Search

Background: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined., Methods: This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach., Discussion: This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research., Trial Registration: This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 ., (© 2022. The Author(s).)

Background: We conducted a pilot 2-arm randomized controlled trial to assess the feasibility of a digital health intervention to increase moderate-to-vigorous physical activity in patients with colorectal cancer (CRC) during chemotherapy., Objective: This study aimed to determine whether a digital health physical activity intervention is feasible and acceptable during chemotherapy for CRC., Methods: Potentially eligible patients with CRC expected to receive at least 12 weeks of chemotherapy were identified in person at the University of California, San Francisco, and on the web through advertising. Eligible patients were randomized 1:1 to a 12-week intervention (Fitbit Flex, automated SMS text messages) versus usual care. At 0 and 12 weeks, patients wore an Actigraph GT3X+ accelerometer for 7 days and completed surveys, body size measurements, and an optional 6-minute walk test. Participants could not be masked to their intervention arm, but people assessing the body size and 6-minute walk test outcomes were masked. The primary outcomes were adherence (eg, Fitbit wear and text response rate) and self-assessed acceptability of the intervention. The intervention would be considered feasible if we observed at least 80% complete follow-up and 70% adherence and satisfaction, a priori., Results: From 2018 to 2020, we screened 240 patients; 53.3% (128/240) of patients were ineligible and 26.7% (64/240) declined to participate. A total of 44 patients (44/240, 18%) were randomized to the intervention (n=22) or control (n=22) groups. Of these, 57% (25/44) were women; 68% (30/44) identified as White and 25% (11/44) identified as Asian American or Pacific Islander; and 77% (34/44) had a 4-year college degree. The median age at enrollment was 54 years (IQR 45-62 years). Follow-up at 12 weeks was 91% (40/44) complete. In the intervention arm, patients wore Fitbit devices on a median of 67 out of 84 (80%) study days and responded to a median of 17 out of 27 (63%) questions sent via SMS text message. Among 19 out of 22 (86%) intervention patients who completed the feedback survey, 89% (17/19) were satisfied with the Fitbit device; 63% (12/19) were satisfied with the SMS text messages; 68% (13/19) said the SMS text messages motivated them to exercise; 74% (14/19) said the frequency of SMS text messages (1-3 days) was ideal; and 79% (15/19) said that receiving SMS text messages in the morning and evening was ideal., Conclusions: This pilot study demonstrated that many people receiving chemotherapy for CRC are interested in participating in digital health physical activity interventions. Fitbit adherence was high; however, participants indicated a desire for more tailored SMS text message content. Studies with more socioeconomically diverse patients with CRC are required., Trial Registration: ClinicalTrials.gov NCT03524716; https://clinicaltrials.gov/ct2/show/NCT03524716., (©Erin L Van Blarigan, Anand Dhruva, Chloe E Atreya, Stacey A Kenfield, June M Chan, Alexandra Milloy, Iris Kim, Paige Steiding, Angela Laffan, Li Zhang, Sorbarikor Piawah, Yoshimi Fukuoka, Christine Miaskowski, Frederick M Hecht, Mi-Ok Kim, Alan P Venook, Katherine Van Loon. Originally published in JMIR Cancer (https://cancer.jmir.org), 11.01.2022.)

Introduction: There are no formal guidelines for the management of patients with primary gastrointestinal (GI) cancers who have lung-exclusive or lung-predominant metastases. We performed a retrospective analysis to evaluate host and tumor characteristics of this patient population, model patterns and rates of growth, and describe treatment approaches., Materials and Methods: Eligible patients had a GI cancer with either synchronous or metachronous lung metastases but no other visceral or peritoneal sites of involvement. In addition to collecting detailed patient-specific and tumor-specific information, all imaging studies (computed tomography±positron emission tomography scans) were reviewed by an independent radiologist. Up to 5 lung metastases were tracked through each patient's clinical course. Growth rate was estimated using a linear mixed model analysis., Results: Forty patients met eligibility criteria (18 pancreatic, 15 colorectal, 6 hepatobiliary, 1 gastroesophageal; synchronous vs. metachronous, 13 and 27, respectively). Median time from original cancer diagnosis to onset of metachronous lung lesions was 16 months. Interval from first appearance of lung metastases to treatment initiation was 6.2 months. Average growth rate of the largest lesion was 0.21 mm/mo (95% confidence interval, 0.12-0.30), with substantial intrapatient and interpatient variability. Sixty percent of patients underwent locoregional interventions in addition to or in lieu of systemic therapy for their lung metastases. Median survival of the entire study cohort from first appearance of lung metastases was 54 months., Conclusions: Lung metastases from primary GI cancers have a variable but overall indolent natural history and are generally associated with prolonged survival outcomes. Further efforts to define patterns of growth of lung metastases, informed by size, number, and clinical/molecular features, are needed to guide appropriate timing and selection of therapy as well as surveillance strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To ensure availability of hospital beds and improve COVID-19 patients' well-being during the ongoing pandemic, hospital care could be offered at home. Retrospective studies show promising results of deploying remote hospital care to reduce the number of days spent in the hospital, but the beneficial effect has yet to be established., Methods: We conducted a single centre, randomised trial from January to June 2021, including hospitalised COVID-19 patients who were in the recovery stage of the disease. Hospital care for the intervention group was transitioned to the patient's home, including oxygen therapy, medication and remote monitoring. The control group received in-hospital care as usual. The primary endpoint was the number of hospital-free days during the 30 days following randomisation. Secondary endpoints included health care consumption during the follow-up period and mortality., Results: A total of 62 patients were randomised (31 control, 31 intervention). The mean difference in hospital-free days was 1.7 (26.7 control vs. 28.4 intervention, 95% CI of difference -0.5 to 4.2, p = 0.112). In the intervention group, the index hospital length of stay was 1.6 days shorter (95% CI -2.4 to -0.8, p < 0.001), but the total duration of care under hospital responsibility was 4.1 days longer (95% CI 0.5 to 7.7, p = 0.028)., Conclusion: Remote hospital care for recovering COVID-19 patients is feasible. However, we could not demonstrate an increase in hospital-free days in the 30 days following randomisation. Optimising the intervention, timing, and identification of patients who will benefit most from remote hospital care could improve the impact of this intervention.

Purpose: A metastatic cancer diagnosis is associated with high levels of distress in patients and caregivers, which may be alleviated by mindfulness interventions. Research on scalable, tailored, online mindfulness training programs is needed. We sought to test the feasibility and acceptability of a remotely delivered 8-week mindfulness-based intervention, Being Present 2.0 (BP2.0)., Methods: We performed a single-arm feasibility study of BP2.0 among patients with any metastatic gastrointestinal cancer receiving chemotherapy, with or without an informal caregiver. Participants were instructed to practice mindfulness using pre-recorded guided meditations 5 times per week using a study-specific website and to attend a weekly live, interactive virtual meeting facilitated by a trained instructor. The web-based platform enabled direct measurement of adherence., Results: The study enrolled 46 of 74 (62%) patients contacted, together with 23 caregivers (69 participants total), from May to October 2018. Median patient age was 52 (range 20-70 years), 39% were male, 67% non-Hispanic white, 65% had colorectal cancer, and 78% lived outside of San Francisco. The top reasons cited for participation were to reduce stress/anxiety and learn how to meditate. Mean baseline National Comprehensive Cancer Network Distress Thermometer (NCCN DT) scores were 4.7 (patients) and 5.8 (caregivers). The study discontinuation rate was 20% (eight patients and six caregivers). Among the remaining 55 participants, 43 (78%) listened to at least one audio recording and/or attended at least one virtual meeting, although adherence data was incomplete. The retention rate was 71%, with 39 participants completing at least one follow-up assessment. In post-intervention qualitative interviews, 88% of respondents reported a positive experience. Compared to baseline, participants reported significantly reduced post-intervention NCCN DT scores (mean 3.1; P = .012)., Conclusion: The BP2.0 online mindfulness-based program is feasible and acceptable for patients with metastatic gastrointestinal cancer and caregivers. These results will guide plans for a follow-up efficacy study. ClinicalTrials.gov Identifier: NCT03528863., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Purpose of Review: Enhanced Recovery After Surgery (ERAS) protocols and interventional locoregional anesthesia (LRA) techniques continuously evolve. This review outlines the latest recommendations for the use of regional anesthesia in ERAS protocols and emerging interventional analgesia techniques., Recent Findings: Research in ultrasound-guided regional anesthesia has led to a refinement of the traditional techniques and the introduction of a number of new approaches to complement ERAS strategies. The efficacy and versatility of LRA enable its use in an increasing number of ERAS indications., Summary: The implementation of ERAS protocols in different surgical procedures reduces overall complications and recovery time. Multimodal analgesia strategies with regional anesthesia techniques are some of the key interventions contributing to the improvement in postoperative outcomes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Loneliness and social isolation are significant public health problems that are being exacerbated during the coronavirus disease 2019 pandemic. Little is known about the associations between loneliness and symptom burden in oncology patients before and during the pandemic. Study purposes include determining the prevalence of loneliness in a sample of oncology patients; evaluating for differences in demographic, clinical, and symptom characteristics between lonely and nonlonely patients; and determining which demographic, clinical, and symptom characteristics were associated with membership in the lonely group., Methods: A convenience sample (n = 606) completed online surveys that evaluated the severity of loneliness, social isolation, and common symptoms (ie, anxiety, depression, fatigue, sleep disturbance, cognitive dysfunction, and pain) in oncology patients. Parametric and nonparametric tests were used to evaluate for differences in scores between the lonely and nonlonely groups. Logistic regression analysis was used to determine risk factors for membership in the loneliness group., Results: Of the 606 patients, 53.0% were categorized in the lonely group. The lonely group reported higher levels of social isolation, as well as higher symptom severity scores for all of the symptoms evaluated. In the multivariate model, being unmarried, having higher levels of social isolation, as well as higher levels of anxiety and depressive symptoms were associated with membership in the lonely group., Conclusions: Study findings suggest that a significant number of oncology patients are experiencing loneliness, most likely as a result of mandate social distancing and isolation procedures. The symptom burden of these patients is extremely high and warrants clinical evaluation and interventions., (© 2021 American Cancer Society.)

