Current treatment and future directions in the management of anal cancer.

Although rare, the rate of squamous cell carcinoma of the anus (SCCA) is rising globally. Most patients present with nonmetastatic disease and are curable with appropriate treatment, which has evolved significantly over the last several decades. Before the 1970s, SCCA was managed with radical surgery, resulting in a permanent colostomy. Researchers found that preoperative treatment with chemotherapy and concurrent radiation could achieve a pathologic complete response. After this observation, definitive therapy shifted from radical surgery to sphincter-preserving chemoradiation. Investigations into the necessity of chemotherapy and the optimal regimen found that chemotherapy with mitomycin-C and 5-fluorouracil is required for cure. Further studies evaluating the addition of induction or maintenance chemotherapy, monoclonal antibody therapy, or higher radiation doses have demonstrated no significant benefit to disease control. Advanced radiation delivery with intensity-modulated radiotherapy techniques is now considered the standard of care because of its prospectively determined, favorable acute toxicity profile compared with 3-dimensional conformal radiation. It is important to note that chemoradiation treatment response may be slow (up to 26 weeks) and should be assessed through serial clinical examinations. Today, surgical management of SCCA is reserved only for the lowest risk, early stage tumors or for recurrent/persistent disease. Current studies are evaluating radiation dose de-escalation in early stage disease and radiation dose escalation and the addition of immune checkpoint inhibitors in locally advanced cancers. In reviewing how and why modern-day treatment of SCCA was established, the objective of this report is to reenforce adherence to current treatment paradigms to assure the best possible outcomes for patients.

Retrospective comparative effectiveness research: Will changing the analytical methods change the results?

In medicine, retrospective cohort studies are used to compare treatments to one another. We hypothesize that the outcomes of retrospective comparative effectiveness research studies can be heavily influenced by biostatistical analytic choices, thereby leading to inconsistent conclusions. We selected a clinical scenario currently under investigation: survival in metastatic prostate, breast or lung cancer after systemic vs systemic + definitive local therapy. We ran >300 000 regression models (each representing a publishable study). Each model had various forms of analytic choices (to account for bias): propensity score matching, left truncation adjustment, landmark analysis and covariate combinations. There were 72 549 lung, 14 904 prostate and 13 857 breast cancer patients included. In the most basic analysis, which omitted propensity score matching, left truncation adjustment and landmark analysis, all of the HRs were <1 (generally, 0.60-0.95, favoring addition of local therapy), with all P-values <.001. Left truncation adjustment landmark analysis produced results with nonsignificant P-values. The combination of propensity score matching, left truncation adjustment, landmark analysis and covariate combinations generally produced P-values that were >.05 and/or HRs that were >1 (favoring systemic therapy alone). The use of more statistical methods to reduce the selection bias caused reported HR ranges to approach 1.0. By varying analytic choices in comparative effectiveness research, we generated contrary outcomes. Our results suggest that some retrospective observational studies may find a treatment improves outcomes for patients, while another similar study may find it does not, simply based on analytical choices.

Impact of radiation therapy facility volume on survival in patients with cancer.

