Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer.

PURPOSE OF REVIEW: To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). RECENT FINDINGS: Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5-15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy. The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer.

BACKGROUND: The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. METHODS: The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. RESULTS: A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. CONCLUSIONS: In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society.

Impact of rheumatoid arthritis on radiation-related toxicity and cosmesis in breast cancer patients: a contemporary matched-pair analysis.

PURPOSE: To evaluate the impact of rheumatoid arthritis (RA) on toxicity and cosmesis in women undergoing radiotherapy for breast cancer. METHODS: We queried an institutional database for women with RA treated with external beam radiotherapy for breast cancer between 1981 and 2016. Matching each patient to three controls without RA was attempted. Radiation toxicity was graded using CTCAE 4.0. Cosmesis was graded using the Global Harris Scoring System of Excellent, Good, Fair, or Poor. Grade 2+ (G2+) acute and late toxicities were compared between women with RA and their matched pairs using a generalized estimating equation (GEE). Wilcoxon test and mixed effects model were used to compare the cosmesis between two groups. RESULTS: Forty women with RA at time of radiation were matched to 117 controls. The median radiation dose was 60 Gy (50-66 Gy) and the median follow-up was 94 months (1-354 months). When comparing the women with RA to their matched pairs, there was no significant difference in the rates of G2+ acute toxicity (25.0 vs. 13.7%, O 2.1, CI 0.91-4.9) or G2+ late toxicity (7.5 vs. 4.3%, OR 1.8, CI 0.48-6.8). Mean cosmesis was between Good and Excellent for both groups of patients, although women with RA were less likely to get Excellent cosmesis compared to their matched pairs (OR 0.35, CI 0.15-0.84). CONCLUSIONS: Among women with RA, radiation for breast cancer was well tolerated without significantly increased toxicity. Their cosmesis was generally Good to Excellent, although they might be less likely to get Excellent cosmesis compared to their matched pairs.

Disparities in the Local Management of Breast Cancer in the US according to Health Insurance Status.

Although standard practice guidelines for breast cancer are clear, the interplay between insurance and practice patterns for the US is poorly defined. This study was performed to test for associations between patient insurance status and presentation of breast cancer as well as local therapy patterns in the US, via a large national dataset. We queried the NCI Surveillance, Epidemiology, and End Results data base for breast cancer cases diagnosed from 2007 to 2011 in women aged 18-64 with nonmetastatic ductal/lobular cancers, treated surgically. We tested for associations between insurance status (insured/Medicaid/uninsured) and choice of surgical procedure (mastectomy/breast conserving surgery [BCS]), omission of radiotherapy (RT) following BCS, and administration of post-mastectomy radiation (PMRT). There were 129,565 patients with localized breast cancer analyzed. The health insurance classification included insured (84.5%), Medicaid (11.5%), uninsured (2.1%) and unknown (1.9%). Medicaid or uninsured status was associated with large, node positive tumors, black race, and low income. The BCS rate varied by insurance status: insured (52.2%), uninsured (47.7%), and Medicaid (45.2%), p < 0.001. In multivariable analysis, Medicaid insurance remained significantly associated with receipt of mastectomy (OR [95% CI] = 1.07 [1.03-1.11]), while RT was more frequently omitted after BCS in both Medicaid (OR [95% CI] = 1.14 [1.07-1.21]) and uninsured (OR [95% CI] = 1.29 [1.14-1.47]) patients. Insurance status was associated with significant variations in breast cancer care in the US. Although patient choice cannot be determined from this dataset, departure from standard of care is associated with specific types of insurance coverage. Further investigation into the reasons for these departures is strongly suggested.

The need for androgen deprivation therapy in patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiation therapy.

INTRODUCTION: To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era. MATERIALS AND METHODS: This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (>= 23 months), or those with follow up < 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates. RESULTS: Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS >= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates. CONCLUSION: Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT.

Patterns of multidisciplinary care in the management of non-metastatic invasive breast cancer in the United States Medicare patient.

