Early-stage Non-small Cell Lung Research Articles

P37-4 Efficacy and toxicity of pemetrexed and cisplatin in early stage non-small cell lung cancer: a systematic review of RCTs

P37-4 Efficacy and toxicity of pemetrexed and cisplatin in early stage non-small cell lung cancer: a systematic review of RCTs

Soluble PD-L1 shows no association to relapse and overall survival in early stage non-small cell lung cancer (NSCLC)

BackgroundCancer immune evasion is critical in non-small cell lung cancer (NSCLC) and has been targeted by immunotherapy. High soluble (s)PD-L1 is associated with reduced survival and treatment failure in advanced stages. Here we evaluated the effects of sPD-L1 on T cells, relapse free survival, and overall survival in early stage NSCLC. MethodsIn vitro T cell stimulation was performed in the presence of sPD-L1 to evaluate its immunomodulatory activity. Data from The Cancer Genome Atlas (TCGA) were investigated for PD-L1 splice variants and enzymes involved in proteolytic cleavage (i.e. ADAM10). Plasma from 74 NSCLC (stage IA-IIIB), as well as an additional 73 (control cohort) patients was collected prior to curative surgery. Thereafter sPD-L1 levels from an immunosorbent assay were correlated with patient outcome. ResultsIn vitro sPD-L1 inhibited IFN-γ production and proliferation of T cells and induced a terminal effector CD4 T cell subtype expressing CD27. Data from the TCGA demonstrated that elevated mRNA levels of ADAM10 is a negative predictor of outcome in NSCLC patients. To investigate the clinical relevance of these in vitro and TCGA findings, we quantified sPD-L1 in the plasma of early-stage NSCLC patients. In the first cohort we found significantly higher sPD-L1 levels in relapsing NSCLC patients, with a multivariate analysis revealing high sPD-L1 (>1000 pg/mL) as an independent predictor of survival. However, these findings could not be validated in two independent control cohorts. DiscussionAlthough in vitro and TCGA data support the suppressive effect of sPD-L1 we were unable to translate this in our clinical setting. These results may be due to the small patient number and their heterogeneity as well as the lack of a standardized sPD-L1 ELISA. Our inconclusive results regarding the value of sPD-L1 in early stage NSCLC warrant assay validation and further investigation in larger (neo-)adjuvant trials.

1232P Assessing uncertainty and vulnerability of clinical trials with immune-checkpoint inhibitors and chemotherapy (ICI+CT) in early stage non-small cell lung cancer (NSCLC) by informative censoring and survival inferred fragility index (SIFI)

1232P Assessing uncertainty and vulnerability of clinical trials with immune-checkpoint inhibitors and chemotherapy (ICI+CT) in early stage non-small cell lung cancer (NSCLC) by informative censoring and survival inferred fragility index (SIFI)

1238TiP Combining immunotherapy with Trop2 ADc in early stage non-small cell lung cancer (CITADEL)

1238TiP Combining immunotherapy with Trop2 ADc in early stage non-small cell lung cancer (CITADEL)

1226P Predictive value of circulating tumor DNA (ctDNA) before and shortly after curative treatment in early stage non-small cell lung cancer (NSCLC), and exploration of (pre-)analytical factors

1226P Predictive value of circulating tumor DNA (ctDNA) before and shortly after curative treatment in early stage non-small cell lung cancer (NSCLC), and exploration of (pre-)analytical factors

Comprehensive Analysis of Immune Responses to Neoadjuvant Immunotherapy in Resectable Non-small Cell Lung Cancer.

Neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of early stage non-small cell lung cancer (NSCLC). However, little is known about which patients are likely to benefit most from neoadjuvant immunotherapy. In this study, we performed a multiplatform analysis on samples from resectable NSCLC treated with neoadjuvant immunotherapy to explore molecular characteristics related to immune responses. A total of 17 patients with resectable stage IB-IIIA NSCLC treated with neoadjuvant immunotherapy were included. A multiplex cytokine assay, bulk TCR sequencing in peripheral blood, and multiplexed immunohistochemistry were performed. Low levels of stromal cell-derived factor (SDF)-1alpha at baseline were associated with unfavorable disease-free survival (DFS). Patients with major pathologic response (MPR) showed a decrease in HGF after one cycle of neoadjuvant immunotherapy. An increase in IDO and IP-10 was observed in patients who developed immune-related adverse events (irAEs) after neoadjuvant immunotherapy. There were no correlations between irAEs and MPR or DFS. The MPR group presented a significant decrease in white blood cells and neutrophil count after neoadjuvant immunotherapy. The high peripheral baseline TCR convergence was correlated with MPR and favorable DFS in lung squamous cell carcinoma (LUSC) receiving neoadjuvant immunotherapy. Neoadjuvant immunotherapy led to a significant increase in CD4+, CD8+, and CD8+CD39+ T-cell infiltration in tumor areas. This study suggests the potential roles of cytokines and TCR convergence for predicting ICIs response in resectable NSCLC and LUSC. CD8+CD39+T cells and CD4+ T cells could be involved in the action of neoadjuvant immunotherapy.

Multidisciplinary Collaboration is Essential for the Effective Surgical Management of Early Stage Non-small Cell Lung Cancer

Multidisciplinary Collaboration is Essential for the Effective Surgical Management of Early Stage Non-small Cell Lung Cancer

Recent Advancements in Minimally Invasive Surgery for Early Stage Non-Small Cell Lung Cancer: A Narrative Review.

Introduction: Lung cancer remains a global health concern, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Early detection of lung cancer has led to an increased number of cases identified in the earlier stages of NSCLC. This required the revaluation of the NSCLC treatment approaches for early stage NSCLC. Methods: We conducted a comprehensive search using multiple databases to identify relevant studies on treatment modalities for early stage NSCLC. Inclusion criteria prioritized, but were not limited to, clinical trials and meta-analyses on surgical approaches to early stage NSCLC conducted from 2021 onwards. Discussion: Minimally invasive approaches, such as VATS and RATS, along with lung resection techniques, including sublobar resection, have emerged as treatments for early stage NSCLC. Ground-glass opacities (GGOs) have shown prognostic significance, especially when analyzing the consolidation/tumor ratio (CTR). There have also been updates on managing GGOs, including the non-surgical approaches, the extent of lung resection indicated, and the level of lymphadenectomy required. Conclusions: The management of early stage NSCLC requires a further assessment of treatment strategies. This includes understanding the required extent of surgical resection, interpreting the significance of GGOs (specifically GGOs with a high CTR), and evaluating the efficacy of alternative therapies. Customized treatment involving surgical and non-surgical interventions is essential for advancing patient care.

CtDNA-Lung-DETECT: ctDNA outcomes for resected early stage non-small cell lung cancers at 12 months.