BACKGROUND: This study examined whether radiation therapy facility volumes correlate with survival after curative intent treatment of solid tumors. METHODS: The National Cancer Database was queried for patients with solid tumors treated with curative-intent radiation therapy from 2004-2013. Facilities were stratified into 4 volume categories: low, intermediate, high, and very high. Primary cancer sites were divided into neoadjuvant, adjuvant, or definitive radiation subgroups. Kaplan-Meier curves of 5-year postradiation survival probability, stratified by facility volume, were generated with log-rank tests for group comparisons. Cox proportional hazard models were used to evaluate the effect of facility volume on survival, adjusted for multiple covariates. RESULTS: There were 253,422 patients treated at 1289 facilities: 6231 received neoadjuvant radiation, 147,980 received adjuvant radiation, and 99,211 received definitive radiation without surgery. Among patients receiving neoadjuvant radiation, survival correlated with facility volume for patients with rectal cancer (hazard ratio [HR], 0.75; 95% CI, 0.6-0.94; P = .01). For cancers of the breast and uterus, patients receiving adjuvant radiation at very high-volume facilities (vs low volume) had improved survival (HR, 0.83; 95% CI, 0.77-0.90; P < .001 and HR, 0.77, 95% CI, 0.62-0.97; P = .03, respectively). For patients receiving definitive radiation for prostate, non-small cell lung, pancreas, and head and neck cancer, there was an improvement in survival for patients treated at very high-volume centers (P < .05). CONCLUSIONS: For select cancer patients, treatment with curative radiation at higher volume facilities is associated with improved survival. In particular, patients receiving radiation therapy in the definitive setting without surgery may benefit most from treatment at high-volume centers.

Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): An international systematic review and meta-analysis.

BACKGROUND: The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy with concurrent chemotherapy (CFRT) for the definitive treatment of locally advanced pancreatic cancer. The primary outcome measure was efficacy, defined by 2-year overall survival (OS). Secondary outcomes were incidence of any grade 3/4 toxicity and 1-year OS. METHODS: A PICOS/PRISMA/MOOSE selection protocol was used to identify eligible studies. Inclusion criteria were: 1) patients diagnosed with locally advanced N0-1 M0 pancreatic cancer; 2) CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions; 3) either no control group or another definitive chemotherapy or radiation therapy arm; 4) at least 1 of the outcome measures reported; and 5) single or multi-arm phase 2/3 prospective study for CFRT and/or phase 1/2 or retrospective study for SBRT. Neoadjuvant and/or adjuvant chemotherapy was prescribed per protocol specifications. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method to characterize summary effect sizes for each outcome. RESULTS: A total of 470 studies were initially screened; of these, 9 studies assessed SBRT and 11 studies assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. For CFRT, doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies delivering 50.4 Gy in 28 fractions with concurrent gemcitabine. The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for 1-year OS was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. The random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant. CONCLUSION: These results suggest that SBRT for LAPC may result in a modest improvement in 2-year OS with decreased rates of acute grade 3/4 toxicity and no change in 1-year-OS or late toxicity. Further study into the use of stereotactic body radiation therapy for these patients is needed.

Magnetic Resonance Guided Radiotherapy for Rectal Cancer: Expanding Opportunities for Non-Operative Management.

Colorectal cancer is the third most common cancer in men and the second most common in women worldwide, and the incidence is increasing among younger patients. 30% of these malignancies arise in the rectum. Patients with rectal cancer have historically been managed with preoperative radiation, followed by radical surgery, and adjuvant chemotherapy, with permanent colostomies in up to 20% of patients. Beginning in the early 2000s, non-operative management (NOM) of rectal cancer emerged as a viable alternative to radical surgery in select patients. Efforts have been ongoing to optimize neoadjuvant therapy for rectal cancer, thereby increasing the number of patients potentially eligible to forgo radical surgery. Magnetic resonance guided radiotherapy (MRgRT) has recently emerged as a treatment modality capable of intensifying preoperative radiation therapy for rectal cancer patients. This technology may also predict which patients will achieve a complete response to preoperative therapy, thereby allowing for more appropriate selection of patients for NOM. The present work seeks to illustrate the potential role MRgRT could play in personalizing rectal cancer treatment thus expanding the role of NOM in rectal cancer.

Clinical Trial Accrual at Initial Course of Therapy for Cancer and Its Impact on Survival.