Objective: To describe the burden of colorectal cancer (CRC) in Mexico and understand mortality patterns based on sex, geography, and insurance status., Materials and Methods: Mortality data (1998-2018) from the Instituto Nacional de Estadística y Geografía was obtained. We included colon (C18.0, C18.2-18.9) and rectal cancer ICD-10 codes (C19, C20), and estimated age-standardized national, state-level and health insurance mortality rates. We estimated the average annual percent change using joinpoint regression., Results: Between 1998 and 2018, the observed women and men mortality rate increased annually by 1.3 and 2.7%, respectively. Higher CRC mortality was observed in northern and more urbanized states and in groups with greater access to health insurance, which currently facilitates but does not routinely cover screening., Conclusion: CRC mortality in Mexico is increasing rapidly, with marked differences based on sex, geography, and insurance status. Our findings underscore potential benefits of increased investment in comprehensive screening, diagnosis, and treatment strategies for the general population.

Context.—: Breast cancer biomarker assessment is critical in determining treatment and prognosis. In Tanzania, immunohistochemistry (IHC) is limited to surgical specimens and core biopsies. However, performing IHC on fine-needle aspiration biopsy cell blocks would offer numerous advantages., Objective.—: To compare the performance between estrogen receptor (ER) IHC performed at Muhimbili National Hospital (MNH) in Tanzania and ER IHC performed at University of California, San Francisco (UCSF), to demonstrate feasibility of performing IHC using cell blocks in Tanzania., Design.—: Patients with breast masses were recruited prospectively from the fine-needle aspiration biopsy clinic at MNH. Estrogen receptor IHC results on cell blocks, performed at both MNH and UCSF, and corresponding tissue blocks, performed at MNH, were compared to determine concordance., Results.—: Eighty-six cell blocks were evaluated by ER IHC at MNH, with 41 of 86 (47.7%) positive and 45 of 86 (52.3%) negative. Among 65 UCSF and MNH cell block pairs, overall ER IHC concordance was 93.8% (61 of 65) and positive concordance was 93.5% (29 of 31) (κ = 0.88, P > .99). Among 43 paired UCSF cell blocks and MNH tissue blocks, overall ER IHC concordance was 88.3% (38 of 43) and positive concordance was 90.5% (19 of 21) (κ = 0.77, P > .99). We compared 62 MNH cell block and tissue block pairs. Overall ER IHC concordance was 90.3% and positive concordance was 87.9% (κ = 0.81, P = .69)., Conclusions.—: Pairwise comparisons between ER IHC at MNH, on cell blocks and tissue blocks, with ER IHC at UCSF on cell blocks showed excellent concordance. We demonstrate that ER IHC on fine-needle aspiration biopsy specimens can be implemented in resource-constrained settings.

Background: Moral distress and burnout are highly prevalent among oncology clinicians. Research is needed to better understand how resource constraints and systemic inequalities contribute to moral distress in order to develop effective mitigation strategies. Oncology providers in low- and middle-income countries are well positioned to provide insight into the moral experience of cancer care priority setting and expertise to guide solutions., Methods: Semistructured interviews were conducted with a purposive sample of 22 oncology physicians, nurses, program leaders, and clinical advisors at a cancer center in Rwanda. Interviews were recorded, transcribed verbatim, and analyzed using the framework method., Results: Participants identified sources of moral distress at three levels of engagement with resource prioritization: witnessing program-level resource constraints drive cancer disparities, implementing priority setting decisions into care of individual patients, and communicating with patients directly about resource prioritization implications. They recommended individual and organizational-level interventions to foster resilience, such as communication skills training and mental health support for clinicians, interdisciplinary team building, fair procedures for priority setting, and collective advocacy for resource expansion and equity., Conclusion: This study adds to the current literature an in-depth examination of the impact of resource constraints and inequities on clinicians in a low-resource setting. Effective interventions are urgently needed to address moral distress, reduce clinician burnout, and promote well-being among a critical but strained oncology workforce. Collective advocacy is concomitantly needed to address the structural forces that constrain resources unevenly and perpetuate disparities in cancer care and outcomes., Implications for Practice: For many oncology clinicians worldwide, resource limitations constrain routine clinical practice and necessitate decisions about prioritizing cancer care. To the authors' knowledge, this study is the first in-depth analysis of how resource constraints and priority setting lead to moral distress among oncology clinicians in a low-resource setting. Effective individual and organizational interventions and collective advocacy for equity in cancer care are urgently needed to address moral distress and reduce clinician burnout among a strained global oncology workforce. Lessons from low-resource settings can be gleaned as high-income countries face growing needs to prioritize oncology resources., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Background: In response to the increasing burden of cancer in Tanzania, the Ministry of Health, Community Development, Gender, Elderly and Children launched National Cancer Treatment Guidelines (TNCTG) in February 2020. The guidelines aimed to improve and standardize oncology care in the country. At Ocean Road Cancer Institute (ORCI), we developed a theory-informed implementation strategy to promote guideline-concordant care. As part of the situation analysis for implementation strategy development, we conducted focus group discussions to evaluate clinical systems and contextual factors that influence guideline-based practice prior to the launch of the TNCTG., Materials and Methods: In June 2019, three focus group discussions were conducted with a total of 21 oncology clinicians at ORCI, stratified by profession. A discussion guide was used to stimulate dialogue about facilitators and barriers to delivery of guideline-concordant care. Discussions were audio recorded, transcribed, translated, and analyzed using thematic framework analysis., Results: Participants identified factors both within the inner context of ORCI clinical systems and outside of ORCI. Themes within the clinical systems included capacity and infrastructure, information technology, communication, efficiency, and quality of services provided. Contextual factors external to ORCI included interinstitutional coordination, oncology capacity in peripheral hospitals, public awareness and beliefs, and financial barriers. Participants provided pragmatic suggestions for strengthening cancer care delivery in Tanzania., Conclusion: Our results highlight several barriers and facilitators within and outside of the clinical systems at ORCI that may affect uptake of the TNCTG. Our findings were used to inform a broader guideline implementation strategy, in an effort to improve uptake of the TNCTGs at ORCI., Implications for Practice: This study provides an assessment of cancer care delivery systems in a low resource setting from the unique perspectives of local multidisciplinary oncology clinicians. Situational analysis of contextual factors that are likely to influence guideline implementation outcomes is the first step of developing an implementation strategy for cancer treatment guidelines. Many of the barriers identified in this study represent actionable targets that will inform the next phases of our implementation strategy for guideline-concordant cancer care in Tanzania and comparable settings., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Background/aim: The majority of colorectal cancer (CRC) cases, which are microsatellite stable (MSS) and do not harbor mismatch repair deficiency/microsatellite instability, are resistant to immunotherapy. Identification of patients with exceptional responses in MSS CRC and predictive biomarkers is an unmet need that needs to be addressed., Case Report: We report three cases of MSS CRC with durable clinical benefit from immunotherapy with anti-PD-1 checkpoint inhibitors. Two cases bear a POLE P286R mutation, which has been associated with lack of immunotherapy response in MSS CRC. Two cases bear alterations in Ataxia-Telangiectasia Mutated (ATM) which may contribute to observed responses, including interaction with a co-administered intratumoral stimulator of interferon genes (STING) pathway agonist in one patient., Conclusion: Novel DNA damage repair alterations, including mutations in ATM, can provide insight into additional mechanisms by which genomic alterations can sensitize MSS CRC to diverse immunotherapies., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: No information is available on cancer patients' knowledge of and experiences with COVID-19. We undertook an evaluation of differences in COVID-19 symptom occurrence rates, COVID-19 testing rates, clinical care activities, knowledge of COVID-19, and use of mitigation procedures between patients who were and were not receiving active cancer treatment., Methods: Patients enrolled were > 18 years of age; had a diagnosis of cancer; and were able to complete the emailed study survey online., Results: Of the 174 patients who participated, 27.6% (n = 48) were receiving active treatment, 13.6% were unemployed because of COVID-19, 12.2% had been tested for COVID-19, and 0.6% had been hospitalized for COVID-19. Patients who were not on active treatment reported a higher mean number of COVID-19 symptoms (3.1 (± 4.2) versus 1.9 (± 2.6)), and patients who reported a higher number of COVID-19 symptoms were more likely to be tested. Over 55% of the patients were confident that their primary care provider could diagnose COVID-19, and the majority of the patients had high levels of adherence with the use of precautionary measures (e.g., social distancing, use of face coverings)., Conclusion: The high level of COVID-19 symptoms and the significant overlap of COVID-19 and cancer-related symptoms pose challenges for clinicians who are assessing and triaging oncology patients for COVID-19 testing. For patients on active treatment, clinicians face challenges with how to assess and manage symptoms that, prior to COVID-19, would be ascribed to acute toxicities associated with cancer treatments or persistent symptoms in cancer survivors.

