Risk of Stroke After Colorectal Surgery for Cancerous Versus Benign Conditions.

BACKGROUND: Cancer treatment, specifically surgical intervention, as a possible stroke trigger is understudied. METHODS: Using the Nationwide Readmissions Database and validated diagnosis and procedure codes, we identified adults with index admissions for colorectal surgery for colorectal adenocarcinoma (Group A) and compared them to admissions for colorectal surgery for benign conditions (Group B) and hepatobiliary or pancreatic surgery for benign conditions (Group C). Within the colorectal cancer cohort, we further identified patients who underwent open versus laparoscopic surgery. The primary outcome was readmission for ischemic or hemorrhagic stroke up to 1 year. Cumulative risk of ischemic stroke was calculated using risk survival statistics, and hazard ratios (HR) were calculated using adjusted Cox regression. RESULTS: Patients in Group A had higher 3-month readmission rates for ischemic and hemorrhagic strokes than those in Groups B and C. Higher risk of ischemic stroke (HR 1.46, 95% confidence interval [CI] 1.20-1.79) in Group A compared to Group B was eliminated following adjustments for illness severity and vascular risk factors. Comparing types of colorectal surgical intervention for cancer, there was significantly greater risk of ischemic stroke with open versus laparoscopic surgery, despite adjusting for vascular risk factors (HR 1.70, 95% CI 1.15-2.52). CONCLUSIONS: We found elevated risk of ischemic stroke up to 1 year following open surgery for colorectal adenocarcinoma compared to laparoscopic. More research is necessary to clarify the underlying surgery-related mechanisms that contribute to elevated risk.

Sense-making under ignorance.

Much of cognition allows us to make sense of things by explaining observable evidence in terms of unobservable explanations, such as category memberships and hidden causes. Yet we must often make such explanatory inferences with incomplete evidence, where we are ignorant about some relevant facts or diagnostic features. In seven experiments, we studied how people make explanatory inferences under these uncertain conditions, testing the possibility that people attempt to infer the presence or absence of diagnostic evidence on the basis of other cues such as evidence base rates (even when these cues are normatively irrelevant) and then proceed to make explanatory inferences on the basis of the inferred evidence. Participants followed this strategy in both diagnostic causal reasoning (Experiments 1-4, 7) and in categorization (Experiments 5-6), leading to illusory inferences. Two processing predictions of this account were also confirmed, concerning participants' evidence-seeking behavior (Experiment 4) and their beliefs about the likely presence or absence of the evidence (Experiment 5). These findings reveal deep commonalities between superficially distinct forms of diagnostic reasoning-causal reasoning and classification-and point toward common inferential machinery across explanatory tasks.

Hormonal Therapy and Radiation Therapy in Prostate Cancer: 5-Year Outcomes From a Trial Evaluating Combined Androgen Blockade With 5-Alpha Reductase Inhibitors as an Alternative to Gonadotropin Releasing Hormone Agonists.

BACKGROUND: We previously reported that for men undergoing combined androgen deprivation therapy (ADT) and radiation therapy (RT) for prostate cancer, substitution of LHRH-agonists with 5-α- reductase inhibitors (5-ARIs) led to improved preservation of 6-month hormonal quality of life (hQOL). With longer term follow-up, we evaluated disease control. METHODS: In this non-randomized trial, men with unfavorable intermediate or high-risk prostate cancer, aged ≥70 years or with Charlson Comorbidity Index ≥2, were treated with RT (78-79.2 Gy in 39-44 fractions) and either oral ADT (oADT; 5-ARI with antiandrogen) or standard of care ADT (SOC; leuprolide with antiandrogen) for up to 28 months. The primary endpoint was EPIC hQOL; secondary endpoints included biochemical control and survival as well as changes in cholesterol and hemoglobin levels. RESULTS: Between 2011 and 2018, 70 men were enrolled (40 in oADT; 30 in SOC). Median follow-up was 65 months [IQR 36-94]. Five-year freedom from biochemical failure for oADT and SOC was 89% versus 86%, disease free survival was 62% versus 69%, cancer-specific survival was 100% versus 96%, and overall survival was 70% versus 81% (all P>.1). Testosterone (2 mo through 3 yr) and hemoglobin levels (2 mo through 2 yr) were higher, and cholesterol levels (1 yr) were lower in the oADT groups (all P < .05). CONCLUSIONS: In this non-randomized study, men treated with combined RT and oADT had better preservation of hQOL and comparable 5-year disease outcomes to men treated with SOC. Eugonadal testosterone with this approach may yield measurable benefits in cholesterol and hemoglobin levels.

Point/Counterpoint #2: Current Clinical Considerations With Nonoperative Management of Rectal Cancer.

ABSTRACT: Locally advanced rectal cancer has historically been treated with multimodal therapy consisting of radiation therapy, chemotherapy, and total mesorectal excision. However, recent prospective trials and registry studies have demonstrated similar disease outcomes with nonoperative management for patients who experience an excellent clinical response to radiation and chemotherapy. This article reviews data regarding nonoperative management for rectal cancer, and highlights current challenges and limitations in a point-counterpoint format, in the context of two clinical cases.

Synergizing radiotherapy and immunotherapy: Current challenges and strategies for optimization.

