Resected Non-small Cell Lung Cancer Research Articles

A new, potential and safe neoadjuvant therapy strategy in epidermal growth factor receptor mutation-positive resectable non-small-cell lung cancer-targeted therapy: a retrospective study.

Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC. This retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital. Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3-4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea. Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.

Frequency and predictive factors of nodal micro-metastasis (NMM) in resectable non-small cell lung cancer.

The frequency of lymph nodal micrometastasis (NMM) in resectable non-small cell lung cancer (NSCLC) is frequently underestimated when relying solely on standard hematoxylin and eosin staining during pathological examination. This is a retrospective cross-sectional diagnostic research. Medical records of resectable pN0 NSCLC patients who underwent curative resection in Maharaj Nakorn Chiang Mai Hospital between January 2006 to December 2017 were retrospectively reviewed. Immunohistochemistry (IHC) staining using cytokeratin AE1/AE3, p53 and BerEP4 markers was employed to detect NMM. Primary objective of this study was to determine frequency of NMM in pN0 resectable NSCLC. This study included 98 patients with pN0 NSCLC, of which 47 were male and 51 were female. NMM was detected in 21 of 98 patients (21.43%). Lymph node station 10 and 7 were the most common site of micrometastasis among patients with N1 and N2 micrometastasis, respectively. Cytokeratin AE1/AE3 was the most sensitive antibody in detecting micrometastasis in lymph nodes, identifying 25 out of 27 positive lymph nodes. Tumor size greater than 4 cm was a statistically significant predictive factor for NMM with risk ratio 6.69 [95% confidence interval (CI): 2.38-18.85, P<0.001]. NMM was identified in 21.43% of pN0 resectable NSCLC patients and tumor size greater than 4 cm is predictive factor for NMM.

Prognostic Value and Pathological Correlation of Peritumoral Radiomics in Surgically Resected Non-Small Cell Lung Cancer

ObjectivesTo determine the additional value of peritumoral radiomics in predicting overall survival (OS) in surgically resected non-small cell lung cancer (NSCLC) and its correlation with pathological findings. MethodsA total of 526 patients with surgically resected NSCLC were included (191 training, 160 internal validation, and 175 external validation cohorts). CT images were used to segment the gross tumor volume (GTV) and peritumoral volume (PTV) within distances of 3, 6, 9 mm from the tumor boundary (PTV3, PTV6, and PTV9), and radiomic features were extracted. Four prognostic models for OS (GTV, GTV + PTV3, GTV + PTV6, and GTV + PTV9) were constructed using the training cohort. The prognostic ability and feature importance were evaluated using the validation cohorts. Pathological findings were compared between the two patient groups (n = 30 for each) having the top 30 and bottom 30 values of the most important peritumoral feature. ResultsThe GTV + PTV3 models exhibited the highest predictive ability, which was higher than that of the GTV model in the internal validation cohort (C-index: 0.666 vs. 0.616, P = 0.027) and external validation cohort (C-index: 0.705 vs. 0.656, P = 0.048). The most important feature was GLDM_Dependence_Entropy, extracted from PTV3. High peritumoral GLDM_Dependence_Entropy was associated with a high proportion of invasive histological types, tumor spread through air spaces, and tumor-infiltrating lymphocytes (all P < 0.05). ConclusionsThe GTV and PTV3 combination demonstrated a higher prognostic ability, compared to GTV alone. Peritumoral radiomic features were associated with various pathological prognostic factors.

Prognostic Impact of Preoperative Assessment of Muscle Mass and Strength in Surgically Resected Lung Cancer.

The association between resected non-small cell lung cancer (NSCLC) and long-term outcomes of muscle mass depletion and muscle weakness has also not been well documented. This study evaluated whether muscle mass depletion assessed by bioelectrical impedance analysis (BIA) and low muscle strength assessed by the peak expiratory flow rate as a percentage of predicted value (%PEFR) were associated with surgical outcomes in patients with resected NSCLC. This retrospective study included 219 patients with resected NSCLC between 2016 and 2021. The cutoff value for muscle mass depletion was according to guidelines, for low muscle strength, we defined by receiver operating characteristics analysis for recurrence-free survival (RFS). Survival analysis was performed, and postoperative outcomes were compared. A total of 76 patients (34.7%) had muscle mass depletion, and 114 patients (52.1%) had low muscle strength. Muscle mass depletion and low muscle strength were independent poor prognostic factors for overall survival [hazard ratio (HR)=2.631, p=0.003; HR=1.983, p=0.044] and RFS (HR=3.120, p<0.001; HR=1.857, p=0.028) in multivariate analysis. Postoperative complication was associated with low muscle strength (p=0.009). Postoperative recurrence was associated with muscle mass depletion (p=0.03). Preoperative muscle mass depletion assessed by BIA and low muscle strength determined by %PEFR are worse prognostic factors after surgical resection for NSCLC. Our results may provide some important information for preoperative management.

