Telephone-Based Rehabilitation Intervention to Optimize Activity Participation After Breast Cancer: A Randomized Clinical Trial.

Importance: Following treatment, breast cancer survivors face challenges participating in valued activities. Objective: To determine whether a telephone-based coaching rehabilitation intervention enhances activity participation in the year following breast cancer treatment. Design, Setting, and Participants: In this multisite, single-blind randomized clinical trial (Optimizing Functional Recovery of Breast Cancer Survivors), recruitment occurred between August 28, 2019, and April 30, 2022. Data collection was completed by April 1, 2023. Participants were recruited from 2 cancer centers (Dartmouth College and the University of Alabama at Birmingham) and via social media advertisements. Women aged 18 years or older who had completed primary treatment for stage I to III breast cancer within 1 year and reported participation restrictions were eligible to participate. Randomization was stratified by site, treatment, and time since treatment. Interventions: The intervention, delivered via telephone over 9 sessions, used behavioral activation and problem-solving principles to promote activity participation. The education-based attention control condition was delivered via telephone at matched intervals. Main Outcomes and Measures: The primary outcome was participation, assessed using 5 measures, including Patient-Reported Outcomes Measurement Information System (PROMIS) social participation-satisfaction measure. One individualized outcome allowed participants to specify activities for which they wanted to foster recovery. Outcomes were collected by telephone by blinded coordinators at baseline and at 8, 20, and 44 weeks. The individualized outcome was assessed at the first and last intervention and control session. Results: Among 1996 patients identified, 303 were eligible and enrolled. Of these, 284 women (94%; mean [SD] age, 56.1 [10.2] years) completed baseline assessments and were randomized, and 81% or more of each group completed the final assessment with no adverse events. Of those who completed the final assessment, 118 of 114 (82%) were in the intervention group, and 113 of 140 (81%) were attention control participants. Between-group differences were not statistically significant for the main measures of PROMIS satisfaction (week 20: Cohen d, 0.1 [95% CI, -0.09 to 0.29] and week 44: Cohen d, -0.08 [95% CI, -0.27 to 0.11]) and ability (week 20: Cohen d, 0.15 [95% CI, -0.06 to 0.37] and week 44: Cohen d, -0.08 [95% CI, -0.27 to 0.11]). On the individualized outcome, intervention participants reported significantly greater improvements in activity satisfaction (Cohen d, 0.76 [95% CI, 0.48-1.02]) and performance (Cohen d, 0.60 [95% CI, 0.32-0.87]). Conclusions and Relevance: In this randomized clinical trial, the intervention catalyzed greater improvements in self-selected activity participation and goal disengagement but did not otherwise accelerate recovery compared with the control condition. Future research should determine what intervention features may lead to the greatest reductions in participation restrictions and other measures that may detect functional recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT03915548.

Financial Toxicity: Unveiling the Burden of Cancer Care on Patients in Rwanda.

INTRODUCTION: Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda. METHODS: This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country's cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin's and non-Hodgkin's lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics. RESULTS: 239 patients were included; 75% (n = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n = 106/239) of respondents sold property, 29% (n = 70/239) asked for charity from public, family, or friends, and 16% (n = 37/239) took loans with interest to fund cancer treatment. CONCLUSION: Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care.

Near-Infrared Spectral Tomography for Predicting Residual Cancer Burden during Early-Stage Neoadjuvant Chemotherapy for Breast Cancer.

