Differential expression of immunohistochemical markers in primary lung and breast cancers enriched for triple-negative tumours.

AIMS: In breast cancer patients presenting with a lung lesion, the distinction between lung and breast origin is clinically important. Lung and breast cancers are both CK7(+) /CK20(-) , so additional immunohistochemical markers are needed. METHODS AND RESULTS: We examined the expression of oestrogen receptor (ER), progesterone receptor (PR), thyroid transcription factor-1 (TTF-1), gross cystic disease fluid protein-15 (GCDFP-15), p63 and Wilms' tumour 1 (WT1) in a series of tissue microarrays comprising 266 non-small-cell lung cancers and 837 primary breast cancers enriched for triple-negative tumours (TNBC). Staining for ER, PR, TTF-1 and GCDFP-15 was present in 63%, 49%, 0% and 25% of breast and 6%, 9%, 59% and 1% of lung cancers, respectively. Strong staining for p63 was present in 63 (97%) lung squamous cell carcinomas and only eight (9%) TNBC. WT1 nuclear staining was rare; however, cytoplasmic staining was identified in 49 (40%) TNBC and 10 (5%) lung cancers. Cluster analysis segregated TNBC from lung cancers with TTF-1 and/or p63 staining favouring lung origin, and GCDFP-15 or WT1 staining favouring breast origin. Cancers negative for all four markers (17%) were 60% breast and 40% lung origin. CONCLUSION: An immunohistochemical panel incorporating ER, TTF-1, GCDFP-15, p63 and WT1 can help to distinguish lung cancer from metastatic breast cancer, including TNBC.

Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH.

The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 ≥2, or tumor cell percentage with ≥15 signals ≥10%, or average number of signals/tumor cell nucleus ≥6. Low-level amplification was defined as tumor cell percentage with ≥5 signals ≥50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; P<0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P=0.88, HR=1.04, 95% confidence interval (CI)=0.67-1.60) or overall survival (P=0.97, HR=1.01, 95% CI=0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method to detect FGFR1 amplification. No relationship was detected between patient outcome and FGFR1 amplification.

Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization.

Rearrangements of anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) define a molecular subgroup of tumors characterized clinically by sensitivity to ALK tyrosine kinase inhibitors such as crizotinib. Although ALK rearrangements may be detected by reverse transcriptase-PCR, immunohistochemistry or fluorescence in situ hybridization (FISH), the optimal clinical strategy for identifying ALK rearrangements in clinical samples remains to be determined. We evaluated immunohistochemistry using three different antibodies (ALK1, 5A4 and D5F3 clones) to detect ALK rearrangements and compared those with FISH. We report the frequency and clinicopathologic features of lung cancers harboring ALK translocations in 594 resected NSCLCs (470 adenocarcinomas; 83 squamous carcinomas, 26 large cell carcinomas and 15 other histological subtypes) using a tissue microarray approach. We identified an ALK gene rearrangement in 7/594 cases (1%) by FISH and all anti-ALK antibodies correctly identified the seven ALK-positive cases (100% sensitivity), although the intensity of staining was weak in some cases. These data indicate that the use of antibodies with high sensitivity and avidity to ALK may provide an effective pre-screening technique to complement the more expensive and labor-intensive approach of ALK FISH testing.

Lung cancer in Victoria: are we making progress?

OBJECTIVES: To identify areas to improve patient management in lung cancer, which remains the greatest cause of death from cancer in Australia. DESIGN AND SETTING: Retrospective survey of all cases of lung cancer reported to the Victorian Cancer Registry from 1 January to 30 June 2003 and followed up for 5 years. MAIN OUTCOME MEASURES: Patient and disease characteristics, investigations, staging, treatment, cause of death, survival. RESULTS: 841 patients were included. Smoking data were available for 799, of whom 63 (7.9%) had never smoked. Of 655 non-small cell lung cancer (NSCLC) cases, 198 (30.2%) were treated with curative intent, 125 (19.1%) by surgery and 73 (11.1%) by radiotherapy with or without chemotherapy. Only 7 (6.9%) of surgical patients with complete R0 resection had adjuvant chemotherapy. Of 101 small cell lung cancer (SCLC) cases, a third had limited stage disease which was mostly treated with curative intent by chemotherapy with or without radiotherapy. Patients whose cases were discussed at a multidisciplinary meeting (MDM) were significantly more likely to receive anticancer treatment and had longer survival; on multivariate analysis, MDM discussion was an independent prognostic factor. Compared with a similar survey 10 years earlier, the median age of patients diagnosed with lung cancer had increased by almost 3 years, the proportion of affected men decreased and adenocarcinoma was more frequent, while 10% of patients continued to have no pathologically confirmed diagnosis and 26% continued to receive no anticancer treatment. The number of patients with NSCLC who went on to a definitive surgical procedure fell with no detriment to survival, which likely reflected better staging with the introduction of positron emission tomography scanning. CONCLUSIONS: Opportunities to improve patient management included increasing the proportion with a pathologically confirmed diagnosis and greater use of postsurgical adjuvant chemotherapy. A high proportion of patients received no treatment, with underuse of chemotherapy and radiotherapy. Critically, the low rate of case discussions at MDMs needs to increase. However, effective strategies are required to identify cases early, as over two-thirds currently present with incurable disease.