8018 Background: ctDNA Lung DETECT is a multicentre investigator initiated prospective study at 3 thoracic surgery centres in the Greater Toronto Area assessing ctDNA detection and association with recurrence free survival (RFS) in patients with early stage non-small cell lung cancer (NSCLC) (NCT05254782). Patients who have ctDNA detected perioperatively are offered ctDNA Lung RCT, a randomized trial investigating the benefit of adjuvant chemo-immunotherapy in patients where the standard of care is observation alone after surgery (NCT04966663). Herein, we report on ctDNA outcomes at 12 months for patients with resected early stage NSCLC. Methods: Patients with stage I (T1-2N0) or multifocal T3-4 < 4cm N0 NSCLC planned for resection at University Health Network consented to plasma ctDNA assessment before and after surgery, and at 12 months post-operatively or relapse using the tumor-informed RaDaR® assay, which detects up to 48 tumor-specific variants in plasma with a Limit of Detection (LoD₉₅) of 0.0011% variant allele fraction. Results: From July 2021 to January 2024, 178 patients were enrolled; 115 had sufficient tissue for assessment. Of these, 68/72 patients have 12 month post-resection ctDNA results available (3 withdrew, 1 sample failed). ctDNA was detected pre-operatively in 18 patients; 99% (71/72) had ctDNA clearance post-operatively, and 93% (62/67) remained ctDNA negative at 12 months. Median follow up time was 18.7 months (range 12.0– 28.3); 8/72 (11%) patients (5 stage I, 3 stage II) experienced lung cancer recurrence. Median time to recurrence was 13.9 months (range 6.2- 24.9). Of these, 3 had ctDNA detected on their preoperative and 12-month or recurrence sample, 1 had ctDNA detected at 12 months prior to relapse, 1 had ctDNA detected at 12 months and recurred around the same time, 2 had negative ctDNA samples and 1 missed sample collection preoperatively. The recurrence rate was 16.7% (3/18, 95% exact CI 3.6-41.4%) in patients with ctDNA detected pre-operatively vs. 7.5% (4/53, CI 2.1-18.2%) in those without. New lung cancers were diagnosed in 5/72 (median time to new primary 15.3 months, range 4.9-14.2) and 2/72 patients had new cancers diagnosed (ovarian/liposarcoma). For those with new lung primaries, 1 had ctDNA detected preoperatively but none had ctDNA detected at time of new primary diagnosis. Of 4 patients who have died, 2 were from recurrent lung cancer and 2 from new primaries (lung/sarcoma). Conclusions: This study represents one of the largest prospective cohorts of ctDNA kinetics in patients with resected lung cancer. Of patients with at least 12 months follow up, 8/72 experienced a lung cancer recurrence with a higher rate in those with pre-operative ctDNA detected (16.7% vs 7.5%). Pre-operative ctDNA detection may help identify patients with resected stage I NSCLC that could benefit from treatment intensification, currently under study in ctDNA Lung RCT (NCT04966663). Clinical trial information: NCT05254782 .

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

3058 Background: Lung cancer remains the leading cause of cancer deaths, largely due to late-stage diagnosis. Early detection significantly improves survival rates, but current methods like chest X-rays and low-dose CT (LDCT) scans face limitations in sensitivity and specificity. MicroRNAs (miRNAs) are small non-coding RNAs whose dysregulation has been widely observed in different stages of cancer. Evidence suggests that circulating miRNAs could be promising biomarkers for early diagnosis of lung cancer. In this study, we developed and validated a 15-miRNA panel as a blood-based minimally invasive test for early detection of non-small cell lung cancer (NSCLC) using the proprietary multiplex quantitative real-time PCR (qPCR). Methods: 332 serum samples (182 Stage I&II NSCLC, 150 healthy controls) were divided into training (n=266) and validation (n=66) cohorts. Differentially expressed serum miRNAs were screened with Miseq sequencing followed by qPCR validation. The multi-miR panel was developed with a logistic regression model and validated using an independent cohort. Receiver operating characteristic curves were constructed to evaluate the diagnostic accuracy of the panel. A stem-loop quadruplex qPCR assay was invented for concurrent detection of 4 miRs in a single reaction. Results: 15 differentially expressed miRNAs were selected for logistic model construction based on their Ct values (Ct<35) and high diagnostic accuracy of stage I&II NSCLC (AUC>0.7). The 15-miRNA panel model achieved 88.4% sensitivity, 81.7% specificity (AUC = 0.912) in the training cohort (Table), and was validated with 94.4% sensitivity, 73.3% specificity (AUC = 0.892) in the validation cohort. Quantification of 15 miRs and 1 internal control was performed in 4 reactions tubes via quadruplex qPCR assay. Conclusions: The serum 15-miR panel developed and validated in this retrospective study exhibited robust performance for detection of early stage NSCLC. The panel demonstrates potential diagnostic applications and clinical utility to be implemented together with LDCT in current lung cancer screening program as a blood biomarker to reduce false positive results. In addition, the proposed stem-loop quadruplex qPCR system offers an efficient and promising approach for miRNA profiling in future clinical applications. [Table: see text]

Ultrasensitive circulating tumor DNA (ctDNA) minimal residual disease (MRD) detection in early stage non-small cell lung cancer (NSCLC).

