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The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment. [ABSTRACT FROM AUTHOR]

Objectives: Precision oncology is generating vast amounts of multiomic data to improve human health and accelerate research. Existing clinical study designs and attendant data are unable to provide comparative evidence for economic evaluations. This lack of evidence can cause inconsistent and inappropriate reimbursement. Our study defines a core data set to facilitate economic evaluations of precision oncology.Methods: We conducted a literature review of economic evaluations of next-generation sequencing technologies, a common application of precision oncology, published between 2005 and 2018 and indexed in PubMed (MEDLINE). Based on this review, we developed a preliminary core data set for informal expert feedback. We then used a modified-Delphi approach with individuals involved in implementation and evaluation of precision medicine, including 2 survey rounds followed by a final voting conference to refine the data set.Results: Two authors determined that variation in published data elements was reached after abstraction of 20 economic evaluations. Expert consultation refined the data set to 83 unique data elements, and a multidisciplinary sample of 46 experts participated in the modified-Delphi process. A total of 68 elements (81%) were selected as required, spanning demographics and clinical characteristics, genomic data, cancer treatment, health and quality of life outcomes, and resource use.Conclusions: Cost-effectiveness analyses will fail to reflect the real-world impacts of precision oncology without data to accurately characterize patient care trajectories and outcomes. Data collection in accordance with the proposed core data set will promote standardization and enable the generation of decision-grade evidence to inform reimbursement. [ABSTRACT FROM AUTHOR]

• MET exon 14 skipping is a targetable driver alteration. • The prevalence was 2.1 % in the British Columbia population. • There was modest disease control with crizotinib, platinum-doublet and immunotherapy. • Co-mutations with TP53 common. MET exon 14 skipping is a potentially targetable molecular alteration. The goals of this study were to identify patients treated in British Columbia with MET exon 14 skipping to understand prevalence, biology and response to treatment, and to identify molecular signatures that may predict for response or resistance to targeted MET therapy in the setting of advanced disease. A retrospective review was completed of patients found to have MET exon 14 skipping alterations between January 2016-September 2019. Information was collected on baseline characteristics, response to systemic treatments, and outcomes. Out of 1934 advanced, non-squamous and never-smoking squamous NSCLC patients tested, 41 patients were found to have MET exon 14 skipping (2.1 %). MET alteration types: 2% CBL binding-domain mutations, 34 % poly-pyrimidine tract deletions, 63 % splice donor mutations or deletions. The most common co-mutation was TP53 (22 %). Thirty-three patients received systemic therapy. Physician-assessed disease control was 68 % among 19 evaluable patients treated with crizotinib, 80 % among 10 evaluable patients treated with platinum-based chemotherapy, and 70 % among 10 evaluable patients treated with immunotherapy. Median time to treatment discontinuation was 3.0, 2.8, and 2.4 months, respectively. Median overall survival for metastatic patients treated with any systemic therapy was 15.4 months. In this small cohort, there were no clear correlations between molecular aberrations and response, time to treatment discontinuation, or survival for crizotinib, chemotherapy, and immunotherapy. The prevalence of MET exon 14 skipping in a North American population was 2.1 %. Unlike other targetable mutations, patients were older and more commonly current or former smokers. Patients with MET exon 14 skipping alteration demonstrate disease control with crizotinib, platinum-based chemotherapy and immunotherapy. Co-mutations with TP53 were commonly noted, but correlation between co-mutations and efficacy of therapy were not identified in this cohort. [ABSTRACT FROM AUTHOR]

Purpose: Germ cell tumours are the most common cancer of male adolescents and young adults (AYA, age 18–39). Men in this age group have been healthy much of their lives, and a diagnosis of cancer can cause significant psychosocial distress. We therefore sought to examine the psychosocial needs of patients with germ cell tumour and determine whether needs vary based on age (AYA vs non-AYA). We hypothesized that AYA experience more anxiety and distress in emotional, practical and physical domains. Methods: We evaluated the responses of all patients referred to British Columbia (BC) Cancer who completed a pre-consultation health assessment form. This is a validated screening questionnaire for distress, subclinical/clinical symptoms of depression and anxiety and includes the Canadian Problem Checklist domains of emotional, informational, practical, spiritual, social/family and physical concerns. Results: Data were collected for 349 patients (2011–2015). Patient population was predominantly AYA (n = 227) with median age 33 (range 18–83). The top 3 AYA concerns were financial, work/school, frustration and anger. AYA patients more commonly scored positive for symptoms of subclinical/clinical anxiety than non-AYA (39.4% vs. 27.9%, p = 0.028). Those AYA patients with subclinical/clinical anxiety symptoms experienced more fears and worries, concerns regarding work/school, lack of understanding of their disease, finances and frustration and anger. Conclusions: The results of this study indicate that AYA with testicular cancer have unique needs and experience more self-reported anxiety symptoms with emotional, informational and practical concerns. This is valuable information to stakeholders for allocation of resources to address cancer survivorship amongst these patients. [ABSTRACT FROM AUTHOR]

Background: Advances in curative treatment for breast, colorectal, NSCLC and prostate cancer have led to improvements in cancer survival. Cancer treatment and recovery time can vary depending on the recommended modalities and intensity of therapy. Our objective was to determine the current real world duration of curative treatments for the four common cancers.Methods: A retrospective review was completed of patients referred to BC Cancer from 2010 to 2016, ≤ 65 years old, newly diagnosed with stage I-III breast, colorectal, NSCLC or prostate cancer who received curative intent treatment. Information was collected on baseline characteristics, date of diagnosis, surgery, type, duration and intent of both radiotherapy and chemotherapy.Results: In total, 22,275 patients were included: 55.7% breast, 22.4% colorectal, 9.2% NSCLC, 12.7% prostate cancer. Stage I/II/III at diagnosis: breast 47.2/38.7/14.1%, colorectal 26.5/30.1/43.5%, NSCLC 46.5/18.1/35.4%, prostate 7.7/62.9/29.4%. Patients treated with definitive surgery only: breast 35.9%, colorectal 58%, NSCLC 52.2%, prostate 40.1%. The median duration of multimodality treatment was breast 24.6 weeks, colorectal 26.7 weeks, NSCLC 9.1 weeks, and prostate 6.0 weeks.Conclusions: Approximately half of patients who undergo curative cancer treatment require definitive radiotherapy or multimodality treatment. The median duration of therapy for the most commonly treated cancers ranged from 6.0-26.7 weeks. Multimodality curative treatment can be prolonged for selected cancers when accounting for the duration of adjuvant chemotherapy and radiotherapy and recovery time between modalities. [ABSTRACT FROM AUTHOR]

Purpose: Adolescents and young adults (AYA) (18–40) are a population of patients with cancer, who have distinctive developmental and psychosocial pressures. Using validated distress screening tools, we investigated psychosocial needs of AYA compared to older adults with cancer at diagnosis. Methods: AYA and older adult patients from British Columbia, Canada, between 2011 and 2016, who completed the Canadian Problem Checklist (CPC) and the PsychoSocial Screen for Cancer-Revised (PSSCAN-R) within 6 months of their cancer diagnosis were included in the study. Emotional, informational, physical, practical, social, and spiritual domain concerns are identified using the CPC. Psychosocial needs and distress are evaluated using the PSSCAN-R. Baseline demographics were obtained from the cancer registry. Based on gender, primary tumor site, and presence of metastasis, a 3:1 case match was performed with older adults (>40 years old). Statistical analyses included Chi square and Fisher's exact tests. Results: Two thousand and forty five AYA were case matched with 6050 older adults. Majority of patients were female (61.9%), and at diagnosis, 12.1% had metastatic disease. Top three tumor types were breast (20.4%), lymphoma (11.5%), and gastrointestinal (10.8%). The top five concerns for AYA (% AYA, % adults) were fear/worry (56.6, 42.9), understanding of illness (47.6, 41.4), sleep (35.2, 28.9), sadness (34.1, 20.0), and finances (33.8, 15.0). AYA reported higher symptoms of anxiety at baseline (% AYA, % older adults), both moderate (26.0, 19.9) and severe (26.6, 17.1) p < 0.01. Conclusion: Significant differences in psychosocial needs for AYA were seen at diagnosis across multiple domains, specifically, higher emotional, informational, physical, and financial distress. Development of supportive programming geared toward these domains early at diagnosis could benefit this distinct population. [ABSTRACT FROM AUTHOR]