BACKGROUND: This retrospective cohort study sought to characterize the accrual of patients with cancer into clinical trials at the time of diagnosis and analyze the impact of accrual on survival. METHODS: The National Cancer Database (NCDB) was queried for patients enrolled in clinical trials at their initial course of treatment for 46 cancers from 2004 through 2015. Descriptive statistics were used to characterize the accrual of patients with cancer in clinical trials at diagnosis, and Kaplan-Meier graphical displays, log-rank tests, odds ratios, and stratified Cox proportional hazards models were used to analyze the impact of accrual on overall survival (OS). Strata were defined using 10 variables. Model-based adjusted survival curves of 2 groups were reverse-generated based on a Weibull distribution. RESULTS: Of 12,097,681 patients in the NCDB, 11,576 (0.1%) were enrolled in trials. Patients in clinical trials typically had metastatic disease (30.9% vs 16.4%; P<.0001), were white (88.0% vs 84.8%; P<.0001), had private/managed care insurance (56.4% vs 41.8%; P<.0001), had fewer comorbidities (Charlson-Deyo score 0: 81.9% vs 75.7%; P<.0001, and Charlson-Deyo scores 1-3: 18.1% vs 24.3%; P<.0001) compared with those not in trials. At a median follow-up of 64 months, enrollment in a clinical trial was associated with improved OS in univariate and stratified analyses, with a median survival of 60.0 versus 52.5 months (hazard ratio, 0.876; 95% CI, 0.845-0.907; P<.0001). Stratified analysis with matched baseline characteristics between patients enrolled and not enrolled in a clinical trial showed superior OS at 5 years (95.0% vs 90.2%; P<.0001). CONCLUSIONS: Enrollment in clinical trials at first line of therapy in the United States is exceedingly low and favors young, healthy, white patients with metastatic disease and private insurance who are treated at academic medical centers. Patients with cancer treated in clinical trials live longer than those not treated in trials.

Esophagogastric Cancer: The Current Role of Radiation Therapy.

Radiation therapy is an effective treatment modality in the management of patients with esophageal cancer regardless of tumor location (proximal, middle, or distal esophagus) or histology (squamous cell vs adenocarcinoma). The addition of neoadjuvant CRT to surgery in patients who are surgical candidates has consistently shown a benefit in terms of locoregional recurrence, pathologic downstaging, and overall survival. For patients who are not surgical candidates, CRT has a role as definitive treatment.

Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas.

PURPOSE: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered. METHODS AND MATERIALS: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, or 3) based on adequacy. A score of 1 indicated no deviation, 2 indicated minor deviation, and 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score. RESULTS: Forty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic and 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets and 4 for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT and 7 (17.9%) with hypofractionated RT. Five cases (13%) required revision before treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2, and 11 (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded. CONCLUSIONS: Despite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. Although clinical outcomes did not appear to have been affected, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.

Treatment Terminations During Radiation Therapy: A Ten-Year Experience.

PURPOSE: Patients undergoing radiation therapy may terminate treatment for any number of reasons. The incidence of treatment termination (TT) during radiation therapy has not been studied. Herein we present a cohort of TT at a large multi-center radiation oncology department over 10 years. METHODS AND MATERIALS: TTs between 1/2013 and 1/2023 were prospectively analyzed as part of an ongoing departmental quality and safety program. TT was defined as any premature discontinuation of therapy after initiating radiation planning. The rate of TT was calculated as a percentage of all patients starting radiation planning. All cases were presented at monthly morbidity and mortality (MM) conferences with a root cause reviewed (RCA). RESULTS: A total of 1,448 TTs were identified out of 31,199 planned courses of care (4.6%). Six hundred eighty-six (47.4%) involved patients treated with curative intent, while 753 (52.0%) with palliative intent, and 9 (0.6%) for benign disease. The rate of TT decreased from 8.49% in 2013 to 3.02% in 2022 with rates decreasing yearly. The most common disease sites for TT were CNS (21.7%), H&N (19.3%), Thorax (17.5%), and Bone (14.2%). The most common causes of TT were hospice and/or patient expiration (35.9%), patient choice unrelated to toxicity (35.2%), and clinician choice unrelated to toxicity (11.5%). CONCLUSION: This 10-year prospective review of TTs identified a year-over-year decrease in TTs as a percentage of planned patients. This decrease may be associated with the addition of RCA for TTs and discussion monthly at MM rounds, coupled with departmental upstream quality initiatives implemented over time. Understanding the reasons behind TTs may help to decrease preventable TTs. While some TTs may be unavoidable, open discourse and quality improvement changes effectively reduce TT incidents over time.

