Public policy interventions to mitigate household food insecurity in Canada: a systematic review.

OBJECTIVE: The objective of this systematic review is to synthesise the evidence on public policy interventions and their ability to reduce household food insecurity (HFI) in Canada. DESIGN: Four databases were searched up to October 2023. Only studies that reported on public policy interventions that might reduce HFI were included, regardless of whether that was the primary purpose of the study. Title and abstract screening, full-text screening, data extraction, risk of bias and certainty of the evidence assessments were conducted by two reviewers. RESULTS: Seventeen relevant studies covering three intervention categories were included: income supplementation, housing assistance programmes and food retailer subsidies. Income supplementation had a positive effect on reducing HFI with a moderate to high level of certainty. Housing assistance programmes and food retailer studies may have little to no effect on HFI; however, there is low certainty in the evidence that could change as evidence emerges. CONCLUSION: The evidence suggests that income supplementation likely reduces HFI for low-income Canadians. Many questions remain in terms of how to optimise this intervention and additional high-quality studies are still needed.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: An Analysis of 5721 Cases.

OBJECTIVE: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). SUMMARY BACKGROUND DATA: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. RESULTS: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS ( P < 0.0001) and OL ( P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P <0.02). Compared to VATS, RL had lower conversion rate ( P <0.0001), shorter hospital stay ( P <0.0001) and a lower postoperative transfusion rate ( P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. CONCLUSIONS: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: Survival Analysis of 6646 Cases.

OBJECTIVE: The aim of this study was to analyze overall survival (OS) of robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VATS), and open lobectomy (OL) performed by experienced thoracic surgeons across multiple institutions. SUMMARY BACKGROUND DATA: Surgeons have increasingly adopted RL for resection of early-stage lung cancer. Comparative survival data following these approaches is largely from single-institution case series or administrative data sets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. Consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Induction therapy patients were excluded. The propensity-score method of inverse-probability of treatment weighting was used to balance baseline characteristics. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to evaluate association among OS and relevant risk factors. RESULTS: A total of 2789 RL, 2661 VATS, and 1196 OL cases were included. The unadjusted 5-year OS rate was highest for OL (84%) followed by RL (81%) and VATS (74%); P =0.008. Similar trends were also observed after inverse-probability of treatment weighting adjustment (RL 81%; VATS 73%, OL 85%, P =0.001). Multivariable Cox regression analyses revealed that OL and RL were associated with significantly higher OS compared with VATS (OL vs. VATS: hazard ratio=0.64, P <0.001 and RL vs. VATS: hazard ratio=0.79; P =0.007). CONCLUSIONS: Our finding from this large multicenter study suggests that patients undergoing RL and OL have statistically similar OS, while the VATS group was associated with shorter OS. Further studies with longer follow-up are necessary to help evaluate these observations.

Prolonged Survival of NUT Midline Carcinoma and Current Approaches to Treatment.

NUT midline carcinoma is a rare malignancy most commonly seen in adolescents and young adults. The disease presents most often in the lung or head and neck area but can be seen occasionally elsewhere. The diagnosis can be difficult and requires a high degree of suspicion with demonstration of the classic fusion rearrangement mutation of the NUTM1 gene with one of a variety of partners by immunohistochemistry, fluorescent in situ hybridization, or genomic analysis. Survival is usually only a number of months with few long-term survivors. Here we report one of the longest-known survivors of this disease treated with surgery and radiation without additional therapy. Systemic treatment approaches including the use of chemotherapy and BET and histone deacetylase inhibitors have yielded modest results. Further studies of these, as well as p300 and CDK9 inhibitors and combinations of BET inhibitors with chemotherapy or CDK 4/6 inhibitors, are being evaluated. Recent reports suggest there may be a role for immune checkpoint inhibitors, even in the absence of high tumor mutation burden or PD-L1 positivity. RNA sequencing of this patient's tumor demonstrated overexpression of multiple potentially targetable genes. Given the altered transcription that results from the causative mutation multi-omic evaluation of these tumors may uncover druggable targets for treatment.