Objectives: Curative intent therapy of stage II NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome.Materials and Methods: A retrospective review was completed of all patients with stage II NSCLC referred to the BC Cancer Agency from 2005 to 2012. Cases were filtered to identify those receiving curative intent therapy including surgery or radiotherapy. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival. We compared survival among patients receiving curative intent radiotherapy versus surgical intervention.Results: A total of 535 patients were referred. Of these, 245 (46%) received curative intent surgery, 132 (25%) curative intent radiotherapy, and 158 (30%) did not receive curative therapy. There were significant differences between cohorts with respect to median age, histology, ECOG PS, smoking status, and weight loss. Median OS was significantly different between cohorts: 61.4 m surgery, 26.5 m curative RT, and 13.1 m non-curative therapy. In a case-matched analysis, median OS remained superior for surgery at 101.6 m vs 28.1 m for curative RT. In a multivariate analysis, ECOG PS, weight loss, and treatment cohort all influenced survival. Among patients receiving curative intent radiotherapy, the use of concurrent chemotherapy and RT dose > = 60Gy were associated with improved outcomes.Conclusions: Among patients with stage II NSCLC, many are unable to undergo standard of care surgical resection. Radiotherapy provides an inferior yet still curative option in the management of inoperable patients. Further work is needed to optimize outcomes in this population. [ABSTRACT FROM AUTHOR]

Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner. [ABSTRACT FROM AUTHOR]

Thyroid cancer management is rapidly changing. The identification of actionable biomarkers through both germline and somatic testing are now an integral part of directing patient management. However, deficiencies and disparities within existing thyroid cancer biomarker test approaches are resulting in inconsistent application for patient care. An expert panel was convened to create consensus biomarker testing algorithms and recommendations on actionable biomarker testing for patients diagnosed with medullary thyroid cancer, non-anaplastic follicular cell-derived thyroid cancer, or anaplastic follicular cell-derived thyroid cancer who may benefit from targeted therapies. A review of international guidelines was performed to determine the current state, and a literature review was carried out to further evaluate the evidence supporting the use of actionable biomarkers in patients diagnosed with thyroid cancer. Thyroid biomarker-related gaps impacting patient care were also discussed, with an emphasis on the importance of a multidisciplinary team approach for optimal patient care. The recommendations are presented with the aim to help physicians navigate the current thyroid cancer biomarker testing landscape with its many challenges, balancing aspirational care with what is practical and feasible in terms of economic realities and jurisdictional constraints. By remaining therapy-agnostic, these algorithms and recommendations are broadly applicable., Competing Interests: Declarations. Ethics Approval: Not applicable for this publication. Consent for Publication: All authors approved the final version and publication of the manuscript. Competing Interests: All authors report honoraria (facilitated via Precision RxDx) from Eli Lilly Canada for participation in working group meetings related to this project. Dr. Ozgur Mete is the Editor-in-Chief of Endocrine Pathology. This article is handled by an independent senior editor as per Springer Nature’s policies. Dr. Mete received honorarium for serving as an advisory board member for Bayer. Dr. Andrée Boucher has received research support from Eisai and has been compensated for being a speaker and serving as a board member or on an advisory panel for Bayer and Eisai. Dr. Omar Abdel-Rahman has received consulting fees from Amgen, Eisai, Ipsen, Lilly, and Roche, honoraria from Bayer. Dr. Houda Bahig has received grants from AstraZeneca, Sanofi and Varian Medical Systems, as well as consulting fees from AstraZeneca and EMD Serono. Dr. Cheryl Ho received grants from AstraZeneca and Roche which were paid to her institution. She received honoraria for advisory board attendance from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Janssen, Jazz, Merck, Novartis, Pfizer, Roche, and Sanofi. Dr. Kasmintan A. Schrader has a consulting and advisory relationship with and has received honoraria from AstraZeneca Canada and Pfizer and research funding from AstraZeneca Canada and Merck. Dr. Eric Winquist received grants from Eli Lilly, Merck, and Novartis which were paid to his institution. He received consulting fees for advisory boards from Bayer, BMS, Eisai, EMD Serono, Merck, and Roche; honoraria from EMD Serono and support for attending meetings from Eisai. Dr. Jonn Wu served as an Executive board member, International Society of Oral Oncology, from 2019 to 2023. Dr. Shereen Ezzat has served as advisory board member/consultant for Bayer, Eisai, Eli Lilly, Ipsen, Novartis, Medunik Canada, Merck, Pfizer, and Recordati Rare Diseases. Dr. Nicole Chau has received research funding from BeiGene, BMS, ERASCA, Merck, and Roche which were paid to her institution. She received consulting fees for advisory boards from Bayer, BMS, Eisai, Eli Lilly, EMD Serono, Ipsen, Merck, Novartis, Pfizer, and Roche. Dr. Olfat Kamel Hasan, Dr. Bernard Lemieux, and Dr. Ralph Wong have no conflicts of interest to declare that are relevant to the content of this article., (© 2024. The Author(s).)

New treatment paradigms for resectable nonsmall cell lung cancer (NSCLC), with an emphasis on personalised care and a multidisciplinary approach, have significantly improved patient outcomes. The incorporation of immune checkpoint inhibitors into neoadjuvant, perioperative and adjuvant treatment algorithms is reshaping the standard of care for resectable NSCLC. Adjuvant targeted therapy trials have also paved the way for a much-needed personalised approach for patients with actionable genomic alterations. Innovative surgical techniques and judicious use of postoperative radiotherapy may mitigate the toxicity associated with a multimodality approach. Amid the many new treatment options, questions remain about the best approach to consider for each patient. Measurement of minimal residual disease and achievement of pathological complete response are emerging biomarkers of interest to help further refine treatment selection. This review summarises the current management of resectable NSCLC, focusing on ongoing and recent advances in surgical approaches, the role of postoperative radiotherapy and the rapidly changing field of systemic therapies., Competing Interests: Conflict of interest: M-F. D'Amours has received honoraria for an educational presentation from Pfizer. C. Ho has received research grants from AstraZeneca and Roche; and honoraria for advisory boards from Abbvie, Amgen, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Janssen, Jazz, Merck, Novartis, Pfizer, Roche, Sanofi and Takeda. F.T.H. Wu has received honoraria for an educational presentation from Bristol Myers Squibb. A. McGuire has received an educational grant from Johnson & Johnson; and honoraria for advisory boards from AstraZeneca, Bristol Myers Squibb and Medtronic. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor ( EGFR ) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice., Methods: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR- mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups., Ethics and Dissemination: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases., Prospero Registration: CRD42022330532., Competing Interests: Competing interests: SL: research funding and honoraria from AstraZeneca. YYS: honoraria from AstraZeneca and Janssen. AGS: research grants (institution) from Elekta AB, Varian, Seagen and BrainLAB; consulting fees from Varian, Elekta (Gamma Knife Icon), BrainLAB, Merck, Abbvie and Roche; honoraria from AstraZeneca, Elekta AB, Varian, BrainLAB, Accuray and Seagen. MBP: speaker fees from AZ, BMS, MSD and Roche. AN: research grants from Varian Medical Systems. RAS: advisory board with Amgen, Astra-Zeneca, Bayer, BMS, Boehringer Ingelheim, Janssen, Lily, Merck, Merck Serono, Novartis, Pfizer, Puma Biotechnology, Roche, Taiho, Takeda, Thermo Fisher and Yuhan Corporation; research grant from Astra-Zeneca and Boehringer Ingelheim. FHJ: clinical trial funding, received honoraria and participated in advisory boards for Astra Zeneca; received payments and honoraria from BeiGene and MSD for lectures and presentations; supported by the Peter Mac Foundation and the Victorian Cancer Agency. BJS: advisory board/honoraria from AstraZeneca, Pfizer, Novartis, Roche, Takeda, Merck, Bristol Mysers Squibb, Janssen, Amgen and Eli Lilly. IWKT: honorarium from Elekta and MSD. CH: advisory boards with Abbvie, Amgen, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Janssen, Jazz, Merck, Novartis, Pfizer, Roche, Sanofi and Takeda; research grants from AstraZeneca, EMD Serono and Roche. CKL: advisory board with Amgen, Astra Zeneca, GSK, Merck KGA, Norvatis, Pfizer, Roche, Takeda, Boehringer-Ingelheim and Yuhan; research funding (institution) from Astra Zeneca, Roche, Merck KGA and Amgen. KPR, AP, MD, DBS, AGS, JT, CNL, WYK, YH, YLEA, JL, CY, MCL and APT have no competing interests. CH, SL, FHJ, CKL, YYS, RAS and IWKT are study chairs on the included trials., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with cancer often have unmet psychosocial needs. Early detection of who requires referral to a counsellor or psychiatrist may improve their care. This work used natural language processing to predict which patients will see a counsellor or psychiatrist from a patient's initial oncology consultation document. We believe this is the first use of artificial intelligence to predict psychiatric outcomes from non-psychiatric medical documents., Methods: This retrospective prognostic study used data from 47,625 patients at BC Cancer. We analyzed initial oncology consultation documents using traditional and neural language models to predict whether patients would see a counsellor or psychiatrist in the 12 months following their initial oncology consultation., Results: Here, we show our best models achieved a balanced accuracy (receiver-operating-characteristic area-under-curve) of 73.1% (0.824) for predicting seeing a psychiatrist, and 71.0% (0.784) for seeing a counsellor. Different words and phrases are important for predicting each outcome., Conclusion: These results suggest natural language processing can be used to predict psychosocial needs of patients with cancer from their initial oncology consultation document. Future research could extend this work to predict the psychosocial needs of medical patients in other settings., (© 2024. The Author(s).)

