Surgically Resectable Non-Small Cell Lung Cancer: A Contemporary Approach.

New treatment paradigms for resectable non-small cell lung cancer (NSCLC), with an emphasis on personalized 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 personalized approach for patients with actionable genomic alterations. Innovative surgical techniques and judicious use of post operative radiotherapy may mitigate the toxicity associated with a multimodality approach. Amidst many new treatment options, questions remain about the best approach to consider for each patient. Measurement of minimal residual disease and achievement of pathologic complete response are emerging biomarkers of interest to help further refine treatment selection. This review summarizes 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.

Improved uptake and survival with systemic treatments for metastatic non-small cell lung cancer: younger versus older adults.

BACKGROUND: Over the past decade, there has been increasing availability of novel therapeutics with improved tolerability and efficacy for advanced non-small cell lung cancer (NSCLC). The study goals were: to compare the uptake of systemic therapy (ST) before and after the availability of targeted tyrosine kinase inhibitors (TKI) and immunotherapy and to examine the changes in overall survival (OS) over time between younger and older adults with advanced NSCLC. METHODS: All patients with advanced NSCLC referred to British Columbia (BC) Cancer in 2009, 2011, 2015 and 2017 were included. One-year time points were based on molecular testing implementation and funded drug availability: baseline (2009), epidermal growth factor receptor TKI (2011), anaplastic lymphoma kinase TKI (2015) and Programed Death-1 (PD-1) inhibitors (2017). Age groups were <70years and ≥70years. Baseline demographics, simplified comorbidity scores (SCS), disease characteristics, and ST details were collected retrospectively. Variables were compared using X2, Fisher's exact tests and logistic-regression analysis. OS was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: 3325 patients were identified. Baseline characteristics were compared between ages < 70 years and ≥ 70 years for each time cohort with significant differences noted in baseline Eastern Cooperative Oncology Group (ECOG) performance status and SCS. The rate of ST delivery trended upwards over time with age <70 years: 2009 44%, 2011 53%, 2015 50% and 2017 52% and age ≥70 years: 22%, 25%, 28% and 29% respectively. Predictors for decreased use of ST for age <70 years: ECOG ≥2, SCS ≥9, year 2011, and smoking history; and age ≥70 years: ECOG ≥2, years 2011 and 2015, and smoking history. The median OS of patients who received ST improved from 2009 to 2017: age <70 years 9.1 m vs. 15.5 m and age ≥70 years 11.4 m vs. 15.0 m. CONCLUSIONS: There was an increased uptake of ST for both age groups with the introduction of novel therapeutics. Although a smaller proportion of older adults received ST, those who received treatment had comparable OS to their young counterpart. The benefit of ST in both age groups was seen across the different types of treatments. With careful assessment and selection of appropriate candidates, older adults with advanced NSCLC appear to benefit from ST.

The perceptions and adoption of environmentally sustainable practices among anesthesiologists-a qualitative study.

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.