8078 Background: Translation of ctDNA MRD in NSCLC has been hampered by suboptimal sensitivity of 1st-generation assays. Here, we explore how improvements in analytical sensitivity can drive improved clinical sensitivity for MRD after surgery in NSCLC. Methods: To understand MRD kinetics, we analyzed longitudinal ctDNA in early stage NSCLC using data from the TRACERx study. Patient-specific mathematical models were generated to predict MRD levels at the postsurgical landmark and estimate the impact of an assay’s 95% limit of detection (LOD95) on clinical sensitivity. To test these predictions, tumor-informed ctDNA testing was performed using an SNV-based assay (CAPP-Seq) and a phased variant-based assay (PhasED-Seq, Foresight Diagnostics) on 269 samples from 46 patients. We also assessed MRD performance for predicting 1) patient outcomes at the landmark timepoint and 2) the effect of adjuvant treatment. Results: ctDNA MRD dynamics were assessed in 23 patients from TRACERx with ≥3 consecutive samples with detectable ctDNA without intervening therapy. MRD kinetics strongly correlated with exponential growth, with a median ctDNA doubling time of 51 days. Extrapolating MRD levels to the postsurgical landmark predicted that improving MRD assay LOD95 from 100 ppm (0.01%) to 1 ppm could increase clinical sensitivity by 2.1-fold. We then evaluated 46 NSCLC cases using two assays. The median LOD95 was 1 ppm for PhasED-Seq and 84 ppm for CAPP-Seq. Twelve cases were MRD+ by PhasED-Seq, all of whom recurred (100%), with MRD levels as low as 0.19 ppm. In contrast, 6 cases were MRD+ by the SNV-based approach, of whom 5 (83%) recurred. Accordingly, PhasED-Seq had a higher clinical sensitivity than the SNV-based method (12/18 [67%] vs. 5/18 [28%], P = 0.022). Kaplan Meier analysis for freedom from recurrence revealed significantly worse outcomes for patients with detectable MRD regardless of the method used; however, outcomes were better stratified using PhasED-Seq (HR 3.1 vs. 11.4). Patients who were MRD- after surgery by both assays had similar outcomes regardless of adjuvant therapy (chemotherapy and/or radiotherapy). However, MRD+ patients by PhasED-Seq receiving adjuvant therapy had significantly better outcomes than those who did not (HR 8.2, P = 0.00035). A similar benefit for adjuvant therapy was not observed with the SNV-based assay. Using PhasED-Seq, 80% (4/5) of MRD+ patients receiving adjuvant therapy cleared their MRD, compared to 0% (0/3) without adjuvant treatment. Conclusions: Ultrasensitive ctDNA detection improved the clinical sensitivity of MRD at key landmarks in early stage NSCLC. PhasED-Seq detected MRD at levels below 1 ppm and was associated with significantly better outcomes, revealing potential benefits of adjuvant therapy in MRD+ patients. This suggests that ultrasensitive MRD detection is promising for use in risk-adapted trials in early stage NSCLC.

Assessing quality of care in early stage resected stage non-small cell lung cancer (NSCLC): An evaluation of epidermal growth factor receptor (EGFR) testing and adjuvant (adj) therapy (tx).