Analysis of Radiation Therapy Quality Assurance in NRG Oncology RTOG 0848.

PURPOSE: NRG/Radiation Therapy Oncology Group 0848 is a 2-step randomized trial to evaluate the benefit of the addition of concurrent fluoropyrimidine and radiation therapy (RT) after adjuvant chemotherapy (second step) for patients with resected pancreatic head adenocarcinoma. Real-time quality assurance (QA) was performed on each patient who underwent RT. This analysis aims to evaluate adherence to protocol-specified contouring and treatment planning and to report the types and frequencies of deviations requiring revisions. METHODS AND MATERIALS: In addition to a web-based contouring atlas, the protocol outlined step-by-step instructions for generating the clinical treatment volume through the creation of specific regions of interest. The planning target volume was a uniform 0.5 cm clinical treatment volume expansion. One of 2 radiation oncology study chairs independently reviewed each plan. Plans with unacceptable deviations were returned for revision and resubmitted until approved. Treatment started after final approval of the RT plan. RESULTS: From 2014 to 2018, 354 patients were enrolled in the second randomization. Of these, 160 patients received RT and were included in the QA analysis. Resubmissions were more common for patients planned with 3-dimensional conformal RT (43%) than with intensity modulated RT (31%). In total, at least 1 resubmission of the treatment plan was required for 33% of patients. Among patients requiring resubmission, most only needed 1 resubmission (87%). The most common reasons for resubmission were unacceptable deviations with respect to the preoperative gross target volume (60.7%) and the pancreaticojejunostomy (47.5%). CONCLUSION: One-third of patients required resubmission to meet protocol compliance criteria, demonstrating the continued need for expending resources on real-time, pretreatment QA in trials evaluating the use of RT, particularly for pancreas cancer. Rigorous QA is critically important for clinical trials involving RT to ensure that the true effect of RT is assessed. Moreover, RT QA serves as an educational process through providing feedback from specialists to practicing radiation oncologists on best practices.

A Decade of Prospective Peer Review: Impact on Safety Culture and Lessons Learned in a Multicenter Radiation Medicine Department.

PURPOSE: Quality assurance (QA) is critical to the success of radiation therapy (RT) for patients with cancer and affects clinical outcomes. We report longitudinal findings of a prospective peer review evaluation system implemented at a major academic health system as part of RT QA during a 10-year period. METHODS AND MATERIALS: All cases treated within our department undergo prospective multidisciplinary peer review and are assigned a grade (A, B, or C). "A" cases require no changes, "B" cases require minor modification, and "C" cases require major modification before treatment planning. The z-ratio test for the significance of the difference between the 5-year baseline (2012-2016) and follow-up (2017-2021) period was used to compare grades between the 2 periods. A 2-tailed P value <.05 was considered significant. RESULTS: Of the 20,069 cases, 15,659 (78%) were curative and were analyzed. The fraction of A cases decreased from 74.8% (baseline) to 64.5% (follow-up), whereas B cases increased from 19.4% to 35.4% and C cases decreased from 5.8% to 0.1%. Of the 9 treatment locations, the main hospital site had a higher percentage of A grades relative to community locations in the baseline (78.6% vs 67.8%; P < .002) and follow-up (66.9% vs 62.3%; P < .002) periods. There was a decrease in the percentage of A cases from the baseline to the follow-up period regardless of plan type (complex vs intermediate vs simple). There was a decrease in the percentage of A cases among specialists from baseline to follow-up (78.2% to 67.7%; P < .002) and among generalists from baseline to follow-up (69.7% to 61.7%; P < .002). CONCLUSIONS: Our 10-year experience in contour peer review identified increased opportunities in improving treatment plan quality over time. The drop in A scores and rise in B scores suggests increased scrutiny and findings-based improvements over time, whereas the drop in C scores indicates amelioration of "major failures" addressed in the startup years. Peer review rounds upstream of treatment planning provide valuable RT QA and should be considered by other departments to enhance the quality and consistency of RT.