RéSUMé: OBJECTIF: Des enquêtes antérieures auprès d'anesthésiologistes ont montré que, malgré un vif intérêt pour la mise en œuvre de pratiques anesthésiques durables sur le plan environnemental, moins d'un tiers les mettent en pratique. La compréhension qualitative de la capacité, des possibilités et des facteurs de motivation qui influencent les comportements « verts ¼ éclairera la conception d'interventions efficaces pour promouvoir des pratiques durables sur le plan environnemental en salle d'opération. MéTHODE: Nous avons mené 23 entretiens semi-structurés avec des anesthésiologistes, avec une saturation des données atteinte. En appliquant la roue du changement de comportement, les questions d'entrevue portaient sur les déterminants du comportement liés à la « capacité ¼, à l'« occasion ¼ et à la « motivation ¼. RéSULTATS: La préférence pour le sévoflurane et la réutilisation des seringues ont été le plus souvent citées comme des pratiques anesthésiques durables. Plusieurs participants ont signalé que le manque de connaissances et de rétroaction constituait un obstacle à des pratiques anesthésiques durables. Parmi les obstacles physiques signalés, mentionnons l'insuffisance des installations de recyclage et l'abondance des fournitures. Les personnes interrogées ont également discuté de l'importance du comportement habituel pour améliorer les compétences et réduire la charge cognitive requise pour mettre en œuvre des pratiques durables. La prise de conscience générale des questions environnementales et l'agrégation des gains marginaux étaient les raisons citées pour lesquelles des mesures écologiquement viables ont été prises en salle d'opération. La pratique organisationnelle et la culture ont joué un rôle important dans la diffusion de pratiques anesthésiques durables, les cadres supérieurs ayant souvent une plus grande influence. Alors que la majorité préférerait une approche descendante pour apporter des changements, d'autres étaient en faveur de l'utilisation d'incitatifs. CONCLUSION: Cette étude donne un aperçu des facteurs qui influencent l'adoption de pratiques durables sur le plan environnemental en salle d'opération. Les mesures visant à promouvoir ces pratiques comprennent l'éducation et la formation, la rétroaction sur les efforts, l'engagement des anesthésistes plus établis ou senior en tant que modèles et gestionnaires du changement, la restructuration environnementale et la conception de politiques qui équilibrent une approche descendante vs une approche ascendante pour influencer le changement.

Use, response and outcomes of second-line chemotherapy in patients with advanced biliary tract cancers.

INTRODUCTION: First-line chemotherapy for advanced biliary tract cancers has been established as gemcitabine and cisplatin; however, there is currently no recognized standard second-line chemotherapy. The purpose of this study is to review and evaluate the outcomes of second-line chemotherapy for advanced biliary tract cancers. METHODS: Patients who received chemotherapy for unresectable or metastatic biliary tract cancers at BC Cancer between August 2009 and December 2015 were retrospectively studied to identify second-line chemotherapy treatments used and to determine overall survival, time-to-treatment discontinuation and characteristics predicting for improved overall survival. RESULTS: Of 325 patients who received first-line chemotherapy for advanced biliary tract cancer, 90 (30%) received second-line chemotherapy. Median overall survival for patients who received only first-line chemotherapy was 9.5 months versus 17.3 months for patients who received second-line chemotherapy. Median time-to-treatment discontinuation for second-line chemotherapy was 2.0 months. Common drugs used in second-line chemotherapy treatments included capecitabine (30%), 5-fluorouracil and irinotecan (17%) and 5-fluorouracil monotherapy (15%). There was no difference in overall survival for patients who received single-agent second-line chemotherapy compared to doublet second-line chemotherapy. CONCLUSIONS: Patients who are fit enough to receive second-line chemotherapy may benefit in terms of overall survival and should be offered treatment with single-agent therapy. Capecitabine was the most common second-line chemotherapy treatment. The improved median overall survival for patients who received second-line chemotherapy may be impacted by independent patient-specific factors which are unknown at this time.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

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.

Defining a Core Data Set for the Economic Evaluation of Precision Oncology.

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.

Real world duration of curative intent breast, colorectal, non-small cell lung, and prostate cancer treatment.

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.

Patient-reported psychosocial distress in adolescents and young adults with germ cell tumours.

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.

Patient-reported outcome measures in patients undergoing radiotherapy for head and neck cancer.