PURPOSE: Multidisciplinary care (MDC) in managing breast cancer is resource-intensive and growing in prevalence anecdotally, although care patterns are poorly characterized. We sought to determine MDC patterns and effects on care in the United States Medicare patient. METHODS: Patients diagnosed with non-metastatic invasive breast cancer from 1992-2009 were reviewed using the Survival, Epidemiology, and End Results (SEER)-Medicare linked dataset. MDC was defined as a post-diagnosis, preoperative visit with a surgical, medical, and radiation oncologist. Same-day MDC (MDCSD) was the MDC subset having all three visits on one date. RESULTS: Among 88,865 patients, MDC was utilized in 2.9 %, with 14.1 % of these having MDCSD. MDC use did not vary by stage, but MDC patients were more likely to be younger, black, receive lumpectomy, have fewer nodes examined, and receive radiotherapy. MDCSD patients were more likely than non-MDC patients to be black, receive mastectomy, and receive radiotherapy. MDC and MDCSD use increased over time and varied by geographic region, with rural patients less likely to receive MDC (OR 0.54 [95 % CI 0.45-0.65]) and MDCSD (OR 0.32 [95 % CI 0.19-0.54]). Radiotherapy after breast conserving surgery, used in 86.2 % of non-MDC patients, was administered to 90.2 % of MDC (p < 0.001) and 92.6 % of MDC(SD) (p = 0.096) patients. Post-mastectomy radiotherapy was administered in 52.0 % of non-MDC patients, 63.8 % of MDC (p = 0.050), and 89.1 % of MDC(SD) (p = 0.011) patients after propensity score adjustment. CONCLUSION: While increasing, few Medicare patients undergo MDC and MDCSD is rare. MDC may improve quality and MDCSD should be considered for patient convenience. While not yet widespread, efforts should integrate MDC and MDCSD across the U.S.

The role of adjuvant radiation in lymph node positive endometrial adenocarcinoma.

OBJECTIVES: The purpose of this study was to examine the impact of adjuvant radiation on overall survival (OS) and cancer specific survival (CSS) in patients with lymph node (LN) positive endometrial cancer. METHODS: We analyzed all women diagnosed with FIGO stage IIIC endometrial adenocarcinoma in the Surveillance, Epidemiology, and End Results database from 2004 to 2012 (n=2177). Patients not undergoing surgery or with missing treatment information were excluded. Chi-squared tests were used to compare predictors of treatment received. Cox proportional hazards model and Kaplan-Meier method were used to assess OS and CSS. RESULTS: The median age was 60 (27-84) and the median follow-up was 31months (2-107). Adjuvant radiation was administered to 1248 (60.3%) patients. A total of 1363 (65.9%) patients had pelvic LN involvement while 658 (31.8%) had para-aortic involvement. The 3-year actuarial OS for patients with and without radiation was 80.5% and 67.6%, respectively (p<0.001). The 3-year actuarial CSS for patients with and without radiation was 83.4% and 73%, respectively (p<0.001). On multivariable analysis, receipt of radiotherapy remained associated with OS (HR 0.61 95% CI 0.51-0.74) and CSS (HR 0.65, 95% CI 0.53-0.80). After propensity matching, radiotherapy continued to be associated with an improved OS (HR 0.65 95% CI 0.54-0.78) and CSS (HR 0.65 95% CI 0.53-0.81). The addition of brachytherapy was not associated with OS or CSS. CONCLUSIONS: In this large population registry analysis, adjuvant radiation was associated with improved OS and CSS in patients with LN positive endometrial cancer. Prospective data is needed to confirm these findings.

ASTRO APEx® and RO-ILS™ are applicable to medical malpractice in radiation oncology.

AIM: To analyze malpractice trials in radiation oncology and assess how ASTRO APEx® and RO-ILS™ apply to such cases. METHODS: The Westlaw database was reviewed using PICOS/PRISMA methods. Fisher's exact and Mann-Whitney U tests were used to find factors associated with outcomes. RESULTS: Of 34 cases identified, external beam was used in 26 (77%). The most common factors behind malpractice were excessive toxicity (80%) and lack of informed consent (66%). ASTRO APEx pillars and ROI-LS had applicability to all but one case. Factors favoring the defendant included statute of limitations (odds ratio: 8.1; 95% CI: 1.3-50); those favoring the plaintiff included patient death (odds ratio: 0.7; 95% CI: 0.54-0.94). CONCLUSION: APEx and RO-ILS are applicable to malpractice trials in radiation oncology.

Total Mastectomy or Breast Conservation Therapy? How Radiation Oncologist Accessibility Determines Treatment Choice and Quality: A SEER Data-base Analysis.

