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The large burden of COVID-19 on health care systems worldwide has raised concerns among medical oncologists about the impact of COVID-19 on the diagnosis and treatment of lung cancer patients. In this retrospective cohort study, we investigated the impact of COVID-19 on lung cancer diagnosis and treatment before and during the COVID-19 era. New lung cancer diagnoses decreased by 34.7% during the pandemic with slightly more advanced stages of disease, there was a significant increase in the utilization of radiosurgery as the first definitive treatment, and a decrease in both systemic treatment as well as surgery compared to the pre-COVID-19 era. There was no significant delay in starting chemotherapy and radiation treatment during the pandemic compared to pre-COVID-19 time. However, we observed a delay to lung cancer surgery during the pandemic time. COVID-19 seems to have had a major impact at our lung cancer center on the diagnoses and treatment patterns of lung cancer patients. Many oncologists fear that they will see an increase in newly diagnosed lung cancer patients in the coming year. This study is still ongoing and further data will be collected and analyzed to better understand the total impact of the COVID-19 pandemic on our lung cancer patient population.

This position statement aims to provide rapid guidance for those performing bronchoscopy in the pediatric and adult populations during the COVID-19 pandemic. These recommendations are based on the ...

Radiotherapy (rt) plays an important role in the treatment of lung cancer. One of the most common comorbidities in patients with lung cancer is pulmonary emphysema. The literature offers conflicting data about whether emphysema increases the occurrence and severity of radiation pneumonitis (rp). As a result, whether high doses of rt (with curative intent) should be avoided in patients with emphysema is still unclear. We measured the documented incidence of rp in patients with and without emphysema who received curative radiation treatment. This retrospective cohort study considered patients in the lung cancer clinical database of the Peter Brojde Lung Cancer Centre. Data from the database has been used previously for research studies, including a recent publication about emphysema grading, based on the percentage of lung occupied by emphysema on computed tomography (ct) imaging. Using previously published methods, chest ct imaging for 498 patients with lung cancer was scored for the presence of emphysema. The analysis considered 114 patients who received at least 30 Gy radiation. Of those 114 patients, 64 (56%) had emphysema, with approximately 23% having severe or very severe disease. The incidence of rp was 34.4% in patients with emphysema (n = 22) and 32.0% in patients with no emphysema (n = 16, p = 0.48). No difference in the incidence of rp was evident between patients with various grades of emphysema (p = 0.96). Similarly, no difference in the incidence of rp was evident between the two treatment protocols&mdash, that is, definitive rt 17 (37%) and combined chemotherapy&ndash, rt 21 (31%, p = 0.5). In our cohort, the presence of emphysema on chest ct imaging was not associated with an increased risk of rp. That finding suggests that patients with lung cancer and emphysema should be offered rt when clinically indicated. However, further prospective studies will be needed for confirmation.

Introduction PD-L1 expression by immunohistochemistry (IHC) testing with Tumor Proportion Score (TPS) ≥50% and ≥1% is required to be eligible for first- and second-line Pembrolizumab treatment for metastatic non-small cell lung cancer (NSCLC) respectively. Stage IV NSCLC often presents with metastasis to multiple distant sites which are easily accessible for biopsy. Knowing whether PD-L1 IHC TPS can be indifferently measured from different metastatic site is therefore an important clinical question. In this study, we evaluated PD-L1 expression in NSCLC from varied distant metastatic sites. Methods A total of 580 NSCLC specimens of distant metastases were retrieved for study, including 35 paired samples from two different metastatic sites. The metastatic sites included brain, bone, remote lymph nodes, serous membranes (pleura, pericardium and peritoneum), extra-thoracic solid organs and skin/soft tissues. The samples were cytology cell blocks, small biopsies or surgical resections. IHC was performed using Dako PD-L1 IHC 22C3 pharmDx. A total of 100 viable tumor cells was required for adequacy. TPS ≥ 50% and 1–49% were defined as high and low PD-L1 expression respectively. Results PD-L1 TPS scores were not significantly different across a range of distant metastatic sites nor between metastases in paired samples. Conclusion Our results suggest that the PD-L1 TPS scoring is similar across different metastatic sites and any site biopsied will yield necessary information for guiding clinical management.

