IIIA Non-small Cell Lung Cancer Research Articles

Case report: hypertrophic osteoarthropathy improves with immune checkpoint inhibitor therapy.

We report a case of a 66 year-old male with recurrent stage IIIA non-small cell lung cancer (NSCLC) and no prior arthritis or bone disease who developed hypertrophic osteoarthropathy (HOA) prior to immunotherapy treatment. Approximately one month after the first durvalumab infusion and without other interventions for symptom management, the patient reported improvements to his hand pain, with complete resolution of symptoms after five durvalumab treatments. Repeat x-ray after nine cycles of durvalumab showed decreased periosteal thickening of the phalanges bilaterally. He had no evidence of recurrent NSCLC based on serial computed tomography one year after durvalumab initiation. To our knowledge, there are no documented reports on the isolated effect of immune-checkpoint inhibitor (ICI) therapy on HOA. This case suggests that durvalumab may have a positive role in the management of HOA in NSCLC patients. Further research is needed to better understand the interaction of ICIs, HOA and other paraneoplastic syndromes.

Lung autotransplantation combined with postoperative chemotherapy and immunotherapy: a three-year follow-up case report

BackgroundLung cancer remains a leading cause of cancer-related mortality worldwide. Autotransplantation has emerged as a potential surgical intervention in select cases, with the aim of achieving curative outcomes. This case report describes a novel approach combining lung autotransplantation with postoperative chemotherapy and immunotherapy, delineating the patient's journey over a period of three years.Case presentationWe report on a 37-year-old patient with stage IIIA non-small cell lung cancer (NSCLC) who underwent lung autotransplantation. Despite the complexity of the procedure, the patient had a favorable postoperative course. Adjuvant therapy included a PD-1 inhibitor and a standard chemotherapy regimen. The patient’s follow-up involved regular clinical assessment, imaging, and functional status evaluation, demonstrating a remarkable disease-free survival at the three-year mark postoperatively.ConclusionThis case highlights the potential for lung autotransplantation coupled with immunotherapy and chemotherapy to yield significant long-term survival benefits in patients with NSCLC. The favorable outcome suggests that this integrative treatment strategy warrants further investigation and may offer hope to patients with similarly advanced lung cancer.

Inclusion of Surgery in Multimodality Treatment is Predictive of Better Survival in Stage IIIA Non-small Cell Lung Cancer: an Inverse Probability Treatment-Weighting Analysis

IntroductionStage IIIA non-small cell lung cancers (NSCLC) are treated with surgical based multimodality approach or definitive chemoradiation therapy plus durvalumab consolidation. It is not clear whether surgery-based multimodality therapy has any survival advantage over definitive chemoradiation plus immunotherapy consolidation. MethodNational Cancer Database (NCDB) was used to identify NSCLC patients at stage IIIA (AJCC8, T3N1/T4N0-1 or T1N2/T2N2) who are treated with surgery-based multimodality approach or definitive chemoradiation plus durvalumab. Survival between groups were compared using inverse probability of treatment weighting (IPTW)-adjusted Kaplan Meier curves and Cox proportional hazards regression analysis. Results were independently confirmed by Landmark Inverse and Clone Censor Weight analyses to address immortal time bias. ResultsFrom 2017 to 2019, 24,170 patients are identified as potentially resectable stage IIIA (T3N1, T4N0-1, T1N2/T2N2). Among them, 2,615 (10.8%) received surgery-based multi-modality therapy and 2,985 (12.4%) received definitive chemoradiation plus durvalumab. Surgery based multimodality approach had significant survival advantage over definitive chemoradiation plus durvalumab (HR 0.74; 95% CI 0.69-0.79, P<0.001). The median overall survival (mOS) for the definitive chemoradiation plus durvalumab group was 48.59 m whereas mOS was not reached for surgery-based multimodality group. This trend persisted in both N2 negative and positive tumors. Neoadjuvant chemotherapy was just as effective as adjuvant chemotherapy and delay of immunotherapy consolidation to 12 weeks after initiation of chemoradiation did not negatively affect survival outcome. ConclusionFor stage IIIA NSCLC patients, surgery-based multimodality treatment outperformed chemoradiation plus durvalumab in survival. DisclosureZH reports grant from Bayer Inc, BMS, Merck, AMG, Legend biotech, BeiGene, Novartis and OncC4. No disclosure from all other authors. MicroAbstractResectable stage IIIA non-small cell lung cancer treated with multi-disciplinary approach with surgical resection survive longer than those who were treated with concurrent chemoradiation therapy plus consolidation durvalumab. Chemotherapy can be given as adjuvant or as neoadjuvant with no survival difference. Delay of immunotherapy consolidation to more than 12 weeks after starting radiation does not compromise survival outcome.

