Screening Implications for Distribution of Colorectal Cancer Subsite by Age and Role of Flexible Sigmoidoscopy.

Objectives: The effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy. Methods: Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000-2020). Tumors from the rectum to the descending colon were categorized as visible by sigmoidoscopy, whereas more proximal tumors required colonoscopy. Differential prognosis between tumor locations, stratified by age groups and stage, was assessed using the overall restricted mean survival time (RMST) at 2, 5, and 10 years. Results: Among 309,466 patients, 58% had tumors visible by sigmoidoscopy, including 73% of those under age 50 (OR 2.10, 95% CI 2.03-2.16 age < 45, OR 2.20, 95% CI 2.13-2.27 age 45-49 versus age ≥ 50). Male sex (OR 1.54, 95% CI 1.51-1.56) and Asian or Pacific Islander race (OR 1.60, 95% CI 1.56-1.64) were also positively associated with tumors visualizable by sigmoidoscopy. Across age groups, for local disease, RMST was comparable for tumors visible versus not visible on sigmoidoscopy. For regional and metastatic cancer, patients with tumors visible by sigmoidoscopy had improved RMST versus those with more proximal tumors. Conclusions: 58% of CRC arises in locations visible by flexible sigmoidoscopy. Flexible sigmoidoscopy should be considered as a viable option for CRC screening, particularly in younger patients unwilling or unable to undergo colonoscopy.

Common Sense (Radiation) Oncology: Redefining targets in radiotherapy.

In 2023, the Common Sense Oncology (CSO) movement was launched with the goal of recalibrating cancer care to focus on outcomes that matter to patients. We extend the three CSO pillars - evidence generation, interpretation and communication - to radiation oncology and advocate for better evidence demonstrating the value of our modality.

Defining Minimum Treatment Parameters of Ablative Radiation Therapy in Patients With Hepatocellular Carcinoma: An Expert Consensus.

PURPOSE: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. METHODS AND MATERIALS: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. RESULTS: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. CONCLUSIONS: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.

Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites.

BACKGROUND: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. METHODS: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. RESULTS: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). CONCLUSIONS: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics.

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity. Tumour delivery and treatment outcomes are superior in old versus young mice, probably due to an age-related decline in the ability of hepatic phagocytes to take up and remove nanoparticles. Transcriptomic- and protein-level analysis at the single-cell and bulk levels reveals an age-associated decrease in the numbers of hepatic macrophages that express the scavenger receptor MARCO in mice, non-human primates and humans. Therapeutic blockade of MARCO is shown to decrease the phagocytic uptake of nanoparticles and improve the antitumour effect of clinically approved cancer nanotherapeutics in young but not aged mice. Together, these results reveal an age-associated disparity in the phagocytic clearance of nanotherapeutics that affects their antitumour response, thus providing a strong rationale for an age-appropriate approach to cancer nanomedicine.

Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century.

The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

Association of Parental Status and Gender With Burden of Multidisciplinary Tumor Boards Among Oncology Physicians.

