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Purpose: We estimated the 5-year overall, age at diagnosis- and stage-specific colorectal cancer survival in patients treated through their coverage with Seguro Popular., Methods: We conducted a retrospective study using a dataset that included 1418 colorectal cancer patients covered by Seguro Popular (Mexico's public health insurance system covering 60 % of the population) between 2013 and 2016. Deaths were identified using the Epidemiologic Death Statistics Subsystem registry, with a specialized algorithm for record linkage. The Kaplan-Meier method was used to estimate overall survival curves and the proportion of patients alive at various follow-up time points. We compared survival curves across subgroups using the log-rank test., Results: In this study the average age at diagnosis was 56 years with 31.9 % of patients diagnosed before the age of 50. Most cases (78.1 %) were diagnosed in advanced stages (i.e., III and IV), with nearly half of the cases originating in the rectum. The overall 5-year survival was 50 %, with higher survival (74 %) for patients with stage I-II and lower survival for those with stage III (58 %) and IV (33 %). While age at diagnosis was not associated with survival for early-stage colorectal cancer, younger patients with metastatic disease had a worse prognosis compared to older patients., Conclusion: The 5-year overall colorectal cancer survival was 50 %, with variation by clinical stage. Almost 80 % of the population was diagnosed with advanced stages, underscoring the need for screening programs. Younger patients with metastatic disease exhibited a worse prognosis, highlighting the need for targeted interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Use of fine-needle aspiration biopsy (FNAB) specimens on Xpert Breast Cancer STRAT4 Assay (STRAT4; Cepheid, Sunnyvale, CA, USA), a CE-marked in-vitro diagnostic medical device, could potentially increase access to breast cancer biomarker testing in resource-constrained settings. We aimed to assess the performance of a research use-only version of STRAT4 using FNAB specimens in Tanzania., Methods: In this prospective diagnostic accuracy study, patients aged 18 years or older with palpable breast masses presenting to the FNAB Clinic at Muhimbili National Hospital (Dar es Salaam, Tanzania) were recruited consecutively. Patients who were pregnant, lactating, or had a previous diagnosis of breast cancer were excluded. STRAT4 testing was performed on off-label FNAB samples using four protocols: the 1 × protocol (using the standard lysate method) on FNAB smears (1 × FNAB), quick lysis and Maui protocols (both on FNAB smears), and the 1 × protocol on formalin-fixed paraffin-embedded (FFPE) cell block material (1 × cell block). For 1 × FNAB and 1 × cell block, tissue was processed using FFPE lysis reagent, incubated at 80°C with proteinase K, and followed by addition of 95% or higher ethanol. Quick lysis was processed using FFPE lysis reagent and 95% or higher ethanol, whereas Maui was processed using a proprietary research-use only lysis reagent. The primary outcomes were overall concordance, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of STRAT4 as compared with immunohistochemistry or immunohistochemistry plus fluorescence in-situ hybridisation performed on cell blocks using clinically validated protocols in a Clinical Laboratory Improvement Amendments-accredited laboratory at the University of California, San Francisco (San Francisco, CA, USA)., Findings: Between Nov 29, 2017, and Dec 17, 2020, 208 patients were enrolled. Of 208 cases, 51 (25%) were excluded from analysis because of insufficient tissue in the cell block or absent cell blocks, leaving 157 participants (all female) for analysis. For oestrogen receptor, 1 × FNAB had the best performance, with an overall concordance of 95% (95% CI 90-100), sensitivity of 94% (85-100), specificity of 97% (90-100), and AUC of 0·96 (0·81-1·00). For progesterone receptor, 1 × cell block had the best overall performance (overall concordance 89% [95% CI 84-95], sensitivity 91% [82-99], and specificity 89% [81-97], with an AUC of 0·93 [0·89-0·99]) and 1 × FNAB performed the best among the smear protocols, with a concordance of 84% (95% CI 74-93), sensitivity of 63% (43-82), specificity of 97% (92-100), and AUC of 0·91 (0·72-0·97). For HER2, Maui had the highest agreement, with an overall concordance of 93% (95% CI 89-98), sensitivity of 96% (88-100), specificity of 92% (87-98), and AUC of 0·95 (0·98-1·00). For Ki67, Maui had the best performance of smear protocols, with a concordance of 73% (95% CI 64-82), sensitivity of 70% (58-81), specificity of 81% (66-96), and AUC of 0·80 (0·54-0·82)., Interpretation: Processing FNAB samples with STRAT4 is feasible in Tanzania, and performance for the oestrogen receptor is robust. Further optimisation of STRAT4 for FNAB has the potential to improve timely access to breast cancer diagnostics in resource-constrained settings., Funding: US National Institutes of Health; UCSF Global Cancer Program, Helen Diller Family Comprehensive Cancer Center; UCSF Department of Pathology; and Cepheid., Competing Interests: Declaration of interests KEH, JW, and MB are employees of Cepheid and own stock shares in Cepheid's parent company, Danaher. DLN and EV received funding, equipment, and study materials for the project from Cepheid. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Clinical practice guidelines are widely used in oncology to guide clinical decision making and inform health policy and planning. In recent years, the National Comprehensive Cancer Network and the American Society of Clinical Oncology, as well as other international groups, have developed resource-stratified guidelines to guide clinicians and policymakers on cancer diagnosis and management in settings with various levels of resource constraints. Current methods for developing resource-stratified guidelines rely heavily on supporting evidence originating from high-income countries. In this commentary, the authors discuss limitations of the existing methods to develop resource-stratified guidelines and offer perspective on ways to strengthen the guidelines and their evidence base. Pulling from conceptual frameworks in the health policy domain, the authors outline a more inclusive approach to evidence synthesis that seeks to integrate the growing volume of cancer research emerging from low- and middle-income countries. The authors also introduce a revised evidence framework that provides transparency into the generalizability of evidence within the guidelines. These changes have the potential to enhance resource-stratified guidelines and bring us one step closer to the goal of evidence-based guidelines that are appropriate for diverse settings and unique patient populations across the world., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

Background: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies., Materials and Methods: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60., Results: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative., Conclusion: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care., (© The Author(s) 2024. Published by Oxford University Press.)

In 1984, 21 years after the first liver transplantation, Thomas Starzl achieved a milestone by performing the world's first combined heart-liver transplantation. While still uncommon, the practice of combined heart-liver transplants is on the rise globally. In this review, the authors delve into the current literature on this procedure, highlighting the evolving landscape and key considerations for anesthesiologists. Over the years, there has been a remarkable increase in the number of combined heart-liver transplantations conducted worldwide. This surge is largely attributed to the growing population of adult survivors with single-ventricle physiology, palliated with a Fontan procedure, who later present with late Fontan failure and Fontan-associated liver disease. Research indicates that combined heart-liver transplantation is an effective treatment option, with reported outcomes comparable with isolated heart or liver transplants. Managing anesthesia during a combined heart-liver transplant procedure is challenging, especially in the context of underlying Fontan physiology. International experience in this field remains somewhat limited, with most techniques derived from expert opinions or experiences with single-organ heart and liver transplants. These procedures are highly complex and performed infrequently. As the number of combined heart-liver transplants continues to rise globally, there is a growing need for clear guidance on periprocedural surgical and anesthetic management. Anesthesiologists overseeing these patients must consider multiple factors, balancing various comorbidities with significant hemodynamic and metabolic shifts. An increase in (multicenter) studies focusing on specific interventions to enhance patient and organ outcomes is anticipated in the coming years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Persistent gastrointestinal (GI) symptoms are frequently experienced by colon cancer survivors and may help identify patients with higher utilization of healthcare services. To assess the relationship between GI symptoms and specialty care utilization among colon cancer survivors., Methods: A prospective longitudinal cohort study at an academic medical center of 126 adults surgically treated for stage I-IV colon cancer between February 2017 and June 2022. Participants reported GI symptoms through the EORTC QLQ-C30 and QLQ-CR29 at enrollment and as frequently as every 6 months for 5 years. Main outcome measures were visits, telephone encounters, and secure messages with a medical provider within specialty oncology clinics within 6 months after each survey completion. Generalized linear mixed regression model for repeated measurements with random trajectory for each participant was performed to estimate the associations between symptoms and healthcare use. Models were adjusted for demographics, clinical and surgical factors, and timing in relation to onset of the COVID-19 pandemic., Results: In the 6 months after each survey time point, patients averaged 1.2 visits, 0.5 telephone encounters, and 3.2 patient-initiated messages. In adjusted models, those with any abdominal pain (RR 1.45; p = 0.002), buttock pain (RR 1.30; p = 0.050), or increased stool frequency (RR 1.26; p = 0.046) had more clinic visits in the following 6 months than those without these symptoms. Including these three symptoms in one model revealed that only abdominal pain was statistically significantly associated with increased clinic visits (RR 1.36; p = 0.016). Patients with any blood or mucus in stool (RR 2.46; p = 0.009) had significantly more telephone encounters, and those with any abdominal pain (RR 1.65; p = 0.002) had significantly more patient-initiated messages than those without these symptoms., Conclusions: Our findings identify GI symptoms associated with increased use of oncologic specialty care among colon cancer survivors, with abdominal pain as an important predictor of utilization., Implications for Cancer Survivors: Early identification and anticipatory management of colon cancer survivors experiencing abdominal pain may decrease healthcare utilization., (© 2024. The Author(s).)