American Radium Society (ARS) Appropriate Use Criteria (AUC) for Extrahepatic Cholangiocarcinoma.

Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic to guide the management of these patients.

Unknown Causes of Death in Cancer Patients.

OBJECTIVES: Deaths from an unknown cause are difficult to adjudicate and oncologic studies of comparative effectiveness often demonstrate inconsistencies in incorporating these deaths and competing events (eg, heart disease and stroke) in their analyses. In this study, we identify cancer patients most at risk for death of an unknown cause. METHODS: This retrospective, population-based study used cancer registry data from the Surveillance, Epidemiology, and End Results database (1992-2015). The absolute rate of unknown causes of death (COD) cases stratified by sex, marital status, race, treatment, and cancer site were calculated and a multivariable logistic regression model was applied to obtain adjusted odds ratios with 95% CIs. RESULTS: Out of 7,154,779 cancer patients across 22 cancer subtypes extracted from Surveillance, Epidemiology, and End Results, 3,448,927 died during follow-up and 276,068 (7.4%) of these deaths were from unknown causes. Patients with an unknown COD had a shorter mean survival time compared with patients with known COD (36.3 vs 65.7 mo, P < 0.001). The contribution of unknown COD to total mortality was highest in patients with more indolent cancers (eg, prostate [12.7%], thyroid [12.3%], breast [10.7%]) and longer follow-up (eg, >5 to 10 y). One, 3, and 5-year cancer-specific survival (CSS) calculations including unknown COD were significantly decreased compared with CSS estimates excluding cancer patients with unknown COD. CONCLUSION: Of the patients, 7.4% died of unknown causes during follow-up and the proportion of death was higher with longer follow-up and among more indolent cancers. The attribution of high percentages of unknown COD to cancer or non-cancer causes could impact population-based cancer registry studies or clinical trial outcomes with respect to measures involving CSS and mortality.

Nonadherence to Multimodality Cancer Treatment Guidelines in the United States.

Purpose: Our purpose was to identify patients with cancer who do not receive guideline-concordant multimodality treatment and to identify factors that are associated with nonreceipt of guideline-concordant multimodality treatment. Methods and Materials: Five cancers for which the multimodal guideline-concordant treatment (with surgery, chemotherapy, and radiation therapy) is clearly defined in national guidelines were selected from the National Cancer Database: (1) nonmetastatic anal cancer, (2) locally advanced cervical cancer, (3) nonmetastatic nasopharynx cancer, (4) locally advanced rectal cancer, and (5) locally advanced non-small cell lung cancer. Multivariable logistic regression was used to determine the odds ratios (with 95% confidence intervals) of receiving the guideline-concordant treatment versus not, adjusting for common confounding variables. Results: 178,005 patients with cancer were included: 32,214 anal, 54,485 rectal, 13,179 cervical, 5061 nasopharyngeal, and 73,066 lung. Overall, 162,514 (91%) received guideline-concordant treatment and 15,491 (9%) did not. Twenty-one percent of patients with cervical cancer, 10% of patients with rectal cancer, 7% of patients with lung cancer, 5% of patients with anal cancer, and 3% of patients with nasopharynx cancer did not receive guideline-concordant treatment. In general, patients who were older, with comorbid conditions, and who were evaluated at low-volume facilities (odds ratios > 1 with P < .05) were less likely to receive guideline-concordant treatment. Conclusions: Nearly 1 in 10 patients in this cohort are not receiving appropriate multimodal cancer therapy. There appear to be significant disparities in receipt of guideline-concordant treatment based on primary tumor site, age, comorbidities, and reporting facility.