EP.08F.20 Stage IIIA Non-Small Cell Lung Cancer (NSCLC): Outcomes by Treatment Strategy

EP.08F.20 Stage IIIA Non-Small Cell Lung Cancer (NSCLC): Outcomes by Treatment Strategy

Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial

Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC. Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union.

Cost-effectiveness of adjuvant icotinib versus chemotherapy for patients with stage II–IIIA EGFR-mutated non-small cell lung cancer in China

ObjectiveIcotinib has been approved for adjuvant treatment of stage II–IIIA non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations in China, yet the long-term costs...

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Molecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).

8005 Background: Osimertinib (osi) is a third-generation, central nervous system-active EGFR-TKI, that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations. Adj osi (3 years [yrs]) is recommended for resected EGFRm stage IB–IIIA NSCLC, based on significant improvements in disease-free survival (DFS) and overall survival (OS) in the Phase III ADAURA study (NCT02511106). A trend towards an increased DFS event rate beyond 3 yrs suggests some pts may benefit from longer adj osi treatment (tx). We explored if plasma ctDNA-based, tumor-informed MRD could predict disease recurrence. Methods: Eligible pts (≥18 yrs [≥20 in Japan/Taiwan], WHO PS 0/1 with completely resected EGFRm [Ex19del/L858R] stage IB, II or IIIA [AJCC 7th edition] NSCLC) were randomized 1:1 to osi 80 mg once daily or placebo (pbo) until disease recurrence, tx completion (up to 3 yrs), or a discontinuation criterion was met. Personalized MRD panels (RaDaR, NeoGenomics) were used, comprised of ≤50 tumor-specific variants, based on whole exome sequencing of resected tumor tissue (variants identified in germline DNA removed). Plasma sample collection: baseline (BL; at randomization surgery and adj Ctx, if received), on tx (every 12 weeks [wks]), tx discontinuation, and post-tx completion (wk 12, wk 24, then every 24 wks until 5 yrs). Plasma samples were analyzed for detection of ctDNA (MRD+). Molecular recurrence or DFS (MRD/DFS) was defined as time from randomization to post-BL MRD+, disease recurrence, or death and was compared across arms. DFS was investigator-assessed. Results: Of 682 pts randomized, 245 (36%) had samples required to produce MRD panels, which were evaluable for 220 (32%) pts across both arms. In the osi vs pbo arms, 5/112 (4%) vs 13/108 (12%) pts were MRD+ at BL; 4/5 pts became MRD– during osi tx vs 0/13 pts on pbo. On tx, MRD detection had clinical sensitivity of 65% (62 MRD+/96 DFS+), specificity of 95% (118 MRD–/124 DFS–) and preceded a DFS event by a median (95% CI) of 4.7 (2.2, 5.6) months (mos) across both arms. Median follow-up time from randomization was 44.2 (95% CI 42.4, 49.1) and 19.1 (95% CI 11.1, 28.3) mos for osi and pbo arms, respectively. Overall, 86% (95% CI 78, 92) vs 36% (95% CI 27, 45) pts in the osi vs pbo arms were MRD/DFS event free at 36 mos (HR: 0.23; 95% CI 0.15, 0.36). MRD/DFS events in the osi arm were detected at any time post-BL in 28 (25%) pts, of whom 19/28 (68%) had events post-adj osi. Most (11/19 [58%]) MRD/DFS events detected occurred within 12 mos of osi tx completion. Conclusions: MRD+ preceded DFS events in most pts with a median lead time of 4.7 mos across both arms. MRD– was maintained for most pts during adj osi tx with the majority of MRD/DFS events occurring after osi tx completion. MRD detection could potentially identify a subset of pts likely to benefit from longer adj osi. Clinical trial information: NCT02511106 .

