Radiotherapy For NSCLC Research Articles

1081: Comparing predictors of radiation-induced lymphopenia in various timeframes in NSCLC radiotherapy

1081: Comparing predictors of radiation-induced lymphopenia in various timeframes in NSCLC radiotherapy

185: Outcomes following radiotherapy for oligoprogressive NSCLC on immune checkpoint inhibitors.

185: Outcomes following radiotherapy for oligoprogressive NSCLC on immune checkpoint inhibitors.

3170: Impact of Tumor Margins on Radiation Pneumonitis Incidence in Advanced Stage NSCLC Radiotherapy

3170: Impact of Tumor Margins on Radiation Pneumonitis Incidence in Advanced Stage NSCLC Radiotherapy

Palliative Thoracic Radiotherapy in the Era of Modern Cancer Care for NSCLC.

Palliative thoracic radiotherapy provides rapid and effective symptom relief in approximately two-thirds of NSCLC patients treated. In patients with poor performance status, the degree of palliation appears unrelated to the radiation dose or fractionation schedule. Conversely, in patients with good performance status, higher radiation doses administered over longer periods have shown modest survival benefits. These findings stem from studies conducted before the advent of immunotherapy and targeted therapy in clinical practice. Currently, there are no large prospective studies specifically dedicated to palliative radiotherapy conducted in this new treatment era. Modern radiotherapy technologies are now widely available and are increasingly used for palliative purposes in selected patients, reflecting the expanded array of therapeutic options for disseminated NSCLC and improved prognosis. Some traditional tenets of palliative thoracic radiotherapy, such as the improvement of overall survival with a protracted radiation schedule and the use of simple, cost-effective radiation techniques for palliative purposes, may no longer hold true for patients receiving immunotherapy or targeted therapy. The application of IMRT or SBRT in the context of palliative radiotherapy for NSCLC is not yet sufficiently explored, and this is addressed in this review. Moreover, new risks associated with combining palliative radiotherapy with these systemic treatments are being explored and are discussed within the context of palliative care. The optimal timing, doses, fractionation schedules, and treatment volumes for radiotherapy combined with immunotherapy or targeted therapy are currently subjects of investigation. In emergencies, radiotherapy should be used as a life-saving measure without delay. However, for other indications of palliative thoracic radiotherapy, decisions regarding doses, timing relative to systemic treatments, and treatment volumes should be made in a multidisciplinary context, considering the patient's prognosis, anticipated outcomes, and access to potentially effective treatments. We still lack robust data from prospective studies on this matter. This review examines and discusses available evidence on the use of palliative thoracic radiotherapy within the framework of modern treatment strategies for NSCLC.

1596: The impact of dosimetric features on interpretable overall survival prediction in NSCLC radiotherapy

1596: The impact of dosimetric features on interpretable overall survival prediction in NSCLC radiotherapy

152 A retrospective audit comparing toxicity and survival outcomes in patients who received palliative radiotherapy for NSCLC using the COVID-19 hypofractionated regime with patients treated pre-pandemic using standard RCR recommended regimes

152 A retrospective audit comparing toxicity and survival outcomes in patients who received palliative radiotherapy for NSCLC using the COVID-19 hypofractionated regime with patients treated pre-pandemic using standard RCR recommended regimes

EP07.02-13 Utilization of Real-time MRI-guided Stereotactic Ablative Body Radiotherapy in NSCLC, One Step forward Precise Targeting in Radiotherapy

EP07.02-13 Utilization of Real-time MRI-guided Stereotactic Ablative Body Radiotherapy in NSCLC, One Step forward Precise Targeting in Radiotherapy

P2.01-04 An Update on the CONCORDE study: A Phase Ib Platform Study of Novel Agents in Combination With Conventional Radiotherapy in NSCLC

P2.01-04 An Update on the CONCORDE study: A Phase Ib Platform Study of Novel Agents in Combination With Conventional Radiotherapy in NSCLC

P1.25-17 Stereotactic Ablative Body Radiotherapy for Early NSCLC: Changes in Pulmonary Function, Dyspnoea and Quality of Life

P1.25-17 Stereotactic Ablative Body Radiotherapy for Early NSCLC: Changes in Pulmonary Function, Dyspnoea and Quality of Life

Effect of Contralateral Esophagus Sparing in Hypofractionated Radiotherapy for Ultra-Central NSCLC