Mastectomy and breast conservation therapy (BCT) are equivalent in survival for treatment of early stage breast cancer. This study evaluated the impact of radiation oncologist accessibility on choice of breast conserving surgery (BCS) versus mastectomy, and the appropriate receipt of radiotherapy after BCS. In the National Cancer Institute Survival, Epidemiology, and End Results data base, the authors selected breast cancer cases from 2004 to 2008 with the following criteria: T2N1M0 or less, lobular or ductal histology, and treatment with simple or partial mastectomy. We combined the Health Resources and Services Administration Area Resource File to define average radiation oncologist density (ROD) by county over the same time period. We evaluated tumor characteristics, demographic information, and ROD with respect to BCS rates and receipt of radiation therapy after BCS in univariable and multivariable analyses. In 118,773 cases analyzed, mastectomy was performed 33.2% of the time relative to BCS. After adjustment for demographic and tumor variables, the odds of having BCS versus mastectomy were directly associated with ROD (multiplicative change in odds for a single unit increase in ROD [95% CI] = 1.02 [1.01-1.03]; p < 0.001). Adjuvant radiation therapy was not administered in 28.2% of BCS cases. When adjusting for demographic and tumor variables, the odds of having BCS without adjuvant radiation were inversely associated with ROD (0.95 [0.94-0.97]; p < 0.001). We observed a direct relationship between ROD and BCS rates independent of demographic and tumor variables, and an inverse trend for omission of radiotherapy after BCS. Access to radiation oncologists may represent an important factor in surgical choice and receiving appropriate BCT in early stage breast cancer.

Vitamin D deficiency is widespread in cancer patients and correlates with advanced stage disease: a community oncology experience.

The purpose of this study was to correlate serum vitamin D levels with potential clinical variables and to determine the extent of vitamin D deficiency in a large, outpatient oncology practice. One hundred ninety-five consecutive patients referred for consultation at a community radiation oncology center from October 8, 2008 to March 17, 2010 had vitamin D levels ordered. Patients who were deficient in vitamin D were treated with replacement therapy. Demographic and medical data were collected prospectively and subsequently analyzed. Pretreatment baseline patient and tumor characteristics were evaluated with respect to vitamin D concentrations. One hundred and sixty patients were analyzed. A total of 74% of patients had 25-hydroxyvitamin D concentrations considered either deficient (<20 ng/mL) or suboptimal (20-30 ng/mL). Replacement therapy raised serum vitamin D levels by an average of 15 ng/mL (95% CI = 11-18, P < 0.01). Lower than median serum vitamin D levels were associated with stage III disease in univariate analysis [OR = 2.6 (95% CI = 1.1-6.2), p = 0.04] as well as multivariate analysis adjusted for age, sex, body mass index, and season of draw [OR = 3.3 (95% CI = 1.1-9.7), P = 0.03]. Three-quarters of patients in our series had suboptimal or deficient circulating concentrations of 25-hydroxyvitamin D. Low serum vitamin D levels, independent of age, sex, and body mass index, predicted advanced stage disease.

Impact of primary tumor-specific growth rate on treatment failure for nonoropharyngeal head and neck cancers.

OBJECTIVES: To investigate the prognostic impact of primary tumor-specific growth rate (TSGR) on treatment outcomes after definitive radiation therapy (RT) for nonoropharyngeal squamous cell carcinoma (non-OPSCC). METHODS: The diagnostic tumor and nodal volumes of 39 non-OPSCC patients were contoured and compared to corresponding RT planning scan volumes to determine TSGR. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were evaluated according to the Kaplan-Meier method; and hazard ratios (HR) were estimated using Cox regression. Based on the 75th percentile TSGR of 2.18%, we stratified patients into a high TSGR group (≥ 2.18% per day) and low TSGR group (< 2.18% per day). RESULTS: The median follow-up was 22 months (range: 1-86 months) and median time between diagnostic and simulation computed tomography scans was 22 days (range: 7-170 days). Median RT dose was 70 Gy (range: 60-79.2 Gy). Based on the 75th percentile TSGR, OS at median follow-up was 50.0% for the high TSGR group compared to 92.5% for the low TSGR group (HR [95% confidence interval (CI)] = 2.12[1.16-11.42], P = 0.018). There was a trend toward worse DFS at median follow-up for the high versus low TSGR groups, at 55.6% and 82.3%, respectively (HR [95% CI] = 2.29[0.82-6.38], P = 0.103). CONCLUSION: Our study contributes to growing literature on TSGR as a temporal biomarker in patients with non-OPSCC. Patients with high TSGR ≥2.18% per day have significantly worse OS compared to those with TSGR below this threshold. Efforts to address treatment initiation delays may benefit patients with particularly aggressive and rapidly growing tumors. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2378-2384, 2020.