Yes to adjuvant osimertinib therapy in EGFR-mutated stage IB–IIIA non-small cell lung cancer post resection, but for how long? (ADAURA/NCT02511106)

Yes to adjuvant osimertinib therapy in EGFR-mutated stage IB–IIIA non-small cell lung cancer post resection, but for how long? (ADAURA/NCT02511106)

Biomarker testing and adjuvant osimertinib use in patients with resectable EGFR-mutated stage IB–IIIA NSCLC: Physician practices, therapy choice, and barriers among US oncologists.

e20007 Background: Epidermal Growth Factor Receptor mutations ( EGFRm) are commonly found in patients with resectable and metastatic non-small cell lung cancer (NSCLC). In December 2020, the FDA approved adjuvant osimertinib, for resectable EGFRm NSCLC, based on results of the ADAURA trial which showed significant survival benefit compared to placebo post-resection, further reinforcing need for biomarker testing in NSCLC. In light of publication of Aduara this study aims to understand US oncologists' biomarker testing practices and adjuvant osimertinib use in resectable EGFRm Stage IB–IIIA NSCLC. Methods: Questions related to biomarker testing and adjuvant therapy decision-making for resectable EGFRm Stage IB–IIIA NSCLC were presented to US-based oncologists/hematologists during live meetings in June and July 2023. In addition, questions related to impact of updated overall survival data from ADAURA trial on physicians’ reported treatment preferences were presented.Up to 108 participants responded to questions, though not all participants answered each question. Aggregate responses were summarized using descriptive statistics. Results: Among respondents, 52% identified as medical oncologists and 46% as hematological oncologists, 41% identified as being from an independent community practice and 75% indicated lung cancer was among the 3 solid tumors they most often treat. For patients with newly diagnosed resectable NSCLC patients, respondents indicated that genetic testing was performed before surgery on initial diagnostic biopsy sample (73%), after surgery (44%), and upon progression/relapse (31%). Commonly utilized diagnostic tools reported by respondents included NGS testing of tissue samples (87%), NGS liquid biopsy (42%), and IHC (31%). Barriers impacting molecular testing practices for resectable NSCLC included access to tissue for testing, cost to patient, disease stage, histology, tumor burden, patient age, patient fitness, and prior authorization or time to approval. Half (50%) of respondents reported prescribing adjuvant osimertinib monotherapy for patients with resectable EGFRm NSCLC in the past 6 months. After reviewing the updated ADAURA data, most (83%) respondents indicated they would prescribe adjuvant osimertinib immediately following surgery for resectable EGFRm NSCLC, and 56% would prescribe adjuvant osimertinib with or without adjuvant chemotherapy, 21% would prescribe adjuvant osimertinib with adjuvant chemotherapy, and 17% would prescribe adjuvant osimertinib only. Conclusions: Overall, nearly three-fourths of medical oncologist respondents prefer pre-operative genetic testing and regardless of test timing, when EGFRm identified &gt; 80% will treat adjuvantly with osimertinib. Unfortunately, multiple barriers complicate this pursuit of evidence-based medicine.

A Single-Center Experience in Combined Oncological-Surgical Treatment for Resectable Locally Advanced Non-Small Cell Lung Cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is the most common pulmonary malignancy, frequently diagnosed at an advanced stage (III/IV). Patients in the Locally Advanced Stage Subgroup (IIIA) are relatively few, yet compose heterogenic phenotypes, posing a diagnostic and treating challenge, leading to a lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, patients with operable stage IIIA NSCLC who underwent surgery between 2013 and 2020 were evaluated on several aspects, including the initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, and overall survival at 2 years and 5 years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 19 patients, of which 25% of cases were defined as a complete pathological response. The 2-year overall survival rate was 65% and the 5-year overall survival rate was 62%. The main pattern of disease recurrence was distant metastasis.

A randomized phase III trial of postoperative surveillance for pathological stage II and IIIA non-small cell lung cancer (JCOG2012, PHOENIX).

The goal of postoperative surveillance following non-small cell lung cancer surgery is to detect recurrence and second primary malignancies while curative treatment is still possible. Although several guidelines recommend that patients have computed tomography (CT) scans every 6months for the first 2years after resection, then once a year, there is no evidence that it is effective for survival, especially in locally advanced non-small cell lung cancer. In October 2022, we launched a multi-institutional, randomized controlled phase III trial for pathological stage II and IIIA non-small cell lung cancer patients to confirm the non-inferiority of less intensive surveillance with less frequent CT scans versus standard surveillance in terms of overall survival. The primary endpoint is overall survival. We intend to enroll 1100 patients from 45 institutions over 4years. The trial has been registered in the Japan Registry of Clinical Trials under the code jRCT1030220361 (https://jrct.niph.go.jp/latest-detail/jRCT1030220361).