PURPOSE: The aim of this study is to investigate whether near-infrared spectral tomography (NIRST) might serve as a reliable prognostic tool to predict residual cancer burden (RCB) in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC) based upon early treatment response measurements. EXPERIMENTAL DESIGN: A total of thirty-five patients with breast cancer receiving NAC were included in this study. NIRST imaging was performed at multiple time points, including: before treatment, at end of the first cycle, at the mid-point, and post-NAC treatments. From reconstructed NIRST images, average values of total hemoglobin (HbT) were obtained for both the tumor region and contralateral breast at each time point. RCB scores/classes were assessed by a pathologist using histologic slides of the surgical specimen obtained after completing NAC. Logistic regression of the normalized early percentage change of HbT in the tumor region (ΔHbT%) was used to predict RCB and determine its significance as an indicator for differentiating cases within each RCB class. RESULTS: The ΔHbT% at the end of the first cycle, as compared with pretreatment levels, showed excellent prognostic capability in differentiating RCB-0 from RCB-I/II/III or RCB-II from RCB-0/I/III (P < 0.001). Corresponding area under the curve (AUC) values for these comparisons were 0.97 and 0.94, and accuracy values were 0.90 and 0.83, respectively. CONCLUSIONS: NIRST holds promise as a potential clinical tool that can be seamlessly integrated into existing clinical workflow within the infusion suite. By providing early assessment of RCB, NIRST has potential to improve breast cancer patient management strategies.

Enhancing Efficiency and Reach Using Facebook to Recruit Breast Cancer Survivors for a Telephone-Based Supportive Care Randomized Trial During the COVID-19 Pandemic.

PURPOSE: Evidence supporting social media-based recruitment of cancer survivors is limited. This paper describes how we used Facebook during the COVID-19 pandemic to augment our recruitment of breast cancer survivors for our two-site telephone-based randomized clinical trial (RCT) at Dartmouth-Hitchcock Medical Center and the University of Alabama at Birmingham. METHODS: Originally a two-site RCT of a telephone-delivered breast cancer survivorship intervention, we extended our clinic-based recruitment to Facebook. Participant characteristics, geographic reach, and baseline outcomes were compared across recruitment sources (ie, two clinics and Facebook) using descriptive statistics and effect sizes. RESULTS: Enrollment rates (20%-29%) were comparable across recruitment sources. The 21-month Facebook marketing campaign accounted for 59% (n = 179/303) of our total sample and had the greatest geographic reach, recruiting women from 24 states. The Facebook campaign reached a total of 51,787 unique individuals and cost $88.44 in US dollars (USD) per enrolled participant. Clinic samples had a greater proportion of women who were widowed (8% v 1%; P = .03) and Facebook had a higher proportion of women with a household income over $40,000 USD (83% v 71%; P = .02). There were no statistically significant differences between Facebook and the two clinics on baseline survey scores. CONCLUSION: Augmenting traditional recruitment with Facebook increased our RCT's geographic and sociodemographic reach and supported meeting recruitment goals in a timely way. In the wake of the COVID-19 pandemic, cancer survivorship researchers should consider using social media as a recruitment strategy while weighing the advantages and potential biases introduced through such strategies.

Alternating 17ß-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer.

PURPOSE: Strategies to implement estrogen therapy for advanced estrogen receptor-positive (ER+) breast cancer are underdeveloped. Preclinical data suggest that cycling treatment with 17ß-estradiol followed by estrogen deprivation can control tumor growth long-term. PATIENTS AND METHODS: Postmenopausal women with advanced ER+/HER2- breast cancer with recurrence or progression on ≥ 1 antiestrogen or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17ß-estradiol (2 mg orally, three times a day) for 8 weeks followed by AI (physician's choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations. RESULTS: Of 19 evaluable patients, clinical benefit rate was 42.1% [95% confidence interval (CI), 23.1%-63.9%] and objective response rate (ORR) was 15.8% (95% CI, 5.7%-37.9%). One patient experienced a grade 3 adverse event related to 17ß-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5 of 12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4 of 7 (57.1%) versus 2 of 9 (22.2%) patients who did versus did not experience clinical benefit from alternating 17ß-estradiol/AI therapy. The only two patients to experience objective responses to initial 17ß-estradiol had tumor ESR1 mutations. CONCLUSIONS: Alternating 17ß-estradiol/AI therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the antitumor activity of 17ß-estradiol differs according to ESR1 mutation status.