Numerous clinical studies are investigating the integration of radiotherapy and immune checkpoint inhibitors (ICI) in the management of advanced or metastatic solid cancers based on preclinical evidence demonstrating a synergistic interaction between these treatments. However, it remains unclear how to optimally integrate these therapeutic modalities in the treatment of cancer patients. Beyond disease-specific factors there exists numerous unanswered questions regarding optimal sequencing of radiation and ICI, as well as, radiation dosing and target selection. Here, we examine the available clinical evidence for combination radiation and ICI approaches and propose strategies to expand investigations of the potential synergy in cancer patients.

Radiation Oncology Resident Evaluations: Current Methods and Resident Perceptions.

Purpose: This study analyzes assessments within radiation oncology (RO) to determine characteristics of existing assessment methods and then report resident perceptions of these methods. We hypothesize familiarity with evaluation methods is predictive of the perceived utility of evaluations and behavioral changes. Methods and materials: This study was conducted in 2 phases. Phase 1 involved requesting resident evaluation forms from RO residency programs to assess the Accreditation Council for Graduate Medical Education 6 Core Competencies. Analysis of variance was used to determine any significant differences between institutions or categories of questions. In phase 2, RO residents were surveyed about familiarity with the Accreditation Council for Graduate Medical Education Milestones and their perceptions about the current methods. Responses to questions were further analyzed using linear regression models. Results: In phase 1, forms were obtained from 13 institutions, and they were based on the 6 Core Competencies with an average of 19 questions (standard deviation, 11; range, 5-47) in total. Analysis of variance did not show significant variation in the number of questions between the categories (F = 0.78, P = .6). A significant difference in the mean number of questions used for assessing each of the competencies was found between institutions (F = 6.6, P < .01). In phase 2, a majority of surveyed residents reported being "not" or only "slightly familiar" with the competencies (59.6%) and the factors used to assess them (73.1%). Resident-reported familiarity with the evaluation methods was not found to be a significant predictor of likelihood of changing postevaluation (coefficient = 0.41, P = .204), intimidation from receiving evaluations (coefficient = -0.06, P = .792), stress of receiving evaluations (coefficient = -0.11, P = .62), or usefulness of evaluations (coefficient = -0.02, P = .83). Conclusions: Familiarity with evaluation methods is not correlated with perceptions or behavioral changes necessitating further investigation of alternative predictor variables. Despite the low familiarity with evaluation tools, most residents reported that evaluations were useful and likely to elicit changes in their behaviors and practice, highlighting the value of current evaluation methods.

Long-term outcomes in patients with recurrent human papillomavirus-positive oropharyngeal cancer after upfront transoral robotic surgery.

BACKGROUND: Clinical course following failure of human papillomavirus (HPV)-positive oropharyngeal cancers (HPV + OPC) is poorly understood. This study aims to characterize disease course following failure after transoral robotic surgery (TORS). METHODS: We identified patients with HPV + OPC-treated upfront with TORS at our institution from 2007 to 2017. HPV status was confirmed with immunohistochemistry or HPV DNA polymerase chain reaction. Patient characteristics, treatment modalities, and post-recurrence outcomes were analyzed for the recurrent cohort. RESULTS: Of the 317 HPV + OPC patients, 28 (8.8%) experienced recurrence, all of HPV 16/18 subtypes. Median post-recurrence survival was 19.8 months (range 2.3-195.8 months) in the 12 locoregional and 16 months (range 2.4-79.5 months) in the 14 distant failures. Sixteen are alive with a median of 39.8 months (range 5.5-209.4 months) after retreatment. CONCLUSION: This is one of the largest series evaluating survival following TORS failure in HPV + OPC. Despite failure, long-term survival and durable remission are possible with single-modal or multiple-modal salvage treatment.

Emotional Quality of Life After Radiation Therapy for Oropharyngeal Carcinoma.

PURPOSE: Substantial research exists on the physical toxicities from radiation therapy (RT) for oropharyngeal cancers, but emotional quality of life is understudied. The purpose of this study is to map the effects and time course of radiation-related changes in mood and anxiety and to investigate the physical factors that drive these changes. METHODS AND MATERIALS: We prospectively collected University of Washington Quality of Life questionnaires and identified patients with oropharyngeal cancer who were treated with curative-intent RT between 2013 and 2016 and had completed questionnaires within 12 months after RT (n = 69). We analyzed swallow, saliva, taste, chewing, speech, pain, mood, and anxiety scores, using a scale from 0 to 100. We conducted a multivariate regression analysis to identify physical functioning predictors of worse emotional scores. RESULTS: Physical functioning scores declined from before RT to 3 months after RT and then began improving but did not rebound to baseline levels within 12 months. Patient mood slightly declined, but anxiety improved immediately after RT, with both generally improving such that scores were higher at the 12-month follow-up than at initial consult. Analysis showed that longer duration of treatment is associated with a higher likelihood of worse mood scores at 12 months (odds ratio [OR], 1.446; P < .01). Worse swallow score is associated with a greater likelihood of worse mood score at 3 months (OR, 0.971; P < .01) and 12 months (OR, 0.975; P < .01). A worse taste score is associated with a greater likelihood of worse anxiety score at 3 months (OR, 0.979; P < .05) and 12 months (OR, 0.982; P < .05). CONCLUSIONS: Emotional changes are associated with certain treatment-associated toxicities. A patient's emotional health is complex and likely multifactorial in nature. Our study identified key associations and time points to potentially intervene upon.