A gene expression-based single sample predictor of lung adenocarcinoma molecular subtype and prognosis.

Disease recurrence in surgically treated lung adenocarcinoma (AC) remains high. New approaches for risk stratification beyond tumor stage are needed. Gene expression-based AC subtypes such as the Cancer Genome Atlas Network (TCGA) terminal-respiratory unit (TRU), proximal-inflammatory (PI) and proximal-proliferative (PP) subtypes have been associated with prognosis, but show methodological limitations for robust clinical use. We aimed to derive a platform independent single sample predictor (SSP) for molecular subtype assignment and risk stratification that could function in a clinical setting. Two-class (TRU/nonTRU=SSP2) and three-class (TRU/PP/PI=SSP3) SSPs using the AIMS algorithm were trained in 1655 ACs (n = 9659 genes) from public repositories vs TCGA centroid subtypes. Validation and survival analysis were performed in 977 patients using overall survival (OS) and distant metastasis-free survival (DMFS) as endpoints. In the validation cohort, SSP2 and SSP3 showed accuracies of 0.85 and 0.81, respectively. SSPs captured relevant biology previously associated with the TCGA subtypes and were associated with prognosis. In survival analysis, OS and DMFS for cases discordantly classified between TCGA and SSP2 favored the SSP2 classification. In resected Stage I patients, SSP2 identified TRU-cases with better OS (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.18-0.49) and DMFS (TRU HR = 0.52; 95% CI = 0.33-0.83) independent of age, Stage IA/IB and gender. SSP2 was transformed into a NanoString nCounter assay and tested in 44 Stage I patients using RNA from formalin-fixed tissue, providing prognostic stratification (relapse-free interval, HR = 3.2; 95% CI = 1.2-8.8). In conclusion, gene expression-based SSPs can provide molecular subtype and independent prognostic information in early-stage lung ACs. SSPs may overcome critical limitations in the applicability of gene signatures in lung cancer.

A successful shift from thoracotomy to video-assisted thoracoscopic lobectomy for non-small cell lung cancer in a low-volume center.

OBJECTIVES: Although video-assisted thoracoscopic surgery (VATS) lobectomy has become the gold standard for pulmonary resections of non-small-cell lung cancer (NSCLC), lobectomy is still performed via thoracotomy in many European and North American centres. VATS lobectomy was implemented overnight from thoracotomy in our low-volume centre in early 2019, after 1 senior surgeon undertook observership VATS-training overseas, and immediately became the mainstay of surgical treatment for NSCLC in Iceland. We aimed to investigate our short-term outcomes of VATS lobectomy. METHODS: This was a retrospective study on all pulmonary resections for NSCLC in Iceland 2019-2022, especially focusing on VATS lobectomies, all at cTNM stage I or II. Data were retrieved from hospital charts, including information on perioperative complications, mortality, length of stay and operation time. RESULTS: Out of 204 pulmonary resections, mostly performed by a single senior cardiothoracic surgeon, 169 were lobectomies (82.9%) with 147 out of 169 (87.0%) being VATS lobectomies. Anterolateral thoracotomy was used in 34 cases (16.7%), including 22 lobectomies (64.7%), and 5 (3.4%) conversions from VATS lobectomy. The median postoperative stay for VATS lobectomy was 4 days and the average operating time decreased from 155 to 124 min between the first and last year of the study (P < 0.001). The rate of major and minor complications was 2.7% and 15.6% respectively. One year survival was 95.6% and all patients survived 30 days postoperatively. CONCLUSIONS: The implementation of VATS lobectomy has been successful in our small geographically isolated centre, serving a population of 390 000. Although technically challenging, VATS lobectomy was implemented fast for most NSCLC cases, with short-term outcomes that are comparable to larger high-volume centres.