Preventing metastatic recurrence in low-risk ER/PR + breast cancer patients-a retrospective clinical study exploring the evolving challenge of persistence with adjuvant endocrine therapy.

PURPOSE: In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients' non-persistence with AET was performed. METHODS: Women who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. 'Low risk' was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test. RESULTS: We identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028). CONCLUSION: Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

Assessing the utilization of cancer medicines in Rwanda: an analysis of treatment patterns.

Introduction: Cancer is a growing public health concern in Africa, especially in low- and middle-income countries (LMICs) like Rwanda. Increased cancer incidences translate into increased utilisation of cancer medicine. Access to affordable cancer medicines in Rwanda is a pressing issue as the National Health Insurance plan does not provide coverage for cancer medicines. In this study, we investigated the utilisation patterns of cancer medicines in Rwanda. Methods: This retrospective cross-sectional study was conducted at all referral hospitals (n = 3) capable of delivering chemotherapy in Rwanda. The data collection was over a period of 6 months, during which a team of trained research assistants reviewed a convenience sample of selected patient charts. Both paper charts and electronic medical records were used to collect patients' data, including cancer type, stage, treatment setting, type of drugs or regimen used and completed cycles. Data were analysed using descriptive statistics. Results: A total of 630 patients received chemotherapy during the study period and were included. Seventy-seven percent (n = 486) were female and mean age was 51 (SD ± 13). Among all patients receiving chemotherapy, 43% (n = 270) had breast cancer, 22% (n = 140) had cervical cancer and 19% (n = 121) had colorectal cancer. The majority of patients (71%) had a community-based insurance. Butaro Cancer Centre treated the most patients (48%, n = 303). Thirty-six percent (221/630) had stage III cancer. The most common regimens within the cohort were adriamycin, cyclophosphamide and taxane, capecitabine and oxaliplatin (CAPOX), paclitaxel + carboplatin and a single agent cisplatin given concurrently with radiotherapy. The proportion of chemotherapy that was given in the curative and palliative setting was 72% and 28% respectively. Conclusion: Access to affordable cancer medicines remains a challenge in Rwanda. The study's findings provide valuable information on the utilisation patterns of cancer medicines in Rwanda, which can be used to guide policy decisions and improve cancer care in the country.

A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART, SWOG S1609).

PURPOSE: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). PATIENTS AND METHODS: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Overall, 17 evaluable patients enrolled. Median age was 60 years (26-85); median number of prior therapy lines was 2 (0-5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. CONCLUSIONS: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.

Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients.

PURPOSE: This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients. METHODS: Tumor-infiltrating lymphocytes (TILs) and CD20+ B-cell frequencies (CD20+), and PD-L1 expression on tumor (PD-L1+carcinoma cells) and immune (PD-L1+TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models. RESULTS: IBC and LABC display similar levels of TILs, CD20+, and combined CD20+ and PD-L1+TILs (CD20+PD-L1+TILs), while LABC contained more PD-L1+TILs and PD-L1+ carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1+ carcinoma cells, and combined CD20+ and PD-L1+ carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1+TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20+ and CD20+PD-L1+TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20+PD-L1+TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC. CONCLUSION: CD20+PD-L1+TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.

Kynurenine-Induced Aryl Hydrocarbon Receptor Signaling in Mice Causes Body Mass Gain, Liver Steatosis, and Hyperglycemia.