OBJECTIVES: Head and neck (H&N) cancer patients experience significant acute side effects from treatment. This study evaluates prospectively collected patient-reported outcomes (PROs) in H&N patients undergoing radiotherapy (RT) to assess feasibility of electronically collecting PROs and to objectively document symptom acuity and trajectory during RT. MATERIALS AND METHODS: H&N patients undergoing radical RT at our multicentre institution completed a 12-item partial survey of the Vanderbilt Head & Neck Symptom Survey 2.0 prior to RT and weekly on RT. Between October 2016 and October 2018, 318 of 333 patients completed a baseline survey and at least one weekly survey. RESULTS: The average number of weekly questionnaires completed was 5 (range 1-8). The mean maximum symptom scores were highest for dysgeusia (5.8/10), pain (5.4/10), mucositis (4.8/10), weight loss due to swallowing (4.5/10) and mucus causing choking/gagging (4.3/10). On multivariate analysis, female gender, sinonasal, nasopharynx and oropharynx primaries were associated with a greater risk of moderate-severe pain (p < 0.05). Sinonasal, nasopharynx, oral cavity, oropharynx and thyroid primaries were associated with a greater risk of moderate-severe mucositis during radiation (p < 0.0001). Salivary gland, sinonasal, nasopharynx and oropharynx primaries and higher radiation dose were associated with a greater risk of moderate-severe dysgeusia (all p < 0.05). CONCLUSIONS: Electronic PRO collection during H&N cancer RT is feasible. H&N cancer patients experience significant symptoms during RT, and the most severe symptoms reported were dysgeusia, pain and mucositis. Oropharynx cancer patients reported the highest symptom scores during RT.

Comparability of laboratory-developed and commercial PD-L1 assays in non-small cell lung carcinoma.

PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to treatment with PD-1 and PD-L1 inhibitors. Different inhibitors have been developed with different PD-L1 assays, which use different PD-1 antibody clones on different immunohistochemistry platforms. Depending on instrument and reagent availability, laboratory-developed tests with cross-platform use of PD-L1 antibodies may have practical benefits over commercial assays. The 22C3 pharmDx Assay (referred to as 22C3 DAKO), the VENTANA PD-L1 SP263 Assay (referred to as SP263 VENTANA) and a lab-developed test using the 22C3 antibody on the VENTANA BenchMark ULTRA IHC/ISH system (referred to as 22C3 VENTANA) were performed on whole sections of 85 NSCLC surgical resections. All sections were independently scored by three pathologists using tumor proportion scores. Correlation coefficients for continuous scores in pairwise comparisons between assays ranged from 0.976 to 0.978. When using a 1% positivity threshold (dichotomous scores), the 22C3 DAKO assay and 22C3 VENTANA assays showed the greatest agreement (93% agreement, κ = 0.86, 95% CI 0.75-0.97), and the 22C3 DAKO and SP263 VENTANA assays tended to show slightly less agreement (84% agreement, κ = 0.66, 95% CI 0.50-0.82). When using a 50% positivity threshold (dichotomous scores), all pairwise comparisons showed similar agreement (96-99% agreement, κ = 0.89-0.97). Overall, there was no significant difference between assays at 1% or 50% thresholds (P = .77). These data are consistent with potential interchangeability of these assays, which may widen the scope of PD-L1 assays available to laboratories and reduce logistical barriers to testing.

Emotional distress and psychosocial needs in patients with breast cancer in British Columbia: younger versus older adults.

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 X2, 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.

Intratumoral heterogeneity in programmed death-ligand 1 immunoreactivity is associated with variation in non-small cell lung carcinoma histotype.

AIMS: Accurate assessment of programmed death-ligand 1 (PD-L1) levels in non-small cell lung carcinoma (NSCLC) samples is complicated by intratumoral heterogeneity. We aimed to: (i) establish whether intratumoral PD-L1 variation is associated with differences in local histotype; (ii) identify histotypes associated with a tendency for there to be higher or lower PD-L1 scores; and (iii) estimate the frequency of clinically significant discordance in PD-L1 levels between intratumoral histotype areas. METHODS AND RESULTS: We reviewed 166 NSCLC resection specimens clinically tested for PD-L1 with the 22C3 pharmDx assay. Multiple histotypes were present in 55% (68/123) of non-mucinous adenocarcinoma samples. Solid histotypes had significantly higher PD-L1 levels than other histotypes, both when samples were grouped by predominant histotype, and when histotype areas within a tumour were compared (P < 0.02). Lepidic areas had significantly lower PD-L1 levels than other histotype areas within the same tumour (P < 0.02). Discordance between intratumoral histotype areas at a clinically relevant threshold (PD-L1 tumour proportion score of 1% or 50%) was present in 32% (22/68) of non-mucinous adenocarcinoma specimens with multiple histotype areas. The lepidic histotype was most frequently involved in discordance. CONCLUSIONS: Intratumoral heterogeneity in PD-L1 is associated with variation in histotype. Over-representation of solid areas may increase the PD-L1 score assigned to a tumour, whereas over-representation of lepidic areas may decrease the PD-L1 score. Evaluation of how histotype representation impacts on the predictive value of PD-L1 testing is warranted.