General and abdominal obesity trajectories across adulthood, and risk of prostate cancer: results from the PROtEuS study, Montreal, Canada.

PURPOSE: Greater body fatness is a probable cause of advanced prostate cancer (PCa). Body fat distribution and timing of exposure may be relevant. We investigated associations between body size trajectories and PCa incidence in a population-based case-control study in Montreal, Canada. METHODS: Cases (n = 1,931), aged ≤ 75 years, were diagnosed with PCa in 2005-2009; 1,994 controls were selected from the electoral list. Interviews were conducted to assess body mass index (BMI) and Stunkard's silhouette at ages 20, 40, 50, 60 years, and before interview. Current waist and hip circumferences were measured, and a predictive model estimated waist circumference in the past. BMI and waist circumference trajectories were determined to identify subgroups. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between anthropometric indicators and PCa. RESULTS: Subjects with a current BMI ≥ 30 kg/m2 had a lower risk of overall PCa (OR 0.71, 95% CI 0.59-0.85). Associations with adult BMI followed similar trends for less and more aggressive tumors, with stronger inverse relationships in early adulthood. Contrastingly, current waist circumference ≥ 102 cm was associated with elevated risk of high-grade PCa (OR 1.33, 95% CI 1.03-1.71). Men with increasing BMI or waist circumference adult trajectories had a lower risk of PCa, especially low-grade, than those in the normal-stable range. This was especially evident among men in the obese-increase group for BMI and waist circumference. CONCLUSION: Abdominal obesity increased the risk of aggressive PCa. The inverse relationship between body size trajectories and PCa may reflect PSA hemodilution, lower detection, and/or a true etiological effect.

Cumulative radiation dose incurred during the management of complex pleural space infection.

BACKGROUND: Complex pleural space infections are commonly managed with antibiotics, pleural drainage, intrapleural fibrinolytic therapy, and surgery. These strategies often utilize radiographic imaging during management, however little data is available on cumulative radiation exposure received during inpatient management. We aimed to identify the type and quantity of radiographic studies along with the resultant radiation exposure during the management of complex pleural space infections. METHODS: Retrospective review of community network healthcare system from January 2015 to July 2018. Patients were identified through billing databases as receiving intrapleural fibrinolytic therapy and/or surgical intervention. Patient demographics, clinical outcomes, and inpatient radiographic imaging was collected to calculate cumulative effective dose. RESULTS: A total of 566 patients were identified with 7275 total radiographic studies performed and a median cumulative effective dose of 16.9 (IQR 9.9-26.3) mSv. Multivariable linear regression analysis revealed computed tomography use was associated with increased cumulative dose, whereas increased age was associated with lower cumulative dose. Over 74% of patients received more than 10 mSv, with 7.4% receiving more than 40 mSv. CONCLUSIONS: The number of radiographic studies and overall cumulative effective dose in patients hospitalized for complex pleural space infection was high with the median cumulative effective dose > 5 times normal yearly exposure. Ionizing radiation and modern radiology techniques have revolutionized medical care, but are likely not without risk. Additional study is warranted to identify the frequency and imaging type needed during complex pleural space infection management, attempting to keep ionizing radiation exposure as low as reasonably possible.

Surgery as a Component of Multimodality Care for Known Stage IIIA-N2 Non-small Cell Lung Cancer.

Locally advanced, stage IIIA-N2 Non-small cell lung cancer (NSCLC) represents a heterogeneous patient population. Considerable controversy exists as to the optimal management of these patients. Local therapy alone with a single modality, namely surgery or radiation, is associated with high recurrence rates and low overall survival. Consequently, multimodality treatment (chemotherapy, radiotherapy, with or without the utilization of surgery) has developed as a means of both local and systemic control for patients with stage IIIA-N2 NSCLC, and has led to improved overall survival. While it is clear that multimodality therapy is beneficial, the ideal composition of the treatment regimen remains a work in progress. As a result, the optimal management of patients with stage IIIA-N2 NSCLC is widely debated, as is the role for surgery in a multimodality treatment regimen. Herein, we review the current literature supporting multimodality therapy for stage IIIA-N2 NSCLC with an emphasis on the data supporting the role of surgery in resectable and potentially resectable patients.

Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection.

BACKGROUND: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. METHODS: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. RESULTS: Median follow-up was 47 (95%CI 41-79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3-70.9) and 47.4% (95%CI 32.3-61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01-1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6-93.6) and 38.2% (95%CI 20.6-55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1-78.8) and 54.2% (95%CI 32.6-71.6) (p = 0.31), respectively. CONCLUSIONS: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.

A Prospective, Ex Vivo Trial of Endobronchial Blockade Management Utilizing 3 Commonly Available Bronchial Blockers.

BACKGROUND: Lung isolation with bronchial blockers is a well-described and accepted procedure, often described for use during the management of massive hemoptysis. Recommendations for balloon inflation are sparse, with some advocating for saline whereas other suggest air, including the manufacturers. We sought to evaluate the optimal method for balloon inflation in an ex vivo trial. METHODS: We performed a prospective trial utilizing 3 commercially available bronchial blockers commonly described for use in lung isolation and massive hemoptysis management. We utilized the Arndt Endobronchial Blocker (Cook Medical), the Cohen Tip Deflecting Endobronchial Blocker (Cook Medical), and the Fogarty Venous Thrombectomy Catheter (Edwards LifeSciences). Balloon size and deflation assessment were tested within 3 different scenarios comparing air versus saline.Welch t test was performed to compare means between groups, and a generalized estimating equation model was utilized to compare balloon diameter over time to account for correlation among repeated measures from the same balloon. RESULTS: All 3 endobronchial blocker systems were observed in triplicate. During free-standing balloon inflation, all 3 endobronchial systems displayed a greater degree of balloon deflation over time with air as opposed to saline (P < .001). Within a stent-based model, inflation with air of all 3 endobronchial systems, according to manufacturer recommendations, demonstrated significantly decreased time until fluid transgression occurred when compared to a saline model (P < .001). Within a stent-based model, inflation with air, according to clinical judgment, demonstrated significantly decreased time until fluid transgression in the Arndt (P = .016) and the Fogarty (P < .001) system, but not the Cohen (P = .173) system, when compared with saline. CONCLUSIONS: The utilization of saline for balloon inflation during bronchial blockade allows for more consistent balloon inflation. The use of saline during balloon inflation appears to delay passive, spontaneous balloon deflation time when compared to air during a model of endobronchial blockade. The approach of saline inflation should be tested in humans to demonstrate the overall applicability and validity of the current findings.

Tunneled pleural catheter use for pleural palliation does not increase infection rate in patients with treatment-related immunosuppression.

PURPOSE: Concerns for infections resulting from antineoplastic therapy-associated immunosuppression may deter referral for symptom palliation with a tunneled pleural catheter (TPC) in patients with malignant/para-malignant pleural effusions (MPE/PMPE). While rates of TPC-related infections range from 1 to 21%, those in patients receiving antineoplastic therapy with correlation to immune status has not been established. We aimed to assess TPC-related infection rates in patients on antineoplastic therapy, determine relation to immune system competency, and assess impact on the patient. METHODS: Patients with a MPE/PMPE undergoing TPC management associated with antineoplastic therapy, from 2008 to 2016, were reviewed and categorized into those with an immunocompromised versus immunocompetent immune status. RESULTS: Of the 150 patients, a TPC-related infection developed in 13 (9%): pleural space in 11 (7%) and superficial in 2 (1%). Ninety-three percent (139/150) were identified to be immunocompromised during their antineoplastic therapy. No difference in TPC-related infections was seen in patients with an immunocompromised (9%, 12/139) versus immunocompetent status (9%, 1/11); p = 0.614. The presence of a catheter-related infection did not negatively impact overall survival over a median follow-up of 144 days (interquartile range 41-341); p = 0.740. CONCLUSIONS: These results suggest that antineoplastic therapy may not significantly increase the overall risk of TPC-related infections, as the rate remains low and comparable to rates in patients not undergoing antineoplastic therapy. Regardless of immune status, the presence of a catheter-related infection did not negatively impact overall survival. These results should reassure clinicians that the need to initiate antineoplastic therapy should not delay definitive pleural palliation with a TPC.

