The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the Classification of Residual Tumor After Resection for the Forthcoming (Ninth) Edition of the TNM Classification of Lung Cancer.

INTRODUCTION: The goal of surgical resection is to completely remove a cancer; it is useful to have a system to describe how well this was accomplished. This is captured by the residual tumor (R) classification, which is separate from the TNM classification that describes the anatomic extent of a cancer independent of treatment. The traditional R-classification designates as R0 a complete resection, as R1 a macroscopically complete resection but with microscopic tumor at the surgical margin, and as R2 a resection that leaves gross tumor behind. For lung cancer, an additional category encompasses situations in which the presence of residual tumor is uncertain. METHODS: This paper represents a comprehensive review of evidence regarding these R categories and the descriptors thereof, focusing on studies published after the year 2000 and with adjustment for potential confounders. RESULTS: Consistent discrimination between complete, uncertain, and incomplete resection is revealed with respect to overall survival. Evidence regarding specific descriptors is generally somewhat limited and only partially consistent; nevertheless, the data suggest retaining all descriptors but with clarifications to address ambiguities. CONCLUSION: On the basis of this review, the R-classification for the ninth edition of stage classification of lung cancer is proposed to retain the same overall framework and descriptors, with more precise definitions of descriptors. These refinements should facilitate application and further research.

Revisiting vitamin D status and supplementation for in-patients with intellectual and developmental disability in the North of England, UK.

AIMS AND METHOD: To re-evaluate vitamin D testing and supplementation among in-patients with intellectual and developmental disability (IDD) and examine any correlates with physical health conditions, including COVID-19. Records of all in-patients between January 2019 and July 2020 (n = 78) were examined for 25-hydroxyvitamin D (25(OH)D) level, ward area, supplementation status, test seasonality, medication and health status. RESULTS: The mean 25(OH)D level for supplemented (800 IU/day) patients was 75 nmol/L (s.d. = 20), compared with 40 nmol/L (s.d. = 19) in the non-supplemented group (P < 0.001). Thirty-eight percent of those who were in-patients during the first wave of the COVID-19 pandemic developed symptoms, but the small sample size could not establish vitamin D levels as a predictor of outcome. CLINICAL IMPLICATIONS: Vitamin D (800 IU/day) supplementation is effective but the adequacy of the nationally recommended dose of 400 IU/day is unclear. Links to COVID-19 merit further research.

500 Meters Is a Result of 6-Minute Walk Test Which Differentiates Patients with High and Low Risk of Postoperative Complications after Lobectomy-A Validation Study.

The 6-min walk test (6MWT) is a simple method of identifying patients with a high risk of postoperative complications. In this study, we internally validated the previously obtained threshold value of 500 m in the 6MWT as differentiating populations with a high and a low risk of postoperative complications after a lobectomy. Between November 2011 and November 2016, 624 patients who underwent a lobectomy and performed the 6MWT preoperatively entered this study. We compared the complication rates of two groups of patients-those who walked more than and those who walked less than 500 m. The patients who did not reach the distance of 500 m in the 6MWT were older (70 vs. 63 years p < 0.001), had worse pulmonary function tests (FEV1% 84 vs. 88 p = 0.041) and had a higher Charlson Comorbidity Index (p < 0.001). The patients who had a worse result in the 6MWT had a higher complication rate (52% vs. 42% p = 0.019; OR: 1.501 95% CI: 1.066-2.114) and a longer median postoperative hospital stay (7 vs. 6 days p = 0.010). In a multivariate analysis, the result of the 6MWT and pack-years proved to independently influence the risk of postoperative complications. This internal validation study confirms that 500 m is a result of the 6MWT which differentiates patients with a higher risk of postoperative complications and a prolonged hospital stay after a lobectomy.

Performance of various risk prediction models in a large lung cancer screening cohort in Gdansk, Poland-a comparative study.