Background: Through the introduction of tumor agnostic therapies, people with metastatic cancer and their treating physicians are facing new treatment choices that have differing side effect and efficacy profiles from conventional chemotherapy., Objective: The present study undertakes a scoping review of research into the experiences of people with advanced or metastatic cancer across various solid tumor types with the goal of developing a tumor-agnostic conceptual model., Design: Automated queries on three internet search engines were performed to identify qualitative interview studies that focused on people with metastatic cancer. No limits were imposed for dates nor location of studies., Results: Of the 173 hits generated from the searches, 25 peer-reviewed papers were selected for the review with dates that ranged from 2007 to 2022. All papers originated from the USA, Europe, Australia, or Japan. Three major themes emerged that formed the basis for the tumor-agnostic conceptual model: symptoms, loss of autonomy, and adaptation/coping., Conclusions: The explication of the interplay between the physical and emotional symptoms experienced by those with advanced and metastatic cancer using a multi-tumor approach provides the potential to make generalizations about the needs of this population. An opportunity exists to potentially address these needs through matching patient needs and preferences with the characteristics of novel therapeutics., Implications for Cancer Survivors: In the era of tumor agnostic therapies, the elicitation of patient preferences across the spectrum of anatomical origins has the potential to enhance shared decision making in the setting of metastatic disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Management of cancer during pregnancy requires careful consideration of risks and benefits from maternal and fetal perspectives. For advanced lung adenocarcinomas, with no targetable driver mutations, there is evidence-based guidance on the use of carboplatin-paclitaxel chemotherapy after first trimester. In contrast, for epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged metastatic lung adenocarcinomas, there is a paucity of clinical data on the safety of EGFR and ALK tyrosine kinase inhibitors to mother and fetus for official guidelines to recommend the use of these otherwise-first-line therapies in pregnancy. Considering this knowledge gap, we present a case of a young gravida 1 para 0 (G1P0) woman who continued alectinib 300 mg oral two times per day for ALK-rearranged metastatic lung adenocarcinoma throughout all 36 weeks of her pregnancy and delivered a healthy baby at term via caesarean section (C-section)., Competing Interests: Competing interests: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: all authors have declared that no financial support was received from any organisation for the submitted work. Financial relationships: CH has received honoraria paid to self from Abbvie, Amgen, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Sanofi, Janssen, Jazz, Merck, Novartis, Pfizer, Roche, Takeda and has research grants paid to institution from AstraZeneca and Roche. RR has received honoraria paid to self from AstraZeneca and has research grants from AstraZeneca. FW has received an honorarium from BMS. Other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Circulating tumor DNA (ctDNA) has shown promise in capturing primary resistance to immunotherapy. BR.36 is a multi-center, randomized, ctDNA-directed, phase 2 trial of molecular response-adaptive immuno-chemotherapy for patients with lung cancer. In the first of two independent stages, 50 patients with advanced non-small cell lung cancer received pembrolizumab as standard of care. The primary objectives of stage 1 were to ascertain ctDNA response and determine optimal timing and concordance with radiologic Response Evaluation Criteria in Solid Tumors (RECIST) response. Secondary endpoints included the evaluation of time to ctDNA response and correlation with progression-free and overall survival. Maximal mutant allele fraction clearance at the third cycle of pembrolizumab signified molecular response (mR). The trial met its primary endpoint, with a sensitivity of ctDNA response for RECIST response of 82% (90% confidence interval (CI): 52-97%) and a specificity of 75% (90% CI: 56.5-88.5%). Median time to ctDNA response was 2.1 months (90% CI: 1.5-2.6), and patients with mR attained longer progression-free survival (5.03 months versus 2.6 months) and overall survival (not reached versus 7.23 months). These findings are incorporated into the ctDNA-driven interventional molecular response-adaptive second stage of the BR.36 trial in which patients at risk of progression are randomized to treatment intensification or continuation of therapy. ClinicalTrials.gov ID: NCT04093167 ., (© 2023. The Author(s).)

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up CT. Associations between the baseline variables and progressive disease (PD) were tested by logistic regression analyses. The results showed 46/138 patients had PD. The baseline CT "number of involved organs" by metastasis and smoking pack years were independently associated with PD ( p < 0.05), and the ROC analysis showed a good performance of the model that integrated these variables in predicting PD (AUC: 0.79). This pilot study suggests that the combination of baseline CT disease and smoking PY can identify who may progress on pembrolizumab monotherapy and can potentially facilitate decision-making for the optimal first-line treatment in the high PD-L1 cohort.

Purpose: Previous surveys of anesthesiologists showed that despite a strong interest in implementing environmentally sustainable anesthetic practices, less than a third do so. Qualitative understanding of the capability, opportunity, and motivational factors that influence "green" behavior will inform the design of effective interventions to promote environmentally sustainable practices in the operating room (OR)., Methods: We conducted 23 semistructured interviews with anesthesiologists, with data saturation achieved. Applying the Behavior Change Wheel, interview questions addressed "capability," "opportunity," and "motivation" determinants of behavior., Results: Preference for sevoflurane and syringe reuse were most commonly cited as existing environmentally sustainable anesthetic practices. Several participants reported lack of knowledge and feedback as impediments to sustainable anesthetic practices. Reported physical barriers included inadequate recycling facilities and abundance of supplies. Interviewees also discussed the importance of habitual behavior in improving skill sets and reducing cognitive load required to perform environmentally sustainable practices. General awareness of environmental issues and aggregation of marginal gains were reasons for environmentally sustainable measures in the OR. Organizational practice and culture played a significant role in the propagation of sustainable anesthetic practices, with senior staff often carrying a greater influence. While the majority preferred a top-down approach to effect change, others favored the use of incentives., Conclusion: This study provides insight into the factors that influence the adoption of environmentally sustainable practices in the OR. Measures to promote these practices include education and training, feedback on efforts, engagement of senior anesthetists as role models and for change management, environmental restructuring, and policy designs that balance a top-down vs bottom-up approach to influencing change., (© 2023. Canadian Anesthesiologists' Society.)