A combined thoracoscopic and laparoscopic approach for high epiphrenic diverticula and the importance of complete myotomy.

BACKGROUND: The traditional approach to epiphrenic diverticula is thoracotomy and diverticulectomy, together with myotomy ± partial fundoplication to address underlying dysmotility. A laparoscopic approach has been advocated but access to more proximal diverticula is problematic. We propose the selective addition of a thoracoscopic approach to overcome these challenges and reviewed our results. METHODS: A retrospective review from 2004 to 2015 identified 17 patients with an epiphrenic diverticulum who underwent surgery. Patients were grouped according to height of the diverticular neck (HDN) above the GEJ: group A < 5 cm, group B > 5 cm. Preoperative evaluation and type of surgery performed were recorded. Postoperative complications, mortality, and clinical outcomes using quality of life metrics and objective testing were assessed. RESULTS: The mean size of the diverticulum was 3.3 cm (2-6 cm) with a mean height above the GEJ of 5.5 cm (0-12 cm). A motility disorder was identified in 15/17. Group A, 9 patients, underwent laparoscopic diverticulectomy, myotomy, and partial fundoplication. For group B, 8 patients, the intended procedure was thoracoscopic diverticulectomy followed by laparoscopic myotomy and partial fundoplication, but this was only completed in 5. In 3 the myotomy was aborted or incomplete with subsequent staple line leaks resulting in 1 death. At a mean follow-up of 21 months, improvement of median QOLRAD scores from 3.42 to 6.2 (p = 0.18); GERD-HRQL from 23 to 1 (p = 0.05), swallowing score from 17.5 to 30 (p = 0.22), and Eckardt scores from 5 to 0 (p < 0.05) were observed. CONCLUSIONS: A minimally invasive strategy for epiphrenic diverticula based HDN above the GEJ and selective thoracoscopy for higher diverticula is feasible and appropriate, and resulted in improved quality of life. Incomplete myotomy was associated with a substantially higher complication rate. Laparoscopic myotomy should precede diverticulectomy for all cases, especially for high diverticula.

Feasibility, safety, and short-term efficacy of the laparoscopic Nissen-Hill hybrid repair.

BACKGROUND: A novel antireflux procedure combining laparoscopic Nissen fundoplication and Hill repair components was tested in 50 patients with paraesophageal hernia (PEH) and/or Barrett's esophagus (BE) because these two groups have been found to have a high rate of recurrence with conventional repairs. METHODS: Patients with symptomatic PEH and/or non-dysplastic BE underwent repair. Quality of life (QOL) metrics, manometry, EGD, and pH testing were administered pre- and postoperatively. RESULTS: Fifty patients underwent repair. There was no mortality and four major complications. At 13-month follow-up, there was one (2%) clinical recurrence, and two (4%) asymptomatic fundus herniations. Mean DeMeester scores improved from 57.2 to 7.7 (p < 0.0001). Control of preoperative symptoms was achieved in 90% with 6% resumption of antisecretory medication. All QOL metrics improved significantly. CONCLUSIONS: The hybrid Nissen-Hill repair for patients with PEH and BE appears safe and clinically effective at short-term follow-up. It is hoped that the combined structural components may reduce the rate of recurrence compared to existing repairs.

Occupational exposure to wood dust and risk of lung cancer in two population-based case-control studies in Montreal, Canada.

