Abigail Doucette

Extended Pleurectomy-Decortication–Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years

BACKGROUND The purpose of this study was to assess survival for patients with malignant pleural mesothelioma (MPM), epithelial subtype, utilizing extended pleurectomy-decortication combined with intraoperative photodynamic therapy (PDT) and adjuvant pemetrexed-based chemotherapy. METHODS From 2005 to 2013, 90 patients underwent lung-sparing surgery and PDT for MPM. All patients had a preoperative diagnosis of epithelial subtype, of which 17 proved to be of mixed histology. The remaining 73 patients with pure epithelial subtype were analyzed. All patients received lung-sparing surgery and PDT; 92% also received chemotherapy. The median follow-up was 5.3 years for living patients. RESULTS Macroscopic complete resection was achieved in all 73 patients. Thirty-day mortality was 3% and 90-day mortality was 4%. For all 73 patients (89% American Joint Commission on Cancer stage III/IV, 69% N2 disease, median tumor volume 550 mL), the median overall and disease-free survivals were 3 years and 1.2 years, respectively. For the 19 patients without lymph node metastases (74% stage III/IV, median tumor volume 325 mL), the median overall and disease-free survivals were 7.3 years and 2.3 years, respectively. CONCLUSIONS This is a mature dataset for MPM that demonstrates the ability to safely execute a complex treatment plan that included a surgical technique that consistently permitted achieving a macroscopic complete resection while preserving the lung. The role for lung-sparing surgery is unclear but this series demonstrates that it is an option, even for advanced cases. The overall survival of 7.3 years for the node negative subset of patients, still of advanced stage, is encouraging. Of particular interest is the overall survival being approximately triple the disease-free survival, perhaps PDT related. The impact of PDT is unclear, but it is hoped that it will be established by an ongoing randomized trial.

First Clinical Report of Proton Beam Therapy for Postoperative Radiotherapy for Non–Small-Cell Lung Cancer

Background and Purpose The characteristic Bragg peak of proton beam therapy (PBT) allows for sparing normal tissues beyond the tumor volume that may allow for decreased toxicities associated with postoperative radiation therapy (PORT). Here we report the first institutional experience with proton therapy for PORT in patients with non–small‐cell lung cancer (NSCLC) and assess early toxicities and outcomes. Materials and Methods We identified 61 consecutive patients treated from 2011 to 2014 who underwent PORT for locally advanced NSCLC for positive microscopic margins and/or positive N2 lymph nodes (stage III), with 27 patients receiving PBT and 34 receiving intensity‐modulated radiation therapy (IMRT). Results Median follow‐up time was 23.1 months for PBT (2.3‐42.0 months) and 27.9 months for IMRT (0.5‐87.4 months). The median radiation dose was 50.4 Gy for PBT (50.4‐66.6 Gy) and 54 Gy for IMRT (50.0‐72.0 Gy). Grade 3 radiation esophagitis was observed in 1 and 4 patients in the PBT and IMRT groups, respectively. Grade 3 radiation pneumonitis was observed in 1 patient in each cohort. Dosimetric analysis revealed a significant decrease in the V5 and mean lung dose (P = .001 and P = .045, respectively). One‐year median overall survival and local recurrence‐free survival were 85.2% and 82.4% (95% confidence interval, 72.8%‐99.7% and 70.5%‐96.2%, P = .648) and 92.3% and 93.3% (82.5%‐100%, 84.8%‐100%, P = .816) for PBT and IMRT cohorts, respectively. Conclusions Postoperative PBT in NSCLC is well‐tolerated and has similar excellent short‐term outcomes when compared with IMRT. Longer follow‐up is necessary to determine if PBT has a meaningful improvement over IMRT for PORT. Micro‐Abstract We investigated the survival outcomes and early toxicity profile of postoperative radiation therapy with proton beam therapy (PBT) versus intensity‐modulated radiation therapy (IMRT) for non–small‐cell lung cancer (NSCLC) in a cohort of 61 patients with positive microscopic margins and/or positive N2 lymph nodes. We found that postoperative PBT in locally advanced NSCLC is well‐tolerated and has similar excellent short‐term outcomes when compared with IMRT.