The use of immune checkpoint inhibitors has dramatically improved outcomes for patients with advanced melanoma and other malignancies. Checkpoint inhibitors are associated with a unique set of toxicities collectively known as immune-related adverse events, the incidence of which is rising in parallel with their increasing use in clinical practice. Immune-related adverse events are widely variable in their presentation and can affect virtually any organ system in the body. Sarcoid-like reactions in patients being treated with immune checkpoint inhibitors are rare and are typically multisystemic in nature with isolated pulmonary involvement representing only a small minority of cases reported in the literature. Herein we describe 2 patients who developed progressively enlarging lymphadenopathy while receiving checkpoint inhibitors for metastatic melanoma. Both patients were initially noted to have an excellent clinical response to immunotherapy but their treatment was interrupted pending further investigation as they were suspected to have progressive disease. They were ultimately diagnosed with sarcoid-like reactions after an endobronchial ultrasound-guided lymph node biopsy revealed noncaseating granulomas and were able to resume their immunotherapy without any further interventions or negative effect on their disease course. These 2 cases illustrate the importance of obtaining a tissue diagnosis when imaging reveals enlarging lymph nodes while on immunotherapy for solid malignancies as the differential diagnosis includes benign entities such as sarcoid-like reactions in addition to disease progression. Timely diagnosis through minimally invasive tissue sampling techniques, such as endobronchial ultrasound, can help rule out malignant etiologies of lymphadenopathy and minimize interruptions in treatment.

There exists a well-established association between sarcoidosis and many solid and hematologic malignancies however it is a less frequently described phenomenon in patients with renal cell carcinoma. Moreover the majority of described cases presented with local sarcoid-like reactions in close proximity to the tumor with comparatively few reports of more distant disease. Given the relatively low number of cases there remains a great deal of uncertainty surrounding the clinical behaviour of sarcoidosis in the setting of renal cell carcinoma. We report the case of a patient with surgically resected renal cell carcinoma who, several years later, developed bilateral pulmonary nodules, intra-thoracic lymphadenopathy as well as splenic, hepatic and osseous lesions. After extensive investigation, culminating in video-assisted thoracoscopic surgical resection, he was found to have sarcoidosis. He remained asymptomatic for many years before being diagnosed with cardiac sarcoidosis, which was found to be inactive and did not require any treatment. Both his sarcoidosis and underlying renal cell carcinoma have remained in remission to date. This case highlights the variable behaviour of sarcoidosis in these patients and underscores the importance of obtaining an accurate tissue diagnosis in the setting of suspected metastatic disease. Additionally, it underscores the importance of close monitoring and long-term follow up as these patients may develop significant organ involvement, even many years after diagnosis. Interestingly the patient's renal cell carcinoma remained in remission, raising questions about whether the development of sarcoidosis portends a better prognosis in patients with an underlying solid malignancy.

PD-L1 immunohistochemistry (IHC) testing is usually carried out on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay.A total of 1419 consecutive cases of non-small-cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as 1%, 1%-49% and ≥50% tumor cells. A total of 100 viable tumor cells were required for adequacy.Of the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P = 0.04), and 29% of surgical resections (P = 0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS ≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001).Our results show that when the TPS ≥50% is used as the end point, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.

Objective Increasing numbers of cancer patients are using Chinese herbs (CHs). However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH formula. The primary objective of this study was to establish the acceptability of taking a standardized CH formula for patients with advanced lung cancer. The secondary objective was to identify any toxicities attributable to this CH formula and to measure changes in quality of life. Methods A single-arm, prospective study of a 6-week intervention with a selected CH formula in 15 patients with stage 4 nonsmall-cell lung cancer (NSCLC, Seventh American Joint Committee on Cancer TNM staging system). Results Patients with advanced lung cancer were interested in using the CH formula. Completion (93%) and adherence (98%) levels were very high and most patients perceived the CH treatment as easy to take and were willing to take the CHs used in the study again if it was available. About half of the patients reported adverse events, all of which were mild (Grade 1 or 2) and only a small minority (8%) were potentially related to CHs. No biochemical or hematological evidence of toxicity was observed. Overall, there were improvement in quality of life, and reduced feelings of tiredness and sleepiness. Conclusion This study provides preliminary evidence that short-term use of a carefully selected and prepared CH formula in patients with stage 4 NSCLC is acceptable and safe.