Purpose: To describe the global landscape of clinical research into interventions for gastroesophageal cancers (GECs), with examination of trial characteristics, geographic distribution of trial sites, and factors associated with trial termination., Methods: We queried ClinicalTrials.gov to identify all completed or terminated phase III interventional studies investigating GECs (esophageal squamous cell carcinoma [ESCC], esophageal adenocarcinoma [EAC], gastroesophageal junctional [GEJ], and gastric adenocarcinoma). Data on all reported trial characteristics were extracted. Pearson's chi-square and Fisher's exact tests were used to compare differences in completed and terminated trials. Multivariate logistic regression evaluated predictors of termination., Results: A total of 179 trials were identified; of these, 90% were therapeutic. Most included sites in Asia (61%) and Europe (32%); few included sites in Africa (4%). Thirty percent included sites in low- and middle-income countries (LMICs). Most (70%) focused on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% on ESCC alone. Sixteen percent (n = 29) of trials terminated prematurely. In multivariate analysis, study site number, location of recruitment sites, and patient population emerged as predictors of termination. Trials recruiting from US-based sites were more likely to terminate (odds ratio [OR], 7.22 [95% CI, 1.59 to 32.69]). Trials conducted exclusively in LMICs were less likely to terminate (OR, 0.04 [95% CI, 0.01 to 0.59] v conducted in high-income countries [HICs] alone). Studies on ESCC were more likely to terminate (OR, 17.74 [95% CI, 1.49 to 210.69])., Conclusion: Although 80% of GECs occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Overall, this study highlights (1) a missed opportunity to recruit patients from high-incidence regions globally; and (2) a pressing need for increasing funding, infrastructure, and support for GEC trials in LMICs.

Background: The CRUCIAL trial (NCT04217421) is investigating the effect of postnatal and perioperative administration of allopurinol on postoperative brain injury in neonates with critical congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass (CPB) shortly after birth., Objective: This study aimed to characterize the pharmacokinetics (PK) of allopurinol and oxypurinol during the preoperative, intraoperative, and postoperative phases in this population, and to evaluate target attainment of the current dosing strategy., Methods: Nonlinear mixed-effects modeling was used to develop population PK models in 14 neonates from the CRUCIAL trial who received up to five intravenous allopurinol administrations throughout the postnatal and perioperative periods. Target attainment was defined as achieving an allopurinol concentration >2 mg/L in at least two-thirds of the patients during the first 24 h after birth and between the start and 36 h after cardiac surgery with CPB., Results: A two-compartment model for allopurinol was connected to a one-compartment model for oxypurinol with an auto-inhibition effect on the conversion, which best described the PK. In a typical neonate weighing 3.5 kg who underwent cardiac surgery at a postnatal age (PNA) of 5.6 days, the clearance (CL) of allopurinol and oxypurinol at birth was 0.95 L/h (95% confidence interval 0.75-1.2) and 0.21 L/h (0.17-0.27), respectively, which subsequently increased with PNA to 2.97 L/h and 0.41 L/h, respectively, before CPB. During CPB, allopurinol and oxypurinol CL decreased to 1.38 L/h (0.9-1.87) and 0.12 L/h (0.05-0.22), respectively. Post-CPB, allopurinol CL increased to 2.21 L/h (1.74-2.83), while oxypurinol CL dropped to 0.05 L/h (0.01-0.1). Target attainment was 100%, 53.8%, and 100% at 24 h postnatally, 24 h after the start of CPB, and 36 h after the end of cardiac surgery, respectively. The combined concentrations of allopurinol and oxypurinol maintained ≥ 90% inhibition of xanthine oxidase (IC90 XO ) throughout the postnatal and perioperative period., Conclusions: The minimal target concentration of allopurinol was not achieved at every predefined time interval in the CRUCIAL trial; however, the dosing strategy used was deemed adequate, since it yielded concentrations well exceeding the IC90 XO . The decreased CL of both compounds during CPB suggests influence of the hypothermia, hemofiltration, and the potential sequestration of allopurinol in the circuit. The reduced CL of oxypurinol after CPB is likely attributable to impaired kidney function., (© 2024. The Author(s).)

