Locally Advanced Non-small Cell Lung Cancer Research Articles

P29.06 Both Endostar and Amifostine Reduced All the Incidence of Pneumonitis Above Grade 2 in Chemoradiotherapy With Locally Advanced NSCLC

The acceptable treatment strategy currently in the treatment of locally advanced non-small cell lung cancer (LA-NSCLC) patients is combination treatment, but concurrent chemoradiotherapy (CCRT) has been associated with significant toxicities. The aim of this study was to assess the ability of Endostar and amifostine (AM) to reduce the incidence of chemoradiotherapy-induced pneumonitis above grade 2 in patients with stage III NSCLC.

Post-operative radiation therapy for non-small cell lung cancer: A comparison of radiation therapy techniques

ObjectivesPost-operative radiation therapy (PORT) in locally advanced non-small cell lung cancer (LA-NSCLC) has historically been associated with toxicity. Conformal techniques like intensity modulated radiation therapy (IMRT) have the potential to reduce acute and long-term toxicity from radiation therapy. Among patients receiving PORT for LA-NSCLC, we identified factors associated with receipt of IMRT and evaluated the association between IMRT and toxicity. MethodsWe queried the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 1, 2006 to December 31, 2014 to identify patients diagnosed with Stage II or III NSCLC and who received upfront surgery and subsequent PORT. Baseline differences between patients receiving 3-dimentional conformal radiation therapy (3D-CRT) and IMRT were assessed using the chi-squared test for proportions and the t-test for means. Multivariable logistic regression was used to identify predictors of receipt of IMRT and pulmonary, esophageal, and cardiac toxicity. Propensity-score matching was employed to reduce the effect of known confounders. ResultsA total of 620 patients met the inclusion criteria, among whom 441 (71.2%) received 3D-CRT and 179 (28.8%) received IMRT. The mean age of the cohort was 73.9 years and 54.7% were male. The proportion of patients receiving IMRT increased from 6.2% in 2006 to 41.4% in 2014 (P < 0.001). IMRT was not associated with decreased pulmonary (OR 0.89; 95% CI, 0.62–1.29), esophageal (OR 1.09; 95% CI, 0.0.75–1.58), or cardiac toxicity (OR 1.02; 95% CI, 0.69–1.51). These findings held on propensity-score matching. Clinical risk factors including comorbidity and prior treatment history were associated with treatment toxicity. ConclusionIn a cohort of elderly patients, the use of IMRT in the setting of PORT for LA-NSCLC was not associated with a difference in toxicity compared to 3D-CRT. This finding suggests that outcomes from PORT may be independent of radiotherapy treatment technique.

Clinical Outcomes After Proton Beam Therapy for Locally Advanced Non-Small Cell Lung Cancer: Analysis of a Multi-institutional Prospective Registry

PurposeFor most disease sites, level 1 evidence is lacking for proton beam therapy (PBT). By identifying target populations that would benefit most from PBT, prospective registries could overcome many of the challenges in clinical trial enrollment. Herein, we report clinical outcomes of patients treated with PBT for locally advanced non-small cell lung cancer (LA-NSCLC). Methods and MaterialsData were obtained from the multi-institutional prospective database of the Proton Collaborative Group (PCG). Inclusion criteria of our study were stage III de novo or recurrent LA-NSCLC, use of PBT, and availability of follow-up data. Overall survival (OS) time was calculated from the start of treatment until death or last follow-up. Kaplan-Meier curves were generated for groups of interest and compared with log-rank tests. Cox regression modeling was used to evaluate the multivariate association between selected covariates and OS. ResultsA total of 195 patients were included in the analysis. PBT was given with a median equivalent dose in 2 Gy fractions (EQD2) of 63.8 Gy (relative biological effectiveness). Pencil beam scanning was used in 20% of treatments. Treatment-related grade 3 adverse events were rare: 1 pneumonitis, 2 dermatitis, and 3 esophagitis. No grade 4 events were reported. Two cardiac-related grade 5 events occurred in patients with multiple risk factors. The median follow-up time for living patients was 37.1 months and the median OS was 19.0 months. On multivariate analysis, good performance status (hazard ratio, 0.27; [95% confidence interval, 0.15-0.46]; P < .0001), pencil beam scanning use (0.55; [0.31-0.97]; P = .04), and increased EQD2 (0.80; [0.71-0.90] - per 10 Gy increase; P = .0002) were associated with decreased mortality. ConclusionsPBT appears to yield low rates of adverse events with an OS similar to other retrospective studies on PBT for LA-NSCLC. PBS use and increased EQD2 can potentially improve OS.