OBJECTIVE: The aryl hydrocarbon receptor (AHR) plays a key role in obesity. In vitro studies revealed that the tryptophan metabolite kynurenine (Kyn) activates AHR signaling in cultured hepatocytes. The objective of this study was to determine whether Kyn activated the AHR in mice to induce obesity. METHODS: Mice were fed a low-fat diet and the same diet supplemented with Kyn. Body mass, liver status, and the expression of identified relevant genes were determined. RESULTS: Kyn caused mice to gain significant body mass, develop fatty liver and hyperglycemia, and increase expression levels of cytochrome P450 1B1 and stearoyl-CoA desaturase 1. The hyperglycemia was accompanied with decreased insulin levels, which may have been due to the repression of genes involved in insulin secretion. Kyn plasma concentrations and BMI were measured in female patients, and a significant association was observed between Kyn and age in patients with obesity but not in patients who were lean. CONCLUSIONS: Results show that (1) Kyn or a metabolite thereof is a ligand responsible for inducing AHR-based obesity, fatty liver, and hyperglycemia in mice; (2) plasma Kyn levels increase with age in women with obesity but not in lean women; and (3) an activated AHR is necessary but not sufficient to attain obesity, a status that also requires fat in the diet.

Surgeon and medical oncologist peer network effects on the uptake of the 21-gene breast cancer recurrence score assay.

BACKGROUND: Drivers behind the adoption of gene expression profiling in breast cancer oncology have been shown to include exposure to physician colleagues' use of a given genomic test. We examined adoption of the Oncotype DX 21-gene breast cancer recurrence score assay (ODX) in the United States after its incorporation into clinical guidelines. The influence of patient-sharing ties and co-location with prior adopters and the role of these potential exposures across medical specialties on peers' adoption of the test were examined. METHODS: We conducted a retrospective cohort study of women with incident breast cancer using a 100% sample of fee-for-service Medicare enrollee claims over 2008-2011. Peer networks connecting medical oncologists and surgeons treating these patients were constructed using patient-sharing and geographic co-location. The impact of peer connections on the adoption of ODX by physicians and testing of patients was modeled with multivariable hierarchical regression. RESULTS: Altogether, 156,229 women identified with incident breast cancer met criteria for cohort inclusion. A total of 7689 ODX prescribing physicians were identified. Co-location with medical oncologists who adopted the test in the early period (2008-2009) was associated with a 1.38-fold increase in the odds of a medical oncologist adopting ODX in 2010-2011 (95% CI = 1.04-1.83), as was co-location with early-adopting surgeons (odds ratio [OR] = 1.25, 95% CI = 1.00-1.58). Patients whose primary medical oncologist was linked to an early-adopting surgeon through co-location (OR = 1.17, 95% CI = 1.04-1.32) or both patient-sharing and co-location (OR = 1.17, 95% CI = 1.03-1.34) were more likely to receive ODX. CONCLUSIONS: Exposure to surgeon early adopters through peer networks and co-location was predictive of ODX uptake by medical oncologists and testing of patients. Interventions focused on the role of surgeons in molecular testing may improve the implementation of best practices in breast cancer care.

Implementation and Impact of a Serious Illness Communication Training for Hematology-Oncology Fellows.

Effective communication between providers and patients with serious illness is critical to ensure that treatment is aligned with patient goals. We developed and tested an implementation strategy for incorporating the previously developed Serious Illness Conversation Guide (SICG), a clinician script, into hematology-oncology fellowship training at a single US academic medical center. Between December 2017 and April 2018, we trained 8 oncology fellows to use and document the SICG. The training included associated communication skills-such as handling emotion and headlining-over 7 didactic sessions. Implementation strategies included training 4 oncology faculty as coaches to re-enforce fellows' skills and an electronic medical record template to document the SICG. We assessed effectiveness using 4 approaches: (1) SICG template use among fellows in the 12 months following training, (2) fellow confidence pre- and post-intervention via survey, (3) performance in 2 simulated patient encounters, and (4) semi-structured interviews after 12 months. Fellows successfully implemented the SICG in simulated patient encounters, though only 2 of 6 fellows documented any SICG in the clinical practice. Most fellows reported greater confidence in their communication after training. Thematic analysis of interviews revealed the following: (1) positive training experience, (2) improved patient preference elicitation, (3) selected SICG components used in a single encounter, (4) prioritize other clinical duties, (5) importance of emotion handling skills, (6) no faculty coaching receive outside training. Despite acquisition of communication skills, promoting new clinical behaviors remains challenging. More work is needed to identify which implementation strategies are required in this learner population.