Esophageal toxicity is a known complication of radiotherapy (RT) for ultra-central lung tumors, with ∼5 - 15% of patients developing grade ≥3 esophagitis. Despite increasing adoption of hypofractionated regimens, there are no consensus recommendations for reducing esophageal toxicity in these patients. We previously demonstrated the utility of a novel contralateral esophagus sparing technique (CEST) in a prospective trial of patients with locally-advanced NSCLC receiving concurrent chemoRT (70 Gy/7 weeks). Whether CEST is effective for hypofractionated RT is unknown. The aims of this study were to identify outcomes and toxicities associated with use of CEST in patients receiving definitive hypofractionated RT to ultra-central lung tumors. We retrospectively analyzed the records of consecutive patients with ultra-central NSCLC who received definitive RT to a dose of ≥60 Gy with fraction size ≥3 Gy per day, from 1/1/2015 to 6/30/2022. The esophageal wall contralateral to the tumor was contoured as an avoidance structure. VMAT planning was used to ensure steep dose fall-off across the esophagus while maintaining full tumor coverage. Treatment was delivered using daily cone-beam CT guidance. Toxicity was graded using CTCAE v 4.0. Descriptive statistics were used to analyze outcomes. The study was approved by the IRB. We identified 45 patients with ultra-central NSCLC treated with definitive RT, with median follow-up of 27.3 months. Median age was 74.5 years old [57.6 - 88.2]. Median ECOG PS was 2 [1 - 3]. Twenty-three patients had PTVs located within 1 cm of the esophagus. Median ITV and PTV volumes were 17 cc [1.6 - 154 cc] and 43.6 cc [8.4 - 292 cc], respectively. Median total dose was 60 Gy [60 - 67.5 Gy] in 20 [10 - 20] fractions. Median esophageal Dmax was 24 Gy [2 - 66.7 Gy] for all patients and 36 Gy [12.3 - 66.7 Gy] for patients with tumors located within 1 cm of the esophagus. For the CE, median Dmax, V20 Gy and V25 Gy were 35.7 Gy [17 - 45.2 Gy], 2.1 cc [0 - 6.7 cc] and 0.95 cc [0 - 3 cc], respectively. There were no episodes of grade ≥2 esophagitis (95% CI, 0-7.9%). The rate of grade 1 esophagitis was 13.3% (6.2 - 26.1%). Esophageal Dmax was higher in patients who developed esophagitis (44.5 vs. 26.1 Gy, t = 2.5, p = 0.038). Two patients developed grade 2 pneumonitis (4.4%, 95% CI 0 - 10.5%). There were no episodes of grade ≥3 pulmonary toxicity. There were 3 (6.7%) local recurrences, with 2-year local recurrence rate of 4.4%. Use of CEST to minimize esophageal dose for treatment of ultra-central NSCLC is associated with reduced rates of esophagitis compared with historical controls, without compromising local control. This technique is readily adaptable for clinical practice. More data are needed to refine the empirically derived CE dose-volume constraints, especially for tumors directly abutting the esophagus.

Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis.

Lung cancer remains the leading cause of cancer-related deaths in both women and men, claiming millions of lives worldwide. Radiotherapy is an effective modality for treating early-stage lung cancer; however, it cannot completely eradicate certain tumor cells due to their radioresistance. Radioresistance is commonly observed in conventionally fractionated radiotherapy, which can lead to treatment failure, metastasis, cancer recurrence, and poor prognosis for cancer patients. Identifying the underlying molecular mechanisms of radioresistance in lung cancer can promote the development of effective radiosensitizers, thereby improving patients' life expectancy and curability. In this study, we identified LNC EBLN3P as a regulator of lung cancer cell proliferation and radiosensitivity. The repression of LNC EBLN3P could increase ROS production and mitochondrial injury in NSCLC cells. In addition, knocking down LNC EBLN3P increased the binding of Nrf2 to Keap1, resulting in enhanced Nrf2 degradation, decreased translocation of Nrf2 to the nucleus, reduced expression of antioxidant protein HO-1, weakened cellular antioxidant capacity, and increased radiosensitivity of NSCLC cells. These findings suggest that targeting LNC EBLN3P could be a promising strategy for developing novel radiosensitizers in the context of conventional radiotherapy for NSCLC.

PD-0159 Association of Statin Intensity With Cardiac Events and Mortality After Radiotherapy for NSCLC

PD-0159 Association of Statin Intensity With Cardiac Events and Mortality After Radiotherapy for NSCLC

MO-0873 Rapid increase in ctDNA at commencement of curative-intent radiotherapy for NSCLC

MO-0873 Rapid increase in ctDNA at commencement of curative-intent radiotherapy for NSCLC

195 - CONCORDE: a phase Ib platform study of novel agents in combination with conventional radiotherapy in NSCLC

195 - CONCORDE: a phase Ib platform study of novel agents in combination with conventional radiotherapy in NSCLC

138 - Baseline cardiovascular disease and risk of cardiac events following radical radiotherapy in NSCLC

138 - Baseline cardiovascular disease and risk of cardiac events following radical radiotherapy in NSCLC

The Effect of Body Mass Index on Survival in Lung Cancer

The prognostic significance of body mass index in lung cancer and the direction of this relationship are not yet clear. This study aimed to evaluate the relationship between BMI and overall survival time of advanced-stage lung cancer patients treated in a center in Turkey, a developing country. In this study, the data of 225 patients diagnosed with stage III or stage IV lung cancer between 2016 and 2020 were analyzed. The effects of BMI and other variables on survival were examined by Cox regression analysis for NSCLC and SCLC. For NSCLC and SCLC, being underweight compared to the normal group, being diagnosed at a more advanced stage, and having a worse performance score were associated with a significantly higher risk of death. Other variables significantly associated with survival were gender, type of radiotherapy for NSCLC, age group, and family history for SCLC. This study showed that being underweight relative to the normal group was associated with worse survival for NSCLC and SCLC but did not support the obesity paradox. Studies that are representative of all BMI categories and free of bias are needed to understand the BMI-lung cancer survival relationship clearly.