Patterns of Multidisciplinary Care of Head and Neck Squamous Cell Carcinoma in Medicare Patients.

Importance: Multidisciplinary care (MDC) yields proven benefits for patients with cancer, although it may be underused in the complex management of head and neck squamous cell carcinoma (HNSCC). Objective: To characterize the patterns of MDC in the treatment of HNSCC among elderly patients in the US. Design, Setting, and Participants: This nationwide, population-based, retrospective cohort study used Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from January 1, 1991, to December 31, 2011, to identify patients 66 years or older diagnosed with head and neck cancer and determine the dates of diagnosis, oncology consultations, treatment initiation, and speech therapy evaluation in addition to MDC completion. Multidisciplinary care was defined in a stage-dependent manner: localized disease necessitated consultations with radiation and surgical oncologists, and advanced-stage disease also included a medical oncology consultation, all before definitive treatment. Data were analyzed between December 2016 and September 2020. Main Outcomes and Measures: Rates of MDC across all subsites of head and neck cancer as measured by the presence of an evaluation for each oncologist on the MDC team and its effect on treatment initiation. Results: This cohort study assessed 28 293 patients with HNSCC (mean [SD] age, 75.1 [6.6] years; 67% male; 87% White) from the SEER-Medicare linked database. The HNSCC subsites included larynx (40%), oral cavity (30%), oropharynx (21%), hypopharynx (7%), and nasopharynx (2%). Overall, the practice of MDC significantly increased over time, from 24% in 1991 to 52% in 2011 (P < .001). For patients with localized (stage 0-II) tumors, 60% received care in the multidisciplinary setting, whereas 28% of those with advanced-stage disease did. A total of 18 181 patients (64%) were treated with initial definitive nonsurgical therapy across all stages. Regardless of stage and subsite, few patients (2%) underwent evaluation by a speech-language pathologist before definitive therapy. Multidisciplinary care prolonged the time to initiation of definitive treatment by 11 days for localized disease and 10 days for advanced disease. Conclusions and Relevance: This cohort study found that most elderly patients with localized HNSCC received MDC, whereas few patients with advanced-stage disease received such care, although a significant proportion received adjuvant therapy. Multidisciplinary care may prolong time to initiation of definitive treatment with an uncertain impact. Consultation with a speech-language pathologist before definitive therapy was rare.

Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer.

OBJECTIVES: To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment. MATERIALS AND METHODS: We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation. RESULTS: We identified 112 patients with no evidence of disease and follow-up ≥ 10 years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7 years (range 0.6-10.6 years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP. CONCLUSION: Iatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation.

