Left upper lobectomy with pulmonary artery reconstruction after neoadjuvant therapy in re-VATS

Video-assisted thoracoscopic surgery (VATS) is considered the gold standard for the treatment of early stage non-small-cell lung cancer. Many studies have demonstrated reduced postoperative pain, hospital stay, and morbidity, while achieving the same oncological results. Indeed, it has become a widespread technique in many countries around the world. VATS can be applied also to challenging surgical procedures, such as plasty of the pulmonary artery, to obtain an oncologically radical resection of the tumor, and in the context of an N2 disease even after a previous operation on the thorax. In this case report, we demonstrate how to carry out this procedure safely to achieve radical resection of the diseased tissue.

Efficacy of concurrent chemoradiotherapy in subgroups of stage III nasopharyngeal carcinoma: an analysis based on 10-year follow-up

Purpose To evaluate the efficacy of concurrent chemoradiotherapy (CCRT) in subgroups of stage III nasopharyngeal carcinoma (NPC) in the context of intensity-modulated radiotherapy (IMRT). Methods A total of 272 patients with stage III NPC who underwent IMRT with or without concurrent chemotherapy were retrospectively reviewed. Clinicopathological features were evaluated by a Cox regression model to identify independent prognostic factors. Survival outcomes were assessed using the Kaplan–Meier method and log-rank test. Results The median follow-up time was 108 months. The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.8%, 80.7%, 68.8%, and 74.9%, respectively. Multivariate analysis showed that the N classification was significantly associated with DMFS (hazard ratio [HR] 3.616, 95% confidence interval [CI] 1.387–9.428, P = 0.009), DFS (HR 2.417, 95% CI 1.291–4.423, P = 0.006), and OS (HR 3.024, 95% CI 1.385–6.602, P = 0.005). In patients with T1-3N2 disease, CCRT was associated with improved 10-year LRFS (89.6% vs. 65.4%, P = 0.005), DFS (71.9% vs. 39.4% P = 0.001) and OS (80.0% vs. 50.5%, P = 0.004) compared with IMRT alone. However, in patients with T3N0-1 disease, no significant survival differences were observed between patients treated with IMRT alone and CCRT (P > 0.05). Conclusions CCRT is an effective therapy in stage III NPC, especially for patients with N2 disease, but IMRT alone may be adequate for N0-1 disease. Individualized treatment strategies are essential for patients with varying disease risks.

Incorporating Surgery in treatment of Stage IIIA – N2 Non- Small Cell Lung Cancer

Stage IIIA-N2 Non-small cell lung cancer includes heterogenous group of patients with a poor 5-year survival ranging from 13% to 36% with surgery alone. Various randomized controlled trials established the role of multimodality treatment either including or excluding surgical resection. In a select group of non-bulky/ single station N2 disease, the better results have been achieved with induction chemotherapy or chemo-radiotherapy followed by surgery.

Efficacy of Concurrent Chemoradiotherapy In Subgroups of Stage III Nasopharyngeal Carcinoma: An Analysis Based On 10-Year Follow-Up

PurposeTo evaluate the efficacy of concurrent chemoradiotherapy (CCRT) in subgroups of stage III nasopharyngeal carcinoma (NPC) in the context of intensity-modulated radiotherapy (IMRT).Methods272 patients with stage III NPC who underwent IMRT with or without concurrent chemotherapy (CCT) were retrospectively reviewed. Clinicopathological features were evaluated by a Cox regression model to identify independent prognostic factors. Survival outcomes were assessed using Kaplan-Meier method and log-rank test.ResultsThe median follow-up time was 108 months. The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.8%, 80.7%, 68.8%, and 74.9%, respectively. Multivariate analysis showed that the N classification was significantly associated with DMFS (hazard ratio [HR] 3.616, 95% confidence interval [CI] 1.387-9.428, P=0.009), DFS (HR 2.417, 95% CI 1.291-4.423, P=0.006), and OS (HR 3.024, 95% CI 1.385-6.602, P=0.005). In patients with T1-3N2 disease, CCRT was associated with improved 10-year LRFS (89.6% vs. 65.4%, P=0.005), DFS (71.9% vs. 39.4%, P=0.001) and OS (80.0% vs. 50.5%, P=0.004) compared with IMRT alone. However, in patients with T3N0-1 disease, no significant survival differences were observed between patients treated with IMRT alone and CCRT (P>0.05). ConclusionCCRT is an effective therapy in stage III NPC, especially for patients with N2 disease but N0-1 disease. Individualized treatment strategies are essential for patients with varying disease risks.