Objective: Current National Comprehensive Cancer Network guidelines for gastroenteropancreatic neuroendocrine tumors (GEPNETs) recommend complete (R0) surgical resection of the primary tumor and metastases, if feasible. However, large multicenter studies of recurrence patterns of GEPNETs after resection have not been performed., Methods: Patients 18 years or older who presented to 7 participating National Comprehensive Cancer Network institutions between 2004 and 2008 with a new diagnosis of a small bowel, pancreas, or colon/rectum neuroendocrine tumor (NET) and underwent R0 resection of the primary tumor, and synchronous metastases, if present, were included in this analysis. Descriptive statistics and Kaplan-Meier estimates were used to calculate recurrence rates and time-associated end points, respectively., Results: Of 294 patients with GEPNETs, 50% were male, 88% were White, and 99% had Eastern Cooperative Oncology Group performance status 0 to 1. The median age was 55 years (range, 20-90). The median follow-up time from R0 resection was 62.1 months. Recurrence rates were 18% in small bowel NETs (n = 110), 26% in pancreatic NETs (n = 141), and 10% in colon/rectum NETs (n = 50). The frequency of surveillance imaging was highly variable., Conclusions: R0 resection was associated with variable risk of recurrence across subtypes. Further research to inform refinement of guidelines for the appropriate duration of surveillance after R0 resection is needed., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Secreted frizzled-related proteins (SFRP) are glycoproteins containing a so-called frizzled-like cysteine-rich domain. This domain enables them to bind to Wnt ligands or frizzled (FzD) receptors, making potent regulators of Wnt signaling. As Wnt signaling is often altered in cancer, it is not surprising that Wnt regulators such as SFRP proteins are often differentially expressed in the tumor microenvironment, both in a metastatic and non-metastatic setting. Indeed, SFRP2 is shown to be specifically upregulated in the tumor vasculature of several types of cancer. Several studies investigated the functional role of SFRP2 in the tumor vasculature, showing that SFRP2 binds to FzD receptors on the surface of tumor endothelial cells. This activates downstream Wnt signaling and which is, thereby, stimulating angiogenesis. Interestingly, not the well-known canonical Wnt signaling pathway, but the noncanonical Wnt/Ca 2+ pathway seems to be a key player in this event. In tumor models, the pro-angiogenic effect of SFRP2 could be counteracted by antibodies targeting SFRP2, without the occurrence of toxicity. Since tumor angiogenesis is an important process in tumorigenesis and metastasis formation, specific tumor endothelial markers such as SFRP2 show great promise as targets for anti-cancer therapies. This review discusses the role of SFRP2 in noncanonical Wnt signaling and tumor angiogenesis, and highlights its potential as anti-angiogenic therapeutic target in cancer.

Esophageal cancer (EC) is a leading cause of cancer morbidity and mortality in Africa. Despite the high burden of disease, optimal management strategies for EC in resource-constrained settings have yet to be established. This systematic review evaluates the literature on treatments for EC throughout Africa and compares the efficacy and safety of varying treatment strategies in this context (PROSPERO CRD42017071546). PubMed, Embase and African Index Medicus were searched for studies published on treatment strategies for EC in Africa from 1980 to 2020. Searches were supplemented by examining bibliographies of included studies and relevant conference proceedings. Methodological quality/risk of bias was assessed using the Cochrane Risk-of-Bias tool and the Newcastle-Ottawa Scale. Forty-six studies were included. Case series constituted the majority of studies: 13 were case series reporting on outcomes of esophagectomies, 17 on palliative luminal or surgical interventions, four on radiotherapy and three on concurrent chemoradiation. Nine randomized controlled trials were identified, of which four prospectively compared different treatment modalities (one investigating radiotherapy vs chemoradiation, three evaluating rigid plastic stents vs other treatments). This review summarizes the research on EC treatments in Africa published over the last four decades and outlines critical gaps in knowledge related to management in this context. Areas in need of further research include (a) evaluation of the safety and efficacy of neoadjuvant therapy in patients with locally advanced disease; (b) strategies to improve long-term survival in patients treated with definitive chemoradiation; and (c) the comparative effectiveness of modern palliative interventions, focusing on quality of life and survival as outcome measures., (© 2020 Union for International Cancer Control.)

Objective: Anal cancer is an uncommon malignancy with the primary treatment for localized disease being concurrent radiation and chemotherapy. Pre-treatment PET/CT is useful for target delineation, with minimal exploration of its use in prognostication. In the post-treatment setting there is growing evidence for advanced PET metrics in assessment of treatment response, and early identification of recurrence essential for successful salvage, however this data is limited to small series., Methods: Patient with non-metastatic anal cancer from a single institution were retrospectively reviewed for receipt of pre- and post-treatment PET/CTs. PET data was co-registered with radiation therapy planning CT scans for precise longitudinal assessment of advanced PET metrics including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), for assessment with treatment outcomes. Treatment outcomes included local recurrence (LR), progression free survival (PFS), and overall survival (OS), as defined from the completed radiation therapy to the time of the event. Cox proportional hazard modeling with inverse probability weighting (IPW) using the propensity score based on age, BMI, T-stage, and radiation therapy dose were utilized for assessment of these metrics., Results: From 2008 to 2017 there were 72 patients who had pre-treatment PET/CT, 61 (85%) had a single follow up PET/CT, and 35 (49%) had two follow up PET/CTs. The median clinical follow-up time was 25 months (IQR: 13-52) with a median imaging follow up time of 16 months (IQR: 7-29). On pre-treatment PET/CT higher MTV2.5 and TLG were significantly associated with higher risk of local recurrence (HR 1.11, 95% CI: 1.06-1.16, p<0.001; and HR 1.12, 95% CI: 1.05-1.19, p<0.001), and worse PFS (HR 1.09, 95% CI: 1.04-1.13, p<0.001; and HR 1.09, 95% CI: 1.03-1.12, p = 0.003) and OS (HR 1.09, 95% CI: 1.04-1.16, p = 0.001; and HR 1.11, 95% CI: 1.04-1.20, p = 0.004). IPW-adjusted pre-treatment PET/CT showed higher MTV2.5 (HR 1.09, 95% CI: 1.02-1.17, p = 0.012) and TLG (HR 1.10, 95% CI: 1.00-1.20, p = 0.048) were significantly associated with worse PFS, and post-treatment MTV2.5 was borderline significant (HR 1.16, 95% CI: 1.00-1.35, p = 0.052)., Conclusion: Advanced PET metrics, including higher MTV2.5 and TLG, in the pre-treatment and post-treatment setting are significantly associated with elevated rates of local recurrence, and worse PFS and OS. This adds to the growing body of literature that PET/CT for patient with ASCC should be considered for prognostication, and additionally is a useful tool for consideration of early salvage or clinical trial of adjuvant therapies., Competing Interests: The authors have declared that no competing interests exist.

Background: East Africa is affected by a disproportionately high burden of esophageal squamous cell carcinoma (ESCC)., Methods: We conducted an incident case-control study in Dar es Salaam, Tanzania with 1:1 matching for gender and age. A questionnaire evaluated known and putative risk factors for ESCC. Cochran-Mantel-Haenszel and multivariable conditional logistic regression analyses were applied to evaluate associations with ESCC risk, with adjustment for geographic zone., Results: Of 471 cases and 471 controls, the majority were male (69%); median ages were 59 and 55, respectively. In a multivariable logistic regression model, a low International Wealth Index (IWI) score [OR 2.57; 95% confidence interval (CI), 1.41-4.68], former smoking (OR 2.45; 95% CI, 1.46-4.13), second-hand smoke in the household (OR 1.67; 95% CI, 1.01-2.77), daily spicy chilies (OR 1.62; 1.04-2.52), and daily salted foods (OR 2.02; 95% CI, 1.06-3.85) were associated with increased risk of ESCC. Daily consumption of raw greens (OR 0.36; 95% CI, 0.16-0.80), fruit (OR 0.47; 95% CI, 0.27-0.82), and smoked fish (OR 0.31; 95% CI, 0.15-0.66) were protective. Permanent residence in the Central (OR 5.03; 95% CI, 2.16-11.73), Northern-Lake (OR 2.40; 95% CI, 1.46-3.94), or Southern Highlands zones (OR 3.18; 95% CI, 1.56-6.50) of Tanzania were associated with increased risk compared with residence in the Eastern zone., Conclusions: Low IWI score, smoke exposure(s), geographic zone, and dietary factors were associated with risk for ESCC in Tanzania., Impact: These findings will inform the development of future hypothesis-driven studies to examine risk factors for the high burden of ESCC in East Africa. See related commentary by McCormack et al., p. 248 ., (©2020 American Association for Cancer Research.)