BACKGROUND: Wood dust is one of the oldest and one of the most common occupational exposures in the world. The present analyses examine the effect of lifetime exposure to wood dust in diverse occupational settings on lung cancer risk. METHODS: We conducted two population-based case-control studies in Montreal: Study I (1979-1986) included 857 cases and two sets of controls (533 population and 1349 cancer controls), and Study II (1996-2001) comprised 736 cases and 894 population controls. Detailed job histories were obtained by interview and each job was evaluated by expert chemist-hygienists to estimate the likelihood and level of exposure to many substances, one of which was wood dust. Odds ratios (ORs) were computed in relation to different indices of exposure to wood dust, adjusting for several covariates including smoking. Three datasets were analysed: Study I with population controls, Study I with cancer controls, and Study II. RESULTS: The most frequently exposed occupations in our study population were in construction, timber and furniture making industries. We found increased risks of lung cancer for substantial cumulative exposure to wood dust in Study I with cancer controls, (OR = 1.4: 95% confidence interval 1.0;-2.0) and in Study II (OR = 1.7: 95% confidence interval 1.1-2.7). There were no excess risks of lung cancer in any of the three datasets among workers whose cumulative exposure was not substantial. These tendencies held equally within strata of low smokers and heavy smokers. CONCLUSION: There was evidence of increased risk of lung cancer among workers with substantial cumulative exposure to wood dust.

The impacts of the Nutrition North Canada program on the accessibility and affordability of perishable, nutritious foods among eligible communities: a scoping review.

The Nutrition North Canada (NNC) program, introduced in April 2011 is a federal strategy to improve access to perishable, nutritious foods for remote and isolated communities in northern Canada by subsidising retailers to provide price reductions at the point of purchase. As of March 2023, 123 communities are eligible for the program. To evaluate existing evidence and research on the NNC program to inform policy decisions to improve the effectiveness of NNC. A scoping review of peer-reviewed articles was conducted in ten databases along with a supplemental grey literature search of government and non-government reports published between 2011 and 2022. The search yielded 172 publications for screening, of which 42 were included in the analysis. Narrative thematic evidence synthesis yielded 104 critiques and 341 recommendations of the NNC program across eight themes. The most-identified recommendations focus on transparency, communication, and support for harvesting, hunting, and community food initiatives. This review highlights recommendations informed by the literature to address critiques of the NNC program to improve food security, increase access to perishable and non-perishable items, and support community-based food initiatives among eligible communities. The review also identifies priority areas for future policy directions such as additional support for education initiatives, communication and transparency amidst program changes, and food price regulations.

Complicated Pleural Infection is Associated With Prolonged Recovery and Reduced Functional Ability.

BACKGROUND: Management of complicated pleural infections (CPIs) had historically been surgical; however, following the publication of the second multicenter intrapleural sepsis trial (MIST-2), combination tissue plasminogen (tPA) and dornase (DNase) offers a less invasive and effective treatment. Our aim was to assess the quality of life (QOL) and functional ability of patients' recovery from a CPI managed with either intrapleural fibrinolytic therapy (IPFT) or surgery. METHODS: We identified 565 patients managed for a CPI between January 1, 2013 and March 31, 2018. There were 460 patients eligible for contact, attempted through 2 phone calls and one mailer. Two questionnaires were administered: the Short Form 36-Item Health Survey (SF-36) and a functional ability questionnaire. RESULTS: Contact was made in 35% (159/460) of patients, and 57% (90/159) completed the survey. Patients had lower QOL scores compared to average US citizens; those managed with surgery had higher scores in physical functioning (surgery: 80, IPFT: 70, P=0.040) but lower pain scores (surgery: 58, IPFT: 68, P=0.045). Of 52 patients who returned to work, 48% (25) reported an impact on their work effectiveness during recovery, similarly between management strategies (IPFT: 50%, 13/26 vs. surgery: 46%, 12/26; P=0.781). CONCLUSION: Patients with a CPI had a lower QOL compared with average US citizens. Surgically managed patients reported improved physical functioning but worse pain compared with patients managed with IPFT. Patients returned to work within 4 weeks of discharge, and nearly half reported their ability to work effectively was impacted by their recovery. With further research into recovery timelines, patients may be appropriately counselled for expectations.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy study: Outcomes and risk factors of conversion during minimally invasive lobectomy.

