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.

Early Improved Functional Outcomes in Head and Neck Cancer Patients with Primary Tumor Detection.

OBJECTIVES: We characterize functional outcomes in head and neck cancer of unknown primary (CUP) based on primary site identification. METHODS: In this retrospective study, CUP cases were categorized as known primaries (KP) if a tumor was localized after diagnostic workup or persisting unknown primaries (UP). Age, sex, HPV status, diagnostic methods, and treatments regimens were collected. Pretreatment and short-term posttreatment (3-6 months after completion of treatment) weights, PHQ-9, Eating Assessment Tool (EAT-10), and Voice Handicap Index (VHI-10) scores were compared between UP and KP. RESULTS: Among 67 CUP patients, 35 (52.2%) had identified primaries (91.4% oropharyngeal and 8.6% nasopharyngeal). KP patients were younger (58 vs. 64, p = 0.04) and more likely to be HPV-positive (88.6% vs. 50%, p = 0.002). Overall detection rates were 16.7% for PET/CT, 34.7% for direct laryngoscopy, and 46.6% for transoral robotic oropharyngectomy. Diagnostic workup was not significantly different between groups. Patients with KP received smaller intermediate radiation dose volumes (436.5 vs. 278.9 cc, p = 0.03) and lower doses to the cricopharyngeal muscle (41.6 vs. 24.6 Gy, p = 0.03).Pretreatment weights, PHQ-9, EAT-10, and VHI-10 scores did not differ between groups. However, posttreatment, UP had greater relative weight loss (-14.1% vs. -7.6%, p = 0.032), higher EAT-10 scores (12.5 vs. 3, p = 0.004), and higher PHQ-9 scores (6 vs. 1.4, p = 0.017). Specifically, UP reported more stressful swallowing, difficulty swallowing solids and pills, and swallowing affecting public eating. CONCLUSION: KP patients experienced less weight loss, depression, and reduced swallowing dysfunction, highlighting an early functional benefit of primary tumor identification likely driven by reduced radiation treatment volumes. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:701-707, 2024.

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.

Development, Usability Testing, and Implementation Assessment of Cancer Related Infertility Score Predictor, an Online Cancer Related Infertility Risk Counseling Tool.

Purpose: Oncofertility counseling of female cancer patients lacks efficient access to tailored and valid infertility risk estimates to support shared decision-making on fertility preservation treatments. The objective was to develop, conduct user-centered design, and plan clinic-based implementation of the Cancer Related Infertility Score Predictor (CRISP), a web-based tool to support infertility risk counseling. Methods: Using a mixed methods design, literature review was undertaken to abstract data on infertility, primary ovarian insufficiency, and amenorrhea risks of common cancer treatments. The CRISP website was programmed to take user input about patient ages and cancer treatments and generate a risk summary. Using user experience methodology and semistructured interviews, usability testing and implementation assessment were conducted with 12 providers recruited from 5 medical centers in Southern California. Results: The web-based CRISP tool encompasses infertility risk data for 60 treatment regimens among 10 cancer types. Usability testing demonstrated that the tool is intuitive and informed minor modifications, including adding crowd-sourced submission of additional cancer treatments. Participants rated the tool as credible, advantageous over current provider methods to ascertain infertility risks, and useful for tailoring treatment planning and counseling patients. A key barrier was lack of information on some cancer treatments. Fit within clinical workflow was feasible, particularly with electronic health record integration. Conclusions: The novel, web-based CRISP tool is a feasible, acceptable, and appropriate tool to address provider knowledge gap about cancer related infertility risks and use for patient counseling. CRISP has significant potential to support tailored oncofertility counseling in the heterogeneous young cancer patient population.

A Multicomponent Telehealth Intervention to Improve Oncofertility Care Delivery Among Young Cancer Patients: A Pilot Study.

