Association Between EGFR and ALK Mutation Status on Patient-Reported Symptoms After Palliative Radiation for Bone Pain in NSCLC.

Introduction: After palliative radiotherapy for bone metastases from NSCLC, up to 30% of patients may derive no symptomatic benefit, and there are a lack of biological predictors for this. The purpose was to investigate whether EGFR and ALK genetic rearrangements were associated with greater rates of pain response to palliative radiotherapy. Methods: Patients were identified from a prospectively collected patient-reported outcomes database for all patients with lung cancer treated with conventional palliative radiotherapy for bone metastases from 2013 to 2016 in the province of British Columbia. Patients were divided on the basis of mutational status into the following: EGFR and ALK wild type (WT), EGFR mutation present (EGFR+), or ALK mutation present (ALK+). Patient-reported outcomes of global pain severity were collected before and after radiotherapy and on an ordinal scale of 0 to 4, with 0 representing no bone pain and 4 representing the maximal possible bone pain. The primary outcome was the rate of partial pain response (any improvement in score), and the secondary outcome was the rate of complete pain response (final pain score of 0). Stepwise, multivariable logistic analysis was used to compare response rates between treatment courses for different mutational statuses. Results: The final cohort consisted of 388 treatment courses for 329 unique patients. For the WT, EGFR+, and ALK+ groups, there were 180, 63, and nine treatment courses, respectively. There were 92 patients with no ALK and EGFR testing. The most common treatment fractionations were 8 Gy in one fraction (188 of 388) and 20 Gy in five fractions (160 of 388), and use of multifraction radiotherapy did not differ between mutation status groups (p = 0.3). Partial pain response rates were as follows: WT 63%, EGFR+ 75%, and ALK+ 78%. On multivariable analysis, rates of partial response were higher for EGFR+ (OR = 5.4, p < 0.001) and for ALK+ (OR = 12.8, p = 0.008) in comparison to WT. Complete response rates were as follows: WT 20.5%, EGFR+ 35%, and ALK+ 67%. On multivariable analysis, complete response was not significantly increased in EGFR+ compared with WT (OR = 1.6, p = 0.127). ALK+ mutation status was associated with a higher rate of complete response compared with WT (OR = 5.2, p = 0.031). Conclusions: There was an association between EGFR+ and ALK+ tumors and increased rates of partial pain response to palliative radiotherapy.

Association Between Regional Nodal Irradiation and Breast Cancer Recurrence-Free Interval for Patients With Low-Risk, Node-Positive Breast Cancer.

PURPOSE: Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population. METHODS AND MATERIALS: Patients aged 40 to 79 years with pT1-2 pN1 (node-positive) breast cancer diagnosed between 2005 and 2014 were identified. The inclusion criteria were modeled off of the TAILOR RT study, which is a randomized noninferiority clinical trial designed to assess the value of RNI in patients with low-risk N1 disease. Eligible patients had breast-conserving surgery or mastectomy and axillary lymph node dissection with 1 to 3 positive nodes, breast-conserving surgery and sentinel lymph node biopsy with 1 to 2 positive nodes, or mastectomy and sentinel lymph node biopsy with 1 positive node. Additionally, patients had luminal A breast cancers, as approximated by estrogen receptor positive (Allred 6-8/8), progesterone receptor (PR) positive (Allred 6-8/8), human epidermal growth factor receptor 2-negative, and grade 1 to 2 immunohistochemical testing. All patients were prescribed hormonal treatment. The primary endpoint of BCRFI, the time to any breast cancer recurrence or breast cancer-related death, was analyzed using a multivariate competing risks analysis. RESULTS: The cohort included 1169 women with a median follow-up of 9.2 years. Radiation treatments were not performed in 151 women treated with mastectomy alone, were delivered to the breast only in 133 women, and were delivered locoregionally in 885 women. Patients undergoing RNI were younger (median age: 58 vs 62 years), more likely to have 2 to 3 macroscopic lymph nodes involved, and more often received chemotherapy (all P < .05). The 10-year estimate of BCRFI was 90% without RNI versus 90% with RNI (P = .5). On multivariable analysis, RNI was not a significant predictor of BCRFI (hazard ratio: 1.0; P = .9). CONCLUSIONS: In this retrospective analysis, RNI was not associated with improved BCRFI for women with biologically low-risk N1 breast cancer. We advocate accrual to the ongoing TAILOR RT study.