Impact of Persistent N2 Disease and Lymph Node Ratio on Oncological Outcomes after Multimodal Treatment in Pre-Operative Histologically Proven N2 Disease Non-Small-Cell Lung Cancer

Objective: The objectives of our retrospective analysis were to estimate the oncological long-term results of patients with ypN2 and to evaluate the impact of lymph node ratio (LNR) on overall (OS) and disease-free survival (DFS). Methods: We analysed all consecutive patients (n=85) undergoing neoadjuvant chemotherapy (NAC) and surgery for pre-operative pathologically proven stage IIIA-B (N2) NSCLC from 2014 to 2020. Median LNR (0.29 or 29%) was selected as threshold for grouping. Survival was estimated using the Kaplan-Meier method. Cox regression was used to test the association between OS, DFS and covariates. Results: Post-operative mortality was 3.5%. The median follow-up was 21 months (range 6-69 months). The 5-year OS and DFS of the cohort were 41% and 20%. Patients with LNR>0.29 (n=13; 15.3%) showed a trend toward worse survival than patients with LNR0 (n=44; 51.8%) with a 5-year OS of 56% VS 14% (p=0.077), confirmed as a trend at the multivariable analysis (HR 2.28; p=0.066). At the univariate analysis a worse DFS was observed for ypN2 patients (n=58; 68.2%) compared with nodal downstaging (46% vs 25% 3-year DFS, p=0.039). DFS was different according to LNR: 3-year DFS was 14% in patients with LNR>0.29 while it reached 44% in patients with LNR 0 (p=0.043) and 62% in LNR<0.29 (p=0.03). LNR>0.29 was the only significant predictor (HR 2.89; p=0.047) of reduced DFS at the multivariable analysis. Conclusion: patients with ypN2 disease after NAC showed acceptable oncological outcomes and this finding is true for patients with low burden of nodal disease assessed by LNR.

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer

Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Many trials investigating neoadjuvant immunotherapy and targeted therapy in this subpopulation have shown promising results, although concerns have risen regarding surgical feasibility. A thorough literature review was performed, analyzing all recent studies regarding surgical morbidity and mortality. Despite the fact that two major trials investigating this subject were terminated early, the overall consensus is that surgical management seems feasible. However, dissection of hilar vessels may be challenging due to hilar fibrosis. Further research is necessary to identify the role of surgery in these multimodality treatment regimens, and to define matters such as the optimal treatment regimen, the dosage of the different agents used, the interval between induction therapy and surgery, and the role of adjuvant therapy.

Validation of National Comprehensive Cancer Network Guidelines (NCCN) at a single institution.