8072 Background: In December 2020, the FDA approved the use of osimertinib in the treatment of stage IB-IIIA (ES) NSCLC patients (pts) with EGFR exon 19 deletions and exon 21 L858R mutations (EGRFm) following tumor resection. Using real-world data, we sought to understand EGFR testing rates among ES pts and whether pts received osimertinib in the adjuvant setting based on EGFRm. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care. From this database, we identified Stage IB – IIIA pts evaluated via medical chart curation who underwent lung cancer resection (R) between 12/1/2021 to 7/31/2023 (N = 803). We assessed adj treatment by stage, EGFR testing rates overall and by stage, EGFR testing rates by adjuvant treatment and non-adj treatment pts, timing of EGFR testing, and treatment rates with an EGFR TKI among EGFRm pts. Descriptive analyses were used and proportions were compared using a chi-squared test. Results: The mean age of the 803 ES R pts in the sample was 69 (SD = 8.3), 53.3% of the pts were female, , and 12% never smoked. We found adj treatment rates among ES R pts to be 56%; these were highest among stage IIIA (N = 245) pts at 70.2%, compared to stage IIB (N = 241) at 68.8%, stage IIA (N = 69) at 53.6% and stage IB (N = 240) at 31.7% (p < 0.001). Among ES R pts, 70% (N = 563) were tested for EGFR; this rate was 78% (N = 455) among ES pts who were R and received adj treatment, compared to 59% (N = 348) among ES R pts who did not receive adj treatment (p < 0.001). EGFR testing rates were highest among stage IIB pts at 76%, compared to stage IIIA pts at 73%, stage IIA pts at 72%, and stage IB pts at 60% (p < .001). Among ES pts who were R and tested for EGFR (N = 563), 14% were tested before surgery, 38% were tested after surgery but before adj treatment, and 48% were tested after initiating adjuvant therapy. EGFRm was found in 10.4% of EGFR tested pts. Among EGFRm ES R pts (N = 59), 54% were treated with an EGFR TKI. EGFRm ES R pts treated with an adj EGFR TKI were highest among stage IIB pts (N = 14) at 93%, compared to stage IIA pts (N = 5) at 60%, stage IB pts (N = 20) at 45%, and stage IIIA pts (N = 20) at 35% (p < 0.01). However, only 69% (N = 41) of EGFRm ES R pts received adj treatment (either chemotherapy or EGFR TKI) and among those pts, 78% (N = 32) received an EGFR TKI. Conclusions: Based on our findings using real-world data for EGFR testing and adjuvant osimertinib use, and in light of the published results from the ADAURA trial which showed disease free survival benefit (HR 0.2) and overall survival benefit (HR 0.49) of adjuvant osimertinib in ES NSCLC, we have identified an opportunity to improve patient outcomes following resection of ES NSCLC by increasing EGFR testing and encouraging treatment with EGFR TKI in exon 19 deletion or exon 21 L858R mutated pts.

Survival analysis after stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a single-institution cohort study

BackgroundStereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality.MethodsFrom August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3–5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30–33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI).ResultsThe median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01–2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06–2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58).ConclusionSABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.

Abstract 986: Mathematical modeling of ctDNA dynamics to predict utility of ultrasensitive MRD assays in early stage non-small cell lung cancer (NSCLC)