Purpose: Minimal residual disease (MRD) detection can identify the recurrence in patients with colorectal cancer (CRC) following definitive treatment. We evaluated a plasma-only MRD assay to predict recurrence and survival in patients with metastatic CRC who underwent curative intent procedures (surgery and/or radiotherapy), with or without (neo)adjuvant chemotherapy. The primary objective of this study was to assess the correlation of postprocedure tumor cell-free DNA detection status with radiographic disease recurrence., Experimental Design: Preprocedure and postprocedure longitudinal samples were collected from 53 patients and analyzed with a multiomic MRD assay detecting circulating tumor DNA (ctDNA) from genomic and epigenomic signals. Preprocedure and postprocedure ctDNA detection correlated with recurrence-free and overall survival (OS)., Results: From 52 patients, 230/233 samples were successfully analyzed. At the time of data cutoff, 36 (69.2%) patients recurred with median follow-up of 31 months. Detectable ctDNA was observed in 19/42 patients (45.2%) with ctDNA analyzed 3 weeks postprocedure. ctDNA detection 3 weeks postprocedure was associated with shorter median recurrence-free survival (RFS; HR, 5.27; 95% CI, 2.31-12.0; P < 0.0001) and OS (HR, 12.83; 95% CI, 3.6-45.9; P < 0.0001). Preprocedure ctDNA detection status was not associated with RFS but was associated with improved OS (HR, 4.65; 95% CI, 1.4-15.2; P = 0.0111). Undetectable ctDNA preprocedure had notable long-term OS, >90% 3 years postprocedure., Conclusions: In this cohort of oligometastatic CRC, detection of ctDNA preprocedure or postprocedure was associated with inferior outcomes even after accounting for known prognostic clinicopathologic variables. This suggests ctDNA may enhance current risk stratification methods helping the evaluation of novel treatments and surveillance strategies toward improving patient outcomes., (©2024 The Authors; Published by the American Association for Cancer Research.)

As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute-designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The primary objective of this study was to determine whether workplace culture in academic oncology differed by gender, during the COVID-19 pandemic., Materials and Methods: We used the Culture Conducive to Women's Academic Success (CCWAS), a validated survey tool, to investigate the academic climate at an NCI-designated Cancer Center. We adapted the CCWAS to be applicable to people of all genders. The full membership of the Cancer Center was surveyed (total faculty = 429). The questions in each of 4 CCWAS domains (equal access to opportunities, work-life balance, freedom from gender bias, and leadership support) were scored using a 5-point Likert scale. Median score and interquartile ranges for each domain were calculated., Results: A total of 168 respondents (men = 58, women = 106, n = 4 not disclosed) submitted survey responses. The response rate was 39% overall and 70% among women faculty. We found significant differences in perceptions of workplace culture by gender, both in responses to individual questions and in the overall score in the following domains: equal access to opportunities, work-life balance, and leader support, and in the total score for the CCWAS., Conclusions: Our survey is the first of its kind completed during the COVID-19 pandemic at an NCI-designated Cancer Center, in which myriad factors contributed to burnout and workplace challenges. These results point to specific issues that detract from the success of women pursuing careers in academic oncology. Identifying these issues can be used to design and implement solutions to improve workforce culture, mitigate gender bias, and retain faculty., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Virtual hospital-at-home care might be an alternative to standard hospital care for patients with infectious diseases. In this study, we explore the potential for virtual hospital-at-home care and a potential design for this population., Methods: This was a retrospective cohort study of internal medicine patients suspected of infectious diseases, admitted between 1 January and 31 December 2019. We collected information on delivered care during emergency department visits, the first 24 h, between 24 and 72 h, and after 72 h of admission. Care components that could be delivered at home were combined into care packages, and the potential number of eligible patients per package was described. The most feasible package was described in detail., Results: 763 patients were included, mostly referred for general internal medicine (35%), and the most common diagnosis was lower respiratory tract infection (27%). The most frequently administered care components were laboratory tests, non-oral medication, and intercollegiate consultation. With a combination of telemonitoring, video consultation, non-oral medication administration, laboratory tests, oxygen therapy, and radiological diagnostics, 48% of patients were eligible for hospital-at-home care, with 35% already eligible directly after emergency department visits., Conclusion: While the potential for virtual hospital-at-home care is high, it depends greatly on which care can be arranged.