Purpose: At the 12th meeting of AORTIC (African Organization for Research and Training in Cancer) in Maputo, Mozambique, held between November 5 and November 8, 2019, a special workshop was organized to focus on the need for collaboration and coordination between governments and health systems in Africa with academic, industry, association, and other nongovernmental organizations to effect sustainable positive change for the care of patients with cancer., Methods: Representatives from seven different projects in Africa presented implementation science and demonstration projects of their to date efforts in cancer system improvement including patient access, South-South partnerships, in-country specialized training, palliative care consortium, treatment outcomes, and focused pathology and diagnostic capacity building. Key partners of the various projects served as moderators and commentators during the session., Results: From across all the presentations, lessons learned and exemplary evidence of the value of partnerships were gathered and summarized., Conclusion: The concluding synthesis of the presentations determined that with the broad needs across cancer requiring in-depth expertise at each point on a patient's journey, no single organization can effect change alone. Multipartner collaborations not only should be the norm but should also be coordinated so that efforts are not duplicated and maximum patient access to cancer diagnosis and care is achieved.

Context: Many advanced patients with cancer have unrealistic prognostic expectations., Objectives: We tested whether offering life expectancy (LE) statistics within palliative chemotherapy (PC) education promotes realistic expectations., Methods: In this multicenter trial, patients with advanced colorectal and pancreatic cancers initiating first or second line PC were randomized to usual care versus a PC educational tool with optional LE information. Surveys at two weeks and three months assessed patients' review of the LE module and their reactions; at three months, patients estimated their LE and reported occurrence of prognosis and end-of-life (EOL) discussions. Wilcoxon tests and proportional odds models evaluated between-arm differences in LE self-estimates, and how realistic those estimates were (based on cancer type and line of treatment)., Results: From 2015 to 2017, 92 patients were randomized to the intervention and 94 to usual care. At baseline most patients (80.9%) wanted "a lot" or "as much information as possible" about the impact of chemotherapy on LE. Among patients randomized to the intervention, 52.0% reviewed the LE module by two weeks and 66.7% by three months-of whom 88.2% reported the information was important, 31.4% reported it was upsetting, and 3.9% regretted reviewing it. Overall, patients' LE self-estimates were very optimistic; 71.4% of patients with colorectal cancer estimated greater than five years; 50% pancreatic patients estimated greater than two years. The intervention had no effect on the length or realism of patients' LE self-estimates, or on the occurrence of prognostic or EOL discussions., Conclusions: Offering LE information within a PC educational intervention had no effect on patients' prognostic expectations., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The eastern corridor of Africa is affected by a high burden of esophageal cancer (EC), with > 90% of patients presenting with advanced disease. Self-expanding metal stents (SEMS) have been previously reported as safe and effective for palliation of malignant dysphagia in resource-limited settings; however, access is limited throughout Eastern Africa., Methods: In response to demand for palliative interventions for patients with dysphagia because of EC, the African Esophageal Cancer Consortium (AfrECC) partnered with the Clinton Health Access Initiative to improve access to SEMS in Eastern Africa. We undertook a stepwise implementation approach to (1) identify barriers to SEMS access, (2) conduct a market analysis, (3) select an industry partner, (4) establish regulatory and procurement processes, (5) develop endoscopic training resources, (6) create a medical device registry, and (7) establish principles of accountability., Results: Following an evaluation of market demand and potential SEMS manufacturers, Boston Scientific Corporation announced its commitment to launch an access program to provide esophageal SEMS to patients in Tanzania, Kenya, Malawi, and Zambia at a subsidized price. Parallel regulatory and procurement processes were established in each participating country. Endoscopy training courses were designed and conducted, using the Training-of-Trainers model. A device registry was created to centralize data for quality control and to monitor channels of SEMS distribution. Principles of accountability were developed to guide the sustainability of this endeavor., Conclusion: The AfrECC Stent Access Initiative is an example of a multisector partnership formed to provide an innovative solution to align regional needs with a supply chain for a high-priority medical device.

Purpose: Clinical breast examination (CBE) is one of the most common methods used for early detection of breast cancer in low- and middle-income countries. CBE alone is limited by lack of specificity and may result in unnecessary diagnostic procedures. We evaluated the feasibility of integrating CBE, fine-needle aspiration biopsy (FNAB), and rapid on-site evaluation (ROSE) in triaging palpable breast masses for specialized cancer care., Materials and Methods: An intensive breast cancer screening event was conducted at a national trade fair by a multidisciplinary team of care providers targeting a healthy population in Dar es Salaam, Tanzania. All adults age ≥ 18 years were invited to participate. CBE was performed by oncologists and/or pathologists. FNAB was performed by a pathologist on palpable masses that were then categorized as benign, indeterminate, or suspicious for malignancy or definitively malignant based on ROSE., Results: A total of 208 individuals (207 females, one male; median age, 36 years; range, 18-68 years) were screened. Most (90.8%, 189 of 208) had normal findings, whereas 7.2% (15 of 208), 1% (2 of 208), and 1% (2 of 208) had a palpable mass, breast pain, and nipple discharge, respectively. Two participants had lesions too small for palpation-guided biopsy and clinically consistent with fibroadenomas; the participants were counseled, and observation was recommended. FNAB was performed on 13 breast masses, with 9 of 13 (69%) categorized as benign and 4 of 13 (31%) suspicious for malignancy. Final cytopathologic review of referred patients confirmed one case to be breast adenocarcinoma, one was suggestive of fibroadenoma, and two showed inflammations., Conclusion: Integration of CBE with ROSE and FNAB was feasible in a breast cancer screening program in Tanzania. In settings with constrained resources for cancer care, this may be an effective method for triaging patients with breast masses.

Colorectal cancer is preventable and treatable by screening and early detection. Fecal immunochemical tests (FIT) for average risk individuals is an effective strategy for screening. Incidence and mortality in Mexico is increasing and large-scale screening programs do not yet exist. The aim of this study was to evaluate the feasibility of FIT-based colorectal cancer screening program in Mexico City. For more than 15 months, average risk individuals in Mexico City were invited to participate at Mexico's Instituto Nacional de Cancerologia (INCan, Mexico City, Mexico). Participants received an FIT kit for stool collection, results ≥20 ng/mL were referred for high quality colonoscopy. Participants' results were classified according to the most advanced clinical finding as: adenocarcinoma, high-risk adenomas, low-risk adenomas, serrated lesions, hyperplastic polyps, and no polyps. Sequential analyses were performed to assess the positive predictive value (PPV) of FIT. A total of 810 participants were eligible, 737 (91.0%) returned the FIT and 112 (15.2%) had an abnormal result. Of these participants, 87 (77.7%) completed colonoscopy. Clinical findings of participants included: seven (8.1%) adenocarcinomas, 18 (20.7%) high-risk adenomas, 23 (26.4%) low-risk adenomas, one (1.2%) serrated lesions, 14 (16.1%) hyperplasic polyps, and 24 (27.6%) no polyps. The PPV of FIT using the ≥20 ng/mL was 8.1% for cancer and 20.7% for high-risk adenomas. In conclusion, colorectal cancer screening with FIT is feasible at INCan in Mexico City, where resources are available. Further studies are needed to determine feasibility of colorectal cancer screening in other settings, as well as optimal hemoglobin detection cut-off points to maximize the population benefits of colorectal cancer screening with FIT in Mexico., (©2020 American Association for Cancer Research.)

Context: No information is available on oncology patients' level of stress and symptom burden during the coronavirus disease 2019 (COVID-19) pandemic., Objectives: To evaluate for differences in demographic and clinical characteristics, levels of social isolation and loneliness, and the occurrence and severity of common symptoms between oncology patients with low vs. high levels of COVID-19 and cancer-related stress. In addition, to determine which of these characteristics were associated with membership in the high-stressed group., Methods: Patients were 18 years and older; had a diagnosis of cancer; and were able to complete an online survey., Results: Of the 187 patients in this study, 31.6% were categorized in the stressed group (Impact of Event Scale-Revised [score of ≥24]). Stressed group's Impact of Event Scale-Revised score exceeds previous benchmarks in oncology patients and equates with probable post-traumatic stress disorder. In this stressed group, patients reported occurrence rates for depression (71.2%), anxiety (78.0%), sleep disturbance (78.0%), evening fatigue (55.9%), cognitive impairment (91.5%), and pain (75.9%). Symptom severity scores equate with clinically meaningful levels for each symptom., Conclusion: We identified alarmingly high rates of stress and an extraordinarily high symptom burden among patients with cancer, exceeding those previously benchmarked in this population and on par with noncancer patients with post-traumatic stress disorder. Given that the COVID-19 pandemic will likely impact cancer care for an indefinite period, clinicians must exhibit increased vigilance in their assessments of patients' level of stress and symptom burden. Moreover, an increase in referrals to appropriate supportive care resources must be prioritized for high-risk patients., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Importance: Diet has been associated with survival in patients with stage I to III colorectal cancer, but data on patients with metastatic colorectal cancer are limited., Objective: To examine the association between diet quality and overall survival among individuals with metastatic colorectal cancer., Design, Setting, and Participants: This was a prospective cohort study of patients with metastatic colorectal cancer who were enrolled in the Cancer and Leukemia Group B (Alliance) and Southwest Oncology Group 80405 trial between October 27, 2005, and February 29, 2012, and followed up through January 2018., Exposures: Participants completed a validated food frequency questionnaire within 4 weeks after initiation of first-line treatment for metastatic colorectal cancer. Diets were categorized according to the Alternative Healthy Eating Index (AHEI), Alternate Mediterranean Diet (AMED) score, Dietary Approaches to Stop Hypertension (DASH) score, and Western and prudent dietary patterns derived using principal component analysis. Participants were categorized into sex-specific quintiles., Main Outcomes and Measures: Multivariable hazard ratios (HRs) and 95% CIs for overall survival., Results: In this cohort study of 1284 individuals with metastatic colorectal cancer, the median age was 59 (interquartile range [IQR]: 51-68) years, median body mass index was 27.2 (IQR, 24.1-31.4), 521 (41%) were female, and 1102 (86%) were White. There were 1100 deaths during a median follow-up of 73 months (IQR, 64-87 months). We observed an inverse association between the AMED score and risk of death (HR quintile 5 vs quintile 1, 0.83; 95% CI, 0.67-1.04; P = .04 for trend), but the point estimates were not statistically significant. None of the other diet scores or patterns were associated with overall survival., Conclusions and Relevance: In this prospective analysis of patients with metastatic colorectal cancer, diet quality assessed at initiation of first-line treatment for metastatic disease was not associated with overall survival.