A novel neoadjuvant therapy for early-stage non-small cell lung cancer in a mouse model.

Lung cancer is the common malignancy with high mortality rate in the world. Even with curative resection for early-stage lung cancer patients, the rate of postoperative recurrence and metastasis is still high. Neoadjuvant nivolumab combined with chemotherapy leads to improved pathological complete response rate and event-free survival in resectable non-small cell lung cancer (NSCLC) patients. However, the neoadjuvant therapy is not only accompanied by grade 3 or above adverse events which resulting in the potential missing out on the window for curative surgery for the patients, but also has low efficacy especially in patients with low programmed death ligand 1 (PD-L1) expression. Hence, it is particularly important to explore innovative ways to inhibit tumour recurrence and metastasis. In the present study, we investigated whether neoadjuvant therapy with intralesional Rose Bengal (RB) elicited specific immune responses compared with control group, and then the lung cancer mouse model was used to evaluated the immunological mechanism. The secondary Lewis lung cancer cells (LLCs) tumour growth was significantly suppressed by RB intralesional injection into subcutaneous tumour; the formation rate of secondary tumours induced by the B16 melanoma cell injection was 100%. Intralesional RB neoadjuvant therapy before surgical resection exhibited effectively enhanced T central memory cells (Tcm) and T memory stem cells (Tscm) + naïve T cells (Tn) infiltration, elicited stronger cytotoxic T lymphocyte (CTL) responses against LLCs, and displayed markedly higher proportions of splenic lymphocytes that produce tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) upon restimulation in a lung cancer mouse model. Based on our preclinical data, neoadjuvant therapy with intralesional RB injection generated immune memory and prevented the recurrence and metastasis of tumour in a lung cancer mouse model, which provides a new strategy for neoadjuvant treatment of early-stage NSCLC.

Gut microbes as medical signature for the effectiveness of immunotherapy in patients with advanced non-small cell lung cancer.

Lung cancer (LC) is the most common cause of cancer-related death worldwide and poses a severe threat to public health. Immunotherapy with checkpoint blockers has improved the outlook for advanced non-small cell lung cancer (NSCLC) therapy. For the treatment of patients with advanced NSCLC, antibodies such as anti-programmed death 1 (anti-PD1), anti-programmed death ligand 1 (anti-PD-L1), and anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) are of paramount importance. Anti-PD-1 and anti-PD-L1 monoclonal antibody therapies are used to block the PD-1/PD-L1 pathway and identify cancerous cells to the body's defenses. Antibodies directed against CTLA-4 (anti-CTLA-4) have also been shown to improve survival rates in patients with NSCLC. Currently, other immunotherapy approaches like neoadjuvant immune checkpoint inhibitors (NAICIs) and chimeric antigen receptor T-cell (CAR-T) therapies are applied in NSCLC patients. NAICIs are used for resectable and early stage NSCLC and CAR-T is used to find more useful epitope sites for lung tumors and destroy cancer cells. A patient's gut microbiota might influence how their immune system reacts to NSCLC immunotherapy. The majority of intestinal microbes stimulate helper/cytotoxic T cells, induce natural killer (NK) cells, activate various toll-like receptors (TLR), build up cluster of differentiation 8 (CD8), increase PD-1 production, and attract chemokine receptors towards cancer cells. Thus, they serve as immune inducers in NSCLC immunotherapy. Nonetheless, certain bacteria can function as immune suppressors by inhibiting DC proliferation, stopping CD28 trafficking, restoring CD80/CD86, increasing immunological tolerance, and upsetting Th17 cells. Therefore, they are prevalent in non-responders with NSCLC immunotherapy.