BACKGROUND: Optimal selection criteria for the lung cancer screening programme remain a matter of an open debate. We performed a validation study of the three most promising lung cancer risk prediction models in a large lung cancer screening cohort of 6,631 individuals from a single European centre. METHODS: A total of 6,631 healthy volunteers (aged 50-79, smoking history ≥30 pack-years) were enrolled in the MOLTEST BIS programme between 2016 and 2018. Each participant underwent a low-dose computed chest tomography scan, and selected participants underwent a further diagnostic work-up. Various lung cancer prediction models were applied to the recruited screenees, i.e., (I) Tammemagi's Prostate, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012), (II) Liverpool Lung Project (LLP) model, and (III) Bach's lung cancer risk model. Patients (I) with 6-year lung cancer probability ≥1.3% were considered as high risk in PLCOm2012 model, (II) in LLP model with 5-year lung cancer probability ≥5.0%, and (III) in Bach's model with 5-year lung cancer probability ≥2.0%. The particular model cut-off values were employed to the cohort to evaluate each model's performance in the screened population. RESULTS: Lung cancer was diagnosed in 154 (2.3%) participants. Based on the risk estimates by PLCOm2012, LLP and Bach's models there were 82.4%, 50.3% and 19.8% of the MOLTEST BIS participants, respectively, who fulfilled the above-mentioned threshold criteria of a lung cancer development probability. Of those detected with lung cancer, 97.4%, 74.0% and 44.8% were eligible for screening by PLCOm2012, LLP and Bach's model criteria, respectively. In Tammemagi's risk prediction model only four cases (2.6%) would have been missed from the group of 154 lung cancer patients primarily detected in the MOLTEST BIS. CONCLUSIONS: Lung cancer screening enrollment based on the risk prediction models is superior to NCCN Group 1 selection criteria and offers a clinically significant reduction of screenees with a comparable proportion of detected lung cancer cases. Tammemagi's risk prediction model reduces the proportion of patients eligible for inclusion to a screening programme with a minimal loss of detected lung cancer cases.

Physiological Biomarkers Assessed by Low-Tech Exercise Tests Predict Complications and Overall Survival in Patients Undergoing Pneumonectomy Due to Lung Cancer.

Due to its debilitating character pneumonectomy this is last-resort procedure. Preoperative results of the 6-min walking test (6MWT) help to identify high risk of postoperative complications and increased mortality in patients undergoing lobectomy for lung cancer. The aim of the study was to validate the value of 500 m in 6MWT as an indicator, which differentiates risk of complications in patients undergoing pneumonectomy. 125 patients who underwent pneumonectomy at Thoracic Surgery Department between 2009 and 2018. On the day preceding the surgery, patients underwent 6MWT. The patients were in median age of 63 years. The cut-off value of 500 m identified patients with increased 90-day mortality [17.9% vs. 3.5%, odds ratio (OR) 6.271, 95% confidence interval (CI) 1.528-25.739], first-year mortality (30.7% vs. 11.6%, OR 3.378, 95%CI 1.310-8.709), and overall survival (p = 0.02). Patients who covered a distance ≤ 500 m had an increased risk of atrial fibrillation (35.9% vs. 16.3%, OR 2.880, 95%CI 1.207-6.870) and cardiac complications (38.4% vs. 19.8%, OR 2.537, 95%CI 1.100-5.849). Patients unable to reach 500 m in 6MWT are in a high risk of postoperative death after pneumonectomy, what may be a result of increased frequency of postoperative cardiac complications. Poor result of 6MWT is a predictor of worse overall survival.

The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non-Small Cell Lung Cancer.

OBJECTIVE: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). METHODS: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. RESULTS: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobe-specific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for R0, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between R0 and R(un) in pN0 cases. CONCLUSIONS: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies.

Lung cancer survival and comorbidities in lung cancer screening participants of the Gdansk screening cohort.

BACKGROUND: In 2010, the World Health Organisation recommended implementation of screening programmes in four groups of diseases-neoplasms, cardiovascular diseases (CVD), diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD). It is due to the fact that they share the same, modifiable risk factors. METHODS: Between 2009 and 2011, 8637 heavy smokers (aged 50-75, smoking history >20 pack-years) were screened in the Pomeranian Pilot Lung Cancer Screening Programme (PPP) in Gdansk, Poland. We looked at 5-year follow-up and analysed the medical events and comorbidities of all participants. One health care provider in the Polish health care system provides a unique opportunity to gather most reliable data on all medical events in each person. RESULTS: In 52.0% of lung cancer screening participants CVD (33.5%), DM (26.0%) and COPD (21.0%) were diagnosed. Prevalence of these diseases is higher in lung cancer patients than in the non-cancer screening group (P < 0.0001). One hundred and seven (1.2%) lung cancers were diagnosed during PPP programme performance and another 382 cases (4.4%) in the 5-year follow-up, so the potential mean annual lung cancer detection rate is 0.77%. CONCLUSIONS: Lung cancer screening programme offers a great potential for joint screening of lung cancer, CVD, diabetes and COPD.