Suggested robotic-assisted thoracic surgery training curriculum.

Robotic-assisted surgery, a technological advancement in the field of surgery, has become increasingly popular among surgeons of many specialties over time. Robotic-assisted thoracic surgery (RATS) is comparable to video-assisted thoracic surgery (VATS) in terms of patient care outcomes; however, the perception of increased operative time and a lack of cost-effectiveness have led to controversy regarding its alleged benefits. Nevertheless, robotic surgery is one of the preferred options for minimally invasive surgery by some thoracic surgeon over VATS, due to its ability to provide 3-D vision, precise wrist movements, enhanced magnification, and instrument stability and articulation. Notably, trainees in the field of thoracic surgery experience difficulty gaining knowledge and learning skills associated with RATS due to its complexity, limited access to robotic instruments, the lack of a standardized curriculum for trainees, and lack of mentorship or proctorship, thus leading to a steeper learning curve compared to laparoscopic or VATS procedures that are cost-friendly, easy to learn, and feasible to practice. Nevertheless, focusing on RATS training for thoracic surgeons will keep them familiar with robotic techniques, including the pre-operative setup and intra-operative process, which will ultimately decrease operative times. In this paper, we will review the literature, express and discuss the most viable training curriculum from authors' point of view to help achieve this goal.

Lung neuroendocrine neoplasms: a single centre surgical series and analysis of staging.

BACKGROUND: To review the outcomes of surgically resected lung neuroendocrine neoplasms (LNEN) at a tertiary referral centre and to validate a previously published LNEN-specific staging system (NETL). METHODS: All patients who were identified on histopathology to have LNEN were included. Pre-, intra- and post-operative outcomes were collected, including long-term survival. Patients were staged by both the TNM (seventh and eighth edition) and NETL staging (seventh and eighth edition definitions). Kaplan-Meier (KM) survival analysis was performed according to histopathology and stage, along with uni- and multivariate analyses. RESULT: A total of 132 patients were included in the study, with a median age of 65 years; 55% were female. Typical carcinoid (TC) was the most common pathology (53.4%) followed by large cell neuroendocrine carcinoma (LCNEC - 23.5%), atypical carcinoid (AC - 20.5%) and small cell carcinoma (3.0%). The most common operation performed was a lobectomy (55.3%). Overall survival at 5 years was 80% (100% TC, 78.2% AC, LCNEC 40.9%) and 5-year disease free survival was 76.8% (TC 94.3%, AC 56.8%, LCNEC 56.4%). KM curves showed a trend towards NETL performing better than TNM, however, in multivariate analysis only the histological subtype was found to be significant in our study. CONCLUSION: This is the largest known Australian series of LNEN to date, showing survival comparable to international outcomes. We have demonstrated large variations in outcome, driven by histological grade. The TNM system does not correlate with survival and we have not been able to show that currently proposed NETL staging is superior.

Use of Indocyanine Green Fluorescence Imaging in Thoracic and Esophageal Surgery.

BACKGROUND: Fluorescence imaging using indocyanine green in thoracic and esophageal surgery is gaining popularity because of the potential to facilitate surgical planning, to stage disease, and to reduce postoperative complications. To optimize use of fluorescence imaging in thoracic and esophageal surgery, an expert panel sought to establish a set of recommendations at a consensus meeting. METHODS: The panel included 12 experts in thoracic and upper gastrointestinal surgery from Asia-Pacific countries. Before meeting, 7 focus areas were defined: intersegmental plane identification for sublobar resections; pulmonary nodule localization; lung tumor detection; bullous lesion detection; lymphatic mapping of lung tumors; evaluation of gastric conduit perfusion; and lymphatic mapping in esophageal surgical procedures. A literature search of the PubMed database was conducted using keywords indocyanine green, fluorescence, thoracic, surgery, and esophagectomy. At the meeting, panelists addressed each focus area by discussing the most relevant evidence and their clinical experiences. Consensus statements were derived from the proceedings, followed by further discussions, revisions, finalization, and unanimous agreement. Each statement was assigned a level of evidence and a grade of recommendation. RESULTS: A total of 9 consensus recommendations were established. Identification of the intersegmental plane for sublobar resections, localization of pulmonary nodules, lymphatic mapping in lung tumors, and assessment of gastric conduit perfusion were applications of fluorescence imaging that have the most robust current evidence. CONCLUSIONS: Based on best available evidence and expert opinions, these consensus recommendations may facilitate thoracic and esophageal surgery using fluorescence imaging.

Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors.

BACKGROUND: Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors. METHODS: Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted >28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed. RESULTS: No DLTs occurred in parts A (n=18) or B (n=85). Grade 3-5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35). CONCLUSIONS: Intravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy. TRIAL REGISTRATION NUMBER: NCT02043665.

Development of an Australia and New Zealand Lung Cancer Clinical Quality Registry: a protocol paper.

INTRODUCTION: Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand. METHODS AND ANALYSIS: Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight. ETHICS AND DISSEMINATION: The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.

Integrated mutation, copy number and expression profiling in resectable non-small cell lung cancer.

BACKGROUND: The aim of this study was to identify critical genes involved in non-small cell lung cancer (NSCLC) pathogenesis that may lead to a more complete understanding of this disease and identify novel molecular targets for use in the development of more effective therapies. METHODS: Both transcriptional and genomic profiling were performed on 69 resected NSCLC specimens and results correlated with mutational analyses and clinical data to identify genetic alterations associated with groups of interest. RESULTS: Combined analyses identified specific patterns of genetic alteration associated with adenocarcinoma vs. squamous differentiation; KRAS mutation; TP53 mutation, metastatic potential and disease recurrence and survival. Amplification of 3q was associated with mutations in TP53 in adenocarcinoma. A prognostic signature for disease recurrence, reflecting KRAS pathway activation, was validated in an independent test set. CONCLUSIONS: These results may provide the first steps in identifying new predictive biomarkers and targets for novel therapies, thus improving outcomes for patients with this deadly disease.

Genomic and Clinical Significance of Multiple Primary Lung Cancers as Determined by Next-Generation Sequencing.

INTRODUCTION: Marked variations in survival rates have brought into question whether standard clinicopathologic classification should be applied to patients presenting with multiple primary lung cancers (MPLCs). This study investigated the genetic profiles of MPLCs in a cohort of patients using next-generation sequencing and correlated results to clinicopathologic data and patient outcome. METHODS: Patients treated surgically with curative intent for two putative primaries of similar histopathology from January 2000 to December 2019 at St Vincent's Hospital Melbourne. DNA and RNA was extracted from formalin-fixed, paraffin-embedded tumor tissue and sequenced on an Ion Torrent Personal Genome Machine system. Patient outcome was determined by overall survival and disease-free survival. RESULTS: A total of 40 cases fulfilled the inclusion criteria. Mutational profiling was concordant with clinicopathologic diagnosis in most cases; however, seven cases (17.5%) revealed shared mutations suggesting metastatic disease and this was associated with a substantial reduction in overall survival (p < 0.05). CONCLUSIONS: Our results suggest that gene sequencing technologies are potentially a more accurate diagnostic and prognostic tool compared with traditional histopathologic evaluation in patients presenting with suspected MPLCs, which could better guide management and predict outcomes.

A predictive model for identifying candidates for adjuvant chemotherapy based on recurrence risk profile of resected, node-negative (N0) non-small cell lung cancer.

BACKGROUND: The decision for administering adjuvant chemotherapy (AC) in completely resected node-negative non-small cell lung cancer (NSCLC) is guided by likelihood of disease recurrence or death based on tumor, node, metastasis (TNM) stage. However, within each TNM stage are sub-groups of patients that are more or less likely to relapse than stage alone predicts. METHODS: In this retrospective cohort study, prospective data from 394 consecutive patients who underwent complete resection of node-negative NSCLC without adjuvant therapies, between 2002 and 2019 was retrospectively analyzed. Independent tumor and host risk factors for recurrence were subjected to multivariate analysis to develop a predictive risk model distributing patients into low-risk or high-risk categories. RESULTS: Recurrence risk was independently predicted by a neutrophil:lymphocyte ratio (NLR) of ≥3.5 [hazard ratio (HR), 1.9; 95% confidence interval (CI), 1.1-3.5], visceral pleural invasion (HR, 2.2; 95% CI, 1.3-3.8), histopathology other than adenocarcinoma or squamous cell (HR, 2.6; 95% CI, 1.2-5.5) and tumor size >33 mm (HR, 3.9; 95% CI, 2.3-6.7). The specific combination of risk factors contributed to a score for a risk model which classified 9% of Stage I and 69% of Stage ≥II patients as high-risk. The predicted 5-year disease-free survival (DFS) for high-risk and low-risk patients as scored by the predictive model was 30% and 85%, respectively. CONCLUSIONS: Our readily reproducible, low-technology model, developed from individually validated tumor/host risk factors, identified sub-groups of resected node-negative NSCLC patients at significantly discordant risk of recurrence to their TNM stage category.