Prognostic factors of resectable anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients: a retrospective analysis based on a single center.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) exhibited a higher propensity for lymph node metastasis (LNM). This study aimed to investigate risk factors of occult lymph node metastasis (OLNM) and recurrence in resectable ALK-rearranged NSCLC patients. This retrospective analysis included patients with ALK-rearranged NSCLC receiving lung resections at Shanghai Pulmonary Hospital from June 2016 to August 2021. Logistic regression analysis was used to ascertain predictors of OLNM, and Cox regression analysis to identify risk factors of recurrence. A total of 603 resectable ALK-rearranged NSCLC patients were included. The mean age was 55 years old. There were 171 patients (28.4%) pathologically confirmed to have LNM, 51.5% of which were occult. Logistic regression analysis identified clinical tumor size and computed tomography (CT) density as independent factors for OLNM. Cox regression analysis showed that pleural invasion and pathological tumor size were independent prognosticators for recurrence in pathologically nodal negative patients. Among pathologically nodal positive patients, adjuvant ALK-tyrosine kinase inhibitors (TKI) showed a similar recurrence-free survival (RFS) to chemotherapy (hazard ratio, 0.454; 95% confidence interval, 0.111-1.864). Assessing the potential risk of OLNM is required for ALK-rearranged NSCLC patients with large tumors characterized by high CT densities. Patients with large pathological tumor size or pleural infiltration should be closely monitored despite being pathologically nodal negative. Additionally, adjuvant ALK-TKI may present a comparable RFS to chemotherapy in pathologically nodal positive patients.

Comparison of different criteria for estimating major pathological response in resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy

BackgroundMajor pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. MethodsWe conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). ResultsThe MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. ConclusionIASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.

Impact of chronic obstructive pulmonary disease on the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy for resectable non-small cell lung cancer: a retrospective cohort study

BackgroundNeoadjuvant immune checkpoint inhibitors(ICIs) combined with chemotherapy can improve non-small cell lung cancer(NSCLC) patients' pathological responses and show promising improvements in survival. Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease, and its associated abnormal inflammatory response affects not only the immunotherapy efficacy but also immune-related adverse events. It remains unclear whether NSCLC patients with COPD can benefit from neoadjuvant ICIs combined with chemotherapy.MethodsA retrospective observational clinical study was conducted on 105 consecutive NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy at the Department of Thoracic Surgery of Tianjin Chest Hospital between April 2020 and April 2023.ResultsA total of 74 NSCLC patients were included in the study, including 30 patients with COPD and 44 patients without COPD. The percentage of patients with a pathological complete response (PCR) was higher in the COPD group than in the non-COPD group (43.3% vs. 20.5%, P = 0.042). Multivariate logistic regression analysis of factors associated with PCR showed that the adjusted odds ratio (OR) was statistically significant for presence of COPD (OR = 3.020, 95%CI: 1.042–8.757; P = 0.042). Major pathological response (66.7% vs. 50%, P = 0.155), R0 resection rate (96.7% vs.93.2%, P = 0.642), N2 lymph node downstaging(92.3% vs. 66.7%, P = 0.182) and objective response rate (70% vs. 63.6%, P = 0.57) were not significantly different between the groups. Progression-free survival(PFS) was not reached in the COPD group and 17 months (95%CI: 12.1–21.9) in the non-COPD group, with statistically significance (χ2 = 6.247, P = 0.012). Multivariate Cox’s regression analysis showed that the adjusted hazard ratio (HRadj) was statistically significant for presence of COPD (HRadj = 0.321, 95%CI: 0.111–0.930; P = 0.036). The grade 3 and grade 4 adverse events in the COPD group were leukopenia (3.3%, 6.7%), neutropenia (3.3%, 6.7%), fatigue (6.7%, 0%), gastrointestinal reactions (3.3%, 0%), and hypothyroidism (3.3%, 0%). In the non-COPD group, the corresponding adverse events were leukopenia (6.8%, 6.8%), neutropenia (3.3%, 6.8%), fatigue (2.3%, 0%), gastrointestinal reactions (2.3%, 0%), and hypothyroidism (2.3%, 0%), respectively.ConclusionsThe present study indicates that the presence of COPD may improve PCR, prolong PFS, and have an acceptable safety profile in NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy.

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

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. 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. 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. The implementation of VATS lobectomy has been successful in our small geographically isolated centre, serving a population of 390000. Although technically challenging, VATS lobectomy was implemented fast for most NSCLC cases, with short-term outcomes that are comparable to larger high-volume centres.