Importance: Predicting short- and long-term survival of patients with cancer may improve their care. Prior predictive models either use data with limited availability or predict the outcome of only 1 type of cancer., Objective: To investigate whether natural language processing can predict survival of patients with general cancer from a patient's initial oncologist consultation document., Design, Setting, and Participants: This retrospective prognostic study used data from 47 625 of 59 800 patients who started cancer care at any of the 6 BC Cancer sites located in the province of British Columbia between April 1, 2011, and December 31, 2016. Mortality data were updated until April 6, 2022, and data were analyzed from update until September 30, 2022. All patients with a medical or radiation oncologist consultation document generated within 180 days of diagnosis were included; patients seen for multiple cancers were excluded., Exposures: Initial oncologist consultation documents were analyzed using traditional and neural language models., Main Outcomes and Measures: The primary outcome was the performance of the predictive models, including balanced accuracy and receiver operating characteristics area under the curve (AUC). The secondary outcome was investigating what words the models used., Results: Of the 47 625 patients in the sample, 25 428 (53.4%) were female and 22 197 (46.6%) were male, with a mean (SD) age of 64.9 (13.7) years. A total of 41 447 patients (87.0%) survived 6 months, 31 143 (65.4%) survived 36 months, and 27 880 (58.5%) survived 60 months, calculated from their initial oncologist consultation. The best models achieved a balanced accuracy of 0.856 (AUC, 0.928) for predicting 6-month survival, 0.842 (AUC, 0.918) for 36-month survival, and 0.837 (AUC, 0.918) for 60-month survival, on a holdout test set. Differences in what words were important for predicting 6- vs 60-month survival were found., Conclusions and Relevance: These findings suggest that models performed comparably with or better than previous models predicting cancer survival and that they may be able to predict survival using readily available data without focusing on 1 cancer type.

Background: non-small cell lung cancer (NSCLC) outcomes remain suboptimal for early-stage disease despite emerging advances in systemic therapy for the peri-operative period. Next-generation sequencing (NGS) identifies driver mutations for which targeted therapies have been developed that improve survival. The BC lung cancer screening program, which was initiated in May 2022, is expected to identify people with early and late stages of NSCLC. It is crucial to first understand the molecular epidemiology and patterns of time to initiate treatment across its five health authorities (HA) to optimize the delivery of care for NSCLC in BC. In this way, we may harness the benefits of targeted therapy for more people with NSCLC as novel advances in therapy continue to emerge. Objective: to compare (a) the frequency of actionable NSCLC molecular alterations among HAs and (b) the time to treatment initiation. Methods: a retrospective observational study was conducted with prospectively collected data from the BC CGL Database. Adults with late stage NSCLC who underwent targeted NGS were included for the time period from May 2020 to June 2021. Demographics, actionable molecular alterations, PDL-1 expression, and time to treatment across HAs were examined. Using appropriate statistical tests for comparison among HAs, p>0.05 was deemed significant. Results: 582 patients underwent NGS/IHC and analysis during the study period. The mean age was 71 (10.1), and 326 (56%) patients were female. A significantly higher proportion of all EGFRm+ were identified within Vancouver Coastal Health (VCHA) and Fraser Health Authority (FHA) compared to the other health authorities (p < 0.001). This also holds true for common sensitizing EGFRm+ alone (p < 0.001) and for sensitizing EGFRm+ when adjusted for females and smoker status (OR 0.75; 95% CI 0.62, 0.92; p = 0.005). Patients residing within the Northern, Interior, and Island HAs were less likely to receive treatment at the same rate as those in VCHA and FHA HAs. Conclusion: actionable NSCLC driver mutations are present in all regional HAs, with disparity noted in time to initiate treatment between HAs. This provides evidence for the importance of molecular testing for patients in all BC HAs to guide personalized and timely NSCLC treatment.

Background: A fixed dose of 200 mg of pembrolizumab every 3 weeks (Q3W) is the standard of care for patients with stage IV non-small cell lung cancer (NSCLC) and PDL1 ≥50%. In April 2020, based on pharmacokinetic modeling without formal comparative studies, the FDA approved 400 mg every 6 weeks (Q6W). Pharmacokinetic studies also suggested comparable target engagement with weight-based and flat dosing for the respective schedules. The objective of this study was to determine if overall survival (OS) differs based on the Q3W vs. Q6W dosing schedule of pembrolizumab., Methods: BC Cancer patients with stage IV NSCLC and PDL1 ≥50% treated with pembrolizumab were retrospectively reviewed. Patients were treated with weight-based dosing, per institution standard, of pembrolizumab 2 mg/kg Q3W or 4 mg/kg Q6W. Patient demographics, treatment and outcome were recorded. Patients were assigned to Q3W or Q6W according to the schedule that was used for the majority of treatment (greater than 50%)., Results: 718 patients with NSCLC and PDL1 ≥50% received first-line pembrolizumab between 2017 and2021, Q3W/Q6W dosing 677/41 patients. Baseline characteristics with respect to age, sex, smoking status, histology and performance status (PS) were similar between groups. In the multivariate model, including age, sex, PS and dosing schedule, the hazard ratio for death (HR) for OS Q3W vs. Q6W was 0.759 ( p = 0.230). A 2:1 case-matched analysis for OS was performed, controlling for sex, age ± 5 years, PS and duration on pembrolizumab ± 2 months for Q3W vs. Q6W ( n = 113) with a HR 0.834 ( p = 0.500)., Conclusions: There was no OS difference demonstrated with pembrolizumab dosing Q3W compared to Q6W in a multivariate analysis that included age, sex and PS. A case-matched analysis that controlled for these variables and for duration of treatment confirmed these findings. This study supports the use of Q6W pembrolizumab dosing, allowing for less frequent interactions with the medical system.

Health technology assessment (HTA) can be used to make healthcare systems more equitable and efficient. Advances in precision oncology are challenging conventional thinking about HTA. Precision oncology advances are rapid, involve small patient groups, and are frequently evaluated without a randomized comparison group. In light of these challenges, mechanisms to manage precision oncology uncertainties are critical. We propose a life-cycle HTA framework and outline supporting criteria to manage uncertainties based on real world data collected from learning healthcare systems. If appropriately designed, we argue that life-cycle HTA is the driver of real world evidence generation and furthers our understanding of comparative effectiveness and value. We conclude that life-cycle HTA deliberation processes must be embedded into healthcare systems for an agile response to the constantly changing landscape of precision oncology innovation. We encourage further research outlining the core requirements, infrastructure, and checklists needed to achieve the goal of learning healthcare supporting life-cycle HTA., (© 2022. The Author(s).)

Purpose: Limited English-proficient (LEP) patients with non-small-cell lung cancer (NSCLC) may receive less palliative care services and more likely to receive aggressive end-of-life (EoL) care. Goals of this retrospective cohort study are to compare access to community palliative home care (CPHC), do not resuscitate (DNR) form completion, place of death, and health resource utilization at EoL between English-proficient (EP) and LEP patients with NSCLC in Vancouver, Canada., Methods: All patients with advanced NSCLC referred in 2016 and received medical care were included. Patients were classified as LEP if seen with a medical interpreter. Descriptive statistics and univariate and multivariate analyses were used to compare the outcomes between the two groups., Results: One hundred eighty-six patients were referred, 66% EP. Rates of CPHC referral and DNR form completion were the same for both groups (84% and 92%, P = 1.00). LEP patients received earlier access to CPHC (15 v 10 weeks before death, P = .039). Rates of ER visits within 6 months and 30 days of death were 0.89 for EP patients and 0.7 for LEP patients, P = .374, and 0.1 for EP patients and 0.13 for LEP patients, P = .244. Hospitalization rates within 6 months and 30 days of death were 1.4 for EP patients and 1.59 for LEP patients, P = .640, and 0.67 for EP patients and 0.81 for LEP patients, P = .091. EP patients were more likely to have a home death (26% v 14%), whereas LEP patients died in acute care (23% v 14%) or a tertiary palliative care unit (24% v 19%). This was not statistically significant ( P = .335). LEP patients had better median overall survival (8.5 v 5.4 months, P < .001), but when controlled by age, mutation, and EP status, only receipt of palliative-intent systemic therapy was statistically significant., Conclusion: EP and LEP patients with NSCLC have similar referral rates to CPHC, DNR form completion, and EoL health resource utilization. The measured EoL variables did not demonstrate significant disparities between EP and LEP patients.