Objective: The literature supports an increased risk of malignancy in systemic sclerosis, including lung cancer. Our objective was to identify potential independent predictors of lung cancer risk in systemic sclerosis. Methods: We used a cohort of 1560 systemic sclerosis patients from the Canadian Scleroderma Research Group, enrolled from 2004 and followed for a maximum of 11 years. Time to lung cancer was calculated from the onset of the first non-Raynaud’s symptoms. Baseline demographic, clinical, and serological characteristics of patients with and without lung cancer were compared. Cox proportional hazards models were used to estimate the effects of demographic variables, exposure to smoking, disease duration, disease subset (diffuse vs limited), immunosuppressant drug exposure, and presence of interstitial lung disease on the risk of lung cancer. Results: Over the 5519 total person-years of follow-up, 18 SSc patients were diagnosed with lung cancer after cohort entry (3.2 cancers per 1000 person-years). In univariate comparisons, cancer cases were more likely to be male, to have a smoking history, and to have interstitial lung disease than non-cases. In multivariate analysis, interstitial lung disease was independently associated with the risk of lung cancer (hazard ratio: 2.95, 95% confidence interval: 1.10–7.87). Conclusion: In addition to known demographic (male sex) and lifestyle risk factors (smoking), interstitial lung disease is an independent risk factor for lung cancer in systemic sclerosis. These results have implications for lung cancer screening in systemic sclerosis.

e20611 Background: An increasing number of patients with lung cancer use natural products concurrently with conventional treatments, one of which is curcumin, or diferuloylmethane, the main ingredient in the popular spice known as curry. Curcumin has been shown to have anti-carcinogenic effects on human lung cancer cell lines and in vivo models, as well as the potential to modulate all three known pathways accounting for resistance to EGFR-TKIs. More specifically, curcumin dose-dependently suppresses EGFR expression, reduces transactivation of the MET oncogene, and reduces inflammation in the tumor microenvironment by selectively inhibiting TGF-β, IL-6, C-reactive protein (CRP) as well as TNF-α. Despite these promising findings, no studies have yet assessed the safety of introducing curcumin alongside EGFR-TKIs in a lung cancer population. Methods: We performed a phase 1 open prospective cohort study to assess the safety and feasibility of using an enhanced bioavailable formulation of curcumin (CURCUViva TM at 80 mg/ 1 capsule per day) approved and licensed by Health Canada (NPN 80027414) in conjunction with an EGFR-TKI in patients with advanced NSCLC (ClinicalTrials.gov: NCT02321293). The primary objective was to determine safety and feasibility. Exploratory objectives were monitoring changes in health-related quality of life using the standardized FACT-L questionnaire and evaluating anti-inflammatory properties of curcumin by measuring CRP. Results: 55 patients were approached, of whom 75% were interested in using curcumin. Completion rate (80%) and adherence (82%) levels were very high; most patients perceived the product as easy to take and were willing to take it again if it were available. Nine patients refused to participate solely due to frequent clinic visits. A total of 37 adverse events were reported, all of which were mild (Grade 1 or 2). The vast majority were pre-existing and related to TKI treatment. No biochemical or hematological evidence of toxicity was observed. Overall, there was improvement in quality of life, and improvement in the LCS of the FACT-L (p = 0.06). There was no significant change in CRP levels. Conclusions: This study provides preliminary evidence that short-term use of curcumin in EGFR-positive patients treated with TKIs is feasible and safe. We report high treatment adherence and improved quality of life with curcumin. These findings, as well as efficacy data and the effect of curcumin on other inflammation-associated biomarkers, warrant investigation in a larger phase 2 study. Clinical trial information: NCT02321293.

IntroductionMalignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial cells lining the pleura. Most commonly, it presents as a unilateral pleural effusion. MPM usually develops on the parietal pleural surface and later spreads to the visceral pleura. Visceral pleural involvement entails a more advanced disease stage and is therefore an important prognostic factor. Pleural fluid (PF) cytology is often the first diagnostic test, but the sensitivity in the literature varies from 4 to 77%. However, no data are available for the diagnostic yield of cytological PF analysis with regard to the visceral pleural involvement. The aim of this study is to assess whether PF cytological yield is related to the extent and pattern of visceral pleural invasion, as assessed by thoracoscopy.MethodsMedical records of all patients who underwent thoracoscopy for suspicion of malignant pleural effusion from two hospitals were reviewed. Patients were selected if they initially underwent a diagnostic thoracentesis before thoracoscopy, if visceral pleural appearance during thoracoscopy was clearly documented, and MPM confirmed on pleural tissue biopsy.ResultsSeventy-five patients were selected. Forty-five patients had a positive PF cytology on thoracentesis, while 30 had a negative PF cytology. Thoracoscopy showed parietal pleural invasion in all subjects. Interestingly, 82% of patients with positive PF cytology on thoracentesis had visceral pleural involvement, whereas only 30% of those with negative PF cytology had visceral pleural invasion. The pattern of visceral pleural invasion consisted of pleural masses, nodules, or pleural thickening. A multivariate regression identified visceral pleural invasion (p < 0.001) as the only independent factor predicting the positivity of cytology on pleural effusion.ConclusionIn epithelioid MPM, PF cytological yield was significantly higher in patients with visceral pleural invasion assessed by thoracoscopy. Positive PF cytology is associated with a more advanced disease.