1176P Neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in patients with potentially resectable NSCLC: An open-label, single-arm, phase II trial

Previous studies showed neoadjuvant therapy with a programmed cell death protein 1 (PD-1) inhibitor could benefit patients (pts) with resectable non-small-cell lung cancer (NSCLC). On this basis, we initiated a phase II clinical trial to report the safety and effectiveness of neoadjuvant Toripalimab plus chemotherapy in local advanced NSCLC.

1180P Anlotinib combined with radiotherapy in locally advanced non-small cell lung cancer (LANSCLC): A prospective, single-arm, phase II study

The standard treatment for patients with good performance status with unresectable LANSCLC is concurrent chemoradiotherapy (CRT), The new treatment strategies of patients who could not tolerate CRT or refused chemotherapy are necessary. Anlotinib is a novel multi-target antiangiogenesis agent that inhibits VEGFR, FGFR, PDGFR, c-kit, which showed encouraging efficacy and good tolerability for advanced NSCLC in ALTER-0303 trial. Emerging clinical data suggested that antiangiogenic drugs could enhance the efficacy of radiotherapy by alleviating tumor hypoxia and improving perfusion.

Optimal surgical timing and radiotherapy dose for trimodality therapy in locally advanced non‐small cell lung cancer

Purpose/ObjectivesData are conflicting on the effects of time interval from neoadjuvant chemoradiation (NCRT) to surgery for locally advanced non‐small‐cell lung cancer (LA‐NSCLC). This study investigated the impact of surgical timing after NCRT and radiation dose on postoperative mortality and overall survival (OS).Materials and MethodsUsing the National Cancer Database, we identified 3489 LA‐NSCLC patients treated with NCRT and surgery. Multivariate Cox proportional hazards analysis (MVA) was used to examine the effects of surgery >7 weeks from NCRT completion on OS. Propensity score (PS)‐matched survival analysis for surgery ≤7 and >7 weeks was performed. Postoperative mortality was assessed.ResultsMedian OS for surgery ≤7 weeks and >7 weeks after NCRT were 56.9 versus 45.6 months (hazard ratio, HR 1.18 [1.07–1.30]; p < 0.001). Surgery >7 weeks correlated with decreased OS on MVA (HR 1.15 [1.04–1.27]; p = 0.009) and PS matching (HR 1.16 [1.049–1.29]; p = 0.004). Time as a continuous variable correlated with OS on MVA (HR 1.003 [1.001–1.006]; p = 0.0056) and PS matching (HR 1.004 [1.001–1.006]; p = 0.004). Among 2902 lobectomy patients, the mortality rate for surgery ≤66 days was 5.2% versus 8.1% for >66 days (MVA HR 1.59 [1.02–2.49]; p = 0.04). Higher neoadjuvant radiotherapy dose correlated with surgery >7 weeks and lobectomy >66 days on MVA.ConclusionsIncreased interval >7 weeks from NCRT to surgery for LA‐NSCLC is correlated with worse OS and lobectomy ≤66 days correlated with improved OS. Surgery ≤7weeks may improve tumor control, whereas higher mortality for surgery >66 days may relate to late NCRT manifestations. Neoadjuvant doses of 44–50.4 Gy may minimize risks of radiation‐induced lung injury and surgical complications and facilitate surgery within the optimal 7‐week interval.

Metformin in Combination With Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer

Unresected locally advanced non-small cell lung cancer (LA-NSCLC) shows poor survival outcomes even after aggressive concurrent chemoradiotherapy. Whether metformin, a diabetes agent that inhibits the mitochondria oxidative phosphorylation chain, could improve radiotherapy and chemotherapy response in LA-NSCLC remains to be studied. To examine whether metformin, given concurrently with chemoradiotherapy and as consolidation treatment, could improve outcomes in patients with LA-NSCLC. The Ontario Clinical Oncology Group Advanced Lung Cancer Treatment With Metformin and Chemoradiotherapy (OCOG-ALMERA) study was a multicenter phase 2 randomized clinical trial. Patients were stratified for stage IIIA vs IIIB LA-NSCLC and use of consolidation chemotherapy. The trial was designed to enroll 96 patients with unresected LA-NSCLC who did not have diabetes. The trial was conducted from September 24, 2014, to March 8, 2019. Patients were randomized to platinum-based chemotherapy, concurrent with chest radiotherapy (60-63 Gy), with or without consolidation chemotherapy or the same treatment plus metformin, 2000 mg/d, during chemoradiotherapy and afterward for up to 12 months. The primary outcome was the proportion of patients who experienced a failure event (ie, locoregional disease progression, distant metastases, death, and discontinuation of trial treatment or planned evaluations for any reason within 12 months). Proportions were compared using a 2-sided Fisher exact test. Conventional progression-free and overall survival were estimated using the Kaplan-Meier method. Adverse events were graded with Common Terminology Criteria for Adverse Events, version 4.03. All randomized patients were included in an intention-to-treat analysis. The trial was stopped early due to slow accrual. Between 2014 and 2019, 54 patients were randomized (26 in experimental arm and 28 in control arm). Participants included 30 women (55.6%); mean (SD) age was 65.6 (7.6) years. Treatment failure was detected in 18 patients (69.2%) receiving metformin within 1 year vs 12 (42.9%) control patients (P = .05). The 1-year progression-free survival rate was 34.8% (95% CI, 16.6%-53.7%) in the metformin arm and 63.0% (95% CI, 42.1%-78.1%) in the control arm (hazard ratio, 2.42; 95% CI, 1.14-5.10) The overall survival rates were 47.4% (95% CI, 26.3%-65.9%) in the metformin arm and 85.2% (95% CI, 65.2%-94.2%) in the control arm (hazard ratio, 3.80; 95% CI, 1.49-9.73). More patients in the experimental arm vs control arm (53.8% vs 25.0%) reported at least 1 grade 3 or higher adverse event. In this randomized clinical trial, the addition of metformin to chemoradiotherapy was associated with worse treatment efficacy and increased toxic effects compared with combined modality therapy alone. Metformin is not recommended in patients with LA-NSCLC who are candidates for chemoradiotherapy. ClinicalTrials.gov Identifier: NCT02115464.