Long-term outcomes of pulmonary metastasectomy: a multicentre analysis.

BACKGROUND: Many extrapulmonary neoplasms metastasize to the lungs. We conducted a retrospective review of all patients who underwent pulmonary metastasectomy for oligometastatic disease at two centres in order to determine long-term outcomes. METHODS: The study institutions' thoracic surgery databases were searched for all patients who underwent pulmonary metastasectomy from 2000 to 2017. RESULTS: There were a total of 476 patients who underwent pulmonary metastasectomy. Mean age at time of surgery was 57.2 ± 15.9 years. Mean number of pulmonary lesions was 1.9 ± 1.6. Mean disease-free interval (DFI) was 3.6 ± 4.3 years. The most common primary neoplasms were colorectal cancer (CRC) in 35.1% (167/476), sarcoma in 23.9% (114/476), melanoma in 16.2% (77/478), renal cell carcinoma (RCC) in 7.3% (35/476) and germ cell tumour (GCT) in 4.4% (21/476). Hospital mortality was 0.4% (2/476). Mean follow-up time was 3.8 ± 2.9 years. Survival was 88.9% (95% confidence interval 85.77-91.5) at 1 year and 49.6% (95% confidence interval 44.4-54.6) at 5 years. On multivariate Cox-regression analysis GCT (P = 0.004), CRC (P = 0.03), DFI of 36+ months (P = 0.007), R0 resection (P = 0.002) and non-anatomical, sub-lobar (wedge) resection (P = 0.002) were protective against mortality. CONCLUSION: Pulmonary metastasectomy is associated with survival of 50% at 5-year follow-up. DFI of over 36 months, R0 resections, lesions resectable by wedge resection rather than anatomic resection and GCT and CRC primary cancers were associated with improved survival.

EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) mutations are an uncommon and heterogeneous group of non-small cell lung cancers (NSCLCs), resistant to conventional EGFR tyrosine kinase inhibitors (TKIs). Characteristics and outcomes of patients with EGFR ex20-ins have not been fully established; we sought to clarify them using a multinational patient database. PATIENTS AND METHODS: Patients with NSCLC from six Australian institutions with EGFR exon 20 mutations (ex20-mut), excluding T790M, were retrospectively reviewed. Clinical characteristics and outcomes with systemic treatments were collected and analyzed using comparative statistics. RESULTS: Among 109 patients with ex20-mut, 61% were females and 75% were Caucasians. More males presented with de novo metastatic disease (84% vs. 51%; P = .002). Central nervous system (48%) and liver (24%) metastases were common within metastatic patients (n = 86). Thirty-nine patients received platinum-based chemotherapy (PBC) and achieved a 43% objective response rate (ORR), median progression-free survival (mPFS) of 6.9 months, and median overall survival (mOS) of 31.0 months. Twenty-three of the patients with ex20-ins received conventional TKIs, resulting in an ORR of 13%, mPFS of 3.4 months (95% confidence interval [CI], 1.91-6.25), and mOS of 31.0 months (95% CI, 15.09-not reached). Nine patients with S786I mutations received TKIs, resulting in an ORR of 50%, mPFS of 18.2 months (2.79-not reached), and mOS of 33.4 months (95% CI, 16.14-not reached). Twenty-three patients received immune checkpoint inhibitor monotherapy (ICIm), resulting in an ORR of 4%, mPFS of 2.6 months (95% CI, 1.91-4.83), and mOS of 30.8 months (95% CI, 17.62-41.62). CONCLUSION: Although phenotypically similar to patients with common EGFR mutations, patients with EGFR ex20-mut had worse survival, perhaps due to the lack of targeted therapies. Chemotherapy was superior to conventional EGFR TKIs in patients with EGFR ex20-ins, although there was moderate activity of TKIs in S768I mutations. ICIm was ineffective.

Locally advanced non-small cell lung cancer: the place of specialist thoracic surgery in the multidisciplinary team.

