Introduction: Medical assistance in dying (MAiD) was legalized in Canada in 2016. Cancer accounts for 60% to 65% of MAiD cases. Lung cancer, the most common cause of cancer death, is expected to makeup a large number of MAiD cases. Lung cancer treatment has advanced in recent years; however, involvement of oncology specialists and use of systemic therapy in patients who receive MAiD are unknown.

Methods: All patients with lung cancer referred to the Champlain Regional MAiD Program from June 17, 2016, to November 30, 2020, were reviewed. Baseline demographics, diagnostic, referral, and treatment details were collected by retrospective review. Coprimary end points were the proportion of patients who met a medical oncologist or who received systemic therapy.

Results: During the study period, 255 patients with cancer underwent MAiD. Of these, 45 (17.6%) had lung cancer, comprising our final study population. Baseline characteristics: median age 72 years, 64% female, 85% former or current smoking history, 82% non-small cell, 4% small cell, and 13% clinical diagnosis without biopsy. Most patients (78%) were seen by a medical oncologist, though only 16 (36%) received systemic therapy for advanced disease. In subpopulations of interest, 45% of patients with programmed death-ligand 1 greater than or equal to 50% received immunotherapy and 75% with an oncogenic driver mutation received targeted therapy. There were 26 patients (58%) who had a documented discussion with their oncologist regarding the transition to best supportive care.

Conclusions: Most patients with lung cancer are assessed by an oncology specialist before MAiD, though less than half received systemic therapy. Among patients with more treatable forms of lung cancer, many patients still undergo MAiD without accessing, or in some cases being assessed for, these treatment options.

Keywords: Assisted suicide; Canada; End of life care; Lung cancer.

We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each component suggested that mutations in RB1, TP53, and SMAD4 and apparent loss of heterozygosity of TP53 and SMAD4 accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including PTEN, MST1R, and PIK3CA were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma. Combined DNA and RNA analysis using Todai OncoPanel revealed that transdifferentiation to different pathologic subtypes occurred in a single tumor through the accumulation of gene mutations.

Keywords: Case report; Clonal analysis; EGFR; Gene mutations; NSCLC; Pathologic subtypes.

Purpose: This study aims to determine if the presence of specific clinical and computed tomography (CT) patterns are associated with epidermal growth factor receptor (EGFR) mutation in patients with non-small cell lung cancer.

Methods: A systematic literature review and meta-analysis was carried out in 6 databases between January 2002 and July 2021. The relationship between clinical and CT patterns to detect EGFR mutation was measured and pooled using odds ratios (OR). These results were used to build several mathematical models to predict EGFR mutation.

Results: 34 retrospective diagnostic accuracy studies met the inclusion and exclusion criteria. The results showed that ground-glass opacities (GGO) have an OR of 1.86 (95%CI 1.34 -2.57), air bronchogram OR 1.60 (95%CI 1.38 - 1.85), vascular convergence OR 1.39 (95%CI 1.12 - 1.74), pleural retraction OR 1.99 (95%CI 1.72 - 2.31), spiculation OR 1.42 (95%CI 1.19 - 1.70), cavitation OR 0.70 (95%CI 0.57 - 0.86), early disease stage OR 1.58 (95%CI 1.14 - 2.18), non-smoker status OR 2.79 (95%CI 2.34 - 3.31), female gender OR 2.33 (95%CI 1.97 - 2.75). A mathematical model was built, including all clinical and CT patterns assessed, showing an area under the curve (AUC) of 0.81.

Conclusions: GGO, air bronchogram, vascular convergence, pleural retraction, spiculated margins, early disease stage, female gender, and non-smoking status are significant risk factors for EGFR mutation. At the same time, cavitation is a protective factor for EGFR mutation. The mathematical model built acts as a good predictor for EGFR mutation in patients with lung adenocarcinoma.

Keywords: ALK, anaplastic lymphoma kinase mutation; AUC, area under the curve; Biopsy; CT, computed tomography; Computed tomography; EGFR TKI, epidermal growth factor receptor tyrosine kinase inhibitors; EGFR mutation; EGFR, epidermal growth factor; FN, False negatives; FP, False positives; GGO, Ground glass opacities; KRAS, Kirsten rat sarcoma viral oncogene homolog; Lung adenocarcinoma; Lung cancer; NSCLC, non-small cell lung carcinoma; Non-small cell lung cancer; OR, Odds ratios; PRISMA, Preferred Reporting Items for Systematic Review and Meta-analysis; QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies-2; ROC, Receiver Operating Characteristics; TN, True Negative; TP, True Positive.

