Early-stage Non-small Cell Lung Research Articles

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.

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.

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 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.

Assessment of the Functioning Profile of Patients with Lung Cancer Undergoing Lobectomy in Relation to the ICF Rehabilitation Core Set.

Lung cancer often presents with pain and breathlessness, frequently necessitating surgical procedures, such as lung lobectomy. A pivotal component of postoperative care is rehabilitation, aimed not only at improving the clinical condition but also at influencing the patient's functional profile. In a study conducted at the Clinic of Thoracic Surgery and Respiratory Rehabilitation in the Regional Multispecialist Center for Oncology and Traumatology of the Nicolaus Copernicus Memorial Hospital in Lodz, the effectiveness of rehabilitation intervention was assessed in 50 patients (n = 27 M, n = 23 F) postlobectomy due to early stage nonsmall cell lung cancer (NSCLC). The International Classification of Functioning, Disability, and Health-ICF Rehabilitation Core Set was used to evaluate the functional profile, the modified Laitinen scale for pain assessment, and the modified Borg scale for breathlessness evaluation. Additionally, lung-expansion time was monitored. The significance level of the statistical tests in this analysis was set at α = 0.05. The study employed an analysis of the normality of the distributions of the numerical variables, reporting of variable distributions, estimation of differences between groups, estimation of differences within groups, estimation of the independence of categorical variables, and regression analysis. The research confirmed that rehabilitation partially improves the functional profile of patients and reduces the sensation of breathlessness postsurgery. The study highlighted the need for future research with a larger number of participants and an extended observation period to gain a deeper understanding of the impact of rehabilitation on patients after lung lobectomy procedures.

477P A comparative study of sublobar resection and stereotactic body radiation therapy (SBRT) for elderly patients with early stage non-small cell lung cancer

477P A comparative study of sublobar resection and stereotactic body radiation therapy (SBRT) for elderly patients with early stage non-small cell lung cancer

EP07.04-29 Hyperspectral Multiplex Immunohistochemistry and Recurrence in Resected Early Stage Non-small Cell Lung Cancer

EP07.04-29 Hyperspectral Multiplex Immunohistochemistry and Recurrence in Resected Early Stage Non-small Cell Lung Cancer

EP07.02-15 Longitudinal ctDNA Testing in Resected, Early Stage Non-small Cell Lung Cancers

EP07.02-15 Longitudinal ctDNA Testing in Resected, Early Stage Non-small Cell Lung Cancers

EP07.02-07 Prospective Study of Hypofractionated Proton Therapy for Inoperable Early Stage Non-small Cell Lung Cancer

EP07.02-07 Prospective Study of Hypofractionated Proton Therapy for Inoperable Early Stage Non-small Cell Lung Cancer

EP07.04-22 Current Biomarker Testing Practices for Early Stage Non-small Cell Lung Cancer (NSCLC) In Community and Academic Centers in the US

EP07.04-22 Current Biomarker Testing Practices for Early Stage Non-small Cell Lung Cancer (NSCLC) In Community and Academic Centers in the US

Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer.

We report a personalized tumor-informed technology, Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) using deep sequencing of 50 patient-specific variants to detect molecular residual disease (MRD) with a limit of detection of 0.004%. PROPHET and state-of-the-art fixed-panel assays were applied to 760 plasma samples from 181 prospectively enrolled early stage non-small cell lung cancer patients. PROPHET shows higher sensitivity of 45% at baseline with circulating tumor DNA (ctDNA). It outperforms fixed-panel assays in prognostic analysis and demonstrates a median lead-time of 299days to radiologically confirmed recurrence. Personalized non-canonical variants account for 98.2% with prognostic effects similar to canonical variants. The proposed tumor-node-metastasis-blood (TNMB) classification surpasses TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET shows potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings highlight the potential advantages of personalized cancer techniques in MRD detection.