Cancer during pregnancy is relatively rare but is increasing in frequency in countries in which the maternal child-bearing age continues to rise. The complexities of medical decision making are underscored by the need to weigh the potential benefits of any intervention for the mother against the risks to the fetus. A majority of diagnostic evaluations can be performed safely in the setting of pregnancy and should not be delayed. Noninvasive prenatal testing that shows discordance with fetal karyotype can be a clue to an underlying maternal malignancy. After diagnosis, a multidisciplinary team should formulate a care plan for both the mother and the fetus. Key topics for discussion should include the mother's prognosis, standard treatment plan, and predictions of how modifications for a continuing pregnancy will affect the treatment plan and overall prognosis. In the context of this knowledge, frank discussions about pregnancy termination should be addressed with the patient, if appropriate. Selection of a plan for oncologic management in the case of a pregnant woman is based on the type of cancer, the tumor biology, and the tumor stage. Additional complexities for pregnant patients are typically related to the gestational age of the fetus, the dynamic physiologic changes of pregnancy, and the limited safety data for administration of most anticancer therapies during pregnancy. In this article, we summarize data related to different classes of anticancer therapies as well as considerations for the management of selected cancers. Finally, we provide some key principles that should be considered in the management of patients with cancer during pregnancy.

Background: Anal squamous cell carcinoma (ASCC) is uncommon, yet seen more frequently in the setting of the human immunodeficiency virus (HIV). Chemoradiotherapy is the definitive modality of treatment for patients with ASCC; this study examines factors impacting clinical outcomes in a large cohort of HIV-positive and HIV-negative patients., Methods: A retrospective review was conducted of patients treated for nonmetastatic ASCC at a single institution between 2005 and 2018. Freedom from local recurrence (FFLR), freedom from distant metastasis, and overall survival (OS) were calculated using the Kaplan-Meier method, and univariate and multivariate analysis were performed using the Cox proportional hazards model., Results: During the study period, 111 patients initiated definitive treatment for ASCC. Median age of the entire cohort was 56.7 years (interquartile range, 51.5-63.5), with 52 patients (46.8%) being HIV-positive. At median follow-up of 28.0 months, the 2- and 5-year FFLR were 78.2% (95% confidence interval [CI], 70.4-87.0) and 74.6% (95% CI, 65.8-84.5), respectively. Multivariate analysis revealed time from diagnosis to treatment initiation (median, 8 weeks; hazard ratio, 1.06; 95% CI, 1.03-1.10) to be significantly associated with worse FFLR and OS. HIV-positive patients had a trend toward worse FFLR (log-ranked p = .06). For HIV-positive patients with post-treatment CD4 less than 150 cells per mm 3 , there was significantly worse OS (log-ranked p = .015)., Conclusion: A trend toward worse FFLR was seen in HIV-positive patients, despite similar baseline disease characteristics as HIV-negative patients. Worse FFLR and OS was significantly associated with increased time from diagnosis to treatment initiation. Poorer OS was seen in HIV-positive patients with a post-treatment CD4 count less than 150 cells per mm 3 ., Implications for Practice: Human immunodeficiency virus (HIV)-positive patients with anal squamous cell carcinoma can represent a difficult clinical scenario. Definitive radiation with concurrent chemotherapy is highly effective but can result in significant toxicity and a decrease in CD4 count that could predispose to HIV-related complications. As HIV-positive patients have largely been excluded from prospective clinical trials, this study seeks to provide greater understanding of their outcomes with radiation therapy, potential predictors of worse local control and overall survival, and those most at risk after completion of treatment., (© AlphaMed Press 2020.)

Background: OX40 (CD134) is a costimulatory molecule of the tumor necrosis factor receptor superfamily that is currently being investigated as a target for cancer immunotherapy. However, despite promising results in murine tumor models, the clinical efficacy of agonistic αOX40 antibodies in the treatment of patients with cancer has fallen short of the high expectation in earlier-stage trials., Methods: Using lymphocytes from resected tumor, tumor-free (TF) tissue and peripheral blood mononuclear cells (PBMC) of 96 patients with hepatocellular and colorectal cancers, we determined OX40 expression and the in vitro T-cell agonistic activity of OX40-targeting compounds. RNA-Seq was used to evaluate OX40-mediated transcriptional changes in CD4+ and CD8+ human tumor-infiltrating lymphocytes (TILs)., Results: Here, we show that OX40 was overexpressed on tumor-infiltrating CD4+ T cells compared with blood and TF tissue-derived T cells. In contrast to a clinical candidate αOX40 antibody, treatment with an Fc-engineered αOX40 antibody (αOX40&#95;v12) with selectively enhanced FcγRIIB affinity, stimulated in vitro CD4+ and CD8+ TIL expansion, as well as cytokine and chemokine secretions. The activity of αOX40&#95;v12 was dependent on FcγRIIB engagement and intrinsic CD3/CD28 signals. The transcriptional landscape of CD4+ and CD8+ TILs shifted toward a prosurvival, inflammatory and chemotactic profile on treatment with αOX40&#95;v12., Conclusions: OX40 is overexpressed on CD4+ TILs and thus represents a promising target for immunotherapy. Targeting OX40 with currently used agonistic antibodies may be inefficient due to lack of OX40 multimerization. Thus, Fc engineering is a powerful tool in enhancing the agonistic activity of αOX40 antibody and may shape the future design of antibody-mediated αOX40 immunotherapy., Competing Interests: Competing interests: JW, TSF, KC, WY, IN, YAY and SS-A are employees of Pfizer and have stocks and ownership interests (including patents) at Pfizer., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The coronavirus disease 2019 (COVID-19) pandemic has forced oncology clinicians and administrators in the United States to set priorities for cancer care owing to resource constraints. As oncology practices adapt to a contracted health care system, expertise gained from partnerships in low-resource settings can be used for guidance. This article provides a primer on priority setting in oncology and ethical guidance based on lessons learned from experience with cancer care priority setting in low-resource settings., Observations: Lessons learned from real-world experiences are myriad. First, in the setting of limited resources, a utilitarian approach to maximizing survival benefit should guide decision-making. Second, conflicting principles will often arise among stakeholders and decision makers. Third, fair decision-making procedures should be established to ensure moral legitimacy and accountability. Fourth, proactive safeguards must be implemented to protect vulnerable individuals, or disparities in cancer treatment and outcomes will only widen further. Fifth, communication with patients and families about priority setting decisions should be intentional and standardized. Sixth, moral distress among clinicians must be addressed to avoid burnout during a time when resilience is critical., Conclusions and Relevance: Although the need to triage cancer care may be new to those who underwent training and now practice oncology in high-resource settings, it is familiar for those who practice in low- and middle-income countries. Oncologists in the United States facing unprecedented decisions about prioritization can draw on ethical frameworks and lessons learned from real-world cancer care priority setting in resource-constrained environments.

Importance: Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote., Objective: To determine whether a PC educational video and booklet at treatment initiation could improve patients' understanding of its benefits and risks., Interventions: Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review., Design, Setting, and Participants: Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019., Main Outcomes and Measures: The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding "not at all likely" to "What is your understanding of how likely the chemotherapy is to cure your cancer?" (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy-General emotional well-being subscale)., Results: Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted "a lot" of information or "as much information as possible" about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%; P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar., Conclusions and Relevance: Provision of an educational video and booklet did not alter patients' expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies., Trial Registration: ClinicalTrials.gov Identifier: NCT02282722.