Background: Lower survival rates for many cancer types correlate with changes in nuclear size/scaling in a tumor-type/tissue-specific manner. Hypothesizing that such changes might confer an advantage to tumor cells, we aimed at the identification of commercially available compounds to guide further mechanistic studies. We therefore screened for Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved compounds that reverse the direction of characteristic tumor nuclear size changes in PC3, HCT116, and H1299 cell lines reflecting, respectively, prostate adenocarcinoma, colonic adenocarcinoma, and small-cell squamous lung cancer. Results: We found distinct, largely nonoverlapping sets of compounds that rectify nuclear size changes for each tumor cell line. Several classes of compounds including, e.g., serotonin uptake inhibitors, cyclo-oxygenase inhibitors, β-adrenergic receptor agonists, and Na⁺/K⁺ ATPase inhibitors, displayed coherent nuclear size phenotypes focused on a particular cell line or across cell lines and treatment conditions. Several compounds from classes far afield from current chemotherapy regimens were also identified. Seven nuclear size-rectifying compounds selected for further investigation all inhibited cell migration and/or invasion. Conclusions: Our study provides (a) proof of concept that nuclear size might be a valuable target to reduce cell migration/invasion in cancer treatment and (b) the most thorough collection of tool compounds to date reversing nuclear size changes specific to individual cancer-type cell lines. Although these compounds still need to be tested in primary cancer cells, the cell line-specific nuclear size and migration/invasion responses to particular drug classes suggest that cancer type-specific nuclear size rectifiers may help reduce metastatic spread.

The gastrointestinal tract is one of the locations that lung cancers cause metastasis. A 70-year-old male underwent right lower lobectomy while presenting fecal occult blood with a preoperative colonoscopy showing colon polyps as the cause. The pathological diagnosis was pleomorphic carcinoma of the lung, with stage pT3N0M0. Seven months after the lung surgery, the patient presented with sudden-onset abdominal pain and severe anemia. Computed tomography scanning revealed a large mass in the abdominal cavity, and subsequent intestinal endoscopy demonstrated jejunum tumors. Partial jejunum resection was successfully performed. The patient developed multiple peritoneal nodules suggesting metastatic tumors but well responded to an immune checkpoint inhibitor. It can be challenging to diagnose gastrointestinal metastasis in routine radiography; therefore, endoscopic examination, including the small intestine, might be an important option when a lung cancer patient with advanced clinical stage presents with abdominal symptoms, including fecal occult blood.

There is no consensus on the choice of systemic and ophthalmic treatment for patients who develop ocular toxicity with erlotinib in the few cases reported previously. Various ocular complications related to erlotinib have been reported, with one of the most serious being corneal perforation. Our patient was at risk of potential corneal perforation because of severe cicatricial ectropion and diffuse punctate corneal epitheliopathy. Therefore, erlotinib treatment was temporarily discontinued with the approval of the oncology department and the patient was closely followed. She was prescribed steroid eye ointment, single-use preservative-free artificial tears, and eye lubricant gel to protect the ocular surface. On day 4 of treatment, the patient's findings were significantly improved. After 1 week, the cicatricial ectropion had dramatically improved and the patient's complaints were completely resolved. To our knowledge, there is no case report of a patient with both ocular toxicity after long-term use that shows dramatic improvement with drug cessation, and severe cicatricial ectropion affecting the entire lower eyelid. Here, we described a patient who used erlotinib for 3 years due to non-small cell lung cancer and developed severe cicatricial ectropion which improved dramatically within one week of temporarily discontinuing erlotinib and discussed the possible reasons. Although ocular complications with erlotinib are usually encountered early in treatment, it should be kept in mind that erlotinib-related ocular complications may also arise with long-term use.

Keywords: Ectropion; cicatricial ectropion; erlotinib; long-term erlotinib; lung cancer; ocular toxicity.

Increased remodeling of the extracellular matrix in malignant tumors has been shown to correlate with tumor aggressiveness and a poor prognosis. This remodeling involves degradation of the original extracellular matrix (ECM) and deposition of a new tumor-supporting ECM. The main constituent of the ECM is collagen and collagen turnover mainly occurs in a sequential manner, where initial proteolytic cleavage of the insoluble fibers is followed by cellular internalization of large well-defined collagen fragments for lysosomal degradation. However, despite extensive research in the field, a lack of consensus on which cell types within the tumor microenvironment express the involved proteases still exists. Furthermore, the relative contribution of different cell types to collagen internalization is not well-established. Here, we developed quantitative ex vivo collagen degradation assays and show that the proteases responsible for the initial collagen cleavage in two murine syngeneic tumor models are matrix metalloproteinases produced by cancer-associated fibroblasts and that collagen degradation fragments are endocytosed primarily by tumor-associated macrophages and cancer-associated fibroblasts from the tumor stroma. Using tumors from mannose receptor-deficient mice, we show that this receptor is essential for collagen-internalization by tumor-associated macrophages. Together, these findings identify the cell types responsible for the entire collagen degradation pathway, from initial cleavage to endocytosis of fragments for intracellular degradation.