Identifying Breast Cancer Care Quality Measures for a Cancer Facility in Rural Sub-Saharan Africa: Results of a Systematic Literature Review and Modified Delphi Process.

PURPOSE: The burden of cancer is growing in low- and middle-income countries (LMICs), including sub-Saharan Africa. Ensuring the delivery of high-quality cancer care in such regions is a pressing concern. There is a need for strategies to identify meaningful and relevant quality measures that are applicable to and usable for quality measurement and improvement in resource-constrained settings. METHODS: To identify quality measures for breast cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda, we used a modified Delphi process engaging two panels of experts, one with expertise in breast cancer evidence and measures used in high-income countries and one with expertise in cancer care delivery in Rwanda. RESULTS: Our systematic review of the literature yielded no publications describing breast cancer quality measures developed in a low-income country, but it did provide 40 quality measures, which we adapted for relevance to our setting. After two surveys, one conference call, and one in-person meeting, 17 measures were identified as relevant to pathology, staging and treatment planning, surgery, chemotherapy, endocrine therapy, palliative care, and retention in care. Successes of the process included participation by a diverse set of global experts and engagement of the BCCOE community in quality measurement and improvement. Anticipated challenges include the need to continually refine these measures as resources, protocols, and measurement capacity rapidly evolve in Rwanda. CONCLUSION: A modified Delphi process engaging both global and local expertise was a promising strategy to identify quality measures for breast cancer in Rwanda. The process and resulting measures may also be relevant for other LMIC cancer facilities. Next steps include validation of these measures in a retrospective cohort of patients with breast cancer.

Molecular matching and treatment strategies for advanced stage lung cancer at Dartmouth-Hitchcock Medical Center: A three-year review of a Molecular Tumor Board.

Matching of actionable tumor mutations with targeted therapy increases response rates and prolongs survival in lung cancer patients. Drug development and trials targeting genetic alterations are expanding rapidly. We describe the role of a Molecular Tumor Board (MTB) in the design of molecularly informed treatment strategies in our lung cancer patient population. Tumor DNA was sequenced using a 50-gene targeted next-generation sequencing panel. Cases were evaluated by a multidisciplinary MTB who suggested a course of treatment based on each patient's molecular findings. During a three-year period, 21 lung cancer patients were presented at the MTB. All patients lacked common activating EGFR mutations and ALK rearrangements. One patient had Stage IIIb disease; all others were Stage IV; 18 patients had received ≥1 prior line of therapy (range 0-5). Suggestions for treatment with a targeted therapy were made for 19/21 (90.5%) patients, and four patients (21%) underwent treatment with a targeted agent, two as part of a clinical trial. Identified barriers to treatment with targeted therapy included: ineligibility for clinical trials (n â€‹= â€‹2), lack of interest in study/distance to travel (n â€‹= â€‹2), lack of disease progression (n â€‹= â€‹2), poor performance status (n â€‹= â€‹5), decision to treat next with immunotherapy (n â€‹= â€‹3), and unknown (n â€‹= â€‹1). For the majority of lung cancer patients, the MTB provided recommendations based on tumor genetic profiles. Identified barriers to treatment suggest that presentation to the MTB at earlier stages of disease may increase the number of patients eligible for treatment with a genetically informed targeted agent.

Plasma DNA as a "liquid biopsy" incompletely complements tumor biopsy for identification of mutations in a case series of four patients with oligometastatic breast cancer.

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a "liquid biopsy" for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1-3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 ± 11.81% (mean ± SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).

Treatment of Patients With Late-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline.