Effect of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

Micro‐Abstract The role of prophylactic cranial irradiation (PCI) in metastatic small‐cell lung cancer (SCLC) is controversial. Using the National Cancer Database we show that patients treated with PCI have improved survival outcomes. In light of conflicting randomized trials, this study adds information to help guide physician and patient decision‐making about the utility of PCI in metastatic SCLC. Introduction Patients with small‐cell lung cancer (SCLC) have a high incidence of occult brain metastases and are often treated with prophylactic cranial irradiation (PCI). Despite a small survival advantage in some studies, the role of PCI in extensive stage SCLC remains controversial. We used the National Cancer Database to assess survival of patients with metastatic SCLC treated with PCI. Patients and Methods Metastatic SCLC patients without brain metastases were identified. To minimize treatment selection bias, patients with an overall survival (OS) < 6 months were excluded. Cox regression identified variables associated with OS. Patients were propensity score‐matched on factors associated with receipt of PCI or OS. The effect of PCI on OS was examined using Kaplan–Meier estimates. Results In the overall cohort (n = 4257), treatment with PCI (n = 473) was associated with improved survival (hazard ratio, 0.66; 95% confidence interval, 0.60‐0.74; P < .0001). Comparisons of propensity score‐matched cohorts revealed a significant survival benefit for patients who received PCI in median OS (13.9 vs. 11.1 months; P < .0001), as well as 1‐ and 2‐year OS (61.2% vs. 44.0% and 19.8% vs. 11.5%, respectively; P < .0001). This survival benefit persisted even after excluding patients who survived < 9 months (median: 15.3 vs. 12.9 months; P < .0001). In multivariable analysis, predictors of receipt of PCI were Caucasian race, younger age, and lower Charlson–Deyo score. Conclusion Using a modern population‐based data set, we showed that metastatic SCLC patients treated with PCI have significantly improved OS. This large retrospective study helps address the conflicting prospective data.

Impact of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small Cell Lung Cancer: A Propensity Score Matched Analysis of Patients in the National Cancer Database

to receive surgery and more likely to succumb to their cancer compared to their Caucasian (C) counterparts. Recent advancements in surgery (such as minimally invasive techniques) and radiation therapy (such as stereotactic body therapy) have resulted in improved short and long-term outcomes in early stage NSCLC. Herein, we designed a population-based study that sought to understand how racial disparities in the treatment and outcome of stage I NSCLC have changed in the past decade. Materials/Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to retrieve a case list of biopsy-proven stage I NSCLC patients above the age of 60. Patients who were diagnosed between the years of 2004-2012 were selected, excluding any patients without definitive records for local therapy. Patients were divided into one of four racial cohorts: C, AA, American Indian (AI), Asian/Pacific Islander (API), or Unknown (U). Demographics, local therapy, and survival metrics were compared using the following statistical analyses: chi-squared test, Kaplan-Meier method, and Cox multivariate analysis. Survival at 23 months was used as a proxy for 2-year survival to include the 2011 data in the final analysis. Results: There were 62,312 patients who met criteria for analysis. AA and AI were less likely to receive surgery than the typical stage I NSCLC patient (55.9% and 57.6% compared to 66.7% overall, P<.05). Two-year OS for C was 70%, AAwas 65%, AI was 60%, API was 76%, and U was 89% (P<.05). Two-year CSS for C was 79%, AA was 76%, AI was 73%, API was 84%, and U was 91% (P<.05). The median CSS for AI and AA was less than that of the typical stage I NSCLC patient (49 months and 80 months, respectively, compared to 107 months, P<.05). This difference in CSS disappeared on multivariate analysis, largely accounted for by sex (using female as reference, male HR Z 1.17), age (unit RR Z 1.01), treatment (using observation as reference, surgery HR Z 0.44, radiation HR Z 0.70, both surgery and radiation HR Z 0.48), and T stage (using T1 as reference, T2 HR Z 1.25) (all P<.05). Conclusion: Despite advancements in surgery and radiation in the last decade, both AA and AI continue to have higher rates of overall and cancer-specific mortality from early stage NSCLC compared to Caucasians. The poor outcomes in stage I NSCLC in AAs and AIs may be due to the association of these populations with more adverse risk factors, such as older age of diagnosis, male sex, T2 stage, and tendency to forgo surgery and receive no treatment. Author Disclosure: S.M. Dalwadi: None. G. Lewis: None. E. Butler: None. B.S. Teh: None. A. Farach: None.