Ten years of experience in lung cancer screening in Gdansk, Poland: a comparative study of the evaluation and surgical treatment of 14 200 participants of 2 lung cancer screening programmes†.

OBJECTIVES: The European Society of Thoracic Surgeons' recommendations confirm the implementation of lung cancer screening in Europe. We compared 2 screening programmes, the Pilot Pomeranian Lung Cancer Screening Programme (pilot study) and the Moltest Bis programme, completed in a single centre. METHODS: A total of 8649 healthy volunteers (aged 50-75 years, smoking history ≥20 pack-years) were enrolled in a pilot study between 2009 and 2011, and a total of 5534 healthy volunteers (aged 50-79, smoking history ≥30 pack-years) were enrolled in the Moltest Bis programme between 2016 and 2017. Each participant had a low-dose computed tomography scan of the chest. Participants with a nodule diameter of >10 mm or with suspected tumour morphology underwent a diagnostic work-up in the pilot study. In the Moltest Bis programme, the criteria were based on the volume of the detected nodule on the baseline low-dose computed tomography scan and the volume doubling time in the subsequent rounds. RESULTS: Lung cancer was diagnosed in 107 (1.24%) and 105 (1.90%) participants of the pilot study and of the Moltest Bis programme, respectively (P = 0.002). A total of 300 (3.5%) and 199 (3.6%) patients, respectively, were referred for further invasive diagnostic work-ups (P = 0.69). A total of 125 (1.5%) and 80 (1.5%) patients, respectively, underwent surgical resection (P = 0.74). The number of resected benign lesions was similar: 44 (35.0%) and 20 (25.0%), respectively (P = 0.13), but with a downwards trend. Lobectomies and/or segmentectomies were performed in 84.0% and 90.0% of patients with lung cancer, respectively (P = 0.22). Notably, patients in the Moltest Bis programme underwent video-assisted thoracoscopic surgery more often than did those in the pilot study (72.5% vs 24.0%, P < 0.001). Surgical patients with stages I and II non-small-cell lung cancer (NSCLC) accounted for 83.4% of the Moltest patients and 86.4% of the pilot study patients (P = 0.44). CONCLUSIONS: Modified inclusion criteria in the screening programme lead to a higher detection rate of NSCLC. Growing expertise in lung cancer screening leads to increased indications for minimally invasive surgery and an increased proportion of lung-sparing resections. A single-team experience in lung cancer screening does not lead to a major reduction in the rate of diagnostic procedures and operations for non-malignant lesions.

Result of the 6-min walk test is an independent prognostic factor of surgically treated non-small-cell lung cancer.

OBJECTIVES: Pathological tumour, node and metastasis (TNM) stage remains the most significant prognostic factor of non-small-cell lung cancer (NSCLC). Meanwhile, age, gender, pulmonary function tests, the extent of surgical resection and the presence of concomitant diseases are commonly used to complete the prognostic profile of the patient with early stage of NSCLC. The aim of this study is to assess how the result of a 6-min walk test (6MWT) further assists in predicting the prognosis of NSCLC surgical candidates. METHODS: Six hundred and twenty-four patients who underwent surgical treatment for NSCLC between April 2009 and October 2011 were enrolled in this study. All patients were accepted for surgery on the basis of a standard evaluation protocol. Additionally, patients completed the 6MWT on the day before the surgery, and threshold values of the test were assessed based on both the Akaike information criterion and the coefficient of determination R2. Cox proportional hazards regression analysis was used to analyse the effect of important prognostic factors on the overall survival. RESULTS: Three hundred and ninety men and 234 women with a mean age of 64 years underwent radical surgical treatment for primary lung cancer. Five hundred and twenty-five lobectomies (84%), 77 pneumonectomies (12%) and 24 (4%) lesser resections were performed. Three hundred and thirty-one patients (53%) were treated for stage I NSCLC, 191 patients (31%) for stage II and 102 patients (16%) for stages IIIA-IV. A distance of 525 m in the 6MWT [hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.41-0.78, P < 0.001] was the threshold value differentiating the patients' prognoses (P < 0.001). Using the Cox proportional hazards regression analysis, pathological TNM stage (IIA: HR = 1.87, 95% CI 1.95-2.92, P = 0.006; IIB: HR = 2.03, 95% CI 1.23-3.37, P = 0.006; IIIA-IV: HR = 2.37, 95% CI 1.49-3.75, P < 0.001), male gender (HR = 1.88, 95% CI 1.26-2.79, P = 0.001), pneumonectomy (HR = 1.78, 95% CI 1.17-2.70, P < 0.001) and the results of the 6MWT (HR = 0.50, 95% CI 0.36-0.70, P < 0.001) were considered as independent predictive factors of overall survival. CONCLUSIONS: The result of a 6MWT is an independent and convenient prognostic factor of surgically treated non-small-cell lung cancer.