PURPOSE: To provide expert guidance to clinicians and policymakers in resource-constrained settings on the management of patients with late-stage colorectal cancer. METHODS: ASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines, conducted a modified ADAPTE process, and used a formal consensus process with additional experts for two rounds of formal ratings. RESULTS: Existing sets of guidelines from four guideline developers were identified and reviewed; adapted recommendations from five guidelines form the evidence base and provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% on all recommendations. RECOMMENDATIONS: Common elements of symptom management include addressing clinically acute situations. Diagnosis should involve the primary tumor and, in some cases, endoscopy, and staging should involve digital rectal exam and/or imaging, depending on resources available. Most patients receive treatment with chemotherapy, where chemotherapy is available. If, after a period of chemotherapy, patients become candidates for surgical resection with curative intent of both primary tumor and liver or lung metastatic lesions on the basis of evaluation in multidisciplinary tumor boards, the guidelines recommend patients undergo surgery in centers of expertise if possible. On-treatment surveillance includes a combination of taking medical history, performing physical examinations, blood work, and imaging; specifics, including frequency, depend on resource-based setting.Additional information is available at www.asco.org/resource-stratified-guidelines.

Feasibility of Brigade-Style, Multiphasic Cancer Screening in Rural Honduras.

PURPOSE: To evaluate the feasibility of brigade-style, multiphasic cancer screening in Honduras, exploring data from 3 screening events that each tested for multiple cancers on single occasions. METHODS: This series of 3 studies each used a single-arm, post-test-only design to explore the feasibility of implementing multiphasic, community-based cancer screening at the same rural location in 2013, 2016, and 2017. The 2013 event for women screened for 2 cancers (breast and cervix), and the 2016 event for women screened for 3 cancers (breast, cervix, and thyroid). The 2017 event for men screened for 5 cancers (skin, prostate, colorectal, oropharynx, and testes). RESULTS: Totals of 473 and 401 women participated in the 2013 and 2016 events, respectively, and 301 men participated in the 2017 event. Staffing for each event varied from 33 to 44 people and relied primarily on in-country medical students and local community members. High rates (mean, 88%) of compliance with referral for follow-up testing at clinics and primary care facilities were observed after the screening events. CONCLUSION: The multiphasic, community-based approach proved feasible for both women and men and resulted in high rates of compliance with follow-up testing. This approach appears highly replicable: it was conducted multiple times across the years with different screening targets, which could be further scaled elsewhere using the same technique.

Study protocol for a multisite randomised controlled trial of a rehabilitation intervention to reduce participation restrictions among female breast cancer survivors.

INTRODUCTION: Many breast cancer survivors report an inability to fully participate in activities of daily living after completing cancer treatment. Reduced activity participation is linked to negative consequences for individuals (eg, depression, reduced quality of life) and society (reduced workforce participation). There is currently a lack of evidence-based interventions that directly foster cancer survivors' optimal participation in life roles and activities. Pilot study data suggest rehabilitation interventions based on behavioural activation (BA) and problem-solving treatment (PST) can facilitate post-treatment role resumption among breast cancer survivors. METHODS AND ANALYSIS: This protocol describes a multisite randomised controlled trial comparing a 4-month long, nine-session BA and PST-informed rehabilitation intervention (BA/PS) against a time-matched, attention control condition. The overall objective is to assess the efficacy of BA/PS for enhancing breast cancer survivors' activity participation and quality of life over time. A total of 300 breast cancer survivors reporting participation restrictions after completing curative treatment for stage 1-3 breast cancer within the past year will be recruited across two sites (Dartmouth-Hitchcock Medical Center and University of Alabama at Birmingham). Assessments are collected on enrolment (T1) and 8 (T2), 20 (T3) and 44 (T4) weeks later. ETHICS AND DISSEMINATION: Study procedures are approved by the Committee for the Protection of Human Subjects at Dartmouth College, acting as the single Institutional Review Board of record for both study sites (STUDY 00031380). Results of the study will be presented at national meetings and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03915548; Pre-results.