Introduction: Small cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet., Methods: A retrospective cohort analysis was conducted of referred ES SCLC between 2015 and 2017 in British Columbia, Canada. Patient demographics, staging, treatment, and survival data were collected through the Cancer Registry. Retrospective chart review was completed to extract past medical history and missing variables. CASPIAN/IMPower133 excluded patients with autoimmune diseases, active infection, and performance status (PS) ≥2., Results: Between 2015 and 2017, 349 patients were diagnosed with ES SCLC. In patients who received platinum-doublet chemotherapy (n=227), 15 had medical contraindication to ICI: inflammatory bowel disease (n=4), rheumatoid arthritis (n=4), idiopathic pulmonary fibrosis (n=3), lupus (n=1), Sjogren's (n=1), Takayasu arteritis (n=1), and active tuberculosis (n=1). ECOG PS was 0-1 in 96 (45%), PS was 2 in 61 (29%), and ≥3 in 51 (10%). Prior to cycle 1, 82 (36%) patients were eligible for ICI in addition to platinum doublet, 23% of the entire ES population. After cycles 1 and 2, additional 15 (7%) and 8 (4%) patients became PS 0-1, respectively. mOS for ES SCLC who received first-line platinum doublet, non-platinum chemotherapy, and best supportive care was 8.4 1.9 and 1.5 months (p<0.001)., Discussion: By CASPIAN/IMpower133 trial eligibility, only 36% of our real-world platinum-treated patients would have been eligible for the addition of ICI, which is 23% of the entire ES population in one Canadian province. After one or two cycles of chemotherapy, an additional 11% of patients showed PS improvement to 0-1. While the results of CASPIAN/IMpower133 are practice-changing, the majority of the patients will not meet clinical trial eligibility and clinical trials including patients with poor PS are necessary., Competing Interests: RR declared research grants from AstraZeneca. CH declared research grants from AstraZeneca, EMD Serono, and Roche. CH declared honoraria for advisory boards from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Merck, Novartis, Pfizer, Roche, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rittberg, Leung, Al-Hashami and Ho.)

Tumor mutation burden (TMB) is a measure to predict patient responsiveness to immune checkpoint immunotherapy because with increased mutation frequency, the likelihood of a greater neoantigen burden is increased. Although neoantigen prediction tools exist, tumor neoantigen burden has not been adopted as a measure to predict immunotherapy response. With both measures, current guidelines are limited to the coding regions, but ectopic expression of sequences in the noncoding space may potentially be a source of neoantigens. A pan-cancer cohort of 574 advanced disease stage patients with whole genome and transcriptome sequencing was analyzed to report mutation burden and neoantigen counts within the coding and noncoding regions. The efficacy of tumor neoantigen burden, reported as tumor neoantigen count (TNC), including neoantigens derived from the expression of noncoding regions, compared with TMB as a predictor of response to immunotherapy for 80 patients who had received treatment, was evaluated. TMB was found to be the best predictor of response to immunotherapy, whereas expression-derived TNC from the noncoding regions did not improve prediction of response. Therefore, there is minimal benefit in extending the calculation of TNC to the noncoding space for the purposes of predicting response. However, it is likely that there is a wealth of neoantigens derived from the noncoding space that may impact patient outcomes and treatments., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Accelerated approval (AA) by the FDA enables earlier access to promising new therapies. Health Canada has a similar process. Canada implemented a national health technology assessment (HTA) for reimbursement decisions in 2011. This study evaluated regulatory and funding timelines and decisions for FDA AA cancer therapies in Canada. The FDA's AA of malignant hematology and oncology from January 2000-December 2019 was reviewed. Dates from Health Canada, HTA decisions and provincial listings were collected. There were 94 FDA AAs, two of which were subsequently withdrawn. Of the 92 AAs, 70 received full (46)/conditional (24) Health Canada approval, and 22 were not filed. Since the introduction of HTA, 31 out of 45 of Health Canada's approved indications underwent HTA review: 18 received a positive recommendation conditional on cost-effectiveness, 8 were not recommended and 5 were withdrawn/suspended. The median time from the AA to any Health Canada approval is 9.4 months, from any Health Canada approval to HTA decision is 5.8 months and from HTA decision to the first formulary listing is 12.0 months. The access and timeline for the first formulary listing differences were observed between the USA and Canada due to the decision of pharmaceutical companies to submit (or not) to regulatory/HTA bodies, national procedural delays with different healthcare delivery models and submission timelines. This study demonstrates that there is delayed access to promising new therapies in Canada.

Purpose: Regulatory agencies such as the US Food and Drug Administration and health technology assessment bodies are increasingly using real-world evidence (RWE). The ability of healthcare systems to reliably generate response rate and progression-free survival from real-world data is unknown. We examined the capacity of a single-payer system to provide RWE by evaluating the frequency of computed tomography (CT) imaging during standard first-line metastatic systemic treatment of breast, colorectal, and lung cancer., Methods: A 1-year cohort of patients with metastatic-at-diagnosis breast, colorectal, and lung cancer treated with first-line systemic therapy (excluding hormone therapy) referred to BC Cancer in 2016 was retrospectively reviewed for first-line treatment and CT imaging. Duration of first-line treatment was calculated from the first to the last dose of therapy. CT imaging was counted from the start of therapy to 8 weeks after the last therapy dose., Results: A cohort of 664 patients was identified from the BC Cancer Registry. Distribution of metastatic disease at diagnosis was breast (n = 82), colorectal (n = 214), and lung (n = 368) cancer. For breast, colorectal, and lung cancer, there was a baseline CT within 4 weeks of treatment initiation in 59%, 51%, and 48% of patients, with median duration of first-line treatment of 14.6, 25.3, and 11.9 weeks and median CT imaging interval of 9.1, 9.0, and 6.1 weeks., Conclusion: In our publicly funded healthcare system, availability of baseline CT imaging was 48% to 59% and the frequency of assessment ranged from 6.1 to 9.1 weeks, subject to patterns of practice and resource availability. Our system was not capable of providing RWE for image-based end points. Alternative end points should be considered to capitalize on the wealth of real-world data., Competing Interests: Cheryl HoConsulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Roche, Eisai, Novartis Canada Pharmaceuticals Inc, BayerResearch Funding: Eisai, Genzyme, AstraZenecaTravel, Accommodations, Expenses: Roche Canada Dean A. RegierHonoraria: Roche CanadaTravel, Accommodations, Expenses: Illumina Howard LimHonoraria: Ipsen, Merck, Roche Canada, Eisai, Taiho Pharmaceutical, AmgenResearch Funding: Taiho PharmaceuticalTravel, Accommodations, Expenses: Eisai, Taiho PharmaceuticalNo other potential conflicts of interest were reported.

Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented., Objective: Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults., Design: Observational prospective cohort study., Setting: Six Canadian oncology centers (3 pediatric, 1 adult and 2 both)., Patients: Three hundred adults and 300 children planned to receive cisplatin therapy., Measurements: During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort., Methods: Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival., Limitations: It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge., Conclusions: ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices., 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.)