Assessing the psychosocial needs of newly diagnosed patients with nonsmall cell lung cancer: Identifying factors associated with distress.

OBJECTIVE: The Psychosocial Screen for Cancer (PSSCAN-R) questionnaire is a validated screening tool used to identify the psychosocial needs of patients with cancer. It assesses patients' perceived social supports and psychosocial needs, and the presence of symptoms of depression and anxiety. The study goals were to assess the prevalence and factors associated with distress in patients with newly diagnosed nonsmall cell lung cancer (NSCLC). METHODS: All patients with NSCLC referred to BC Cancer centers from 2011 to 2015, who completed a prospective PSSCAN-R questionnaire at the time of their first visit, were included in the study. Demographics and baseline disease characteristics were collected retrospectively. The chi-squared test, Fisher exact test, and logistical regression analysis were used to compare factors associated with the presence of distress based on sex, age, stage of disease, and performance status (PS). RESULTS: A total of 4281 NSCLC patients completed the PSSCAN-R questionnaire. Baseline characteristics: 70% were greater than or equal to 65, 50% female, 52% metastatic disease, 47% Eastern Cooperative Oncology Group (ECOG) greater than or equal to two. Patients who were female, less than 65, have metastatic disease and poor PS were more likely to report subclinical or clinical symptoms of anxiety. Symptoms of depression were associated with younger, female, poor PS patients, and social isolation. CONCLUSIONS: Newly diagnosed patients with NSCLC are likely to report clinical symptoms of anxiety and depression and have a high number of concerns in multiple psychosocial domains. Resource development for lung cancer patients should be based on their care needs with careful consideration of patients' age, gender, stage, and social situation to optimally support their psychosocial needs during treatment and follow-up.

Buprenorphine shared medical appointments for the treatment of opioid dependence in a homeless clinic.

BACKGROUND: Opioid misuse and dependence are prevalent and rising problems in the United States. Treatment with buprenorphine is a successful treatment option for individuals with opioid dependence. This study describes and preliminarily evaluates a unique delivery system that provides buprenorphine treatment via a shared medical appointment. METHODS: A retrospective medical record review on all 77 opioid-dependent patients referred for a buprenorphine shared medical appointment in a homeless clinic from 2010 to 2012. RESULTS: Most patients were currently homeless (61%), unemployed (92%), had an Axis I psychiatric diagnosis (81%), and had recent polysubstance use (53%). Of the 77 patients, 95% attended at least 1 shared medical appointment. Treatment retention at 12 and 24 weeks was 86% and 70%, respectively. CONCLUSIONS: In a patient population with complex social and mental health histories, buprenorphine treatment via a shared medical appointment had high retention rates. Findings can help guide the development of unique delivery systems to serve real-world complex patients with opioid dependence.

Radiographic patterns and survival of patients with early and late brain metastases in EGFR wild type and mutant non small cell lung cancer.

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.

Treating anaplastic lymphoma kinase (ALK) fusion-driven metastatic non-small cell lung cancer (NSCLC) with alectinib through pregnancy.

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).

Predicting which patients with cancer will see a psychiatrist or counsellor from their initial oncology consultation document using natural language processing.

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.