Background: Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve all patients who would benefit from it. Allocation systems are needed to guide patient prioritization for radiotherapy in resource-limited contexts. These systems should be informed by allocation principles deemed relevant to stakeholders. This study explores the ethical dilemmas and views of decision-makers engaged in real-world prioritization of scarce radiotherapy resources at a cancer center in Rwanda in order to identify relevant principles., Methods: Semi-structured interviews were conducted with a purposive sample of 22 oncology clinicians, program leaders, and clinical advisors. Interviews explored the factors considered by decision-makers when prioritizing patients for radiotherapy. The framework method of thematic analysis was used to characterize these factors. Bioethical analysis was then applied to determine their underlying normative principles., Results: Participants considered both clinical and non-clinical factors relevant to patient prioritization for radiotherapy. They widely agreed that disease curability should be the primary overarching driver of prioritization, with the goal of saving the most lives. However, they described tension between curability and competing factors including age, palliative benefit, and waiting time. They were divided about the role that non-clinical factors such as social value should play, and agreed that poverty should not be a barrier., Conclusions: Multiple competing principles create tension with the agreed upon overarching goal of maximizing lives saved, including another utilitarian approach of maximizing life-years saved as well as non-utilitarian principles, such as egalitarianism, prioritarianism, and deontology. Clinical guidelines for patient prioritization for radiotherapy can combine multiple principles into a single allocation system to a significant extent. However, conflicting views about the role that social factors should play, and the dynamic nature of resource availability, highlight the need for ongoing work to evaluate and refine priority setting systems based on stakeholder views., (© 2024. The Author(s).)

This study evaluated the robustness of multi-isocenter Volumetric Modulated Arc Therapy Total Body Irradiation dose distribution in the overlapping region between the head-first and feet-first computed tomography scans, considering the longitudinal isocenter shifts recorded during treatment delivery. For 15 out of 22 patients, the dose distribution in the overlapping region fulfilled all three the robustness criteria. The overlapping region dose distribution of the remaining 7 cases fulfilled two robustness criteria. The dose distribution was found to be robust against daily recorded longitudinal isocenter shifts, as a consequence of the patient position verification procedure, of up to 16 mm., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objectives: In a sample of patients with cancer (n=1145) who were assessed during the height of the COVID-19 pandemic, latent profile analysis was used to identify subgroups of patients with distinct stress profiles and to evaluate for differences in demographic and clinical characteristics and symptom severity scores among these subgroups., Methods: Patients completed measures of cancer-specific and COVID-19 stress, global stress, social isolation, loneliness, depression, state and trait anxiety, morning and evening fatigue, morning and evening energy, sleep disturbance, cognitive function, and pain. Latent profile analysis was used to identify subgroups of patients with distinct stress profiles. Differences among the subgroups in study measures were evaluated using parametric and non-parametric tests., Results: Using clinically meaningful cut-off scores for the stress measures, four distinct stress profiles were identified (ie, none class (51.3%); low stress and moderate loneliness class (24.4%), high stress and moderate loneliness class (14.0%), and very high stress and moderately high loneliness class (high, 10.3%)). Risk factors associated with membership in the high class included: younger age, lower annual household income, lower functional status and higher comorbidity burden. The two worst stress profiles reported clinically meaningful levels of all of the common symptoms associated with cancer and its treatments., Conclusion: Findings from this study, obtained prior to the availability of COVID-19 vaccines and anti-viral medications, provide important 'benchmark data' to evaluate for changes in stress and symptom burden in patients with cancer in the postvaccine era and in patients with long COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Context.—: Rapid onsite evaluation (ROSE) is critical in determining sample adequacy and triaging cytology samples. Although fine-needle aspiration biopsy (FNAB) is the primary method of initial tissue sampling in Tanzania, ROSE is not practiced., Objective.—: To investigate the performance of ROSE in determining cellular adequacy and providing preliminary diagnoses in breast FNAB in a low-resource setting., Design.