Objectives: Little is known about how psychosocial factors and distress affect older patients with cancer and their survival. The study goals were to: 1) observe the prevalence of anxiety (ANX) and depression (DEP) symptoms at diagnosis in patients aged ≥65 years, 2) observe the association between social isolation (isolation) and distress, and 3) evaluate the impact on overall survival (OS)., Materials and Methods: A retrospective cohort study was completed for all patients ≥65 years (N = 25,382) referred to the provincial cancer care program in British Columbia, Canada from 2011 to 2016. Patients who completed the Psychosocial Screen for Cancer within 6 months of diagnosis were included. Baseline and disease characteristics were collected retrospectively., Results: Subclinical/clinical levels of ANX and DEP were found in 32% and 23%, respectively. Thirty-six percent of patients reported at least one indicator for isolation. Factors associated with distress at presentation included female, age 65-69, lung cancer, metastatic disease, and presence of any risk indicator for isolation (p-values <0.001). Patients with any risk indicator for isolation had higher rates of subclinical/clinical levels of ANX and DEP. On multivariate analysis including age, sex and stage, hazard ratio (HR) for death was increased with ANX (1.30), DEP (1.51) and isolation (1.12) (p < 0.001)., Conclusions: Older adults with cancer with symptoms of distress are more likely to be female, aged 65-69, socially isolated, have metastatic disease or have lung cancer. ANX, DEP, and isolation are independent negative prognostic variables for OS. This vulnerable population should receive psychological support to improve outcomes., Competing Interests: Declaration of Competing Interest Cheryl Ho reports grants and personal fees from Astra Zeneca, personal fees and other from Boehringer Ingelheim, personal fees from BMS, personal fees and other from Roche, personal fees from Lilly, grants and personal fees from Eisai, personal fees from Merck, personal fees from Bayer, outside the submitted work. Bonnie Leung reports personal fees from Astra Zeneca, Purdue, and Takeda, outside the submitted work. Alan Bates reports a grant from Pfizer and personal fees from Eisai, outside the submitted work. Aria Shokoohi has none to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: PD-L1 expression may be used as a biomarker predictive of non-small cell lung carcinoma (NSCLC) response to PD-L1 inhibitor treatment. Spatial and temporal heterogeneity in PD-L1 expression and variation in PD-L1 test interpretation may contribute to differences in PD-L1 test results between samples of the same patient's disease., Methods: Retrospective chart review identified 77 NSCLC patients with 22C3 PharmDx PD-L1 assays performed on two different tumor samples. Patients clinically suspected to have two separate primaries were excluded. PD-L1 test results in different score categories (<1%, 1-49% and ≥50%) were considered discordant. Clinical and pathologic factors associated with discordance were assessed., Results: 28 (36%) of the 77 cases had discordant PD-L1 scores between samples. Patients with an initial test result of 1-49% were most likely to have a discordant second test result. Specimen type (cytology, small biopsy or resection), specimen site (lung, lymph node, pleura/pleural effusion or distant metastasis), time between specimen collection, and treatment between specimen collection were not significantly associated with the rate of discordance., Conclusions: Repeat PD-L1 testing of the same patient's NSCLC results frequently resulted in discordant test results, independent of whether the samples differed in clinical or pathologic factors. This discordance rate underscores the extent to which PD-L1 levels are heterogeneous and difficult to accurately represent with a single test value. Further study of the predictive value of PD-L1 scores in cases with discordant results is needed., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pericardiocentesis is a potentially life-saving procedure. We compared two low-cost models-an agar-based model and a novel model, Centesys-in terms of ultrasound image quality and realism, effectiveness of the model, and learners' confidence and satisfaction after training., Methods: In this pilot randomised 2x2 crossover trial stratified by physician seniority, participants were assigned to undergo pericardiocentesis training either with the agar-based or Centesys model first, followed by the other model. Participants were asked to rate their confidence in performing ultrasound-guided pericardiocentesis, clarity and realism of cardiac structures on ultrasound imaging, and satisfaction on a 7-point Likert scale before and after training with each model., Results: Twenty participants with median postgraduate year of 4 (interquartile range [IQR] 3.75-6) years were recruited. Pre-training, participants rated themselves a median score of 2.5 (IQR 2-4) for level of confidence in performing pericardiocentesis, which improved to 5 (IQR 4-6) post-training with Centesys ( P =0.007). Centesys was recognised to be more realistic in simulating cardiac anatomy on ultrasound (median 5 [IQR 4-5] versus 3.5 [IQR 3-4], P =0.002) than the agar-based model. There was greater satisfaction with Centesys (median 5 [IQR 5-6] versus 4 [IQR 3.75-4], P <0.001). All 20 participants achieved successful insertion of a pericardial drain into the simulated pericardial sac with Centesys., Conclusion: Centesys achieved greater learner satisfaction as compared to the agar-based model, and was an effective tool for teaching ultrasound-guided pericardiocentesis and drain insertion.

Background: EGFR T790M testing is the standard of care for activating EGFR mutation (EGFRm) non-small cell lung cancer (NSCLC) progressing on 1st/2nd generation TKIs to select patients for osimertinib. Despite sensitive assays, detection of circulating tumour deoxyribonucleic acid (ctDNA) is variable and influenced by clinical factors. The number and location of sites of progressive disease at time of testing were reviewed to explore the effect on EGFR ctDNA detection. The prognostic value of EGFR ctDNA detection on survival outcomes was assessed., Methods: Following extraction of cell-free DNA from plasma using the QIAamp Circulating Nucleic Acid Kit, custom droplet digital polymerase chair reaction (ddPCR) assays were used to assess EGFR ctDNA using the Bio-Rad QX200 system. The ddPCR assay has a limit of detection of ≤0.15% variant allele fraction. Baseline characteristics and imaging reports at time of EGFR ctDNA testing were reviewed retrospectively for a 1 year period., Results: The study included 177 patients who had an EGFR ctDNA test. Liver (aOR 3.13) or bone (aOR 2.76) progression or 3-5 sites of progression (aOR 2.22) were predictive of EGFR ctDNA detection. The median OS from first ctDNA test after multiple testing iterations was 12.3 m undetectable EGFR ctDNA, 7.6 m for original EGFR mutation only and 24.1 m with T790M (P=0.001)., Conclusions: Patients with liver or bone progression and 3-5 progressing sites are more likely to have informative EGFR ctDNA testing. Detection of EGFR ctDNA is a negative prognostic indicator in the absence of a T790M resistance mutation, potentially reflecting the disease burden in the absence of targeted therapy options., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-9-581). AP reports personal fees from Bristol-Myers Squibb, Guardant Health, grants from Roche Canada during the conduct of the study. CH reports other from AstraZeneca outside the submitted work. TT reports grants from Astra Zeneca outside the submitted work. JL reports grants from Roche, AstraZeneca, personal fees from Roche, Pfizer, Takeda outside the submitted work. SY reports personal fees from Amgen, Bayer, Novartis, Roche outside the submitted work. CH reports grants from Astra Zeneca during the conduct of the study; grants and personal fees from Astra Zeneca, Eisai, personal fees and other from Boehringer Ingelheim, Roche, personal fees from BMS, Lilly, Merck, Bayer, Novartis outside the submitted work. The other authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and represents a heterogeneous group of tumors, the majority of which are treated with a combination of surgery, radiation, and chemotherapy. Fluoropyrimidine (5-FU) and its oral prodrug, capecitabine, are commonly prescribed treatments for several solid tumor types including HNSCC. 5-FU-associated toxicity is observed in ∼30% of treated patients and is largely caused by germline polymorphisms in DPYD , which encodes dihydropyrimidine dehydrogenase, a key enzyme of 5-FU catabolism and deactivation. Although the association of germline DPYD alterations with toxicity is well-described, the potential contribution of somatic DPYD alterations to 5-FU sensitivity has not been explored. In a patient with metastatic HNSCC, in-depth genomic and transcriptomic integrative analysis on a biopsy from a metastatic neck lesion revealed alterations in genes that are associated with 5-FU uptake and metabolism. These included a novel somatic structural variant resulting in a partial deletion affecting DPYD , a variant of unknown significance affecting SLC29A1 , and homozygous deletion of MTAP There was no evidence of deleterious germline polymorphisms that have been associated with 5-FU toxicity, indicating a potential vulnerability of the tumor to 5-FU therapy. The discovery of the novel DPYD variant led to the initiation of 5-FU treatment that resulted in a rapid response lasting 17 wk, with subsequent relapse due to unknown resistance mechanisms. This suggests that somatic alterations present in this tumor may serve as markers for tumor sensitivity to 5-FU, aiding in the selection of personalized treatment strategies., (© 2020 Majounie et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: The PACIFIC study established durvalumab as a standard of care for consolidation therapy in patients treated with radical intent chemoradiation for stage III inoperable non-small cell lung cancer. In clinical practice, many patients are not eligible for trials, yet radical intent chemoradiation may still be used., Methods: A virtual anonymous tumour board Delphi-model was used in order to generate consensus on the use of durvalumab in six clinical situations where chemoradiation is used in clinical practice and recommended in guidelines, yet not PACIFIC eligible. Two anonymous iterations were sent and recommendations were circulated for approval and comment. Results are presented using a modified PICOT format (patients, intervention, control, outcomes, and ongoing trials)., Results: In three of the scenarios, consensus was reached and recommendations were for the use of consolidation durvalumab, but being respectful of potentially increased toxicity/reduced benefit in comparison to PACIFIC results (treatment of stage IIB inoperable, recurrent mediastinal disease, and residual gross disease post attempted surgical removal). There was a recommendation against using durvalumab in resected stage III disease with R1 or R0 margins, even if chemoradiation were considered. There was not consensus on the use of consolidation durvalumab in the setting of oligometastatic disease or in the setting of large cell neuroendocrine carcinoma or combined small cell carcinoma., Conclusion: Treatment of 'real-world' lung cancer often involves chemoradiation in settings outside of stage III and eligible for the PACIFIC study. This paper offers recommendations in these scenarios based on a consensus approach., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study evaluates the prevalence of emotional distress and psychosocial needs in young adult (YA, age 18-39) patients at the time of their breast cancer diagnosis compared to older patients., Methods: Through a province-wide program, BC Cancer patients complete the PsychoSocial Scan for CANcer-Revised (PSSCAN-R) questionnaire, which screens for the presence of symptoms of anxiety and depression and assesses psychosocial needs using the Canadian Problem Checklist (CPC). The study population comprised all breast cancer patients who completed the questionnaire within 6 months of their cancer diagnosis between 2011 and 2016. Clinical information was retrospectively collected from electronic health records. Univariate and multivariate analyses using the X 2 , Fisher's exact test, and logistical regression were used to compare patient age groups., Results: The cohort included 10,734 breast cancer patients: median age 62, 4% YA, 99% female, and 96% presented with non-metastatic disease. After adjusting for clinical and demographic variables, YA patients were more likely to report depression (33.6% vs. 25.5%, OR 1.47, p = 0.001) and anxiety symptoms (58.6% vs. 35.7%, OR 2.49, p < 0.001) than older patients. Psychosocial needs regarding work/school (OR 3.79, p < 0.001), intimacy/sexuality (OR 2.82, p < 0.001), and finances (OR 2.78, p < 0.001) were more common among YA than older adults., Conclusions: After a breast cancer diagnosis, YAs have higher levels of emotional distress compared to older patients. Differences in specific psychosocial needs likely reflect differences in life stage between these age groups. The data suggest that YAs warrant specific attention with respect to early psychosocial assessment and tailored intervention.