Abstract Background: ctDNA assay use for minimal residual disease (MRD) detection in early stage NSCLC has been limited by suboptimal sensitivity of first generation assays. It is unclear how improving assay limit of detection (LOD) would translate to improvements in clinical sensitivity. Here, we performed mathematical modeling of ctDNA dynamics after curative-intent treatment in early stage NSCLC to predict the clinical impact of MRD assays with improved analytical sensitivity. Methods: We analyzed a recently reported dataset of post-surgical ctDNA MRD surveillance in early stage NSCLC (Abbosh et al., Nature 2023) to investigate ctDNA growth dynamics. Of 70 relapsed patients in this cohort, 23 had 3 consecutive ctDNA-positive samples with no intervening therapy. We used these to generate patient-specific mathematical models for ctDNA variant allele fractions (VAF) over time, initially assuming exponential growth. We assessed this assumption by creating log-linear models for ctDNA increase in these cases. Using slopes of the log-linear models, we calculated patient-specific doubling times and assessed their relation to stage, histology, and outcome. We used the log-linear models to simulate a VAF distribution each day after surgery, enabling projection of clinical sensitivities and estimation of lead times for recurrence detection at varying LODs. Results: For the 23 cases with 3+ consecutive ctDNA positive samples, we developed log-linear models for ctDNA VAF growth, which were strongly correlated (r &amp;gt; 0.5) in 18/23 (78%) patients (median r = 0.89), supporting that ctDNA can be modeled as exponential growth. We calculated ctDNA doubling times for the 18 patients with exponential ctDNA kinetics and 10 patients with 2 consecutive ctDNA positive samples. Doubling times were remarkably consistent with median 51 days (IQR 40-79). Doubling times were longer for stage I tumors compared to stage II/III (p = 0.04) but were not different between NSCLC subtypes. Doubling time correlated with time to clinical relapse, with patients having more rapid ctDNA growth relapsing earlier (r = 0.52, p=0.03). Finally, we used patient-specific log-linear models to project ctDNA VAFs at a landmark 30 days after surgery. By improving the LOD for ctDNA detection from 10−4 to 10−6, the projected clinical sensitivity doubled (from 43% to 86%). Simulations predicted that this improvement in sensitivity would increase median lead time from 183 days for LOD=10−4 to 349 days for LOD=10−6 (p&amp;lt;0.0001). Conclusion: For most relapsed NSCLC patients, the natural history of ctDNA MRD growth can be reliably modeled with exponential growth kinetics. ctDNA doubling time is associated with stage and clinical outcome. Ultrasensitive MRD assays with LOD of 10−6 are predicted to meaningfully improve clinical sensitivity at the post-surgical landmark and to increase the lead time for MRD detection before relapse. Citation Format: Jordan S. Goldstein, Christopher Abbosh, Ash A. Alizadeh, Maximilian Diehn, David M. Kurtz. Mathematical modeling of ctDNA dynamics to predict utility of ultrasensitive MRD assays in early stage non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 986.

Stereotactic body radiotherapy in lung cancer: a contemporary review.

The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is still the gold standard treatment type for operable patients. For inoperable patients stereotactic body radiotherapy (SBRT) should be offered, reaching very high local control and overall survival rates. With SBRT we can precisely irradiate small, well-defined lesions with high doses. To select the appropriate fractionation schedule it is important to determine the size, localization and extent of the lung tumor. The introduction of novel and further developed planning (contouring guidelines, diagnostic image application, planning systems) and delivery techniques (motion management, image guided radiotherapy) led to lower rates of side effects and more conformal target volume coverage. The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of increasing local control and overall rates in "fit," operable patients as well, so SBRT would be eligible in place of surgery.

Comparison of postoperative complications in mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: Protocol for a systematic review and meta-analysis.

Lung cancer is the primary cause of cancer-related deaths worldwide, with high rates of morbidity and mortality. The most effective treatment for early stage (I-II) non-small cell lung cancer (NSCLC) is surgical resection. However, the extent of mediastinal lymph nodes removal required and the impact of their removal remains controversial. This systematic review and meta-analysis aimed to evaluate the postoperative complications in patients with stage I-II NSCLC who received mediastinal lymph node dissection (MLND) or mediastinal lymph node sampling (MLNS). According to the predefined inclusion criteria, we will conduct a comprehensive search for randomized controlled trials (RCTs) and observational studies examining the postoperative complications of MLND compared to MLNS in patients with stage I-II NSCLC. The search will be performed across multiple databases including PubMed, Embase, the Cochrane Library, CNKI, WanFang, Sinomed, VIP, Duxiu, and Web of Science from inception to February 2024. Additionally, relevant literature references will be retrieved and hand searching of pertinent journals will be conducted. Screening, data extraction, and quality assessment will be performed by two independent reviewers. Review Manager 5.4 will be applied in analyzing and synthesizing. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess the quality of evidence for the whole RCTs and used Newcastle-Ottawa scale to assess the methodologic quality of observational studies. This study did not include personal information. Ethical approval was not required for this study. This study is based on a secondary analysis of the literature, so ethical review approval is not required. The final report will be published in a peer-reviewed journal. This systematic review will contribute to compare the safety and survival benefits of these two surgical techniques for the treatment of early stage NSCLC, to further guide the selection of surgical approaches. The protocol of the systematic review has been registered on Open Science Framework, with a registration number of DOI https://doi.org/10.17605/OSF.IO/N2Y5D.