One reason that lung cancer is the leading cause of cancer mortality worldwide, is that surgical intervention is highly dependent on earlier tumor stage and good patient condition. As large proportion of cases are already metastatic at presentation and many are locally advanced, curative surgery is only possible in a minority of fit patients. Increasing the number of patients achieving complete resection is one of the avenues to increase overall survival using our existing technology. In the past, complex cases may have been sporadically discussed between various specialists in order to achieve better outcomes. More recently, the idea of discussing those cases on a routine basis, rather than an accident of geography or referral pattern, gave rise to the multidisciplinary team. Lung cancer management is now increasingly complex, especially with novel modalities such as targeted therapies, immune checkpoint inhibitors and stereotactic body radiotherapy delivery. Likewise, in thoracic surgery, minimally invasive techniques, early recovery after surgery protocols and complex techniques for resecting locally advanced tumours or preserving lung parenchyma must all be deployed appropriately to continue our incremental gains in survival and quality of life. To highlight the role of specialist thoracic surgeon in the multidisciplinary care of locally advanced non-small cell lung cancer, we conducted a search of English language publications for its multidisciplinary-based surgical management. We limited our search to the last decade, then hand-searched relevant references. In addition, we used our large prospective database as a team-oriented specialized thoracic surgical service to benchmark and demonstrate the benefits of specialist surgeons in the modern multidisciplinary team. In conclusion, patients with locally advanced non-small cell lung cancer should have any surgical option withheld without a specialist thoracic surgical opinion as part of the multidisciplinary team discussion.

Attitudes and Perceptions to Prehabilitation in Lung Cancer.

Background: Prehabilitation to maximize exercise capacity before lung cancer surgery has the potential to improve operative tolerability and patient outcomes. However, translation of this evidence into clinical practice is limited. Aims: To determine the acceptability and perceived benefit of prehabilitation in lung cancer among thoracic surgeons. Procedure: 198 cardiothoracic surgeons within Australia and New Zealand were surveyed to evaluate their attitudes and perceived benefits of prehabilitation in lung cancer. Results: Response rate was 14%. A moderate proportion of respondents reported that there is a need to refer lung resection patients to preoperative physiotherapy/prehabilitation, particularly high-risk patients or those with borderline fitness for surgery. 91% of surgeons were willing to delay surgery (as indicated by cancer stage/type) to optimize patients via prehabilitation. The main barriers to prehabilitation reported were patient comorbidities and access to allied health professionals, with 33% stating that they were unsure who to refer to for prehabilitation in thoracic surgery. This is despite 60% of the cohort reporting that pulmonary rehabilitation is available as a preoperative resource. 92% of respondents believe that further research into prehabilitation in lung cancer is warranted. Conclusion: The benefits of prehabilitation for the oncology population have been well documented in the literature over recent years and this is reflected in the perceptions surgeons had on the benefits of prehabilitation for their patients. This survey demonstrates an interest among cardiothoracic surgeons in favor of prehabilitation, and therefore further research and demonstration of its benefit is needed in lung cancer to facilitate implementation into practice.

Excision of Giant Schwannoma in a Nonagenarian-operative techniques for enhanced recovery after thoracotomy in the high-risk patient.

Thoracotomy is acknowledged as one of the most painful procedures in surgical practice, with the potential to result in significant acute and chronic sequelae, which become especially relevant in high-risk patient populations. Certain pathologies necessitate this surgical approach, and in those circumstances we must aim to mitigate postoperative complications by employing surgical techniques that decrease the risk of nerve injury, rib fracture, and unnecessary soft tissue trauma. We describe an approach to thoracotomy that incorporates evidence-based strategies to lessen the risk of these potential complications, which resulted in rapid postoperative recovery in a nonagenarian.

Distinct initiating events underpin the immune and metabolic heterogeneity of KRAS-mutant lung adenocarcinoma.

The KRAS oncoprotein, a critical driver in 33% of lung adenocarcinoma (LUAD), has remained an elusive clinical target due to its perceived undruggable nature. The identification of dependencies borne through common co-occurring mutations are sought to more effectively target KRAS-mutant lung cancer. Approximately 20% of KRAS-mutant LUAD carry loss-of-function mutations in KEAP1, a negative regulator of the antioxidant response transcription factor NFE2L2/NRF2. We demonstrate that Keap1-deficient KrasG12D lung tumors arise from a bronchiolar cell-of-origin, lacking pro-tumorigenic macrophages observed in tumors originating from alveolar cells. Keap1 loss activates the pentose phosphate pathway, inhibition of which, using 6-AN, abrogated tumor growth. These studies highlight alternative therapeutic approaches to specifically target this unique subset of KRAS-mutant LUAD cancers.