Low-dose computed tomography screening reduces lung cancer mortality.

Lung cancer causes an estimated 1.6 million deaths each year, being the leading cause of cancer-related deaths in the world. Late diagnosis and, in some cases, the high aggressiveness of the tumour result in low overall five-year survival rates of 12% among men and 7% among women. The cure is most likely in early-stage disease. The poor outcomes of treatment in lung cancer resulting from the fact that most cases are diagnosed in the advanced stage of the disease justify the implementation of an optimal lung cancer prevention in the form of smoking cessation and screening programmes that would offer a chance to detect early stages of the disease, while fitting within specific economic constraints. The National Lung Screening Trial (NLST) - the largest and most expensive randomised, clinical trial in the USA demonstrated a 20% mortality rate reduction in patients who had undergone chest low-dose computed tomography (LDCT) screening, as compared to patients screened with a conventional chest X-ray. Results of the NLST enabled the implementation of lung cancer screening programme among highrisk patients in the USA and parts of China. In 2017, recommendations of the European Society of Thoracic Surgeons also strongly recommend an implementation of a screening programme in the EU. Further studies of improved lung cancer risk assessment scores and of effective molecular markers should intensify in order to reduce all potential harms to the high-risk group and to increase cost-effectiveness of the screening.

Video-assisted thoracoscopic bronchial sleeve lobectomy - a case report.

Bronchial sleeve lobectomy offers a chance to avoid excessive resections such as pneumonectomy in central lung tumors. Recent technical advances enable complex procedures such as video-assisted thoracoscopic bronchial sleeve lobectomy (VABSL). We present a case of a 64-year-old patient who underwent the right upper VABSL due to adenocarcinoma. During resection the bronchus was transsected and a specimen removed due to tumor proximity. Intraoperative frozen section revealed no neoplastic infiltration in the bronchial cut line. Due to a stiff round shape of the bronchial defect, impossible to approximate by direct suturing without kinking, sleeve lobectomy was undertaken. Bronchial section was performed through utility incision partly under direct vision. End-to-end anastomosis was led with open surgery needle holder, forceps and with continuous Maxon 4-0. Postoperative stay was uncomplicated and bronchoscopy revealed wide lumen of anastomosis.  .

Improvement in lung cancer outcomes with targeted therapies: an update for family physicians.

In the past decade the advent of target therapy has led to a silent revolution in the treatment of lung cancer. Thanks to the specificity of their target, new tailored drugs are able to achieve a larger benefit and lower toxicity and provide better quality of life than cytotoxic drugs in a limited number of patients, selected by molecular profile. Nowadays, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase inhibitor crizotinib, are targeted agents approved for treatment of non-small-cell lung cancer. Family physicians play an important role in the treatment, detection, and management of common toxicities and in providing emotional support. Therefore this review integrates molecular profile assessment with evidence of the efficacy and toxicity of tyrosine kinase inhibitors to provide an updated overview of the treatment of non-small-cell lung cancer, which radically changed after the advent of targeted therapies. It also aims to promote a more intensive and interactive collaboration between specialists and family physicians in the management of all phases of cancer care.