Keywords: ATCC, American Type Culture Collection; CAF, cancer-associated fibroblast; CPM, counts per minute; CRC, colorectal cancer; Cancer-associated fibroblasts; Collagen degradation; Collagen endocytosis; ECM, extracellular matrix; ELISA, enzyme-linked immunosorbent assay; Extracellular matrix remodeling; FAP, fibroblast activation prot; FMO, fluorescence minus one; FSP-1, fibroblast-specific protein 1; IL, interleukin; LC, lung cancer; MMP, matrix metalloproteinase; MR, mannose receptor; Matrix metalloproteinases; NK, natural killer cell; OvC, ovarian cancer; PDGFR, platelet-derived growth factor receptor; TAM, tumor-associated macrophage; TME, tumor microenvironment; TNF, tumor necrosis factor; Tumor microenvironment; Tumor-associated macrophages; uPARAP, urokinase plasminogen activator receptor-associated protein; α-SMA, α-smooth muscle actin.

Introduction: The burden of chronic breathlessness on individuals, family, society and health systems is significant, and set to increase exponentially with population ageing, complex multimorbidity and coronavirus disease 2019 (COVID-19)-related disability. Breathlessness support services are effective; however, reach and access are limited. Delivering online breathlessness interventions may build capacity and resilience within health systems to tackle chronic breathlessness through supported self-management. The aim of this study was to explore accessibility and willingness of patients with chronic breathlessness to use an internet-based breathlessness self-management intervention (SELF-BREATHE).

Methods: Semi-structured telephone interviews were conducted with adults living with advanced malignant and non-malignant disease and chronic breathlessness (July to November 2020). Interviews were analysed using conventional and summative content analysis.

Results: 25 patients (COPD: n=13; lung cancer: n=8; interstitial lung disease (ILD): n=3; bronchiectasis: n=1) were interviewed: 17 male, median (range) age 70 (47-86) years and Medical Research Council dyspnoea score 3 (2-5). 21 patients had internet access. Participants described greater use, acceptance and normalisation of the internet since the advent of the COVID-19 pandemic. They described multifaceted internet use: functional, self-investment (improving health and wellbeing) and social. The concept of SELF-BREATHE was highly valued, and most participants with internet access were willing to use it. In addition to technical limitations, personal choice and perceived value of the internet were important factors that underpinned readiness to use online resources.

Conclusion: These findings suggest that patients living with chronic breathlessness that have access to the internet would have the potential to benefit from the online SELF-BREATHE intervention, if given the opportunity.

Background: Pulmonary inflammatory myofibroblastic tumor (PIMT) is an extremely rare disease. The aim of this study was to share the surgical outcomes of these tumors.

Methods: Patients who were operated for pulmonary myofibroblastic tumors between January 2005 and January 2021 were determined by retrospectively scanning patient files. Patients' demographic characteristics, tumor location, surgical techniques, and other parameters were obtained from the patient files. The KaplanMeier method was used for survival calculations, whereas the log-rank test was used for comparison of survival calculations.

Results: PIMTs were noted in 14 patients (0.12%) in a total of 11,108 thoracic procedures performed in our institution between January 2005 and January 2021. The mean age of the patients was 28.2 (range: 2-67) years. Of the patients, six were male and eight were female, with 50% (n = 7) aged under 18 years. A total of 17 surgical procedures were performed on 14 patients. One patient underwent pneumonectomy, two patients lobectomy, ten0 patients wedge resection, and one patient underwent debulking surgery. A total of 11 patients had complete surgery, whereas three patients had incomplete surgery. The 10-year overall survival was 84.6% and the 10-year disease-free survival (DFS) was 75.0%. Complete resection was found to be the only and significant factor that had an effect on survival (P = 0.004) and DFS (P = 0.012).

Conclusion: PIMTs are extremely rare. Complete surgery should be considered an effective factor in survival and DFS.

Keywords: Lung neoplasm; myofibroblastic tumor; pulmonary inflammatory myofibroblastic tumor; surgical treatment; survival.

Quantitative chemometric widefield endogenous fluorescence microscopy (CFM) maps the endogenous absolute chromophore concentration and spatial distribution in cells and tissue sections label-free from fluorescence color images under broadband excitation and detection. By quantifying the endogenous chromophores, including tryptophan, elastin, reduced nicotinamide adenine dinucleotide [NAD(P)H], and flavin adenine dinucleotide (FAD), CFM reveals the biochemical environment and subcellular structure. Here we show that the chromophore information entropy, marking its spatial distribution pattern of quantitative chemometric endogenous fluorescence at the microscopic scale, improves photonic lung cancer diagnosis with independent diagnostic power to the cellular metabolism biomarker. NAD(P)H and FAD's information entropy is found to decrease from normal to perilesional to cancerous tissue, whereas the information entropy for the redox ratios [FAD/tryptophan and FAD/NAD(P)H] is smaller for the normal tissue than both perilesional and cancerous tissue. CFM imaging of the specimen's inherent biochemical and structural properties eliminates the dependence on measurement details and facilitates robust, accurate diagnosis. The synergy of quantifying absolute chromophore concentration and information entropy achieves high accuracies for a three-class classification of lung tissue into normal, perilesional, and cancerous ones and a three-class classification of lung cancers into grade 1, grade 2, and grade 3 using a support vector machine, outperforming the chromophore concentration biomarkers.