Lung cancer epidermal growth factor receptor mutations and radiotherapy response: A multicentre clinical study.

PURPOSE: To examine the impact of epidermal growth factor receptor (EGFR) mutations on objective response to palliative lung radiotherapy in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multicentre retrospective study was conducted of patients with metastatic NSCLC diagnosed between March 2010 and June 2012 who received palliative radiotherapy to the chest. Patients included for study had baseline imaging and follow-up imaging 1-3 months after radiotherapy. The primary endpoint was 1-3 month local objective imaging response by the Response Evaluation Criteria in Solid Tumours (RECIST). Patients were divided into EGFR mutation positive (EGFR+) and EGFR wild type (WT) cohorts for analysis. RESULTS: There were 121 patients for study inclusion: 89 (74%) were EGFR WT and 32 (26%) were EGFR+. The response rate between EGFR WT and EGFR+ cohorts was not significantly different (49 vs. 63%, p = 0.21). On multivariate analysis, initiation of a tyrosine kinase inhibitor (TKI) after radiotherapy was associated with a higher rate of response (OR: 5.07, 95%CI: 1.08-23.69, p = 0.039) but EGFR mutation status was not. For the EGFR+ cohort, patients with disease progression after initial management on a TKI had a worse response rate compared to patients who were TKI-naïve before starting radiotherapy (30 vs. 77%, p = 0.018). Local control was not statistically different between the EGFR cohorts. CONCLUSION: The EGFR mutation status alone was not an independent predictor of objective radiographic response to palliative thoracic radiotherapy. Acquired resistance to TKI therapy may be associated with disease cross-resistance to palliative radiotherapy.

External Beam Radiation Therapy in pT4 Well-Differentiated Thyroid Cancer: A Population-Based Study of 405 Patients.

PURPOSE: The benefit of external beam radiation therapy (EBRT) in locally advanced, well- differentiated thyroid cancer (WDTC) is uncertain. The purpose of this study is to evaluate locoregional recurrence (LRR), progression-free survival, and cause-specific survival (CSS) of patients with pT4 well-differentiated thyroid carcinoma. METHODS AND MATERIALS: A population-based retrospective review was conducted of consecutive patients with pT4 WDTC (per the American Joint Committee on Cancer, 8th edition, criteria) treated provincially between 1985 and 2013. The primary endpoints were cumulative incidence of LRR and CSS. To account for the competing risks of death from other causes, a Fine-Gray's test was used. A Cox-proportional hazards model was used to analyze overall survival (OS). Multivariate models and propensity matching were used to account for the effects of covariates. RESULTS: A total of 405 patients were identified with a median follow-up time of 14.3 years for a total of 4209 person-years of follow up. The median age at the time of diagnosis was 53 years (range, 20-87). There were 211 patients (52%) who received EBRT. EBRT was associated with age ≥55 years (56% vs 35%; P < .001), airway involvement (42% vs 8%; P < .001), and R1/2 resection (81% vs 51%; P < .001). The 10-year outcomes for the non-EBRT and EBRT groups were 21.6% versus 11.4%, respectively, for LRR, 84.1% versus 93.1%, respectively, for CSS, and 85.7% versus 67.5%, respectively, for OS. On multivariate analysis, EBRT was associated with a lower rate of LRR (hazard ratio [HR]: 0.334; P < .001), but not associated with CSS (HR: 1.56; P = .142) nor OS (HR: 1.216; P = .335). After propensity score matching, the EBRT cohort had lower rates of LRR relative to the non-EBRT cohort (HR: 0.261; P = .0003), but there were no differences in CSS or OS. CONCLUSIONS: In this large, population-based analysis of patients with pT4 WDTC, EBRT was associated with lower rates of LRR, but no difference in CSS or OS.

Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Cancer incidence has continuously increased over the past few centuries and represents a major health burden worldwide. Purpose: To evaluate the possible causal relationship between intake of red and processed meat and cancer mortality and incidence. Data Sources: Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019 without language restrictions. Study Selection: Cohort studies that included more than 1000 adults and reported the association between consumption of unprocessed red and processed meat and cancer mortality and incidence. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias; 1 reviewer evaluated the certainty of evidence, which was confirmed or revised by the senior reviewer. Data Synthesis: Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose-response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer. Limitation: Limited causal inferences due to residual confounding in observational studies, risk of bias due to limitations in diet assessment and adjustment for confounders, recall bias in dietary assessment, and insufficient data for planned subgroup analyses. Conclusion: The possible absolute effects of red and processed meat consumption on cancer mortality and incidence are very small, and the certainty of evidence is low to very low. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Patterns of Red and Processed Meat Consumption and Risk for Cardiometabolic and Cancer Outcomes: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Studying dietary patterns may provide insights into the potential effects of red and processed meat on health outcomes. Purpose: To evaluate the effect of dietary patterns, including different amounts of red or processed meat, on all-cause mortality, cardiometabolic outcomes, and cancer incidence and mortality. Data Sources: Systematic search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and ProQuest Dissertations & Theses Global from inception to April 2019 with no restrictions on year or language. Study Selection: Teams of 2 reviewers independently screened search results and included prospective cohort studies with 1000 or more participants that reported on the association between dietary patterns and health outcomes. Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Data Synthesis: Eligible studies that followed patients for 2 to 34 years revealed low- to very-low-certainty evidence that dietary patterns lower in red and processed meat intake result in very small or possibly small decreases in all-cause mortality, cancer mortality and incidence, cardiovascular mortality, nonfatal coronary heart disease, fatal and nonfatal myocardial infarction, and type 2 diabetes. For all-cause, cancer, and cardiovascular mortality and incidence of some types of cancer, the total sample included more than 400 000 patients; for other outcomes, total samples included 4000 to more than 300 000 patients. Limitation: Observational studies are prone to residual confounding, and these studies provide low- or very-low-certainty evidence according to the GRADE criteria. Conclusion: Low- or very-low-certainty evidence suggests that dietary patterns with less red and processed meat intake may result in very small reductions in adverse cardiometabolic and cancer outcomes. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies.

OBJECTIVE:  To determine the frequency of survival, stroke, atrial fibrillation, structural valve deterioration, and length of hospital stay after surgical replacement of an aortic valve (SAVR) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis. DESIGN:  Systematic review and meta-analysis of observational studies. DATA SOURCES:  Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to June 2016. STUDY SELECTION:  Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years. METHODS:  Reviewers, independently and in duplicate, evaluated study eligibility, extracted data, and assessed risk of bias for patient important outcomes. We used the GRADE system to quantify absolute effects and quality of evidence. Published survival curves provided data for survival and freedom from structural valve deterioration, and random effect models provided the framework for estimates of pooled incidence rates of stroke, atrial fibrillation, and length of hospital stay. RESULTS:  In patients undergoing SAVR with a bioprosthetic valve, median survival was 16 years in those aged 65 or less, 12 years in those aged 65 to 75, seven years in those aged 75 to 85, and six years in those aged more than 85. The incidence rate of stroke was 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54) and atrial fibrillation 2.90 per 100 patient years (1.78 to 4.79). Post-SAVR, freedom from structural valve deterioration was 94.0% at 10 years, 81.7% at 15 years, and 52% at 20 years, and mean length of hospital stay was 12 days (95% confidence interval 9 to 15). CONCLUSION:  Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis, and a low incidence of stroke and, up to 10 years, of structural valve deterioration. The rate of deterioration increases rapidly after 10 years, and particularly after 15 years.