Predicting therapeutic response to neoadjuvant immunotherapy based on an integration model in resectable stage IIIA (N2) non-small cell lung cancer

ObjectiveAccurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remains clinically challenging. In this study, we investigate the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase II trial. MethodsBlood samples were prospectively collected from 45 stage IIIA (N2) NSCLC patients undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the CT-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. ResultsAt baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 Muts/Mb was associated with significantly higher MPR rates (77.8% vs. 38.5%, p = 0.042), and longer disease-free survival (DFS, p = 0.043), but not overall survival (p = 0.131), compared to bTMB < 11 Muts/Mb in 35 patients with bTMB available. The developed DL model achieved an area under the curve (AUC) of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an AUC of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathological response and survival. Compared to ctDNA residual, ctDNA clearance before surgery was associated with significantly higher MPR rates (88.2% vs. 11.1%, p < 0.001) and improved DFS (p = 0.010). ConclusionsThe integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

Triple-induction treatment for locally advanced non-small cell lung cancer: a case report of pathological complete response

BackgroundIn patients with resectable stage III non-small cell lung cancer (NSCLC), induction chemoimmunotherapy followed by surgical resection has shown unprecedented rates of pathological response and event-free survival. However, a triple-induction including radiochemotherapy and immunotherapy followed by surgical resection has not been routinely established in clinical practice.Case presentationWe report the case of a 47-year-old patient with stage IIIA NSCLC who was treated in a combined concept including induction concurrent radiochemotherapy, followed by 4 cycles of pembrolizumab and subsequent intrapericardial left-sided pneumonectomy. Histological analysis revealed a pathological complete response.ConclusionsThe case demonstrates that the combination of neoadjuvant chemo-, radio- and immunotherapy in advanced NSCLC may lead to a relevant down-staging and may enable a R0-resection of a borderline resectable tumor. However, the combination of four different treatment modalities requires resilience and a good performance status. A triple induction treatment may be a promising option for selected patients with locally advanced NSCLC and good performance status.

Abstract CT281: The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC)

Abstract Background: Pembrolizumab (pembro; anti-PD-1) is indicated as adjuvant monotherapy following resection and adjuvant chemotherapy in patients (pts) with stage IB (T2a ≥4 cm), II, or IIIA NSCLC (per AJCC v7). However, many pts experience disease recurrence, and have limited treatment options available. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens that is specifically tailored and manufactured for each pt derived from their tumor. V940 as monotherapy and in combination with pembro has shown preliminary antitumor activity in the phase 1 KEYNOTE-603 study in several solid tumor types, including NSCLC. Additionally, in pts with completely resected, high-risk stage IIIB/C/D and IV cutaneous melanoma in the KEYNOTE-942 primary analysis, V940 plus pembro demonstrated significant improvements in recurrence-free survival (HR, 0.561 [95% CI, 0.309-1.017]; P = 0.0266) and distant metastasis-free survival (HR, 0.347 [95% CI, 0.145-0.828]; P = 0.0063) vs pembro alone. Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro in pts with completely resected and chemotherapy-treated stage II-IIIB (N2) NSCLC (AJCC v8). Methods: Eligible pts aged ≥18 years with completely resected stage II, IIIA, or IIIB (N2) squamous or nonsquamous NSCLC (per AJCC v8.0) where EGFR-directed therapy is not indicated as primary therapy (ie, absence of sensitizing EGFR mutations e.g. DEL19 or L858R), who have received 1-4 doses of adjuvant platinum-doublet chemotherapy, have ECOG PS 0 or 1, and have available tumor tissue for next-generation sequencing and PD-L1 testing will be enrolled. Pts must not have received previous neoadjuvant therapy for NSCLC and must not have received or be candidates for adjuvant radiotherapy. Pts will be randomized 1:1 to receive V940 1 mg IM or placebo Q3W for up to 9 doses plus pembro 400 mg IV Q6W for up to 9 cycles or until disease recurrence, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (squamous vs nonsquamous), PD-L1 TPS (&amp;lt;1% vs 1%-49% vs ≥50%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). The primary endpoint is disease-free survival per investigator review. Secondary endpoints include distant metastasis-free survival per investigator assessment, OS, lung cancer‒specific survival, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter. Enrollment began in October 2023 and is ongoing globally (NCT06077760). Citation Format: Jonathan D. Spicer, Santosh M. Nair, Adnan Khattak, Jay M. Lee, Michelle Brown, Robert S. Meehan, Nazly Shariati, Xuan Deng, Ayman Samkari, Jamie E. Chaft. The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT281.