Adjuvant and neo-adjuvant therapy for non-small cell lung cancer without EGFR mutations or ALK rearrangements.

Surgical resection is the most effective therapeutic option for the cure in early stage resectable non-small-cell lung cancer (NSCLC). However, despite complete resection, up to 70% of patients die within 5 years mainly due to tumor recurrence in extra-thoracic organs. Adjuvant or neoadjuvant platinum-based chemotherapy may improve postoperative survival, but the absolute survival benefit is modest with an around 5% improvement at 5 years. Recent advance in systemic therapy has changed treatment strategy for advanced unresectable NSCLC, and also has provided a paradigm shift in treatment strategy for resectable NSCLC. For NSCLC without oncogenic driver alterations, immunotherapy using immune-checkpoint inhibitors may improve clinical outcomes in preoperative neoadjuvant setting as well as in postoperative adjuvant setting. Here, we overview recent evidence of adjuvant and neoadjuvant therapy and discuss emerging clinical questions in decision-making of treatment for potentially resectable patients with NSCLC harboring no oncogenic alterations.

Identification of protein biomarkers for prediction of response to platinum-based treatment regimens in patients with non-small cell lung cancer.

The majority of patients with resected stage II-IIIA non-small cell lung cancer (NSCLC) are treated with platinum-based adjuvant chemotherapy (ACT) in a one-size-fits-all approach. However, a significant number of patients do not derive clinical benefit, and no predictive patient selection biomarker is currently available. Using mass spectrometry-based proteomics, we have profiled tumour resection material of 2 independent, multi-centre cohorts of in total 67 patients with NSCLC who underwent ACT. Unsupervised cluster analysis of both cohorts revealed a poor response/survival sub-cluster composed of ~ 25% of the patients, that displayed a strong epithelial-mesenchymal transition signature and stromal phenotype. Beyond this stromal sub-population, we identified and validated platinum response prediction biomarker candidates involved in pathways relevant to the mechanism of action of platinum drugs, such as DNA damage repair, as well as less anticipated processes such as those related to the regulation of actin cytoskeleton. Integration with pre-clinical proteomics data supported a role for several of these candidate proteins in platinum response prediction. Validation of one of the candidates (HMGB1) in a third independent patient cohort using immunohistochemistry highlights the potential of translating these proteomics results to clinical practice.

Significance of preoperative evaluation of modified advanced lung cancer inflammation index for patients with resectable non-small cell lung cancer.

Body composition and systemic inflammation/nutrition have been identified as important clinical factors in cancer patients. The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation/nutrition, is defined as appendicular skeletal muscle index × serum albumin/neutrophil-lymphocyte ratio. This retrospective study aimed to investigate associations between preoperative mALI and surgical outcomes in non-small cell lung cancer (NSCLC) patients. We examined 665 patients with resectable stage I-III NSCLC who underwent pulmonary resection. Patients were divided into low-mALI (n = 168) and high-mALI (n = 497) based on the lower quartile. Kaplan-Meier curves and Cox regression analysis were used to assess the prognostic value of mALI. We then performed 1:1 propensity score matching (PSM) for high- and low-mALI to further investigate impacts on survival. Overall survival (OS) and recurrence-free survival (RFS) were both significantly poorer in the low-mALI group than in the high-mALI group (58.2% vs. 79.6%, P < 0.001; 48.8% vs. 66.7%, P < 0.001, respectively). Multivariate analysis revealed low-mALI as an independent predictor of OS (hazard ratio [HR], 2.116; 95% confidence interval (CI) 1.458-3.070; P < 0.001) and RFS (HR, 1.634; 95% CI 1.210-2.207; P = 0.001). After PSM, low-mALI remained as an independent predictor of OS (HR, 2.446; 95% CI 1.263-4.738; P = 0.008) and RFS (HR 1.835; 95% CI 1.074-3.137; P = 0.026). Preoperative mALI appears to offer an independent predictor of poor surgical outcomes as a simple, routinely available, and inexpensive biomarker in patients with resectable NSCLC.

