Focal radiotherapy boost to MR-visible tumor for prostate cancer: a systematic review.

PURPOSE: The FLAME trial provides strong evidence that MR-guided external beam radiation therapy (EBRT) focal boost for localized prostate cancer increases biochemical disease-free survival (bDFS) without increasing toxicity. Yet, there are many barriers to implementation of focal boost. Our objectives are to systemically review clinical outcomes for MR-guided EBRT focal boost and to consider approaches to increase implementation of this technique. METHODS: We conducted literature searches in four databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. We included prospective phase II/III trials of patients with localized prostate cancer underdoing definitive EBRT with MR-guided focal boost. The outcomes of interest were bDFS and acute/late gastrointestinal and genitourinary toxicity. RESULTS: Seven studies were included. All studies had a median follow-up of greater than 4 years. There were heterogeneities in fractionation, treatment planning, and delivery. Studies demonstrated effectiveness, feasibility, and tolerability of focal boost. Based on the Phoenix criteria for biochemical recurrence, the reported 5-year biochemical recurrence-free survival rates ranged 69.7-100% across included studies. All studies reported good safety profiles. The reported ranges of acute/late grade 3 + gastrointestinal toxicities were 0%/1-10%. The reported ranges of acute/late grade 3 + genitourinary toxicities were 0-13%/0-5.6%. CONCLUSIONS: There is strong evidence that it is possible to improve oncologic outcomes without substantially increasing toxicity through MR-guided focal boost, at least in the setting of a 35-fraction radiotherapy regimen. Barriers to clinical practice implementation are addressable through additional investigation and new technologies.

Adjuvant Radiation in Resectable Node-Positive Merkel Cell Carcinoma in the Immunotherapy Era: Implications for Future and Ongoing Trials.

Merkel cell carcinoma (MCC) is a cutaneous malignancy often treated with surgical resection followed by adjuvant radiation therapy (RT). In the node-positive setting, adjuvant RT reduces the risk of locoregional recurrence, but historical data suggest that distant failure is a persistent issue and often fatal. This has prompted new efforts to intensify treatment in these patients with the addition of neoadjuvant or adjuvant immune checkpoint inhibitor therapy. However, newer diagnostic techniques have led to stage migration in patients with previously subclinical metastatic disease; consequently, preventing locoregional recurrence may be a higher priority in node-positive MCC patients than was previously believed. Recent trials in node-positive MCC, such as ADMEC-O, have had lower rates of adjuvant RT utilization in treatment versus control arms, which may have attenuated the observed effect of adjuvant immunotherapy. The low utilization of adjuvant RT may have also resulted in a higher recurrence rate in patients who did not have a complete response to neoadjuvant immunotherapy in the CHECKMATE 358 trial. Altogether, these are important considerations for ongoing and future immunotherapy trials in MCC and may affect the interpretation of their results. Ongoing clinical trials may determine which patients are at low risk of recurrence when treated with immunotherapy and whether adjuvant RT could be omitted in select patients.

International Socioeconomic Predictors of Colon and Rectal Cancer Mortality: Is Colorectal Cancer a First World Problem?

PURPOSE: Colorectal cancer (CRC) is a leading cause of international morbidity and is the second highest cause of cancer-related mortality in the world. The purpose of this study was to investigate the relationship between international health care spending on CRC mortality over time. METHODS: This is a retrospective study using a publicly available data from the WHO Global Health Observatory database. General estimating equations were used to analyze the relationship between total health care expenditure per capita (THEpc) and CRC mortality at the country level. The primary predictors of interest were quartiles of THEpc. Other exposure variables included gross domestic product per capita (GDPpc), smoking (% of adult population smoking), physician density (per 10,000), and time. RESULTS: Mortality decreased significantly from 2000 to 2016 (coefficient [95% CI], -2.2 [-3.3 to -1.1]; P < .001). THEpc, GDPpc, time, and percentage of adult population smoking were significant predictors of CRC mortality. Patients in the top two quartiles of THEpc had 3% higher rates of CRC mortality compared with countries in Q1 THEpc (Q3: 3.4 [1.9-4.8], P < .001; Q4: 3.2 [1.4-5.0], P = .001). Similar trends were seen in GDPpc (Q4: 3.2 [1.4-5.0], P = .001; Q3: 3.4 [1.9-4.8], P < .001; Q2: 1.7 [0.7-2.6], P < .001; Q1: reference). CONCLUSION: Overall, mortality decreased significantly over the study period. Countries with higher health expenditures and higher gross domestic products experienced higher rates of CRC mortality. Further research will be necessary to determine the cause for this, but we postulate that it may be a result of more robust diagnostic and follow-up methods in countries with more resources.