Background: In middle-income countries, the burden of colorectal cancer (CRC) is increasing in parallel with resources for diagnosis and treatment. There is a potential benefit of CRC screening programs in Mexico., Objective: Since there are no organized screening programs in the country, we explored the willingness of individuals to complete a faecal immunochemical testing (FIT) based CRC screening program and its potential benefit in Mexico., Methods: We conducted a CRC screening program pilot in Veracruz, Mexico, during 2015-16 using FIT. Individuals with FIT results >100 ng of haemoglobin/ml buffer were referred for diagnostic colonoscopy., Results: Of 473 FIT kits distributed to adults aged 50-75, 85.8% (406) were completed by participants and analysed in the laboratory. Of these, 5.9% (24/406) of test results showed >100 ng haemoglobin/ml. Twenty-one participants completed colonoscopy. The positive predictive value of FIT >100 ng haemoglobin/ml for premalignant lesions was 33%., Conclusion: These results provide preliminary evidence of the willingness of individuals to complete FIT-based CRC screening program in Mexico. However, further evaluation of health systems resources will be needed prior to large-scale implementation of CRC screening programs., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Colorectal cancer (CRC) incidence and mortality are increasing in many low- and middle-income countries (LMICs), possibly due to a combination of changing lifestyles and improved healthcare infrastructure to facilitate diagnosis. Unfortunately, a large proportion of CRC cases in these countries remain undiagnosed or are diagnosed at advanced stages, resulting in poor outcomes. Decreasing mortality trends in HICs are likely due to evidence-based screening and treatment approaches that are not widely available in LMICs. Formative research to identify emerging opportunities to implement appropriate screening and treatment programs in LMICs is, therefore, of growing importance. We sought to identify potential barriers and facilitators for future implementation of fecal immunochemical test (FIT)-based CRC screening in a public healthcare system in a middle-income country with increasing CRC incidence and mortality., Methods: We performed a qualitative study with semi-structured individual and focus group interviews with different CRC screening stakeholders, including 30 lay people at average risk for CRC, 13 health care personnel from a local public clinic, and 7 endoscopy personnel from a cancer referral hospital. All interviews were transcribed verbatim for analysis. Data were analyzed using the constant comparison method, under the theoretical perspectives of the social ecological model (SEM), the PRECEDE-PROCEED model, and the health belief model., Results: We identified barriers and facilitators for implementation of a FIT-based CRC screening program at several levels of the SEM. The main barriers in each of the SEM levels were as follows: (1) at the social context level: poverty, health literacy and lay beliefs related to gender, cancer, allopathic medicine, and religion; (2) at the health services organization level: a lack of CRC knowledge among health care personnel and the community perception of poor quality of health care; and (3) at the individual level: a lack of CRC awareness and therefore lack of risk perception, together with fear of participating in screening activities and finding out about a serious disease. The main facilitators perceived by the participants were CRC screening information and the free provision of screening tests., Conclusions: This study's findings suggest that multi-level CRC screening programs in middle-income countries such as Mexico should incorporate complementary strategies to address barriers and facilitators, such as (1) provision of free screening tests, (2) education of primary healthcare personnel, and (3) promotion of non-fear-based CRC screening messages to the target population, tailored to address common lay beliefs., Competing Interests: Competing interestsNone, (© The Author(s) 2020.)

Background: As survival with metastatic colorectal cancer (CRC) and imaging modalities improve, detection of ovarian metastases may be increasing. The ovary may serve as a sanctuary site for malignant cells; however, there is a paucity of data regarding the role for oophorectomy., Methods: This is a single-institution retrospective study of patients with CRC with ovarian metastases from 2009 to 2017. We evaluated patient, disease, and treatment related factors associated with overall survival (OS) from initial diagnosis of metastatic CRC., Results: Of 108 patients assessed, the median age was 50, 19% had localized disease at initial presentation, 64% had ovarian metastases at initial CRC diagnosis, and 77% underwent oophorectomy. Median OS was 29.6 months across all patients, and it was 36.7 months in patients who underwent oophorectomy versus 25.0 months in patients who did not (hazard ratio [HR] 0.54). In multivariate analysis, the effect of oophorectomy on OS suggested protection but was not statistically significant (HR 0.57). Resection of primary tumor was performed in 71% of patients, which was independently associated with improved OS (HR 0.21). Twelve patients (11%) remained alive at 5 years after diagnosis of metastatic disease., Conclusion: Although it has been previously reported that patients with CRC with ovarian metastases have poor prognosis, the median OS for this cohort was comparable to existing OS data for patients with metastatic CRC. In patients treated with chemotherapy, we did not find the ovarian metastasis to frequently serve as a sanctuary site of disease. However, we found that in carefully selected patients, oophorectomy may confer a survival benefit., Implications for Practice: In colorectal cancer (CRC) ovarian metastasis is not necessarily associated with worse prognosis than metastasis to other sites. In carefully selected patients with ovarian metastases from CRC, oophorectomy may confer a survival benefit. Specifically, development of ovarian metastasis early in the disease course, resection of the primary tumor, and limited extraovarian metastatic disease are clinical features that are potentially associated with benefit from oophorectomy. A subset of patients with ovarian metastasis from CRC have potential to become long-term survivors (>5 years)., (© AlphaMed Press 2020.)

Fibrillins constitute a family of large extracellular glycoproteins which multimerize to form microfibrils, an important structure in the extracellular matrix. It has long been assumed that fibrillin-2 was barely present during postnatal life, but it is now clear that fibrillin-2 molecules form the structural core of microfibrils, and are masked by an outer layer of fibrillin-1. Mutations in fibrillins give rise to heritable connective tissue disorders, including Marfan syndrome and congenital contractural arachnodactyly. Fibrillins also play an important role in matrix sequestering of members of the transforming growth factor-β family, and in context of Marfan syndrome excessive TGF-β activation has been observed. TGF-β activation is highly dependent on integrin binding, including integrin αvβ8 and αvβ6, which are upregulated upon TGF-β exposure. TGF-β is also involved in tumor progression, metastasis, epithelial-to-mesenchymal transition and tumor angiogenesis. In several highly vascularized types of cancer such as hepatocellular carcinoma, a positive correlation was found between increased TGF-β plasma concentrations and tumor vascularity. Interestingly, fibrillin-1 has a higher affinity to TGF-β and, therefore, has a higher capacity to sequester TGF-β compared to fibrillin-2. The previously reported downregulation of fibrillin-1 in tumor endothelium affects the fibrillin-1/fibrillin-2 ratio in the microfibrils, exposing the normally hidden fibrillin-2. We postulate that fibrillin-2 exposure in the tumor endothelium directly stimulates tumor angiogenesis by influencing TGF-β sequestering by microfibrils, leading to a locally higher active TGF-β concentration in the tumor microenvironment. From a therapeutic perspective, fibrillin-2 might serve as a potential target for future anti-cancer therapies., Competing Interests: Declaration of Competing Interest The authors declare to have no conflict of interest.This work was supported by the KWF Cancer Society [2018–11651]., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Diet is associated with colorectal cancer survival. Yet, adherence to nutrition guidelines is low among colorectal cancer survivors., Methods: We conducted a pilot trial among colorectal cancer survivors to evaluate a 12-week remote dietary intervention. Participants received print materials and were randomized (1:1) to intervention (website, text messages) or wait-list control. Primary outcomes included feasibility and acceptability. We also explored change in diet from 0 to 12 and 24 weeks and change from 0 to 12 weeks in anthropometry and circulating biomarkers (Trial Registration: NCT02965521)., Results: We randomized 50 colorectal cancer survivors (25 intervention, 25 control). Retention was 90% at 12 weeks and 84% at 24 weeks. Participants had a median age of 55 years and were 66% female, 70% non-Hispanic white, and 96% had a college degree. The intervention arm responded to a median 15 (71%) of 21 text messages that asked for a reply [interquartile range (IQR) = 8, 19] and visited the website a median of 13 (15%) days (IQR = 1, 33) of the 84 study days., Conclusions: We developed a Web-based dietary intervention for colorectal cancer survivors. Our pilot results suggest that colorectal cancer survivors may engage more with text messages than a study website. Research to improve tailoring of text messages, while maintaining scalability, is needed., Impact: Remote dietary interventions using text messages may be feasible for colorectal cancer survivors. See all articles in this CEBP Focus section, "Modernizing Population Science.", (©2020 American Association for Cancer Research.)