Effect of Eischens Yoga During Radiation Therapy on Prostate Cancer Patient Symptoms and Quality of Life: A Randomized Phase II Trial

PURPOSE A randomized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue, erectile dysfunction, urinary incontinence, and overall quality of life (QOL) in prostate cancer (PCa) patients undergoing external beam radiation therapy (RT). METHODS AND MATERIALS The participants were randomized to yoga and no-yoga cohorts (1:1). Twice-weekly yoga interventions were offered throughout the 6- to 9-week courses of RT. Comparisons of standardized assessments were performed between the 2 cohorts for the primary endpoint of fatigue and the secondary endpoints of erectile dysfunction, urinary incontinence, and QOL before, during, and after RT. RESULTS From October 2014 to January 2016, 68 eligible PCa patients underwent informed consent and agreed to participate in the study. Of the 68 patients, 18 withdrew early, mostly because of treatment schedule-related time constraints, resulting in 22 and 28 patients in the yoga and no-yoga groups, respectively. Throughout treatment, those in the yoga arm reported less fatigue than those in the control arm, with global fatigue, effect of fatigue, and severity of fatigue subscales showing statistically significant interactions (P<.0001). The sexual health scores (International Index of Erectile Function Questionnaire) also displayed a statistically significant interaction (P=.0333). The International Prostate Symptom Score revealed a statistically significant effect of time (P<.0001) but no significant effect of treatment (P=.1022). The QOL measures had mixed results, with yoga having a significant time by treatment effect on the emotional, physical, and social scores but not on functional scores. CONCLUSIONS A structured yoga intervention of twice-weekly classes during a course of RT was associated with a significant reduction in pre-existing and RT-related fatigue and urinary and sexual dysfunction in PCa patients.

Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non–small-cell Lung Cancer: Analysis by Operability, Fractionation Regimen, Tumor Size, and Tumor Location

Background: Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non–small‐cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long‐term outcomes data exist, particularly according to operability. We hypothesized long‐term local control (LC) and cancer‐specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients. Patients and Methods: All consecutive patients with stage I (cT1‐2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression. Results: A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow‐up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%‐99%) and 93.7% (95% confidence interval, 90%‐98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5‐year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes. Conclusions: SBRT has excellent, durable LC and CSS rates for early‐stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities.

Factors associated with fatigue in prostate cancer (PC) patients undergoing external beam radiation therapy (EBRT)

PURPOSE Fatigue is a common adverse effect among cancer patients undergoing external beam radiation therapy (EBRT), yet the underlying disease- and treatment-related factors influencing its development are poorly understood. We hypothesized that clinical, demographic, and treatment-related factors differentially affect fatigue and aimed to better characterize variables related to fatigue development in prostate cancer (PC) patients during EBRT. METHODS AND MATERIALS We identified a cohort of 681 patients with nonmetastatic PC undergoing a 6- to 9-week EBRT course. Patient fatigue scores (range, 0-3) were prospectively recorded by providers during treatment visits using standardized criteria. Clinical and demographic factors including age, race, EBRT details, disease staging, smoking status, comorbidities, urinary symptoms, employment status, weight, and concurrent medication use were assessed for their relationship to fatigue levels. Significant differences in fatigue severity by each variable at the beginning and end of EBRT were assessed by nonparametric means testing, and differences in the level of fatigue increase over the treatment course were assessed using an ordered logistic regression model. RESULTS Significant increases in reported fatigue severity were seen in patients with age <60 years (P = .006), depressive symptoms (P < .001), and use of androgen deprivation therapy before radiation start (P = .04). In addition, the prescription of antiemetics before radiation start was associated with reduced fatigue severity (P = .03). CONCLUSIONS We identify factors associated with increased (young age, depressive symptoms, androgen deprivation therapy) and decreased (antiemetic prescription) fatigue in a large cohort of PC patients receiving EBRT. Continued investigation is needed to further elucidate clinical drivers and biological underpinnings of increased fatigue to guide potential interventions.