(Neo)adjuvant approaches in lung cancer—paving the road to a cure

SummaryImmune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of metastatic non-small-cell lung cancer (NSCLC). During the past few years the focus of research has shifted toward examining these therapies in patients with early-stage NSCLC to improve long-term overall survival and cure rates. As recurrence rates are high and the relapse pattern in patients with completely resected early-stage NSCLC is predominantly systemic, high expectations rest on the integration of ICI therapy in their treatment approach. A large number of studies with adjuvant or neo-adjuvant ICI are ongoing. The first data from phase III studies have demonstrated improvements in disease-free survival and pathologic remissions, but overall survival data are mostly immature. Additionally, targeted therapies have also been explored in early-stage NSCLC. The first very promising results are available from EGFR-mutant and ALK-translocated NSCLC and have already changed our clinical practice for some patient subgroups. This review discusses the most recent results of phase III trials in the neoadjuvant, perioperative, and adjuvant setting for ICI and targeted therapies in early-stage resectable NSCLC.

Outcomes of Completion Lobectomy for Locoregional Recurrence after Sublobar Resection in Patients with Non-small Cell Lung Cancer.

This retrospective study aimed to determine the treatment patterns and the surgical and oncologic outcomes after completion lobectomy (CL) in patients with locoregionally recurrent stage I non-small cell lung cancer (NSCLC) who previously underwent sublobar resection. Data from 36 patients who initially underwent sublobar resection for clinical, pathological stage IA NSCLC and experienced locoregional recurrence between 2008 and 2016 were analyzed. Thirty-six (3.6%) of 1,003 patients who underwent sublobar resection for NSCLC experienced locoregional recurrence. The patients' median age was 66.5 (range, 44-77) years at the initial operation, and 28 (77.8%) patients were men. Six (16.7%) patients underwent segmentectomy and 30 (83.3%) underwent wedge resection as the initial operation. The median follow-up from the initial operation was 56 (range, 9-150) months. Ten (27.8%) patients underwent CL, 22 (61.1%) underwent non-surgical treatments (chemotherapy, radiation, concurrent chemoradiation therapy), and 4 (11.1%) did not receive treatment or were lost to follow-up after recurrence. Patients who underwent CL experienced no significant complications or deaths. The median follow-up time after CL was 64.5 (range, 19-93) months. The 5-year overall survival (OS) and post-recurrence survival (PRS) were higher in the surgical group than in the non-surgical (p<0.001) and no-treatment groups (p<0.001). CL is a technically demanding but safe procedure for locoregionally recurrent stage I NSCLC after sublobar resection. Patients who underwent CL had better OS and PRS than patients who underwent non-surgical treatments or no treatments; however, a larger cohort study and long-term surveillance are necessary.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non–Small Cell Lung Cancer

Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. ClinicalTrials.gov Identifier: NCT04158440.

Favourable surgical outcomes for either second primary lung cancer or intrapulmonary metastasis after resection of non-small-cell lung cancer.

Metachronous lung cancer arising after resection of non-small-cell lung cancer is either a second primary lung cancer (SPLC) or intrapulmonary metastasis (IPM) of the initial lung cancer; however, differential diagnosis is difficult. We evaluated the surgical outcomes of metachronous lung cancer in a combined population of patients with SPLC and IPM. A retrospective study of 3534 consecutive patients with resected non-small-cell lung cancer between 1992 and 2016 was conducted at 4 institutions. A total of 105 patients (66 males; median age, 70 years) who underwent a second pulmonary resection for metachronous lung cancer were included. Most patients (81%) underwent sublobar resection, and there was no 30-day mortality. All metachronous lung cancers were cN0, 5 were pN1-2. The postoperative comprehensive histologic assessment revealed SPLC (n = 77) and IPM (n = 28). The 5-year overall survival rate after the second resection was 70.6% (median follow-up: 69.7 months). A multivariable analysis showed that age >70 years at the second resection (P = 0.013), male sex (P = 0.003), lymph node involvement in metachronous cancer (P < 0.001), pathological invasive size of metachronous cancer >15 mm (P < 0.001) and overlapping squamous cell carcinoma histology of the initial and metachronous cancers (P = 0.003) were significant prognostic factors for poor survival after the second resection, whereas histological IPM was not (P = 0.065). Surgery for cN0 metachronous lung cancer is safe and shows good outcomes. There were no statistically significant differences in the SPLC and IPM results. Caution should be exercised when operating on patients with overlapping squamous cell carcinoma.