Mature Experiences Using Local Therapy for Oligometastases.

Cancer is a heterogeneous disease, consisting of a spectrum of disorders ranging from local-only disease to those that are widely metastatic from their onset. The oligometastatic state, in which tumors harbor a limited number of metastases, may be curable in a subset of patients. The early success of surgical resection of hepatic metastases from colorectal cancer led to investigations into metastatectomy of other sites and, more recently, into the use of stereotactic ablative radiotherapy (SABR) for oligometastatic disease. This article reviews the data establishing the role of surgery for managing limited metastatic disease. Further, we review recent experiences using alternative local therapies, such as SABR, for oligometastases. This review also discusses ongoing trials evaluating local therapies for patients with a limited burden of metastatic cancer.

Survival after palliative radiation therapy for cancer: The METSSS model.

BACKGROUND: We propose a predictive model that identifies patients at greatest risk of death after palliative radiotherapy, and subsequently, can help medical professionals choose treatments that better align with patient choice and prognosis. METHODS: The National Cancer Database was queried for recipients of palliative radiotherapy during first course of treatment. Cox regression models and adjusted hazard ratios with 95% confidence intervals were used to evaluate survival predictors. The mortality risk index was calculated using predictors from the estimated Cox regression model, with higher values indicating higher mortality risk. Based on tertile cutpoints, patients were divided into low, medium, and high risk groups. RESULTS: A total of 68,505 patients were included from 2010-2014, median age 65.7 years. Several risk factors were found to predict survival: (1) location of metastases (liver, bone, lung, and brain); (2) age; (3) tumor primary (prostate, breast, lung, other); (4) gender; (5) Charlson-Deyo comorbidity score; and (6) radiotherapy site. The median survival times were 11.66 months, 5.09 months, and 3.28 months in the low (n=22,621), medium (n=22,638), and high risk groups (n=22,611), respectively. A nomogram was created and validated to predict survival, available online, https://tinyurl.com/METSSSmodel. Harrel's C-index was 0.71 and receiver operator characteristic area under the curve was 0.76 at 4 years. CONCLUSION: We created a predictive nomogram for survival of patients receiving palliative radiotherapy during their first course of treatment (named METSSS), based on Metastases location, Elderly (age), Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy.

Radiotherapy and Receptor Tyrosine Kinase Inhibition for Solid Cancers (ROCKIT): A Meta-Analysis of 13 Studies.

Background: We hypothesized that the addition of receptor tyrosine kinase inhibitors (RTKis, e.g., lapatinib, erlotinib, cetuximab, bevacizumab, panitumumab) to radiotherapy-based treatment for solid tumors does not increase overall survival but may increase toxicity. Methods: Population, Intervention, Control, Outcome, Study Design; Preferred Reporting Items for Systematic Reviews and Meta-Analyses; and Meta-analysis of Observational Studies in Epidemiology methods were used to identify prospective randomized studies including patients with solid tumor cancers treated with radiotherapy with or without RTKis. Extracted variables included use of radiotherapy vs chemoradiotherapy, RTKi type (antibody vs small molecule), outcomes, and toxicities. The primary endpoint was overall survival; the secondary endpoint was grade 3+ toxicity. Random-effects meta-analyses were performed for each outcome measure. All statistical tests were 2-sided. Results: A total of 405 studies met the initial search criteria, of which 13 prospective randomized trials of radiotherapy with or without RTKi met the inclusion criteria, encompassing 5678 patients. The trials included cancers of the head and neck (6 trials, 3295 patients), esophagus (3 trials, 762 patients), lung (2 trials, 550 patients), and brain (2 trials, 1542 patients). Three studies evaluated a small molecule and radiotherapy in 949 patients, and 10 studies evaluated antibodies and radiotherapy in 4729 patients. The addition of RTKis to radiotherapy-based treatment did not improve overall survival (hazard ratio = 1.02, 95% confidence interval = 0.90 to 1.15, P = .76) but increased grade 3+ toxicity (relative risk = 1.18, 95% confidence interval = 1.06 to 1.33, P = .009). Conclusions: The addition of RTKis to radiotherapy does not improve survival and worsens toxicity.

