Second Malignancy Probabilities in Patients With Breast Cancer Treated With Conventional Versus Hypofractionated External Beam Radiation Therapy in the Adjuvant Setting.

AIMS: For women with breast cancer, seminal studies have shown that adjuvant hypofractionated external beam radiation therapy (hEBRT) maintains similar outcomes and may reduce overall costs compared with conventionally fractionated external beam radiation therapy (cEBRT). However, it is unclear whether hEBRT may be associated with differential risk of development of radiation-induced second malignancies compared with cEBRT. Because the occurrence of second malignancies is small, large databases may improve our understanding of the relative risk of second malignancies between hEBRT and cEBRT. MATERIALS AND METHODS: Using the National Cancer Database, we carried out a retrospective cohort analysis of women diagnosed with non-metastatic, stage 0-III breast cancer from 2004 to 2017. All patients had a lumpectomy or mastectomy and a follow-up time of at least 60 months after diagnosis. The probability of second malignancies in women receiving adjuvant cEBRT or hEBRT was compared using multivariable logistic regression adjusting for sociodemographic, geographical, clinical and treatment factors, allowing for relative (but not absolute) comparison of second malignancy risk. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up time were also conducted. RESULTS: Of the 125 228 women in our study, 115 576 (92.3%) received cEBRT and 9652 (7.71%) received hEBRT. The median age of the cohort was 60 (interquartile range 51-68) years at diagnosis and the median follow-up time was 99.61 (interquartile range 77.5-128.49) months. Upon adjusting for sociodemographic and clinical factors, patients who received hEBRT had no difference in relative risk than patients who received cEBRT (odds ratio 0.937, 95% confidence interval 0.869-1.010, P = 0.091). In analyses stratified by year of diagnosis, and stratified by length of follow-up, there was no difference in second malignancy probability between patients who completed hEBRT and patients who completed cEBRT. CONCLUSIONS: In this analysis of over 120 000 women with non-metastatic breast cancer, hEBRT was not associated with different odds of developing second malignancies compared with cEBRT. Our findings may inform patient counselling in the choice of radiation regimens for breast cancer and further support the safety of hypofractionated regimens for breast cancer.

Long-term Cardiovascular Risks of Gonadotropin-releasing Hormone Agonists and Antagonists: A Population-based Cohort Study.

AIMS: Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. MATERIALS AND METHODS: Patients with PCa receiving GnRH agonists or antagonists during 2013-2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. RESULTS: In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0-81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7-5.0 years), 1115 patients (45.0%) had MACEPRONOUNCE and 344 (13.9%) had MACECVM. GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACEPRONOUNCE: Log-rank P = 0.308; MACECVM: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACEPRONOUNCE: Log-rank P = 0.569; MACECVM: Log-rank P = 0.615). CONCLUSIONS: GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors.

Effect of dermatological consultation on survival in patients with checkpoint inhibitor-associated cutaneous toxicity.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) are a common side-effect of immune checkpoint inhibitors (ICIs). However, prior work examining these toxicities in detail has considered only the fraction of events evaluated by dermatologists. Associations between dermatology referral, cirAE treatment and survival outcomes remain underexplored across care settings. OBJECTIVES: To comprehensively categorize cirAE patterns among all patients treated with immunotherapy at our institution, and to evaluate: (i) the effect of dermatology referral on cirAE treatment and (ii) the impact of cirAE treatment on survival. METHODS: This was a retrospective cohort analysis of patients with cancer who initiated ICI therapy between 1 January 2016 and 8 March 2019 and developed one or more cirAEs, as screened for using International Classification of Diseases 10th revision codes and confirmed via manual chart review (n = 358). All relevant information documented prior to 31 March 2020 was included. RESULTS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred (odds ratio 6·08, P < 0·001). Patients who received any cirAE treatment had improved progression-free survival [hazard ratio (HR) 0·59, P = 0·001] and overall survival (HR 0·58, P = 0·007) compared with those who did not. CONCLUSIONS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred, and patients who received any treatment for a cirAE had improved survival outcomes.

International assessment on quality and content of internet information on osteoarthritis.

OBJECTIVE: Osteoarthritis is one of the leading causes of global disability. Numerous studies have assessed the quality and content of online health information; however, how information content varies between multiple countries remains unknown. The primary objective of this study was to examine how the quality and content of online health information on osteoarthritis compares on an international scale. METHODS: Internet searches for the equivalent of "knee osteoarthritis treatment" were performed in ten countries around the world. For each country, the first ten websites were evaluated using a custom scoring form examining: website type; quality and reliability using the DISCERN and Health-on-the-Net (HON) frameworks; and treatment content based on three international osteoarthritis treatment guidelines. Consistency of search results between countries speaking the same language was also assessed. RESULTS: Significant differences in all scoring metrics existed between countries speaking different languages. Western countries scored higher than more eastern countries, there were no differences between the United States and Mexico in any of the scoring metrics, and HON certified websites were of higher quality and reliability. Searches in different countries speaking the same language had at least 70% overlap. CONCLUSIONS: The quality of online health information on knee osteoarthritis varies significantly between countries speaking different languages. Differential access to quality, accurate, and safe health information online may represent a novel but important health inequality. Future efforts are needed to translate online health resources into additional languages. In the interim, patients may seek websites that display the HON seal.