Medicaid Expansion Under the Affordable Care Act and Early Mortality Following Lung Cancer Surgery

Medicaid expansion under the Patient Protection and Affordable Care Act is associated with gains in health insurance coverage, earlier stage diagnosis, and improved survival among patients with cancer. To examine the association of Medicaid expansion with changes in early mortality among adults undergoing surgical resection of non-small cell lung cancer (NSCLC), a setting in which access to care is a major determinant of survival. This cohort study used the National Cancer Database to identify 14 984 adults 45 to 64 years of age who underwent surgical resection of NSCLC between 2008 and 2019. Analysis was conducted between March 28, 2021, and September 1, 2023. State of residence Medicaid expansion status. Descriptive statistics were used to compare study population characteristics by Medicaid expansion status of patients' state of residence. Difference-in-differences analyses were used to evaluate the association between Medicaid expansion and postoperative mortality before implementation of the ACA (2008-2013) vs after (2014-2019). Among 14 984 adults included, the mean (SD) age was 56.3 (5.1) years, 54.6% were women, and 62.1% lived in Medicaid expansion states. Both 30-day (from 0.97% to 0.26%) and 90-day (from 2.63% to 1.32%) postoperative mortality decreased from before the ACA to after among patients residing in Medicaid expansion states (both P < .001) but not in nonexpansion states (30-day mortality before the ACA, 0.75% vs after the ACA, 0.68%; P = .74; and 90-day mortality before the ACA, 2.43% vs after the ACA, 2.20%; P = .57), leading to a difference-in-differences of -0.64 percentage points (95% CI, -1.19 to -0.08; P = .03) for 30-day mortality and -1.08 percentage points (95% CI, -2.08 to -0.08; P = .03) for 90-day mortality. The difference-in-differences for in-hospital mortality was not significant (P = .34) between expansion states (1.41% before the ACA to 0.77% after the ACA; 0.63 percentage point decrease; P = .004) and nonexpansion states (1.49% before the ACA to 1.20% after the ACA; 0.30 percentage point decrease; P = .29). In this cohort study of patients with NSCLC, Medicaid expansion was associated with declines in 30- and 90-day postoperative mortality following hospital discharge. These findings suggest that Medicaid expansion may be an effective strategy for improving access to care and cancer outcomes in this population.

Influence of adjuvant chemotherapy on survival for patients with completely resected high-risk stage IB NSCLC

BackgroundThe use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors.MethodsPatients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not.ResultsIn univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not.ConclusionIn patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

Neoadjuvant vs Adjuvant Chemoimmunotherapy for Stage II-IIIB Non-Small Cell Lung Cancer

BackgroundIn patients with resectable non-small cell lung cancer (NSCLC), recent trials demonstrate survival benefit of chemoimmunotherapy over chemotherapy alone in both the neoadjuvant and adjuvant settings. To date, there is no direct comparison between neoadjuvant and adjuvant protocols. We compared neoadjuvant vs adjuvant chemoimmunotherapy for resectable stage II-IIIB NSCLC. MethodsWe queried the National Cancer Database for patients who had undergone an operation for stage II-IIIB NSCLC and who had received neoadjuvant or adjuvant chemoimmunotherapy between 2015 and 2020. We used inverse probability weighting to adjust for confounding variables and used Kaplan-Meier survival curves and Cox regression to explore the relationship between treatment groups and overall survival (OS) at 3 years postoperatively. ResultsThe inverse probability-weighted cohort represented 2119 weighted patient cases (neoadjuvant, 1034; adjuvant, 1085). Kaplan-Meier analysis demonstrated a significant OS benefit for neoadjuvant chemoimmunotherapy compared with adjuvant chemoimmunotherapy in the weighted cohort (3-year OS: 77% [95% CI, 71%-83%] vs 68% [95% CI, 64%-72%]; P = .035). On adjusted Cox regression, neoadjuvant chemoimmunotherapy was associated with a significant OS benefit (hazard ratio, 0.70; 95% CI, 0.50-0.96; P = .027). Among patients for whom pathologic stage data were available, 25% of patients receiving neoadjuvant chemoimmunotherapy had a pathologic complete response, with an additional 32.5% being downstaged. ConclusionsNeoadjuvant chemoimmunotherapy confers a significant OS benefit over adjuvant chemoimmunotherapy for patients with resectable stage II-IIIB NSCLC. Although randomized trials are needed to confirm our findings, strong consideration should be given to administering neoadjuvant chemoimmunotherapy to patients who are predetermined to receive systemic treatment.