Importance: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited. Objective: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians. Design, Setting, and Participants: Tumor board burden was assessed by a cross-sectional convenience survey posted on social media and by email to Cedars-Sinai Medical Center cancer physicians between March 3 and April 3, 2022. Tumor board start times were independently collected by email from 22 top cancer centers. Main Outcomes and Measures: Tumor board burden was measured on a 4-point scale (1, not at all burdensome; 2, slightly burdensome; 3, moderately burdensome; and 4, very burdensome). Univariable and multivariable probabilistic index (PI) models were performed. Results: Surveys were completed by 111 physicians (median age, 42 years [IQR, 36-50 years]; 58 women [52.3%]; 60 non-Hispanic White [54.1%]). On multivariable analysis, factors associated with higher probability of tumor board burden included radiology or pathology specialty (PI, 0.68; 95% CI, 0.54-0.79; P = .02), attending 3 or more hours per week of tumor boards (PI, 0.68; 95% CI, 0.58-0.76; P < .001), and having 2 or more children (PI, 0.65; 95% CI, 0.52-0.77; P = .03). Early or late tumor boards (before 8 am or at 5 pm or after) were considered very burdensome by 33 respondents (29.7%). Parents frequently reported a negative burden on childcare (43 of 77 [55.8%]) and family dynamics (49 of 77 [63.6%]). On multivariable analysis, a higher level of burden from early or late tumor boards was independently associated with identifying as a woman (PI, 0.69; 95% CI, 0.57-0.78; P = .003) and having children (PI, 0.75; 95% CI, 0.62-0.84; P < .001). Independent assessment of 358 tumor boards from 22 institutions revealed the most common start time was before 8 am (88 [24.6%]). Conclusions and Relevance: This survey study of tumor board burden suggests that identifying as a woman or parent was independently associated with a higher level of burden from early or late tumor boards. The burden of early or late tumor boards on childcare and family dynamics was commonly reported by parents. Having 2 or more children, attending 3 or more hours per week of tumor boards, and radiology or pathology specialty were associated with a significantly higher tumor board burden overall. Future strategies should aim to decrease the disparate burden on parents and women.

From Bragg Peaks to Adaptive Fields-The Need for Evidence-Based Adoption of New Technologies in Radiotherapy.

This Viewpoint discusses the need for multi-institutional prospective randomized trials of new technologies in radiotherapy to improve the therapeutic ratio and safety of radiotherapy treatments.

Screening Implications for Distribution of Colorectal Cancer Subsite by Age.

Objectives: The effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy. Methods: Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000-2020). Tumors from the rectum to descending colon were categorized as visible by sigmoidoscopy, whereas more proximal tumors as requiring colonoscopy. Differential prognosis between tumor locations, stratified by age groups and stage, were assessed using overall restricted mean survival time (RMST) at 2, 5, and 10 years. Results: Among 309,466 patients, 58% had tumors visible by sigmoidoscopy, including 73% of those under age 50 (OR 2.10, 95%CI 2.03-2.16 age <45, OR 2.20, 95%CI 2.13-2.27 age 45-49 versus age > 50). Male sex (OR 1.54, 95%CI 1.51-1.56) and Asian or Pacific Islander race (OR 1.60, 95%CI 1.56-1.64) were also positively associated with tumors visualizable by sigmoidoscopy. Across age groups, for local disease, RMST was comparable for tumors visible versus not visible on sigmoidoscopy. For regional and metastatic cancer, patients with tumors visible by sigmoidoscopy had improved RMST versus those with more proximal tumors. Conclusions: Most CRC arise in locations visible by flexible sigmoidoscopy. Flexible sigmoidoscopy should be considered as a viable option for CRC screening, particularly in younger patients unwilling or unable to undergo colonoscopy.

The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership.

Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.

Current State and Future Directions of Radiation Therapy for Pancreas Adenocarcinoma.

Studies suggest select patients from across the pancreatic adenocarcinoma (PDAC) disease spectrum may benefit from adding radiation therapy (RT) to multi-modality care. In resectable PDAC, there is an evolving role for neoadjuvant RT with adjuvant RT reserved for patients with increased recurrence risk. In borderline resectable PDAC, neoadjuvant chemoradiation likely improves R0 resection rates and in unresectable PDAC, definitive RT may prolong survival for some patients. Recent developments in RT delivery are promising but additional studies are needed to determine the benefit of these technologies and to optimize the role of RT in multi-modality care.

Characteristics and clinical outcomes in young-onset cholangiocarcinoma.