Background: Vital signs are usually recorded once every 8 h in patients at the hospital ward. Early signs of deterioration may therefore be missed. Wireless sensors have been developed that may capture patient deterioration earlier. The objective of this study was to determine whether two wearable patch sensors (SensiumVitals [Sensium Healthcare Ltd., United Kingdom] and HealthPatch [VitalConnect, USA]), a bed-based system (EarlySense [EarlySense Ltd., Israel]), and a patient-worn monitor (Masimo Radius-7 [Masimo Corporation, USA]) can reliably measure heart rate (HR) and respiratory rate (RR) continuously in patients recovering from major surgery., Methods: In an observational method comparison study, HR and RR of high-risk surgical patients admitted to a step-down unit were simultaneously recorded with the devices under test and compared with an intensive care unit-grade monitoring system (XPREZZON [Spacelabs Healthcare, USA]) until transition to the ward. Outcome measures were 95% limits of agreement and bias. Clarke Error Grid analysis was performed to assess the ability to assist with correct treatment decisions. In addition, data loss and duration of data gaps were analyzed., Results: Twenty-five high-risk surgical patients were included. More than 700 h of data were available for analysis. For HR, bias and limits of agreement were 1.0 (-6.3, 8.4), 1.3 (-0.5, 3.3), -1.4 (-5.1, 2.3), and -0.4 (-4.0, 3.1) for SensiumVitals, HealthPatch, EarlySense, and Masimo, respectively. For RR, these values were -0.8 (-7.4, 5.6), 0.4 (-3.9, 4.7), and 0.2 (-4.7, 4.4) respectively. HealthPatch overestimated RR, with a bias of 4.4 (limits: -4.4 to 13.3) breaths/minute. Data loss from wireless transmission varied from 13% (83 of 633 h) to 34% (122 of 360 h) for RR and 6% (47 of 727 h) to 27% (182 of 664 h) for HR., Conclusions: All sensors were highly accurate for HR. For RR, the EarlySense, SensiumVitals sensor, and Masimo Radius-7 were reasonably accurate for RR. The accuracy for RR of the HealthPatch sensor was outside acceptable limits. Trend monitoring with wearable sensors could be valuable to timely detect patient deterioration.

Background: Despite recent international efforts to develop resource-stratified clinical practice guidelines for cancer, there has been little research to evaluate the best strategies for dissemination and implementation in low- and middle-income countries (LMICs). Guideline publication alone is insufficient. Extensive research has shown that structured, multifaceted implementation strategies that target barriers to guideline use are most likely to improve adherence; however, most of this research has been conducted in high-income countries. There is a pressing need to develop and evaluate guideline implementation strategies for cancer management in LMICs in order to address stark disparities in cancer outcomes., Methods: In preparation for the launch of Tanzania's first National Cancer Treatment Guidelines, we developed a theory-driven implementation strategy for guideline-based practice at Ocean Road Cancer Institute (ORCI). Here, we use the Intervention Mapping framework to provide a detailed stepwise description of our process. First, we conducted a needs assessment to identify barriers and facilitators to guideline-based practice at ORCI. Second, we defined both proximal and performance objectives for our implementation strategy. Third, we used the Capability, Opportunity, Motivation and Behavior/Behavior Change Wheel (COM-B/BCW) framework to categorize the barriers and facilitators, choose behavior change techniques most likely to overcome targeted barriers and leverage facilitators, and select a feasible mode of delivery for each technique. Fourth, we organized these modes of delivery into a phased implementation strategy. Fifth, we operationalized each component of the strategy. Sixth, we identified the indicators of the process, outcome, and impact of our intervention and developed an evaluation plan to measure them using a mixed methods approach., Discussion: We developed a robust, multifaceted guideline implementation strategy derived from a prominent behavior change theory for use in Tanzania. The barriers and strategies we generated are consistent with those well established in the literature, enhancing the validity and generalizability of our process and results. Through our rigorous evaluation plan and systematic account of modifications and adaptations, we will characterize the transferability of "proven" guideline implementation strategies to LMICs. We hope that by describing our process in detail, others may endeavor to replicate it, meeting a widespread need for dedicated efforts to implement cancer guidelines in LMICs., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background/aim: Oxaliplatin-induced neurotoxicity (OIN) can be severe and dose-limiting with clinically significant symptoms that persist for years. Few published reports have described postoperative exacerbation of OIN and more longitudinal data are needed to better characterize the phenomenon., Patients and Methods: We identified 13 patients diagnosed with colon (n=7), rectal (n=4) or pancreatic (n=2) cancer who experienced postoperative OIN exacerbation at our medical center. Charts were reviewed for demographic and clinical data regarding OIN., Results: OIN exacerbation was documented 0.5-7.0 months after the first surgery following oxaliplatin exposure, with a median duration of 10.6 months (range=1.4-86.1 months). OIN exacerbation persisted in 3/13 patients at last follow-up, and improved to pre-operative levels in 6/13 patients (with complete resolution in 4/13) within a median of 3.6 months from initial exacerbation., Conclusion: Given the widespread use of oxaliplatin in neoadjuvant and first-line treatment for gastrointestinal cancers, further study is warranted to prospectively and systematically define risks for postoperative OIN exacerbation., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We aimed to described 25-hydroxyvitamin D [25(OH)D] levels in newly diagnosed colorectal cancer (CRC) patients and to re-evaluate levels after chemotherapy., Methods: Permanent residents of the San Francisco Bay Area with a new CRC diagnosis of any stage were recruited prior to any non-surgical therapy. Serum 25(OH)D levels were measured at time of diagnosis and 6-month follow-up. Supplement use was not restricted. The primary endpoint was the frequency of vitamin D deficiency in patients with newly diagnosed CRC of all stages. The Kruskal-Wallis and Spearman correlation tests were used to evaluate associations of patient characteristics with 25(OH)D levels., Results: Median 25(OH)D level at baseline was 27.0 ng/mL (range 7.2, 59.0); 65% of patients had insufficient levels (25(OH)D < 30 ng/mL) (n = 94). Race, disease stage, multivitamin use, vitamin D supplementation, and county of residence were associated with baseline 25(OH)D levels (P < 0.05). The median change in 25(OH)D from baseline to 6 months was - 0.7 ng/mL [- 19.4, 51.7] for patients treated with chemotherapy (n = 58) and 1.6 ng/mL [- 6.4, 33.2] for patients who did not receive chemotherapy (n = 19) (P = 0.26). For patients who received vitamin D supplementation during chemotherapy, the median 25(OH)D change was 8.3 ng/mL [- 7.6, 51.7] versus - 1.6 [- 19.4, 24.3] for chemotherapy patients who did not take vitamin D supplements (P = 0.02)., Conclusion: Among patients with a new diagnosis of CRC, most patients were found to have 25(OH)D levels consistent with either deficiency or insufficiency. In the subset of patients who received chemotherapy and took a vitamin D supplement, serum 25(OH)D levels increased, suggesting that vitamin D repletion is a feasible intervention during chemotherapy.

Following definitive chemoradiation for anal squamous cell carcinoma (ASCC), patients face a variety of chronic issues including: bowel dysfunction, accelerated bone loss, sexual dysfunction, and psychosocial distress. The increasing incidence of this disease, high cure rates, and significant long-term sequelae warrant increased focus on optimal survivorship care following definitive chemoradiation. In order to establish our survivorship care model for ASCC patients, a multi-disciplinary team of experts performed a comprehensive literature review and summarized best practices for the multi-disciplinary management of this unique patient population. We reviewed principle domains of our survivorship approach: (1) management of chronic toxicities; (2) sexual health; (3) HIV management in affected patients; (4) psychosocial wellbeing; and (5) surveillance for disease recurrence and survivorship care delivery. We provide recommendations for the optimization of survivorship care for ASCC patients can through a multi-disciplinary approach that supports physical and psychological wellness.

