest third, 1.90; 95% CI, 1.33 to 2.72). Educational level, functional status, and the patient's role in decision making were not associated with such inaccurate beliefs about chemotherapy. CONCLUSIONS: Many patients receiving chemotherapy for incurable cancers may not understand that chemotherapy is unlikely to be curative, which could compromise their ability to make informed treatment decisions that are consonant with their preferences. Physicians may be able to improve patients' understanding, but this may come at the cost of patients' satisfaction with them. (Funded by the National Cancer Institute and others.).

Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation.

Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively (P < .001). Nearly half of the hospitalizations were due to generalized weakness (17 % of hospitalizations), seizures (16 %), or venous thromboembolism (13 %). On multivariate analysis, age (odds ratio [OR], 1.03; 95 % CI, 1.002-1.060; P = .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97; P < .001) were associated with risk of hospitalization. Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13; P = .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival.

Validation and Application of the Mass Balance Model To Determine the Effectiveness of Portable Air Purifiers in Removing Ultrafine and Submicrometer Particles in an Apartment.

We validated the use of the mass balance model to determine the effectiveness of portable air purifiers in removing ultrafine (<0.10 µm) and submicrometer particles (0.10-0.53 µm) in an apartment. We evaluated two identical portable air purifiers, equipped with high efficiency particulate air filters, for their performance under three different air flow settings and three target air exchange rates: 0.60, 0.90, and 1.20 h(-1). We subsequently used a mixed effects model to estimate the slope between the measured and modeled effectiveness by particle size. Our study showed that effectiveness was highly particle size-dependent. For example, at the lowest target air exchange rate, it ranged from 0.33 to 0.56, 0.51 to 0.75, and 0.60 to 0.81 for the three air purifier flow settings, respectively. Our findings suggested that filtration was the dominant removal mechanism for submicrometer particles, whereas deposition could play a more important role in ultrafine particle removal. We found reasonable agreement between measured and modeled effectiveness with size-resolved slopes ranging from 1.11 ± 0.06 to 1.25 ± 0.07 (mean ± SE), except for particles <35 nm. Our study design can be applied to investigate the performances of other portable air purifiers as well as the influences of various parameters on effectiveness in different residential settings.