Real-World Treatment Patterns and Survival Outcomes for Patients with Non-Metastatic Non-Small-Cell Lung Cancer in Sweden: A Nationwide Registry Analysis from the I-O Optimise Initiative.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with ~40-50% of patients diagnosed with non-metastatic disease (stages IA-IIIC). The treatment landscape is evolving rapidly as immunotherapies and targeted therapy are introduced in the non-metastatic setting, creating a need to assess patient outcomes prior to their introduction. This real-world study using Swedish National Lung Cancer Registry data examined outcomes (overall survival (OS) and time to next treatment or death (TTNTD)) and treatment patterns for adults diagnosed with non-metastatic NSCLC. Baseline characteristics and OS from diagnosis were described for all patients; OS, treatment patterns, and TTNTD from treatment start were described for the treatment subgroup (patients diagnosed from 2014 onwards), stratified by disease stage and initial treatment. OS and TTNTD were described using the Kaplan-Meier estimator. The overall population (2008-2019) included 17,433 patients; the treatment subgroup included 5147 patients. Median OS (interquartile range) overall ranged from 83.3 (31.6-165.3) months (stage I patients) to 10.4 (4.3-24.2) months (stage IIIB patients). Among the treatment subgroup, median OS and TTNTD were longest among patients receiving surgery versus other anticancer treatments. These findings provide a baseline upon which to evaluate the epidemiology of non-metastatic NSCLC as newer treatments are introduced.

Prevalence, molecular markers, and outcome of bronchial squamous carcinoma in situ in high-risk subjects.

Bronchial squamous carcinoma in situ (CIS) is a preinvasive lesion that is thought to precede invasive carcinoma. We conducted prospective autofluorescence and white light bronchoscopy trials between 1992 and 2016 to assess the prevalence, molecular markers, and outcome of individuals with CIS and other preneoplastic bronchial lesions. Biopsies were evaluated at multiple levels and selected biopsies were tested for aneuploidy and DNA sequenced for TP53 mutation. Thirty-one individuals with CIS were identified. Twenty-two cases of CIS occurred in association with concurrent invasive carcinomas. Seven of the invasive tumors were radiographically occult. In two cases, CIS spread from the focus of invasive carcinoma into contralateral lung lobes, forming secondary invasive tumors. In nine cases, CIS occurred as isolated lesions and one progressed to invasive squamous carcinoma at the same site 40 months after discovery. In a second case, CIS was a precursor of carcinoma at a separate site in a different lobe. In seven cases CIS regressed to a lower grade or disappeared. High level chromosomal aneusomy was often associated with TP53 mutation and with invasive carcinoma. CIS most often occurs in association with invasive squamous carcinoma and may extend along the airways into distant lobes. In rare cases, CIS may be observed to directly transform into invasive carcinoma. CIS may be indicative of invasive tumor at a separate distant site. Isolated CIS may regress. Molecular changes parallel histological changes in CIS and may be used to map clonal expansion in the airways.

Resection rate and outcome of pulmonary resections for non-small-cell lung cancer: a nationwide study from Iceland.

BACKGROUND: The proportion of patients with non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent is one measure of effectiveness in treating lung cancer. To the best of our knowledge, surgical resection rate (SRR) for a whole nation has never been reported before. We studied the SRR and surgical outcome of NSCLC patients in Iceland during a recent 15-year period. METHODS: This was a retrospective study of all pulmonary resections performed with curative intent for NSCLC in Iceland from 1994 to 2008. Information was retrieved from medical records and from the Icelandic Cancer Registry. Patient demographics, postoperative tumor, node, metastasis stage, overall survival, and complication rates were compared over three 5-year periods. RESULTS: Of 1530 confirmed cases of NSCLC, 404 were resected, giving an SRR of 26.4%, which did not change significantly during the study period. Minor and major complication rates were 37.4% and 8.7%, respectively. Operative mortality rates were 0.7% for lobectomy, 3.3% for pneumonectomy, and 0% for lesser resection. Five-year survival after all procedures was 40.7% and improved from the first to the last 5-year period (34.8% versus 43.8%, p = 0.04). Five-year survival for stages I and II together was 46.8%, with no significant change in stage distribution between periods. Five-year survival after pneumonectomy was 22.0%, which was significantly lower than for lobectomy (44.6%) and lesser resection (40.7%) (p < 0.005). Unoperated patients had a 5-year survival of 4.8%, as compared to 12.4% for all the NSCLC patients together. CONCLUSION: Compared with most other published studies, the SRR of NSCLC in Iceland is high. Short-term outcome is good, with a low rate of major complications and an operative mortality of only 1.0%. Five-year survival improved significantly over the study period.