Introduction: Second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) appear superior to first-generation TKIs in clinical trials, but at the cost of greater toxicity. It is unclear whether real-world patients, who often suffer worse outcomes, experience similar survival benefits. Using population-based data, we aim to characterize outcome differences by type of treatment., Patients and Methods: We reviewed all patients with advanced non-small-cell lung cancer who initiated treatment with an EGFR TKI at BC Cancer between 2010 and 2015. A propensity score was generated to account for imbalances in patient characteristics between treatment groups. A Cox proportional hazards model based on the propensity score was then used to estimate effects of treatment on survival., Results: A total of 484 patients were identified for analysis. Patients in the second-generation cohort were younger (62 vs. 67 years), had less baseline central nervous system metastases (9% vs. 22%), and more uncommon EGFR mutations (13% vs. 7%). Patients receiving a second-generation TKI had an improved overall survival (hazard ratio, 0.69; P = .05), driven by the subgroup with an EGFR exon 19 deletion. Patients with a L858R mutation did not appear to derive benefit from a second-generation TKI (hazard ratio, 0.91; P = .74). Overall, 40% of patients receiving a second-generation TKI required a dose reduction, but only 1% required discontinuation., Conclusions: Second-generation TKIs tended to be chosen over first-generation TKIs as frontline therapy in younger patients with uncommon EGFR mutations and without central nervous system metastases. The survival benefit of a second-generation TKI seen in clinical trials appeared to be generalizable to real-world patients and is a reasonable first-line therapy., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Curative intent treatment of stage III NSCLC is variable and influenced by both patient and disease characteristics. We performed a real-world analysis of curative therapies in stage III NSCLC, and explored the impact of known prognostic factors on outcome., Methods: A retrospective review was completed of all patients with stage III NSCLC between January 2005 and December 2012. Cases were filtered to identify those receiving curative intent therapy including surgery, radiotherapy (RT), chemoradiotherapy (CRT), and combined modality with surgery (S + RT). Information was collected on known prognostic and predictive factors, and immunotherapy eligibility per the PACIFIC trial. The primary outcome measure was overall survival., Results: A total of 638 patients with stage III NSCLC were referred and received curative intent treatment. Of these, 66 (10%) received surgery, 95 (15%) RT, 410 (64%) CRT, and 67 (11%) combined S + RT. Median overall survival (OS) was similar for surgery (28.6 mo) and CRT (27.0 mo), inferior for RT alone (17.5 mo), and superior for S + RT (55.8 mo). In a multivariate model only, Eastern Cooperative Oncology Group performance status (ECOG PS) and treatment cohort significantly influenced OS. In a case-matched analysis, the median OS for CRT was 31.9 months, compared to 55.8 months with trimodality treatment. Overall, 61% of patients receiving CRT and 88% of those receiving trimodality therapy would have been potentially eligible for adjuvant immunotherapy., Conclusions: In stage III NSCLC, the performance of surgery and CRT are similar after controlling for known prognostic factors. Radiotherapy alone is associated with worse outcomes. Combined S + RT appears to provide a significant benefit above other modalities, albeit in highly selected patients., (Copyright © 2019 International Association for the Study of Lung Cancer. All rights reserved.)

Objectives: Metastatic non-small cell lung cancer (NSCLC) has a poor prognosis. Most patients present with stage IV, and many patients treated curatively with stage I to III develop recurrent metastatic disease. It is unknown whether the natural history differs between patients with recurrent versus de novo metastatic NSCLC. We hypothesized that de novo metastatic status is associated with decreased overall survival compared with recurrent metastatic disease., Materials and Methods: A retrospective review was completed of all patients with NSCLC referred to BC Cancer from 2005 to 2012. Two cohorts were created; de novo metastatic disease and patients treated with curative intent (surgery or radiotherapy) that developed recurrent, metastatic disease. Information was collected on known prognostic and predictive factors. Overall survival was calculated from the date of diagnosis of metastatic disease., Results: A total of 9651 patients were evaluated, 5782 (60%) with de novo stage IV disease, and 3869 (40%) with stage I to III disease. Of the 1658 patients who received curative therapy for stage I to III disease, 757 (46%) developed metastases. Patients in the de novo cohort versus recurrent cohort were more likely male (52% vs. 48%), have poorer performance status (Eastern Cooperative Oncology Group≥2 50% vs. 44%), and receive no palliative systemic therapy (67% vs. 61%). The median overall survival in the de novo cohort was 4.7 versus 6.9 m in the recurrent cohort (P<0.001). De novo status was associated with shorter overall survival and this remained significant in a multivariate model that incorporated known prognostic factors., Conclusions: In a large population-based study of NSCLC, de novo metastatic status was independently associated with decreased overall survival from the time of metastatic disease diagnosis.