—: Patients with breast masses were recruited prospectively from the FNAB clinic at Muhimbili National Hospital. Each FNAB was evaluated by ROSE for overall specimen adequacy, cellularity, and preliminary diagnosis. The preliminary interpretation was compared to the final cytologic diagnosis and histologic diagnosis, when available., Results.—: Fifty FNAB cases were evaluated, and all were adequate for diagnosis on ROSE and final interpretation. Overall percentage of agreement (OPA) between preliminary and final cytologic diagnosis was 84%, positive percentage of agreement (PPA) was 33%, and negative percentage of agreement (NPA) was 100% (κ = 0.4, P < .001). Twenty-one cases had correlating surgical resections. OPA between preliminary cytologic and histologic diagnoses was 67%, PPA was 22%, and NPA was 100% (κ = 0.2, P = .09). OPA between final cytologic and histologic diagnoses was 95%, PPA was 89%, and NPA was 100% (κ = 0.9, P = <.001)., Conclusions.—: False-positive rates of ROSE diagnoses for breast FNAB are low. While preliminary cytologic diagnoses had a high false-negative rate, final cytologic diagnoses had overall high concordance with histologic diagnoses. Therefore, the role of ROSE for preliminary diagnosis should be considered carefully in low-resource settings, and it may need to be paired with additional interventions to improve pathologic diagnosis., (© 2024 College of American Pathologists.)

Colorectal cancer (CRC) is the third most common cancer in the USA and worldwide. In the USA, nearly one-third of CRC cases are anatomically classified as rectal cancer. Over the past few decades, continued refinement of multimodality treatment and the introduction of new therapeutic agents have enhanced curative treatment rates and quality of life outcomes. As treatments improve and the incidence of young onset rectal cancer rises, the number of rectal cancer survivors grows each year. This trend highlights the growing importance of rectal cancer survivorship. Multimodality therapy with systemic chemotherapy, chemoradiation, and surgery can result in chronic toxicities in multiple organ systems, requiring a multi-disciplinary care model with services ranging from appropriate cancer surveillance to management of long-term toxicities and optimization of modifiable risk factors. Here, we review the evidence on these long-term toxicities and provide management considerations from consensus guidelines. Specific topics include bowel dysfunction from radiation and surgery, oxaliplatin-induced neuropathy, accelerated bone degeneration, the impact of fluoropyrimidines on long-term cardiovascular health, urinary incontinence, sexual dysfunction, and psychosocial distress. Additionally, we review modifiable risk factors to inform providers and rectal cancer survivors of various lifestyle and behavioral changes that can be made to improve their long-term health outcomes., (© 2022. The Author(s).)

Tracheostomy is a lifesaving, essential procedure performed for airway obstruction in the case of head and neck cancers, prolonged ventilator use, and for long-term pulmonary care. While successful quality improvement interventions in high-income countries such as through the Global Tracheostomy Collaborative significantly reduced length of hospital stay and decreased levels of anxiety among patients, limited literature exists regarding tracheostomy care and practices in low and middle-income countries (LMIC), where most of the world resides. Given limited literature, this scoping review aims to summarize published tracheostomy studies in LMICs and highlight areas in need of quality improvement and clinical research efforts. Based on the PRISMA guidelines, a scoping review of the literature was performed through MEDLINE/PubMed and Embase using terms related to tracheostomy, educational and quality improvement interventions, and LMICs. Publications from 2000-2022 in English were included. Eighteen publications representing 10 countries were included in the final analysis. Seven studies described baseline needs assessments, 3 development of training programs for caregivers, 6 trialed home-based or hospital-based interventions, and finally 2 articles discussed development of standardized protocols. Overall, studies highlighted the unique challenges to tracheostomy care in LMICs including language, literacy barriers, resource availability (running water and electricity in patient homes), and health system access (financial costs of travel and follow-up). There is currently limited published literature on tracheostomy quality improvement and care in LMICs. Opportunities to improve quality of care include increased efforts to measure complications and outcomes, implementing evidence-based interventions tailored to LMIC settings, and using an implementation science framework to study tracheostomy care in LMICs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Selekwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The interest in finding new targets in the tumor microenvironment for anti-cancer therapy has increased rapidly over the years. More specifically, the tumor-associated blood vessels are a promising target. We recently found that the intermediate filament protein vimentin is externalized