e20556 Background: Invasive mediastinal staging is necessary to identify locally advanced non-small cell lung cancer (NSCLC). We sought to validate NCCN guidelines for invasive mediastinal staging. Methods: We retrospectively reviewed all patients who had curative lung resection for pathologically confirmed NSCLC from October 2018 to December 2019. We excluded patients who had induction therapy without undergoing invasive mediastinal staging first. We evaluated methods of mediastinal staging, staging results, and final pathology. Indications for staging were one or more of the following; mediastinal lymph nodes > 1.0cm in short axis, Standardized Uptake Value of > 3.0 on Positron Emission Tomography, > 50% of tumor on medial side of mid-clavicular line (central vs peripheral), or peripheral lesion > 3.0cm in diameter. Staging methods were mediastinoscopy, endobronchial ultrasound (EBUS), and video-assisted thoracoscopic surgery (VATS) ipsilateral mediastinal staging before resection of main tumor. Results: In total, 457 lung resections were performed. Staging was done in 144/275 indicated cases (52.4%). Mediastinoscopy was completed in 49 patients, with 20.4% (n = 10) N2-positive. The false negative rate of mediastinoscopy was 4.1% (n = 2 at station 7). EBUS was performed in 64 patients and 21.9% (n = 14) were N2 positive. The false negative rate for EBUS was 3.1% (n = 2 at station 7). Two mediastinoscopy and 9 EBUS patients had 0 N2 stations sampled. None of the patients were ultimately N2 positive. Staging of three mediastinal stations (4L, 4R, and 7) was done in 26/49 mediastinoscopies and 15/64 EBUS. Of 20 patients who had VATS ipsilateral mediastinal staging, none were N2 positive and there were 0 false negatives. This left 131 patients who did not received indicated staging. The most common indication in this group was central location, 83.2% (n = 109). Four of these unstaged patients were N2 positive at resection (3.1%). The sole indication for these 4 patients was a centrally located tumor. Clinical tumor sizes were 1.2 cm, 1.3 cm, 1.5 cm, and 1.9 cm. Overall, the N2-positive rate of the staged group was 24/144 (16.7%) vs 4/131 (3.1%) N2 positive in the unstaged group, p < 0.001. Conclusions: The current NCCN staging guidelines accurately reflect the risk of N2 disease for NSCLC. The indication of central location for tumors may benefit from being reevaluated in a larger cohort, particularly given efficacy of adjuvant therapy.

KEYNOTE-B15/EV-304: Randomized phase 3 study of perioperative enfortumab vedotin plus pembrolizumab versus chemotherapy in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC).

TPS4587 Background: Standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection (RC+PLND); however, in time, patients experience disease recurrence or progression. Enfortumab vedotin (EV) is a Nectin-4–directed antibody–drug conjugate comprising a fully human, monoclonal antibody and the microtubule-disrupting agent monomethyl auristatin E. The KEYNOTE-869/EV-103 phase 1/2 study (NCT03288545) showed that the PD-1 inhibitor pembrolizumab + EV had encouraging antitumor activity and acceptable safety as first-line treatment for cisplatin-ineligible patients with metastatic urothelial cancer (Rosenberg JE et al. J Clin Oncol. 2020;38[15 suppl]:5044). Based on these data, investigating EV + pembrolizumab in an earlier setting such as MIBC and in a perioperative fashion is appropriate. KEYNOTE-B15/EV-304 (NCT04700124) is a randomized, open-label, phase 3 study to evaluate the efficacy and safety of perioperative EV + pembrolizumab versus neoadjuvant chemotherapy using gemcitabine/cisplatin in cisplatin-eligible patients with MIBC. Methods: Patients must have histologically confirmed urothelial cancer/MIBC (clinical stage T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology, have nonmetastatic disease (≥N2 disease and/or M1 excluded) confirmed by blinded independent central review (BICR), have ECOG PS 0 or 1, and not have previously received systemic therapy for MIBC. Approximately 784 patients will be randomly assigned 1:1 to receive either 4 cycles of neoadjuvant EV + pembrolizumab followed by 5 cycles of adjuvant EV + 13 cycles of adjuvant pembrolizumab after RC+PLND or 4 cycles of neoadjuvant cisplatin-based chemotherapy followed by observation after RC+PLND. Neoadjuvant and adjuvant pembrolizumab 200 mg + EV 1.25 mg/kg will be administered intravenously every 3 weeks (Q3W), and neoadjuvant chemotherapy will consist of gemcitabine 1000 mg/m2 + cisplatin 70 mg/m2 Q3W. Randomization will be stratified by centrally determined (pathology or imaging) initial T and N stage (T2N0 or T3/T4aN0 or T1-T4aN1), PD-L1 combined positive score (CPS ≥10 or CPS < 10), and geographic region (United States or Europe or most of world). Imaging (CT or MRI) will be performed ≤6 weeks before cystectomy and 6 weeks after cystectomy. After postcystectomy imaging, additional imaging will be performed Q12W up to the end of year 2 (week 96) and at discontinuation. In year 3 and beyond, imaging will be performed Q24W. Primary end points are pathological complete response and event-free survival by BICR. Secondary end points are overall survival, disease-free survival, pathological downstaging, and safety and tolerability. Clinical trial information: NCT04700124.