Objective: The aim of this study was to evaluate postoperative indices of cerebral oxygenation and autoregulation in infants with critical congenital heart disease in relation to new postoperative ischemic brain injury., Methods: This prospective, clinical cohort included 77 infants with transposition of the great arteries (N = 19), left ventricular outflow tract obstruction (N = 30), and single ventricle physiology (N = 28) undergoing surgery at 30 days or less of life. Postoperative near-infrared spectroscopy and physiologic monitoring were applied to extract mean arterial blood pressure, regional cerebral oxygen saturation, fractional tissue oxygen extraction, and regional cerebral oxygen saturation mean arterial blood pressure correlation coefficient (≥0.5 considered sign of impaired cerebral autoregulation). New postoperative ischemic injury was defined as moderate-severe white matter injury or focal infarction on magnetic resonance imaging. Low cardiac output syndrome was measured as lactate greater than 4 mmol/L with pH less than 7.30., Results: After surgery, regional cerebral oxygen saturation was decreased in all congenital heart disease groups with a notable increase in regional cerebral oxygen saturation between 6 and 12 hours after surgery, on average with a factor of 1.4 (range, 1.1-2.4). Both single ventricle physiology and postoperative low cardiac output syndrome were associated with lower regional cerebral oxygen saturation and increased time with correlation coefficient of 0.5 or greater. New postoperative ischemic injury was seen in 39 patients (53%) and equally distributed across congenital heart disease groups. Postoperative regional cerebral oxygen saturation, fractional tissue oxygen extraction, and correlation coefficient were not independently associated with new postoperative white matter injury or focal infarction (mixed-model analysis, all F > 0.12)., Conclusions: Postoperative indices of cerebral oxygenation and cerebral autoregulation are not independent predictors of new ischemic brain injury in infants with critical congenital heart disease. Further exploration of the complex interplay among low regional cerebral oxygen saturation, low cardiac output syndrome, and heart defect is required to identify potential biomarkers enabling early intervention for ischemic brain injury., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: East Africa is one of the fastest growing regions in the world and faces a rising burden of cancer; however, few people are equipped to effectively conduct research in this area., Materials and Methods: A 31-item questionnaire was distributed to current trainees and recent graduates of the Master in Medicine in Clinical Oncology Program at Muhimbili University of Health and Allied Sciences in Tanzania. Areas that were assessed included (a) demographic information, (b) prior research training, (c) prior and current research activities, (d) attitudes toward the importance of research, and (e) supports and barriers to inclusion of research in an oncology career path., Results: A total of 30 individuals responded to the survey, of whom 53% ( n  = 16) were male and 70% ( n  = 21) identified as current trainees. Among the majority of respondents, attitudes toward research were strongly favorable. Although only 37% ( n  = 11) reported receiving any formal training in research methodology, 87% ( n  = 26) reported intentions to incorporate research into their careers. The absence of protected time for research and lack of access to research funding opportunities were identified by a majority of respondents as critical barriers., Conclusion: A majority of current or recent oncology trainees in Tanzania desire to incorporate research into their careers, but most also lack adequate training in research methodology and longitudinal mentorship. Our future collaboration will focus on creation of appropriate research training curriculums and fostering an environment that catalyzes interprofessional development and transforms and extends context-specific cancer research in East Africa., Implications for Practice: Current and recent oncology trainees in East Africa expressed a high enthusiasm for research, driven by a sense of urgency related to the burden from cancer that the region faces. This highlights the need for cancer research training and mentorship in this setting. This work hypothesizes that African principal investigators can operate effectively if proper attention is given to selection and provision of high-quality foundational didactic training to learn the theory and implementation of research as well as to the development of an environment conducive to mentoring., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Introduction: Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol., Methods and Analysis: The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery., Ethics and Dissemination: The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal., Trial Registration Number: ACTRN12617000821392., Competing Interests: Competing interests: YdU is a consultant for MSD and Actelion., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We sought to determine patients' informational needs for post-treatment surveillance and elicit clinicians' and patient advocates' (ie, stakeholders) opinions regarding what patients should know about post-treatment surveillance in the USA., Design: A mixed-methods study, using semi-structured interviews followed by a survey study., Setting: Participants for the interviews were from two large academic medical centres and a safety-net hospital. The stakeholders were recruited from attendees at the Alliance for Clinical Trials in Oncology Network Spring 2016 meeting., Participants: Participants for the in-depth interviews were purposively sampled. Eligible patients were 6 months to 5 years post curative resection for colorectal cancer and were fluent in English. Participants for the anonymous survey were stakeholders., Main Outcomes and Measures: The main outcome was patients' with colorectal cancer informational needs for post-treatment surveillance, using an interview guide. The second outcome was the importance of the identified informational needs using an anonymous survey., Results: Of the 67 patients approached, 31 were interviewed (response rate=46%), the majority were between 1 and 3 years post-treatment (81%) and diagnosed at stage III (74%). Despite a desire to monitor for cancer recurrence, patients had little understanding of the concept of post-treatment surveillance, equating surveillance with screening and a belief that if a recurrence was found early there would be a higher likelihood of cure. The survey suggested that clinicians (n=38) and patient advocates (n=11) had some differing opinions regarding what patients should know about surveillance to be active in decisions. For example, compared with clinicians, patient advocates felt that patients should know recurrence treatment options (100% vs 58%) and likelihood for cure following recurrence treatment (100% vs 38%)., Conclusions: The results of this exploratory mixed-methods study suggest that novel educational interventions targeting both patients and clinicians are needed to address the informational needs for post-treatment surveillance of colorectal cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors., Methods: We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer., Results: All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified., Discussion: CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

Objectives: Gallium (Ga)-DOTATOC is a somatostatin analog used to detect neuroendocrine tumors (NETs). Ki-67 proliferation index (Ki-67 PI) has been established as a prognostic factor in NETs. We aimed to evaluate whether a correlation exists between Ki-67 PI and somatostatin receptor positron emission tomography (SSTR-PET) uptake., Methods: We retrospectively reviewed 238 DOTATOC PET scans between 2014 and 2016. Patients were excluded if DOTATOC PET was performed more than 365 days from the date of biopsy. Maximum standardized uptake values (SUVmax) of SSTR-PET from biopsied lesions were measured and correlated with Ki-67 PI using the Pearson correlation coefficient., Results: Among 110 lesions from 90 patients, DOTATOC PET had 92.7% sensitivity and 100% specificity (102 true positives, 8 false negatives) for detection of NETs. Among 63 lesions from 54 patients with Ki-67 PI available, there were 27 grade 1 lesions [median Ki-67 PI, 1.0%; interquartile range (IQR), 1.0-2.0], 30 grade 2 lesions (median, Ki-67 PI 7.5%; IQR, 5-10), and 6 grade 3 lesions (median Ki-67 PI, 30%; IQR, 26-34). There was a correlation between Ki-67 PI and SUVmax (r = -0.3, P = 0.018)., Conclusions: Our analysis demonstrates an inverse correlation between Ki-67 PI and SUVmax in NETs. Somatostatin receptor-PET provides additional information that can help guide management of NETs.

Active and secondhand tobacco exposures are major causes of cancer. Cancer prevention efforts are particularly relevant in resource-constrained settings in which significant barriers to early detection and cancer treatments contribute to poor outcomes. We assess the associations between exposure to household tobacco smoke and cancer morbidity and mortality. We used household data from Afghanistan Demographic and Health Survey, which was a national cross-sectional survey that applied a two-stage stratified random sampling technique in 2015 and 2016. We performed regression analysis to estimate associations between exposure to household tobacco smoke and cancer morbidity and mortality at the household level. Exposure to household tobacco smoke was significantly associated with household reports of a history of any cancer (Adjusted Odds Ratio (AOR): 1.90; 95% Confidence Interval (CI): 1.44, 2.51), breast cancer (1.59; 1.00, 2.55), lung cancer (2.88; 1.58, 5.27), and liver cancer (2.56; 1.10, 5.96), compared to households with no tobacco smoke exposure. These associations persisted after controlling for household location, wealth index, type of cooking fuel used in house, and location of food preparation. Households in a rural location experienced significantly higher mortality of any cancer (4.40; 95% CI: 1.57, 12.38), breast cancer (2.91; 1.02, 8.25), and liver cancer (3.91; 1.29, 11.89) vs. those in an urban location. Exposure to household tobacco smoke is a risk factor for cancer morbidity in Afghanistan. Strategies to implement comprehensive smoking cessation and smoke free housing policies are urgently needed as primary cancer prevention strategy in Afghanistan and comparable resource-constrained settings., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: The objective of this study was to describe the periprocedural management of patients with well-differentiated neuroendocrine tumors with hepatic metastases who underwent liver-directed procedures., Methods: We performed a retrospective review of patients with metastatic neuroendocrine tumors who underwent liver resection, ablation, or embolotherapy at a single center from 2012 to 2016. The primary outcome was occurrence of documented carcinoid crisis (CC) or hemodynamic instability (HDI), defined as 10 minutes or more of systolic blood pressure less than 80 or greater than 180 mm Hg, or pulse greater than 120 beats per minute., Results: We identified 75 patients who underwent liver resection/ablation (n = 38) or embolotherapy (n = 37). Twenty-four patients (32%) experienced CC or HDI (CC/HDI); CC occurred in 3 patients. No clinicopathologic or procedural factors, including procedure type, octreotide or long-acting somatostatin analog use, and history of carcinoid syndrome, were associated with CC/HDI. Grades 2 to 4 complications were reported in 42% of patients who experienced CC/HDI versus in 16% of patients who did not experience CC/HDI (P < 0.05)., Conclusions: A significant portion of patients developed CC/HDI, and these patients were more likely to develop severe postprocedural complications. Periprocedural octreotide use was not associated with lower CC/HDI occurrence, but continued use is advised given its safety profile until additional studies definitively demonstrate lack of benefit.

Background: Over 1.3 million people live with colorectal cancer in the United States. Physical activity is associated with lower risk of colorectal cancer recurrence and mortality. Interventions are needed to increase physical activity in colorectal cancer survivors., Methods: We conducted a 2-arm non-blinded pilot randomized controlled trial at the University of California, San Francisco among 42 individuals who had completed curative-intent treatment for colorectal cancer to determine the feasibility and acceptability of a 12-week (84 days) physical activity intervention using a Fitbit Flex™ and daily text messages. Participants were randomized 1:1 to receive the intervention with print educational materials or print educational materials alone. We explored the impact of the intervention versus usual care on physical activity using ActiGraph GT3X+ accelerometers pre-/post-intervention., Results: We screened 406 individuals and randomized 42 to intervention (n = 21) or control (n = 21) groups. During the 12-week study, the intervention arm wore their Fitbits a median of 74 days [88% of days in study period, interquartile range: 23-83 days] and responded to a median of 34 (out of 46) text messages that asked for a reply (interquartile range: 13-38 text messages). Among the 16 intervention participants who completed the feedback survey, the majority (88%) reported that the intervention motivated them to exercise and that they were satisfied with their experience. No statistically significant difference in change in moderate-to-vigorous physical activity was found from baseline to 12 weeks between arms., Conclusion: A 12-week physical activity intervention with a Fitbit and text messages was feasible and acceptable among colorectal cancer patients after curative treatment. Larger studies are needed to determine whether the intervention increases physical activity., Trial Registration: Clinicaltrials.gov Identifier NCT02966054 . Registered 17 November 2016, retrospectively registered.