Executive Summary of the American Radium Society Appropriate Use Criteria for Operable Esophageal and Gastroesophageal Junction Adenocarcinoma: Systematic Review and Guidelines.

PURPOSE: Limited guidance exists regarding the relative effectiveness of treatment options for nonmetastatic, operable patients with adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). In this systematic review, the American Radium Society (ARS) gastrointestinal expert panel convened to develop Appropriate Use Criteria (AUC) evaluating how neoadjuvant and/or adjuvant treatment regimens compared with each other, surgery alone, or definitive chemoradiation in terms of response to therapy, quality of life, and oncologic outcomes. METHODS AND MATERIALS: Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was used to develop an extensive analysis of peer-reviewed phase 2R and phase 3 randomized controlled trials as well as meta-analyses found within the Ovid Medline, Cochrane Central, and Embase databases between 2009 to 2019. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in 4 broadly representative clinical scenarios through a well-established consensus methodology (modified Delphi). RESULTS: For a medically operable nonmetastatic patient with a cT3 and/or cN+ adenocarcinoma of the esophagus or GEJ (Siewert I-II), the panel most strongly recommends neoadjuvant chemoradiation. For a cT2N0M0 patient with high-risk features, the panel recommends neoadjuvant chemoradiation as usually appropriate. For patients found to have pathologically involved nodes (pN+) who did not receive any neoadjuvant therapy, the panel recommends adjuvant chemoradiation as usually appropriate. These guidelines assess the appropriateness of various dose-fractionating schemes and target volumes. CONCLUSIONS: Chemotherapy and/or radiation regimens for esophageal cancer are still evolving with many areas of active investigation. These guidelines are intended for the use of practitioners and patients who desire information about the management of operable esophageal adenocarcinoma.

Recommendations for the use of radiation therapy in managing patients with gastrointestinal malignancies in the era of COVID-19.

As of April 6, 2020, there are over 1,200,000 reported cases and 70,000 deaths worldwide due to COVID-19, the disease caused by the SARS-CoV-2 virus, and these numbers rise exponentially by the day [1]. According to the Centers for Disease Control (CDC), the most effective means of minimizing the spread of the virus is through reducing interactions between individuals [2]. We performed a review of the literature, as well as national and international treatment guidelines, seeking data in support of the RADS principle (Remote visits, Avoid radiation, Defer radiation, Shorten radiation) [3] as it applies to gastrointestinal cancers. The purpose of the present work is to guide radiation oncologists managing patients with gastrointestinal cancers during the COVID-19 crisis in order to maintain the safety of our patients, while minimizing the impact of the pandemic on cancer outcomes.

Reducing the Toxicity of Radiotherapy for Pancreatic Cancer With Magnetic Resonance-guided Radiotherapy.

Pancreatic cancer is a highly fatal malignancy for which surgery is currently considered to be the only curative treatment. However, less than a quarter of patients have disease amenable to definitive surgical resection. Local treatment with radiation therapy is a promising alternative to surgery for those patients with unresectable disease. However, conventional radiation techniques with computed tomography (CT)-guided therapy have yielded disappointing results due to the inability to deliver ablative doses of ionizing radiation, while sparing the radiosensitive adjacent organs at risk. Magnetic resonance-guided radiotherapy (MRgRT) has emerged as an alternative to CT-guided radiation treatment which allows for the delivery of higher doses of radiation with low toxicity to surrounding structures. Further study into the use of MRgRT and dose escalation for locally advanced unresectable pancreatic cancer is needed.