Gross tumour volume radiomics for prognostication of recurrence & death following radical radiotherapy for NSCLC

Recurrence occurs in up to 36% of patients treated with curative-intent radiotherapy for NSCLC. Identifying patients at higher risk of recurrence for more intensive surveillance may facilitate the earlier introduction of the next line of treatment. We aimed to use radiotherapy planning CT scans to develop radiomic classification models that predict overall survival (OS), recurrence-free survival (RFS) and recurrence two years post-treatment for risk-stratification. A retrospective multi-centre study of >900 patients receiving curative-intent radiotherapy for stage I-III NSCLC was undertaken. Models using radiomic and/or clinical features were developed, compared with 10-fold cross-validation and an external test set, and benchmarked against TNM-stage. Respective validation and test set AUCs (with 95% confidence intervals) for the radiomic-only models were: (1) OS: 0.712 (0.592–0.832) and 0.685 (0.585–0.784), (2) RFS: 0.825 (0.733–0.916) and 0.750 (0.665–0.835), (3) Recurrence: 0.678 (0.554–0.801) and 0.673 (0.577–0.77). For the combined models: (1) OS: 0.702 (0.583–0.822) and 0.683 (0.586–0.78), (2) RFS: 0.805 (0.707–0.903) and 0·755 (0.672–0.838), (3) Recurrence: 0·637 (0.51–0.·765) and 0·738 (0.649–0.826). Kaplan-Meier analyses demonstrate OS and RFS difference of >300 and >400 days respectively between low and high-risk groups. We have developed validated and externally tested radiomic-based prediction models. Such models could be integrated into the routine radiotherapy workflow, thus informing a personalised surveillance strategy at the point of treatment. Our work lays the foundations for future prospective clinical trials for quantitative personalised risk-stratification for surveillance following curative-intent radiotherapy for NSCLC.

970TiP SKYSCRAPER-05: Phase II study of neoadjuvant atezolizumab (Atezo) + tiragolumab (Tira) with or without platinum-based chemotherapy (CT) in patients (Pts) with locally advanced resectable stage II‒IIIB NSCLC

For resectable NSCLC, surgery (often with neoadjuvant or adjuvant CT), is the standard of care. However, benefit is modest and there is need to improve outcomes. Atezo (anti-PD-L1) has shown promising efficacy as monotherapy and in combination with CT in NSCLC. Inhibition of the PD-L1 pathway may be amplified by inhibition of TIGIT signaling. In CITYSCAPE (phase II; NCT03563716), tira (anti-TIGIT) + atezo was well tolerated and improved objective response rate vs atezo alone in 1L metastatic PD-L1+ NSCLC. Hypothesis: tira + atezo may provide clinical benefit in the neoadjuvant setting by enhancing anti-tumour immune response and eradicating micrometastases, reducing risk of disease recurrence. SKYSCRAPER-05 (NCT04832854) will evaluate safety, tolerability and preliminary efficacy of neoadjuvant tira + atezo ± CT in pts with resectable NSCLC. In this global, open-label study, ∼82 pts with histologically/cytologically confirmed, resectable Stage II, IIIA, or select IIIB (T3N2 only) NSCLC who are eligible for R0 resection with curative intent; without EGFR/ALK mutations; ECOG PS 0–1; with no prior cancer immunotherapy, CT or radiotherapy for NSCLC will be enrolled into two cohorts. Cohort A: pts with PD-L1 TC ≥50% tumours or Cohort B: pts independent of PD-L1 status. Pts will receive 4 cycles of neoadjuvant tira 600 mg IV + atezo 1200 mg IV Q3W (Cohort A) (CT-free option) or in combination with platinum-doublet CT Q3W (Cohort B). Following resection, pts will receive adjuvant tira + atezo or platinum-based CT Q3W (Cohort A) or adjuvant tira + atezo for 16 cycles (Cohort B) until disease recurrence or unacceptable toxicity. Investigator-selected CT options are cisplatin or carboplatin + pemetrexed, carboplatin + paclitaxel, and cisplatin or carboplatin + gemcitabine. Primary endpoints: central pathology laboratory-assessed major pathological response, treatment-related surgical delays, cancellations/complications and safety. Secondary endpoints: pathological complete response and event-free survival. Exploratory biomarkers will be evaluated. Recruitment is ongoing. NCT04832854. Medical writing assistance, under the direction of the authors, was provided by Ashfield MedComms, an Ashfield Health company. F. Hoffmann-La Roche Ltd.

MO-0390 CCI and TNM stage do not influence early mortality risk after definitive radiotherapy in NSCLC

MO-0390 CCI and TNM stage do not influence early mortality risk after definitive radiotherapy in NSCLC

MO-0884 Machine learning on clinical data for mortality risk-stratification after radiotherapy for NSCLC

MO-0884 Machine learning on clinical data for mortality risk-stratification after radiotherapy for NSCLC