1283P Predicting PD-L1 expression using [18F]FDG PET/CT in early stage non-small cell lung cancer (NSCLC)

1283P Predicting PD-L1 expression using [18F]FDG PET/CT in early stage non-small cell lung cancer (NSCLC)

1277P HRD status of patients with early stage non-small cell lung cancer

1277P HRD status of patients with early stage non-small cell lung cancer

Preoperative pulmonary rehabilitation in medical inoperable patients with early stage non-small cell lung cancer and postoperative results

Aims: The impact of postoperative complications after surgery for lung cancer is substantial, with the increasing age of patients and the presence of comorbidities. Impairment in exercise capacity is a potential modifiable risk factor for postoperative complications. This study aimed to assess the contribution of preoperative pulmonary rehabilitation (PR) for increasing operability conditions in non-small cell lung cancer (NSCLC) for patients with limited pulmonary functions and postoperative results.&#x0D; Methods: The patients with NSCLC who had preoperative pulmonary rehabilitation and underwent surgical resection in our clinics between 2010-2019 were evaluated retrospectively. The patients enrolled in a comprehensive, multidisciplinary, supervised outpatient 10-day duration PR program preoperatively, consisting of bronchial hygiene, breathing control, energy conservation techniques, exercise training (endurance and strength), psychological support, and nutritional support. Exercise capacity and VO2 peak were evaluated by using an incremental shuttle walk test (ISWT).&#x0D; Results: Eighteen patients who underwent surgery due to NSCLC and had a pre-operative pulmonary rehabilitation program were evaluated. All the cases were male; the mean age was 66.2 (53-77) years. The squamous cell/adenocarcinoma ratio was 2.6 (13:5), and the mean tumor size was 4.6 (8-18) cm. The postoperative hospital stay was 12.7 (4-42) days, and they were followed up for an average of 30.2 (2-83) months. &#x0D; Conclusion: Complete surgical resection is the most effective curative treatment for lung cancer. However, many patients with lung cancer also have severe COPD, increasing their risk of postoperative complications and their likelihood of being considered "inoperable." Preoperative pulmonary rehabilitation (PR) has been proposed as an intervention for risk modification and to decrease surgical morbidity and mortality. The results of our study also revealed the importance of preoperative pulmonary rehabilitation in centers where lung cancer surgery was performed.

Expression and prognostic value of Cripto-1 in early non-small cell lung cancer.

We aim to explore the expression of Cripto-1 (CR-1) protein in patients with early stage non-small cell lung cancer (NSCLC). We investigated CR-1 expression status in specimens obtained from 240 patients with resected NSCLC and 30 cases of para-carcinous normal lung tissues. Compared with normal lung tissue, the positive expression of CR-1 protein in NSCLC was significantly increased (p < 0.005). Cox multivariate regression analysis showed that the expression of CR-1 protein was an independent prognostic factor for early stage NSCLC (p = 0.002). Detecting CR-1 protein can predict the prognosis and recurrence in patients with NSCLC.

Blood-Derived Systemic Inflammation Markers and Risk of Nodal Failure in Stage Ia Non-Small Cell Lung Cancer: A Multicentric Study.

Unexpected spread to regional lymph nodes can be found in up to 10% of patients with early stage non-small cell lung cancer (NSCLC), thereby affecting both prognosis and treatment. Given the known relation between systemic inflammation and tumor progression, we sought to evaluate whether blood-derived systemic inflammation markers might help to the predict nodal outcome in patients with stage Ia NSCLC. Preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation score (SII, platelets × NLR) were collected from 368 patients who underwent curative lung resection for NSCLC. After categorization, inflammatory markers were subjected to logistic regression and time-event analysis in order to find associations with occult nodal spread and postoperative nodal recurrence. No inflammation marker was associated with the risk of occult nodal spread. SII showed a marginal effect on early nodal recurrence at a quasi-significant level (p = 0.065). However, patients with T1c tumors and elevated PLR and/or SII had significantly shorter times to nodal recurrence compared to T1a/T1b patients (p = 0.001), while patients with T1c and normal PLR/SII did not (p = 0.128). blood-derived inflammation markers had no value in the preoperative prediction of nodal status. Nevertheless, our results might suggest a modulating effect of platelet-derived inflammation markers on nodal progression after the resection of tumors larger than 2 cm.