Background:Malignant pleural effusion (MPE) is encountered at an advanced stage of disease progression and often heralds a poor prognosis. The most reliable predictive factor of survival in such patients is the primary tumor. Thoracoscopy is often performed for accurate diagnosis and/or thoracoscopic talc insufflation as a therapeutic modality. It remains unknown whether pleural tumor burden, as visualized on thoracoscopy, has potential prognostic value. The objective of this study was to determine the prognostic accuracy of pleural tumor extent and localization (parietal, visceral, or diaphragmatic involvement), as assessed during medical thoracoscopy.Methods:Medical records of all patients who underwent thoracoscopy for suspicion of MPE between 2001 and 2008 at a tertiary care referral hospital were reviewed. Patients were included if pleural metastatic invasion was confirmed on tissue biopsy and survival status ascertained.Results:Four hundred twenty-one patients underwent diagnostic or therapeutic medical thoracoscopy at our referral center. Among them, 122 had confirmed metastatic pleural spread, but survival data were lacking in 15. Primary tumor consisted of non-mall cell lung cancer in 56, breast cancer in 23, melanoma in eight, and other malignancies in 20. Median survival of the entire population was 9.4 months. On univariate analysis, the following variables were significantly associated with reduced median overall survival: pleural metastatic melanoma, age less than 60 years, bloody MPE, extensive pleural adhesions, and widespread visceral pleural nodules (p < 0.05). On multivariate analysis, only melanoma as a primary tumor, pleural fluid appearance and extent of pleural adhesions remained independent and significant predictors of survival.Conclusion:No significant association was found between the extent or localization of pleural tumor burden and overall survival.

A 66-year-old man presented with acute respiratory distress due to a tracheal tumor involving the posterior wall of the upper trachea, with nearly complete airway obstruction. Partial debulking of the tumor's endoluminal component, via rigid bronchoscopy and yttrium-aluminum-perovskite laser, allowed timely and effective airway restoration. The diagnosis was benign tracheal glomus tumor. Two weeks later, elective tracheal sleeve resection with end-to-end anastomosis allowed complete resection of the lesion. No tumor recurrence was found at 21-month follow-up. We describe the multidisciplinary management of this extremely rare tracheal tumor, and review its features.

Objective To determine whether the use of angiotensin converting enzyme inhibitors (ACEIs), compared with use of angiotensin receptor blockers, is associated with an increased risk of lung cancer.Design Population based cohort study.Setting United Kingdom Clinical Practice Research Datalink.Participants A cohort of 992 061 patients newly treated with antihypertensive drugs between 1 January 1995 and 31 December 2015 was identified and followed until 31 December 2016Main outcome measures Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident lung cancer associated with the time varying use of ACEIs, compared with use of angiotensin receptor blockers, overall, by cumulative duration of use, and by time since initiation.Results The cohort was followed for a mean of 6.4 (SD 4.7) years, generating 7952 incident lung cancer events (crude incidence 1.3 (95% confidence interval 1.2 to 1.3) per 1000 person years). Overall, use of ACEIs was associated with an increased risk of lung cancer (incidence rate 1.6 v 1.2 per 1000 person years; hazard ratio 1.14, 95% confidence interval 1.01 to 1.29), compared with use of angiotensin receptor blockers. Hazard ratios gradually increased with longer durations of use, with an association evident after five years of use (hazard ratio 1.22, 1.06 to 1.40) and peaking after more than 10 years of use (1.31, 1.08 to 1.59). Similar findings were observed with time since initiation.Conclusions In this population based cohort study, the use of ACEIs was associated with an increased risk of lung cancer. The association was particularly elevated among people using ACEIs for more than five years. Additional studies, with long term follow-up, are needed to investigate the effects of these drugs on incidence of lung cancer.