by endothelial cells of the tumor vasculature. Extracellular vimentin was shown to sustain angiogenesis by mimicking VEGF and supporting cell migration, as well as endothelial cell anergy, the unresponsiveness of the endothelium to proinflammatory cytokines. The latter hampers immune cell infiltration and subsequently provides escape from tumor immunity. Other studies showed that extracellular vimentin plays a role in sustained systemic and local inflammation. Here we will review the reported roles of extracellular vimentin with a particular emphasis on its involvement in the interactions between immune cells and the endothelium in the tumor microenvironment. To this end, we discuss the different ways by which extracellular vimentin modulates the immune system. Moreover, we review how this protein can alter immune cell-vessel wall adhesion by altering the expression of adhesion proteins, attenuating immune cell infiltration into the tumor parenchyma. Finally, we discuss how vimentin-targeting therapy can reverse endothelial cell anergy and promote immune infiltration, supporting anti-tumor immunity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392., Competing Interests: Yves d’Udekem receives consultancy fees from Actelion (Janssen) and travel fees from Berlin Heart., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Background: Esophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC., Methods: We describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA)., Results: We observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort., Conclusions: This study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites., Impact: Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date., (©2023 American Association for Cancer Research.)

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system., Materials and Methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety metrics, and clinical acceptability by two ORCI physician investigators. Dice similarity coefficient (DSC) agreement analysis was conducted between original and new contour sets., Results: The average time to manually develop treatment plans was 7 days. Applying RPA, automated same-day contours and plans were developed for 29 of 30 patients (97%). Of the 29 evaluable contours, all were approved with <2 minutes of edit time. Agreement between clinical and RPA contours was highest for the rectum (median DSC, 0.72) and bladder (DSC, 0.90). Agreement was lower with the primary tumor clinical target volume (CTVp; DSC, 0.69) and elective nodal clinical target volume (CTVn; DSC, 0.63). All RPA plans were approved with <4 minutes of edit time. RPA target coverage was excellent, covering the CTVp with median V45 Gy 100% and CTVn with median V45 Gy 99.9%., Conclusion: Automation-assisted 3DCRT contouring yielded high levels of agreement for normal structures. The RPA met all planning safety metrics and sustained high levels of clinical acceptability with minimal edit times. This tool offers the potential to significantly decrease RT planning timelines while maintaining high-quality RT delivery in resource-constrained settings.

Background: Adherence to the American Cancer Society (ACS) guidelines of avoiding obesity, maintaining physical activity, and consuming a diet rich in fruits, vegetables, and whole grains is associated with longer survival in colorectal cancer (CRC) survivors. Dietary components of the ACS guidelines may act in part by changing the microbiome, which is implicated in CRC outcomes., Objectives: We conducted a pilot cross-sectional study to explore associations between ACS guidelines and the gut microbiome., Methods: Stool samples and questionnaires were collected from 28 CRC survivors at the University of California, San Francisco from 2019 to 2020. ACS scores were calculated based on validated questionnaires. Gut microbial community structure from 16S amplicons and gene/pathway abundances from metagenomics were tested for associations with the ACS score and its components using ANOVA and general linear models., Results: The overall ACS score was not significantly associated with variations in the fecal microbiota. However, fruit and vegetable intake and alcohol intake accounted for 19% (P = 0.005) and 13% (P = 0.01) of variation in the microbiota, respectively. Fruit/vegetable consumption was associated with increased microbial diversity, increased Firmicutes, decreased Bacteroidota, and changes to multiple genes and metabolic pathways, including enriched pathways for amino acid and short-chain fatty acid biosynthesis and plant-associated sugar degradation. In contrast, alcohol consumption was positively associated with overall microbial diversity, negatively associated with Bacteroidota abundance, and associated with changes to multiple genes and metabolic pathways. The other components of the ACS score were not statistically significantly associated with the fecal microbiota in our sample., Conclusions: These results guide future studies examining the impact of changes in the intake of fruits, vegetables, and alcoholic drinks on the gut microbiome of CRC survivors., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)