OBJECTIVE: Conversion to thoracotomy continues to be a concern during minimally invasive lobectomy. The aim of this propensity-matched cohort study is to analyze the outcomes and risk factors of intraoperative conversion during video-assisted thoracoscopic surgery (VATS) and robotic lobectomy (RL). METHODS: Data from consecutive lobectomy cases performed for clinical stage IA to IIIA lung cancer was retrospectively collected from the Pulmonary Open, Robotic, and Thoracoscopic Lobectomy study consortium of 21 institutions from 2011 to 2019. The propensity-score method of inverse-probability of treatment weighting was used to balance the baseline characteristics across surgical approaches. Univariate logistic regression models were applied to test risk factors for conversion. Multivariable logistic regression analysis was conducted using a stepwise model selection method. RESULTS: Seven thousand two hundred sixteen patients undergoing lobectomy were identified: RL (n = 2968), VATS (n = 2831), and open lobectomy (n = 1417). RL had lower conversion rate compared with VATS (3.6% vs 12.9%; P < .0001). In the multivariable regression model, tumor size and neoadjuvant therapy were the most significant risk factors for conversion, followed by prior cardiac surgery, congestive heart failure, chronic obstructive pulmonary disease, VATS approach, male gender, body mass index, and forced expiratory volume in 1 minute. Conversions for anatomical reasons were more common in VATS than RL (66.6% vs 45.6%; P = .0002); however, conversions for vascular reasons were more common in RL than VATS (24.8% vs 14%; P = .01). The rate of emergency conversions was comparable between RL and VATS (0.5% vs 0.7%; P = .25) with no intraoperative mortalities. CONCLUSIONS: Converted minimally invasive lobectomies were not associated with worse perioperative mortality compared with open lobectomy. Compared with VATS lobectomy, RL is associated with a lower probability of conversion in this propensity-score matched cohort study.

Effect of Intrapleural Fibrinolytic Therapy vs Surgery for Complicated Pleural Infections: A Randomized Clinical Trial.

Importance: There is a paucity of high-quality prospective randomized clinical trials comparing intrapleural fibrinolytic therapy (IPFT) with surgical decortication in patients with complicated pleural infections. Objective: To assess the feasibility, safety, and efficacy of an algorithm comparing tissue plasminogen activator plus deoxyribonuclease therapy with surgical decortication in patients with complicated pleural infections. Design, Setting, and Participants: This parallel pilot randomized clinical trial was performed at a single urban community-based center from March 1, 2019, to December 31, 2021, with follow-up for 90 days. Seventy-four individuals were screened and 48 were excluded. Twenty-six patients 18 years or older with clinical pleural infection and positive findings of pleural fluid analysis were included. Of these, 20 patients underwent randomized selection (10 in each group), and 6 were observed. Interventions: Intrapleural tissue plasminogen activator plus deoxyribonuclease therapy vs surgical decortication. Main Outcomes and Measures: Primary outcomes were the percentage of patients enrolled to study completion and multidisciplinary adherence. Secondary outcomes included the number of patients with and the reason for inadequate screening, screening to enrollment failures, time to accrual of 20 patients or the number accrued at 1 year, and clinical data. Results: Twenty-six patients were enrolled, 10 were randomized to each group, and 6 were observed. There was 100% enrollment to study completion in each treatment group, no protocol deviations, 2 minor protocol amendments, and no screening to enrollment failures. It took 32 months to enroll 26 patients. The 20 randomized patients had a median age of 57 (IQR, 46-65) years, were predominantly men (15 [75%]), and had a median RAPID (Renal, Age, Purulence, Infection Source, and Dietary Factors) score of 2 (IQR, 1-3). Treatment failure occurred in 1 patient and 2 crossover treatments occurred, all of which were in the IPFT group. Intraprocedure and postprocedure complications were similar between the groups. There were no reoperations or in-hospital deaths. Median duration of chest tube use was comparable in the IPFT (5 [IQR, 4-8] days) and surgery (4 [IQR, 3-5] days) groups (P = .21). Median hospital stay tended to be longer in the IPFT (11 [IQR, 4-18] days) vs surgery (5 [IQR, 4-6] days) groups, although the difference as not significantly different (P = .08). There were no 30-day readmissions or 30- or 90-day deaths. Conclusions and Relevance: In this pilot randomized clinical trial, the study algorithm was feasible, safe, and efficacious. This provides evidence to move forward with a multicenter randomized clinical trial. Trial Registration: ClinicalTrials.gov Identifier: NCT03873766.