BACKGROUND: While the incidence of cholangiocarcinoma is rising, little is known about young-onset disease. We compared clinical characteristics and outcomes between patients with young-onset cholangiocarcinoma, diagnosed between the ages of 18 and <50 years, and patients with typical-onset cholangiocarcinoma, diagnosed at age 50 years or greater. METHODS: We used the National Cancer Database to identify patients with young-onset cholangiocarcinoma (n = 2520) and typical-onset cholangiocarcinoma (n = 23,826). We compared the frequency of demographic and clinical characteristics between the two groups. We compared overall survival between the two groups using multivariable Cox regression analysis after adjusting for age, gender, race/ethnicity, comorbidity, facility type, tumor location, tumor stage, surgical status, and receipt of radiotherapy, chemotherapy and surgery. RESULTS: When compared to patients with typical-onset disease (median age 68 years), patients with young-onset cholangiocarcinoma (median age 44 years) were more likely to be non-White (35.0% vs. 27.4%, p < 0.01), and had lower overall comorbidity burden. Patients with young-onset disease had a greater proportion of intrahepatic cholangiocarcinoma (56.0% vs. 45.5%, p < 0.001) and stage IV disease (50.5% vs. 43.5%, p < 0.001). Younger patients were more likely than typical-onset patients to receive definitive surgery (30.9% vs. 25.0%, p < 0.001), radiation (27.7% vs. 19.6%, p < 0.001) and chemotherapy (73.1% vs. 50.1%, p < 0.001). In adjusted analyses, patients with young-onset disease had a 15% decreased risk of death, compared with patients with typical-onset disease (HR 0.85 [95% CI 0.80-0.89], p < 0.001). CONCLUSIONS: Patients with young-onset cholangiocarcinoma may represent a demographically and clinically distinct group from those with more typical-onset disease.

Colon Cancer Disparities in Stage at Presentation and Time to Surgery for Asian Americans, Native Hawaiians, and Pacific Islanders: A Study with Disaggregated Ethnic Groups.

BACKGROUND: Vast differences in barriers to care exist among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) groups and may manifest as disparities in stage at presentation and access to treatment. Thus, we characterized AANHPI patients with stage 0-IV colon cancer and examined differences in (1) stage at presentation and (2) time to surgery relative to white patients. PATIENTS AND METHODS: We assessed all patients in the National Cancer Database (NCDB) with stage 0-IV colon cancer from 2004 to 2016 who identified as white, Chinese, Japanese, Filipino, Native Hawaiian, Korean, Vietnamese, Laotian, Hmong, Kampuchean, Thai, Asian Indian or Pakistani, and Pacific Islander. Multivariable ordinal logistic regression defined adjusted odds ratios (AORs), with 95% confidence intervals (CI), of (1) patients presenting with advanced stage colon cancer and (2) patients with stage 0-III colon cancer receiving surgery at ≥ 60 days versus 30-59 days versus < 30 days postdiagnosis, adjusting for sociodemographic/clinical factors. RESULTS: Among 694,876 patients, Japanese [AOR 1.08 (95% CI 1.01-1.15), p < 0.05], Filipino [AOR 1.17 (95% CI 1.09-1.25), p < 0.001], Korean [AOR 1.09 (95% CI 1.01-1.18), p < 0.05], Laotian [AOR 1.51 (95% CI 1.17-1.95), p < 0.01], Kampuchean [AOR 1.33 (95% CI 1.04-1.70), p < 0.01], Thai [AOR 1.60 (95% CI 1.22-2.10), p = 0.001], and Pacific Islander [AOR 1.41 (95% CI 1.20-1.67), p < 0.001] patients were more likely to present with more advanced colon cancer compared with white patients. Chinese [AOR 1.27 (95% CI 1.17-1.38), p < 0.001], Japanese [AOR 1.23 (95% CI 1.10-1.37], p < 0.001], Filipino [AOR 1.36 (95% CI 1.22-1.52), p < 0.001], Korean [AOR 1.16 (95% CI 1.02-1.32), p < 0.05], and Vietnamese [AOR 1.55 (95% CI 1.36-1.77), p < 0.001] patients were more likely to experience greater time to surgery than white patients. Disparities persisted when comparing among AANHPI subgroups. CONCLUSIONS: Our findings reveal key disparities in stage at presentation and time to surgery by race/ethnicity among AANHPI subgroups. Heterogeneity upon disaggregation underscores the importance of examining and addressing access barriers and clinical disparities.