Prospective study investigating hypofractionated proton beam therapy in patients with inoperable early stage non-small cell lung cancer.

To report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection. Data from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity. The median follow-up was 28.9 months (range, 1.1-62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months' post-PBT (p=0.047) and was maintained until 13 months (p=0.028). Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.

Differences between Survival Rates and Patterns of Failure of Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma Who Received Single-Fraction Stereotactic Body Radiotherapy.

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC (p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.

Comparison Results of Three-Port Robot-Assisted and Uniportal Video-Assisted Lobectomy for Functional Recovery Index in the Treatment of Early Stage Non-small Cell Lung Cancer: A Propensity Score-Matched Analysis

BackgroundMinimally invasive lobectomy is the standard treatment for early stage non-small cell lung cancer (NSCLC). The aim of this study is to investigate postoperative recovery in a prospective trial of discharged patients with early stage non-small cell lung cancer undergoing robot-assisted thoracic surgery (RATS) versus uniportal video-assisted thoracic surgery (UVATS).Patients and MethodsThis is a prospective and observational study. From 9 September 2022 to 1 July 2023, 178 patients diagnosed with NSCLC admitted to the Department of Thoracic Surgery of Shandong Provincial Hospital signed informed consent and underwent lobectomy by RATS and UVATS. The functional recovery index included MD Anderson Symptom Inventory, Christensen Fatigue Scale, EORTC QLQ-C30, and Leicester Cough Questionnaire.ResultsAfter propensity score-matched analysis, each group included 42 cases. For the baseline characteristics of patients, operation time (p = 0.01) and length of stay (p = 0.04) were shorter in the RATS group. The number of lymph nodes resected in the RATS group was much more than in the UVATS group. According to our investigation, appetite loss, nausea, diarrhea, and cough severity after RATS were better than after UVATS. After the first week, pain severity degree of the RATS group was higher than UVATS, while there was no difference during the second and third week. The physical score of the RATS group was higher than the UVATS group (p = 0.04), according to the Leicester Cough Questionnaire.ConclusionRATS was associated with severe short-term postoperative pain but less postoperative complications.

Biologically effective dose (BED) value lower than 120Gy improve outcomes in lung SBRT.

Lung SBRT has a well-defined role in the treatment of patients with early stage non-small cell lung cancer who are not surgical candidates or refuse surgery. Biologically effective dose (BED) of greater than or equal to 100Gy has been recommended. However, optimal fractionationremains unclear. Our objective was analyze patients treated with lung SBRT in our institution and evaluate outcomes according prescribed dose. One hundred nine patients with early non-small cell lung cancer and treated with lung SBRT were retrospectively analyzed. Differences between dose received, local control, and survival were evaluated. For comparison of BEDs, the prescribed dose for SBRT was stratified according to two groups: high (BED > 120Gy) and low (BED < 120Gy). A relationship between mortality and total dose (54.7Gy ± 4.8) was observed. Significantly worse survival was observed for patients with higher total doses (p < 0.003). It was found that patients receiving BED > 120 had increased mortality compared to patients receiving BED < 120 (p = 0.021). It was observed mean dose/fraction 12.6Gy/f was a protective factor and decreased the probability of death. Our data suggest that mean total dose lower 54 and a calculated BED < 120Gy is the optimal. Further prospective data are needed to confirm these results and determine the optimal dose fractionation scheme as a function of tumor size and location of volume.