Comparison of Local Control of Brain Metastases With Stereotactic Radiosurgery vs Surgical Resection: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Brain metastases are a common source of morbidity for patients with cancer, and limited data exist to support the local therapeutic choice between surgical resection and stereotactic radiosurgery (SRS). Objective: To evaluate local control of brain metastases among patients treated with SRS vs surgical resection within the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial. Design, Setting, and Participants: This unplanned, exploratory analysis of the international, multi-institutional randomized clinical trial EORTC 22952-26001 (conducted from 1996-2007) was performed from February 9, 2017, through July 25, 2018. The EORTC 22952-26001 trial randomized patients with 1 to 3 brain metastases to whole-brain radiotherapy vs observation after complete surgical resection or before SRS. Patients in the present analysis were stratified but not randomized according to local modality (SRS or surgical resection) and treated per protocol with 1 to 2 brain metastases and tumors with a diameter of no greater than 4 cm. Interventions: Surgical resection or SRS. Main Outcomes and Measures: The primary end point was local recurrence of treated lesions. Cumulative incidence of local recurrence was calculated according to modality (surgical resection vs SRS) with competing risk regression to adjust for prognostic factors and competing risk of death. Results: A total of 268 patients were included in the analysis (66.4% men; median age, 60.7 years [range, 26.9-81.1 years]); 154 (57.5%) underwent SRS and 114 (42.5%) underwent surgical resection. Median follow-up time was 39.9 months (range, 26.0-1982.0 months). Compared with the SRS group, patients undergoing surgical resection had larger metastases (median 28 mm [range, 10-40 mm] vs 20 mm [range, 4-40 mm]; P < .001), more frequently had 1 brain metastasis (112 [98.2%] vs 114 [74.0%]; P < .001), and differed in location (parietal, 21 [18.4%] vs 61 [39.6%]; posterior fossa, 30 [26.3%] vs 12 [7.8%]; P < .001). In adjusted models, local recurrence was similar between the SRS and surgical resection groups (hazard ratio [HR], 1.15; 95% CI, 0.72-1.83). However, when stratified by interval, patients with surgical resection had a much higher risk of early (0-3 months) local recurrence compared with those undergoing SRS (HR, 5.94; 95% CI, 1.72-20.45), but their risk decreased with time (HR for 3-6 months, 1.37 [95% CI, 0.64-2.90]; HR for 6-9 months, 0.75 [95% CI, 0.28-2.00]). At 9 months or longer, the surgical resection group had a lower risk of local recurrence (HR, 0.36; 95% CI, 0.14-0.93). Conclusions and Relevance: In this exploratory analysis, local control of brain metastases was similar between SRS and surgical resection groups. Stereotactic radiosurgery was associated with improved early local control of treated lesions compared with surgical resection, although the relative benefit decreased with time. Trial Registration: ClinicalTrials.gov Identifier: NCT00002899.

Effects of interruptions of external beam radiation therapy on outcomes in patients with prostate cancer.

INTRODUCTION: To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa). METHODS: We included men with localized PCa treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) of escalated dose (≥74 Gy in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI-designated cancer centre. Men receiving androgen deprivation therapy were excluded. The non-treatment day ratio (NTDR) was defined as the number of non-treatment days divided by the total elapsed days of therapy. NTDR was analysed for each National Comprehensive Cancer Network (NCCN) risk group. RESULTS: There were 1728 men included (839 low-risk, 776 intermediate-risk and 113 high-risk), with a median follow up of 53.5 months (range 12-185.8). The median NTDR was 31% (range 23-71%), translating to approximately 2 breaks (each break represents a missed treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The 75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was used as the cutoff for analysis. There were no significant differences in freedom from biochemical failure, freedom from distant metastasis, cancer specific survival, or overall survival for men with NTDR ≥33% compared to NTDR<33% for each risk group. Multivariable analyses including NTDR, age, race, Gleason score, T stage, and PSA were performed using the proportional hazards regression procedure. NTDR≥33% was not significantly associated with increased hazard ratio for outcomes in each risk group compared to NTDR<33%. CONCLUSION: Unintentional treatment breaks during dose escalated external beam radiation therapy for PCa did not cause a significant difference in outcomes, although duration of follow up limits the strength of this conclusion.

Long-term toxicities in 10-year survivors of radiation treatment for head and neck cancer.

OBJECTIVES: To characterize the recognized but poorly understood long-term toxicities of radiation therapy (RT) for head and neck cancer (HNC). MATERIALS AND METHODS: We retrospectively evaluated patients treated with curative-intent RT for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥10years. Long-term toxicities of the upper aerodigestive tract were recorded and assigned to two broad categories: pharyngeal-laryngeal and oral cavity toxicity. Kaplan-Meier estimates and Chi-square tests were used for univariable analysis (UVA). Cox model and logistic regression were used for multivariable analysis (MVA). RESULTS: We identified 112 patients with follow-up ≥10years (median 12.2). The primary tumor sites were pharynx (42%), oral cavity (34%), larynx (13%), and other (11%). Forty-four percent received postoperative RT, 24% had post-RT neck dissection, and 47% received chemotherapy. Twenty-eight (25%) patients developed pharyngeal-laryngeal toxicity, including 23 (21%) requiring permanent G-tube placed at median of 5.6years (0-20.3) post-RT. Fifty-three (47%) developed oral cavity toxicity, including osteoradionecrosis in 25 (22%) at a median of 7.2years (0.5-15.3) post-RT. On MVA, pharyngeal-laryngeal toxicity was significantly associated with chemotherapy (HR 3.24, CI 1.10-9.49) and age (HR 1.04, CI 1.00-1.08); oral cavity toxicity was significantly associated with chemotherapy (OR 4.40, CI 1.51-12.9), oral cavity primary (OR 5.03, CI 1.57-16.1), and age (OR 0.96, CI 0.92-1.00). CONCLUSION: Among irradiated HNC patients, pharyngeal-laryngeal and oral cavity toxicity commonly occur years after radiation, especially in those treated with chemotherapy. Follow-up for more than five years is essential because these significant problems afflict patients who have been cured.

Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

PURPOSE: To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis. METHODS AND MATERIALS: In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs <2.0 and ≥2.5 vs <2.5). RESULTS: A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53). CONCLUSIONS: We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases.

Evaluation of prediction strategy and care coordination for COPD readmissions.

OBJECTIVES: Factors that influence the likelihood of readmission for chronic obstructive pulmonary disease (COPD) patients and the impact of posthospital care coordination remain uncertain. LACE index (L = length of stay, A = Acuity of admission; C = Charlson comorbidity index; E = No. of emergency department (ED) visits in last 6 months) is a validated tool for predicting 30-days readmissions for general medicine patients. We aimed to identify variables predictive of COPD readmissions including LACE index and determine the impact of a novel care management process on 30-day all-cause readmission rate. METHODS: In a case-control design, potential readmission predictors including LACE index were analyzed using multivariable logistic regression for 461 COPD patients between January-October 2013. Patients with a high LACE index at discharge began receiving care coordination in July 2013. We tested for association between readmission and receipt of care coordination between July-October 2013. Care coordination consists of a telephone call from the care manager who: 1) reviews discharge instructions and medication reconciliation; 2) emphasizes importance of medication adherence; 3) makes a follow-up appointment with primary care physician within 1-2 weeks and; 4) makes an emergency back-up plan. RESULTS: COPD readmission rate was 16.5%. An adjusted LACE index of ≥ 13 was not associated with readmission (p = 0.186). Significant predictors included female gender (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.29-0.91, p = 0.021); discharge to skilled nursing facility (OR 3.03, 95% CI 1.36-6.75, p = 0.007); 4-6 comorbid illnesses (OR 9.21, 95% CI 1.17-76.62, p = 0.035) and ≥ 4 ED visits in previous 6 months (OR 6.40, 95% CI 1.25-32.87, p = 0.026). Out of 119 patients discharged between July-October 2013, 41% received the care coordination. The readmission rate in the intervention group was 14.3% compared to 18.6% in controls (p = 0.62). CONCLUSIONS: Factors influencing COPD readmissions are complex and poorly understood. LACE index did not predict 30-days all-cause COPD readmissions. Posthospital care coordination for transition of care from hospital to the community showed a 4.3% reduction in the 30-days all-cause readmission rate which did not reach statistical significance (p = 0.62).

Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer.

PURPOSE: There are limited data regarding clinical and treatment factors associated with radiation pneumonitis (RP) in patients receiving taxane-based trimodality therapy for esophageal cancer. The purpose of this study was to identify predictors of RP in patients undergoing trimodality therapy. METHODS AND MATERIALS: We retrospectively reviewed patients undergoing chemoradiation followed by esophagectomy between 2006 and 2011. The association between clinical and dosimetric factors with RP was assessed using χ2 test and Mann-Whitney U test. Multivariable regression was used to assess the relationship between grade 2+ RP and clinical/dosimetric factors. Receiver operator curves were generated to identify threshold doses for RP. RESULTS: A total of 139 patients were included; 19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic tumors (P = .038) and receiving higher radiation doses (P = .038) were more likely to develop grade 2+ RP. There was no association between taxane-based therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy (V5; P < .001), 10 Gy (P < .001), 20 Gy (V20; P < .001), and 30 Gy (P < .001) was associated with an increased risk of grade 2+ RP. On multivariable regression, the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20 (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated with grade 2+ RP. A V5 ≤65% and V20 ≤25% were identified as optimal thresholds for increased grade 2+ RP. CONCLUSIONS: Dosimetric parameters are strong predictors of symptomatic RP in patients undergoing trimodality therapy for esophageal cancer. Mitigating the risk of RP in these patients should be an important consideration during treatment planning.