Real-world treatment patterns and clinical outcomes in patients with stage III NSCLC in Korea: The KINDLE study.

KINDLE-Korea is part of a real-world KINDLE study that aimed to characterize the treatment patterns and clinical outcomes of patients with stage III non-small cell lung cancer (NSCLC). The KINDLE was an international real-world study that explores patient and disease characteristics, treatment patterns, and survival outcomes. The KINDLE-Korea included stage III NSCLC patients diagnosed between January 2013 and December 2017. A total of 461 patients were enrolled. The median age was 66 years (range: 24-87). Most patients were men (75.7%) with a history of smoking (74.0%), stage IIIA NSCLC (69.2%), and unresectable disease (52.9%). A total of 24.3% had activating EGFR mutation and 62.2% were positive for PDL1 expression. Broadly categorized, 44.6% of the patients received chemoradiation (CRT)-based therapy, 35.1% underwent surgery, and 20.3% received palliative therapies as initial treatment. The most commonly adopted approaches for patients with stage IIIA and IIIB disease were surgery and CRT, respectively. The median PFS was 15.2 months and OS was 66.7 months. Age >65 years, adenocarcinoma histology, and surgery as the initial treatment were significantly associated with longer OS. This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes.

Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p=.0008) and FACT-L scores (DID, 2.47; p=.004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p=.06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

Disparities in Access to Multidisciplinary Cancer Consultations and Treatment for Patients With Early-Stage Non-Small Cell Lung Cancer: A SEER-Medicare Analysis

PurposeDisparities in access to multidisciplinary cancer consultations (MDCc) persist, and the role of physician relationships remains understudied. This study examined the extent to which multilevel factors, including patient characteristics and patient-sharing network measures reflecting the structure of physician relationships, are associated with MDCc and receipt of stereotactic body radiation therapy (SBRT) versus surgery among early-stage non-small cell lung cancer (NSCLC) patients. Materials and MethodsIn this cross-sectional study, we analyzed Surveillance, Epidemiology, and End-Result (SEER)-Medicare data for patients diagnosed with stage I-IIA NSCLC in 2016-2017. We assembled patient-sharing networks and identified cancer specialists who were locally unique for their specialty, herein referred to as “linchpins”. The proportion of linchpin cancer specialists for each hospital referral region (HRR) was calculated as a network-based measure of specialist scarcity. We used multilevel multinomial logistic regression to estimate associations between study variables and the receipt of MDCc and multilevel logistic regression to examine the relationship between MDCc and patient's first treatment. ResultsOur study included 6,120 patients with stage I-IIA NSCLC, of which 751 (12.3%) received MDCc, 1,729 (28.3%) only consulted a radiation oncologist, 2,010 (32.8%) only consulted a surgeon, and 1,630 (26.6%) had no consultations with either specialist within two months following diagnosis. Compared with patients residing in an HRR with a low proportion of linchpin surgeons, those in an HRR with a high proportion of linchpin surgeons had a 2.99 (95% CI: 1.87-4.78) greater relative risk of exclusively consulting a radiation oncologist (vs. MDCc) and a 2.70 (95% CI: 1.68-4.35) greater relative risk consulting neither specialist (vs. MDCc). Patients who received MDCc were 5.32 (95% CI: 4.27-6.63) times more likely to receive SBRT (vs. surgery). ConclusionsPhysician networks are associated with receipt of MDCc and treatment, underscoring the potential for leveraging patient-sharing network analysis to improve access to lung cancer care.

Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial

Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported. Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. None.

Survival outcomes following complete mediastinal lymphadenectomy or selective mediastinal lymphadenectomy in patients with stage I–IIIA non-small cell lung cancer: protocol for a systematic review and meta-analysis

IntroductionLung cancer remains the largest cause of cancer-related deaths worldwide. Surgical removal of non-small cell lung cancer (NSCLC) has the potential to achieve a cure, although there is ongoing debate...