Patients with cancer often need support for their mental health. Early detection of who requires referral to a counsellor or psychiatrist may improve their care. This study trained a type of artificial intelligence (AI) called natural language processing to read the consultation report an oncologist writes after they first see a patient to predict which patients will see a counsellor or psychiatrist. The AI predicted this with performance similar to other uses of AI in mental health, and used different words and phrases to predict who would see a psychiatrist compared to seeing a counsellor. We believe this is the first use of AI to predict mental health outcomes from medical documents written by clinicians outside of mental health. This study suggests this type of AI can predict the mental health needs of patients with cancer from this widely-available document.

Outcomes of patients with advanced epithelial growth factor receptor mutant lung cancer treated with first-line osimertinib who would not have met the eligibility criteria for the FLAURA clinical trial.

OBJECTIVES: Osimertinib is largely used as first-line therapy for metastatic epithelial growth factor receptor (EGFR) mutant lung cancers based on the FLAURA clinical trial. Real-world patient outcomes often differ from clinical trial outcomes. This study evaluated the efficacy of first-line osimertinib in patients treated in British Columbia (BC), Canada. Furthermore, we compared the outcomes of patients who would and would not have been eligible for the original FLAURA trial. METHODS: Consecutive patients receiving first-line osimertinib for metastatic EGFR exon19 or L858R lung cancer were identified using the BC Cancer Pharmacy Database. Patient eligibility for the FLAURA clinical trial were retrospectively reviewed based on the following criteria: ECOG ≥ 2, symptomatic brain metastases or on steroids, hemoglobin < 90 g/L, platelets < 100x109/L, or a creatinine clearance < 50 mL/min. mOS was assessed for the entire population and compared between patients who would have been eligible and ineligible for FLAURA. RESULTS: From January 2020 to October 2021, 311 patients received first-line osimertinib; 44 % (137/311) were deemed FLAURA ineligible, predominantly due to low ECOG (n = 120). After a median follow-up of 26.5 months, the mOS for the entire cohort was 27.4 months (95 %CI 23.8-30.1). The mOS for ineligible patients was 18 months shorter than eligible patients (15.8 vs 34.2, p < 0.001). Ineligible patients had higher rates of de novo stage IV disease, higher rates of stage IVB disease, and more sites of disease than eligible patients. CONCLUSION: In this real-world population, nearly half of patients would have been ineligible for FLAURA. The mOS was one year shorter than reported in FLAURA. However, patients who would have been eligible for the FLAURA clinical trial had similar OS to patients enrolled in FLAURA. Trial ineligible patients had a higher burden of disease at baseline which may have led to inferior outcomes. Further research is needed to improve outcomes in these patients.

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer.

BACKGROUND: Despite advances in targeted therapies, there is an ongoing need to develop new and effective cytotoxic drug combinations in non-small cell lung cancer (NSCLC). Based on preclinical demonstration of additive cytotoxicity, we evaluated the safety and efficacy of combining pemetrexed and nanoparticle albumin bound (nab) paclitaxel with a focus on NSCLC for phase II expansion. METHODS: A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Three dose levels were tested: pemetrexed 500 mg/m(2) day 1 and nab-paclitaxel day 1 at 180, 220, & 260 mg/m(2) every 21 days. Phase II eligibility included advanced NSCLC, ≤2 line prior therapy, PS 0-1, adequate organ function. Primary endpoint for further study was response rate (RR) ≥ 25%. RESULTS: Planned dose escalation was completed without reaching the MTD. The RP2D was pemetrexed 500 mg/m(2) and nab-paclitaxel 260 mg/m(2). The phase II portion accrued 37 pts before early closure due to increasing first-line pemetrexed/platinum doublet use in non-squamous NSCLC. In 31 assessable phase II patients there were 5 partial responses, 12 stable disease, 14 progressive disease. The median overall survival was 8.8 months; progressive disease 4.4 months and disease control 15.6 months. CONCLUSIONS: Pemetrexed 500 mg/m(2) day 1 with nab-paclitaxel 260 mg/m(2) was feasible and well tolerated. The phase II component demonstrated activity in second/third-line therapy of advanced NSCLC; response rate 14% and disease control rate 46%. Treatment practice patterns of advanced NSCLC have evolved; further trials of this regimen are not planned.