Safety of adjuvant atezolizumab after pneumonectomy/bilobectomy in stage II-IIIA non-small cell lung cancer in the randomized phase III IMpower010 trial.

OBJECTIVE: Adjuvant atezolizumab is a standard of care after chemotherapy in completely resected stage II-IIIA programmed death ligand-1 tumor cell 1% or greater non-small cell lung cancer based on results from the phase III IMpower010 study. We explored the safety and tolerability of adjuvant atezolizumab by surgery type in IMpower010. METHODS: Patients had completely resected stage IB-IIIA non-small cell lung cancer (Union Internationale Contre le Cancer/American Joint Committee on Cancer, 7th Ed), received up to four 21-day cycles of cisplatin-based chemotherapy, and were randomized 1:1 to receive atezolizumab 1200 mg every 3 weeks (≤16 cycles or 1 year) or best supportive care. Adverse events and clinical characteristics were investigated by surgery type (pneumonectomy/bilobectomy or lobectomy/sleeve lobectomy) in the randomized stage II-IIIA population who received 1 or more atezolizumab dose or with 1 or more postbaseline assessment (safety evaluable) for best supportive care. RESULTS: Overall, 871 patients comprised the safety-evaluable randomized stage II-IIIA population. In the atezolizumab arm, 23% (100/433) received pneumonectomy/bilobectomy and 77% (332/433) received lobectomy/sleeve lobectomy. Atezolizumab discontinuation occurred in 32% (n = 32) and 35% (n = 115) of the pneumonectomy/bilobectomy and lobectomy/sleeve lobectomy groups, respectively. Grade 3/4 adverse events were reported in 21% (n = 21) and 23% (n = 76) of patients in the atezolizumab arms in the pneumonectomy/bilobectomy and lobectomy/sleeve lobectomy groups, respectively. In the atezolizumab arms of the surgery groups, 13% (n = 13) and 17% (n = 55) had an adverse event leading to hospitalization. Atezolizumab-related adverse events leading to hospitalization occurred in 5% (n = 5) and 7% (n = 23) of the surgery groups. CONCLUSIONS: These exploratory findings support use of adjuvant atezolizumab after platinum-based chemotherapy in patients with completely resected stage II-IIIA programmed death ligand-1 tumor cell 1% or more non-small cell lung cancer, regardless of surgery type.

Therapeutic advances in non-small cell lung cancer.

Despite decades of research, therapeutic advances in non-small cell lung cancer (NSCLC) have progressed at a painstaking slow rate with few improvements in standard surgical resection for early stage disease and chemotherapy or radiotherapy for patients with advanced disease. In the past 18 months, however, we seemed to have reached an inflexion point: therapeutic advances that are centred on improvements in the understanding of patient selection, surgery that is undertaken through smaller incisions, identification of candidate mutations accompanied by the development of targeted anticancer treatments with a focus on personalised medicine, improvements to radiotherapy technology, emergence of radiofrequency ablation (RFA), and last but by no means least, the recognition of palliative care as a therapeutic modality in its own right. The contributors to this review are a distinguished international panel of experts who highlight recent advances in each of the major disciplines.