The Personalized Onco-Genomics (POG) program at BC Cancer integrates whole-genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examined the subgroup of patients with metastatic non-small-cell lung cancer (NSCLC) and report the prevalence of actionable targets, treatments, and outcomes. We identified patients who were enrolled in the POG program between 2012 and 2016 who had a tumor biopsy and blood samples with comprehensive DNA (80×, 40× normal) and RNA sequencing followed by in-depth bioinformatics to identify potential cancer drivers and actionable targets. In NSCLC cases, we compared the progression-free survival (PFS) of "POG-informed therapies" with the PFS of the last regimen prior to POG (PFS ratio). In 29 NSCLC cases, 11 were male (38%), the median age was 60.2 yr (range: 39.4-72.6), and histologies included were adenocarcinoma (93%) and squamous cell carcinoma (7%). Potential molecular targets (i.e., cancer drivers including TP53 mutations) were identified in 26 (90%), and 21 (72%) had actionable targets. Therapies based on standard-of-care mutation analysis, such as EGFR mutations, were not considered POG-informed therapies. Thirteen received POG-informed therapies, of which three had no therapy before POG; therefore a comparator PFS could not be obtained. Of 10 patients with POG-informed therapy, median PFS ratio was 0.94 (IQR 0.2-3.4). Three (30%) had a PFS ratio ≥1.3, and three (30%) had a PFS ratio ≥0.8 and <1.3. In this small cohort of NSCLC, 30% demonstrated longer PFS with POG-informed therapies. Larger studies will help clarify the role of whole-genome analysis in clinical practice., (© 2019 Tsang et al.; Published by Cold Spring Harbor Laboratory Press.)

Introduction: Standard management of stage II non-small-cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. We examined outcomes in this defined patient group., Methods: We reviewed the records of patients with stage II NSCLC treated nonsurgically with curative intent from 2002 to 2012 across 3 academic cancer centers. Data collected included demographics, comorbidities, staging, treatments, and survival. The primary endpoint was overall survival (OS). We assessed factors associated with treatment choice and OS., Results: A total of 158 patients were included: the median age was 74 years (range, 50-91 years), 44% were female, and 68% had a performance status of 0 to 1. The stage II groupings of the patients were T2b-T3 N0 in 55% and N1 in 45%. The most common reasons for inoperability were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median, 60 Gy [range, 48-75 Gy]). Seventy-three percent received RT alone; 24% received concurrent and 3% sequential chemoradiotherapy (CRT). In multivariate analyses, CRT was less likely in older patients (≥ 70 years) (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.70; P = .006) and in patients with higher (> 5) Charlson comorbidity scores (OR, 0.34; 95% CI, 0.13-0.90; P = .03) or normal (< 10 × 10 9 /L) white blood cell counts (OR, 0.26; 95% CI, 0.09-0.73; P = .01). At the time of our analysis, 74% have died. The median OS was 22.9 months (range, 17.1-26.6 months). Patients who had undergone CRT had a significantly longer median OS than those receiving RT alone (39.1 vs. 20.5 months; P = .0019), confirmed in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21-0.69; P = .001)., Conclusion: Nonsurgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared with RT alone. A randomized trial may be warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Brain metastasis (BM) in NSCLC is a negative prognostic indicator. In the era of EGFR mutations we evaluated the difference between early (≤6 months from diagnosis) versus late BM (>6 months), in EGFR wild type (WT) and mutant (MT) NSCLC patients with respect to radiographic patterns and overall survival (OS). A retrospective study was conducted of referred patients with non-squamous NSCLC with known EGFR mutation status treated for BM from Mar 2010-Dec 2012. Radiographic patterns, treatment and survival were collected. 430 patients were identified: 327 WT (207 early vs. 120 late) and 103 MT (65 early vs. 38 late). Early and late BM radiographic patterns were similar in EGFR WT patients. In EGFR MT there was a trend towards multiple lesions in the late compared to early BM group. OS from initial diagnosis early BM: WT 7.1 months versus MT 19.9 months (p < 0.001). OS from initial diagnosis late BM: WT 24.9 months versus MT 25.6 months (p = 0.51). In multivariate analysis chemotherapy, single lesion and late BM were associated with better survival in WT patients whereas age, and systemic treatment but not BM timing or single lesion were predictive of better outcomes in MT patients. In early BM, EGFR MT have an OS comparable to late BM. In contrast, early BM EGFR WT have a significantly reduced survival compared to late BM. The positive outcome in EGFR MT may be secondary to systemic control and EGFR TKI penetrance across the blood brain barrier.

Given the success of targeted agents in specific populations it is expected that some degree of molecular biomarker testing will become standard of care for many, if not all, cancers. To facilitate this, cancer centers worldwide are experimenting with targeted "panel" sequencing of selected mutations. Recent advances in genomic technology enable the generation of genome-scale data sets for individual patients. Recognizing the risk, inherent in panel sequencing, of failing to detect meaningful somatic alterations, we sought to establish processes to integrate data from whole-genome analysis (WGA) into routine cancer care. Between June 2012 and August 2014, 100 adult patients with incurable cancers consented to participate in the Personalized OncoGenomics (POG) study. Fresh tumor and blood samples were obtained and used for whole-genome and RNA sequencing. Computational approaches were used to identify candidate driver mutations, genes, and pathways. Diagnostic and drug information were then sought based on these candidate "drivers." Reports were generated and discussed weekly in a multidisciplinary team setting. Other multidisciplinary working groups were assembled to establish guidelines on the interpretation, communication, and integration of individual genomic findings into patient care. Of 78 patients for whom WGA was possible, results were considered actionable in 55 cases. In 23 of these 55 cases, the patients received treatments motivated by WGA. Our experience indicates that a multidisciplinary team of clinicians and scientists can implement a paradigm in which WGA is integrated into the care of late stage cancer patients to inform systemic therapy decisions.

Rationale: Endocannabinoid, opioid, and dopamine systems interact to exhibit cannabinoid receptor neuromodulation of opioid peptides and D(4) dopamine receptor gene expression in CB(1)-cannabinoid-deficient mouse striatum., Objective: Using CB(1)-transgenic mice, we examine primary age-sex influences and interactions on opioid and dopamine system members' gene expression in striatum., Materials and Methods: Real-time quantitative polymerase chain reaction was used to analyze gene expression of opioid peptides [preproenkephalin (PPENK); preprodynorphin (PPDYN)], opioid receptors [delta-opioid receptor (delta-OR); mu-opioid receptor (micro-OR)] and dopamine receptor subtypes (D(1) through D(5)) in male/female CB(1)(+/+)/CB(1)(-/-) mice striata at two adult ages [young (60-90 days); old (140-300 days)]., Results: (1) Increased PPENK and PPDYN, owing to genotype [CB(1)(+/+) vs. CB(1)(-/-)], depended on sex. When genotype-independent, they depended on sex (PPENK) or age (PPDYN). (2) delta-OR was age-dependent (higher in old). (3) micro-OR, owing to genotype, was age-dependent [higher in old CB(1)(-/-) males]. When genotype-independent, it depended on sex (higher in females). (4) Female D(1) was genotype-independent and age-dependent, while male D(1) was higher in old over young CB(1)(+/+) mice. (5) D(5), owing to genotype, was sex-dependent [higher in young female CB(1)(-/-) mice]. (6) D(2), genotype-independent, was higher in old over young male mice. (7) Young female D(3) was higher in CB(1)(-/-) over CB(1)(+/+) mice. Male D(3) was age-dependent (higher in old mice). (8) D(4), owing to genotype, was sex-dependent [higher in CB(1)(-/-) over CB(1)(+/+) females]. Genotype-independent D(4) was sex-dependent in young mice (higher in females) and age-dependent in males (higher in old)., Conclusions: Greater striatal expression is genotype-dependent in females (opioid-peptides, D(3), D(4), D(5)) and genotype-independent in both females (PPENK, mu-OR, D(4)) and old males (PPDYN, delta-OR, D(2), D(3), D(4)).