Background Airway anastomotic complications remain a major cause of morbidity and mortality after lung transplantation (LT). Few data are available with regard to the use of silicone stents for these airway disorders. The aim of this retrospective study was to evaluate the clinical efficacy and safety of silicone stents for such an indication. Methods Data of adult lung transplant recipients who had procedures performed between January 1997 and December 2007 at our institution were reviewed retrospectively. We included patients with post-transplant airway complications who required bronchoscopic intervention with a silicone stent. Results In 17 of 117 (14.5%) LT recipients, silicone stents were inserted at a mean time of 165 (range 5 to 360) days after surgery in order to palliate 23 anastomotic airway stenoses. Symptomatic improvement was noted in all patients, and mean forced expiratory volume in 1 second (FEV 1 ) increased by 672 ± 496 ml ( p n = 10), mucus plugging ( n = 7) and migration ( n = 7), which were of mild to moderate severity and were successfully managed endoscopically. Mean stent duration was 266 days (range 24 to 1,407 days). Successful stent removal was achieved in 16 of 23 cases (69.5%) without recurrence of stenosis. Overall survival was similar in patients with and without airway complications ( p = 0.36). Conclusions Silicone stents allow clinical and lung function improvement in patients with LT-related airway complications. Stent-related complications were of mild to moderate severity, and were appropriately managed endoscopically. Permanent resolution of airway stenosis was obtained in most patients, allowing definitive stent removal without recurrence.

Refractory hepatic hydrothorax poses a challenging therapeutic dilemma, as treatment options are limited. Herein, we describe the case of a 48-year-old lady with advanced cirrhosis and recurrent transudative pleural effusion despite a sodium-restricted diet, optimal diuretic therapy and transjugular intrahepatic portosystemic shunt. Given the patient’s platelet and coagulation disorders, thoracoscopic pleurodesis was deemed unsafe. Instead, a tunneled pleural catheter (PleurX®) was inserted under local anesthesia. Pleural drainage was achieved at the time of catheter placement and subsequently according to the patient’s symptoms. Symptomatic improvement and gradual decrease of drainage volumes were noted. Six months following placement of PleurX, methicillin-resistant Staphylococcus aureus cellulitis at the insertion site prompted catheter removal. No pleural effusion was seen on chest X-ray at that time. Subsequent follow-up revealed spontaneous pleurodesis, as no recurrence of pleural effusion was seen over a 6-month follow-up period. Very few data are available with regard to the use of indwelling pleural catheters for benign transudative pleural effusion, and more specifically hepatic hydrothorax. Herein, we present this novel potential indication of the indwelling pleural catheter and illustrate the successful clinical outcome.

An elderly gentleman with a chronic cough was found to have a large midtracheal lesion on computed tomography scan. Endotracheal extirpation with an electrocautery snare successfully removed the lesion. Histologic and immunohistochemical analyses revealed the lesion to be a spindle cell lipoma. We provide herein the case presentation and management, the differential diagnosis, and an overview of spindle cell lipoma.

e20646Background: Epidermal growth factor receptor (EGFR) mutation is a strong predictor of response to EGFR tyrosine kinase inhibitors (TKI). However, response duration is variable. The predictive...

Introduction Significant differences in outcome are observed among lung cancer patients belonging to the same tumor node metastasis stage, suggesting phenotypic heterogeneity beyond this staging algorithm. We used a cluster analysis approach to classify patients into distinct phenotypes, and we attempted to validate the clinical relevance of these phenotypes by comparing outcome. Methods We formed a cohort of all stage I to III non–small-cell lung cancer patients seen between January 2004 and October 2010 in a cancer center and followed until death or last follow-up appointment, with prospectively collected data on clinical and tumor characteristics. Multiple correspondence analysis was followed by hierarchical clustering to form homogenous clusters of patients. Overall survival and disease-free survival estimates were compared among clusters. Results The cohort included 367 patients (mean follow-up of 2.5 years), 173 of whom died during that period (191 deaths per 1000 person-years). A four-cluster model was identified, revealing distinct phenotypes with respect to baseline characteristics. Hazard ratios for mortality were 8.1, 5.0, and 3.7 (all statistically significant) for clusters 2, 1, and 3, respectively, when compared with cluster 4—with the most favorable outcome. Conclusion Staging of patients with non–small-cell lung cancer for prognostic purposes may be improved by considering phenotypes that exhibit significant differences in clinical course and outcome.