Purpose: Oncofertility care for pediatric, adolescent, and young adult cancer patients remains under-implemented across adult and pediatric oncology settings. We pilot tested an electronic health record (EHR)-enabled multicomponent oncofertility intervention (including screening, referral, and fertility consult) in an adult academic oncology program and systematically assessed intervention fit to pediatric and community oncology programs. Methods: Using surveys (n = 33), audits (n = 143), and interviews (n = 21) guided by implementation science frameworks, we pilot tested the EHR-enabled intervention for oncofertility care in young cancer patients at an adult oncology program and evaluated implementation outcomes. We interviewed health care providers from seven regional oncology and fertility programs about intervention fit to their clinical contexts. Results: We recruited 33 health care providers from an adult oncology setting and 15 health care providers from seven additional oncology and fertility settings. At the adult oncology setting, the intervention was found to be appropriate, acceptable, and feasible and improved the screening of fertility needs (from 30% pre- to 51% post-intervention); yet, some patients did not receive appropriate referrals to fertility consults. Providers across all settings suggested content and context modifications, such as adding options to the intervention or allowing the screening component to pop up at a second visit, to improve and adapt the intervention to better fit their clinical care contexts. Conclusions: We found that the EHR-enabled intervention increased the rate of goal-concordant oncofertility care delivery at an adult oncology program. We also identified facilitators, barriers, and needed adaptations to the intervention required for implementation and scaling-up across diverse oncology settings.

Split course palliative radiotherapy for advanced lung cancer with 3D planning based analysis of outcome: a retrospective review.

BACKGROUND: Durable palliation of advanced lung cancer is a common objective for radiation oncologists. However, there is no consensus on how to deliver the radiation course. Herein we report our experience of using split course radiotherapy and our assessment of outcomes based on planning from three-dimensional (3D) simulation before each treatment course. METHODS: All lung cancer patients from 2006-2020 were identified. Of these, 52 patients received a split course treatment of 50-60 Gy in 18-25 fractions intended to provide durable palliation for disease not amenable to curative therapy. Treatment involved 3D planning with repeat computed tomography (CT) simulation prior to the second course. Survival and symptomatic response were analyzed via chart review. We categorized rapid responders versus non-rapid responders from the initial radiation course based on ≥30% gross tumor volume (GTV) reduction at the second CT simulation. We evaluated the impact of response on overall survival and palliative response. RESULTS: Among our cohort treated with split course palliative radiotherapy, 33 (63%) had a rapid response to initial treatment. There was no difference in survival between groups [hazard ratio (HR) =1.30, P=0.47]. There was no significant difference in palliative response rates between rapid and non-rapid responders. On multivariable analysis, only female sex (HR =0.26, P<0.01) and receipt of systemic therapy following radiotherapy (HR =0.19, P<0.01) were associated with improved survival. CONCLUSIONS: There is currently significant practice pattern variability for palliative lung radiotherapy. Split course palliative radiation of 50-60 Gy in 18-25 fractions represents an option to consider for patients with advanced lung cancer who do not undergo definitive therapy and may benefit from a higher dose regimen. Our retrospective review suggests that rapid tumor response in a split course model does not predict survival or symptomatic response. Prospective studies are needed to further define which lung cancer patients may benefit from higher dose regimens.

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.

Theory-Guided Development of Fertility Care Implementation Strategies for Adolescent and Young Adult Cancer Survivors.

Purpose: Oncofertility care at cancer diagnosis remains underimplemented across oncology and fertility care settings, with limited tools to scale up effective implementation strategies. Using implementation science theory, we systematically assessed factors that influence oncofertility care implementation and mapped scalable strategies, particularly electronic health record (EHR)-enabled ones, that fit adult and pediatric oncology care contexts. Methods: Using purposeful sampling, we recruited health care providers and female, reproductive-aged survivors of adolescent and young adult (AYA) cancers (AYA survivors) from a comprehensive cancer center and a freestanding children's hospital to semistructured interviews and focus groups. Using thematic analysis combining inductive codes with deductive codes using the Consolidated Framework for Implementation Research (CFIR), we characterized barriers and facilitators to care and designed responsive strategies. Two coders independently coded each transcript. Results: We recruited 19 oncology and fertility providers and 9 cancer survivors. We identified barriers and facilitators to oncofertility care in the CFIR domains of individual, inner setting, outer setting, and process, allowing us to conceptualize oncofertility care to encompass three core components (screening, referral, and fertility preservation counseling) and map five strategies to these components that fit an adult and a children's context and bridge oncology and fertility practices. The strategies were screening using a best practice advisory, referral order, telehealth fertility counseling, provider audit and feedback, and provider education. All but provider education were EHR tools with embedded efficiencies. Conclusion: An implementation science approach systematically assessed oncofertility care and mapped strategies to provide a theory-based approach and scalable EHR tools to support wider dissemination.