Feasibility of intensity modulated radiotherapy with involved field radiotherapy for Japanese patients with locally advanced non-small cell lung cancer

The feasibility of intensity modulated radiotherapy (IMRT) with involved field radiotherapy (IFRT) for Japanese patients with locally advanced non-small cell lung cancer (LA-NSCLC) remains unclear. Here we reviewed our initial experience of IMRT with IFRT for Japanese patients with LA-NSCLC to evaluate the feasibility of the treatment. Twenty LA-NSCLC patients who were treated with IMRT with IFRT during November 2019 to October 2020 were retrospectively analyzed. All patients received 60 Gy in 30 fractions of IMRT and were administered concurrent platinum-based chemotherapy. The median patient age was 71 years old and the group included 15 men and 5 women. The patient group included 2 patients with stage IIB, 11 patients with stage IIIA, 5 patients with stage IIIB, and 2 patients with stage IIIC disease. Histological diagnosis was squamous cell carcinoma in 14 patients, adenocarcinoma in 5 patients, and non-small cell lung cancer in 1 patient. The median follow-up period was 8 months. The incidence of grade 3 or greater pneumonitis was 5%, and grade 3 or greater esophagitis was not observed. None of the patients developed regional lymph node, with only recurrence reported so far. These findings indicate that IMRT with IFRT for Japanese patients with LA-NSCLC is feasible in terms of acute toxicity. Further study with a larger number of patients and longer follow-up to clarify the effect of treatment on patient prognosis is required.

MO21-1 Prognostic value of pneumonitis after durvalumab in locally-advanced non-small cell lung cancer

MO21-1 Prognostic value of pneumonitis after durvalumab in locally-advanced non-small cell lung cancer

Prevention and management of acute esophageal toxicity during concomitant chemoradiotherapy for locally advanced lung cancer.

Standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concomitant chemoradiotherapy. The survival benefit of combined treatment is partially counterbalanced by an increased rate of acute esophageal toxicity. Several pharmaceutical products are available for prevention and management of esophagitis, including Faringel Plus. To assess the incidence and the grade, identify the correlations with clinical, dosimetric, and therapeutic variables, and analyse the role of Faringel Plus as a pharmaceutical preventive measure against acute esophageal toxicity. Patients with LA-NSCLC treated with concomitant radiochemotherapy were retrospectively reviewed. Acute esophagitis and dysphagia were graded according to Common Terminology Criteria for Adverse Events version 5.0. Clinical, dosimetric, and therapeutic correlations were investigated using χ2 test. Among the 23 analysed patients, 18 (78.3%) and 1 (4.3%) developed G2 and G3 esophagitis, respectively; G1-2 dysphagia were reported in 11 cases (47.8%). No statistically significant correlation between the variables considered and acute esophageal toxicity was identified. In the group of patients who received Faringel Plus as preventive treatment (10 subjects, 43.5%), dysphagia presentation time was significantly longer (p = 0.038); esophagitis onset time was longer and symptoms duration was shorter. Faringel Plus allowed a reduction in the use of analgesic drugs. Acute mild esophageal toxicity was confirmed to be a common side effect in this setting. No clinical-dosimetric parameter has been demonstrated to be effective in predicting acute esophageal toxicity. The use of Faringel Plus appears effective as a therapeutic and prophylactic tool to manage acute esophageal toxicity.

Hypofractionated Intensity Modulated Radiation Therapy With Concurrent Chemotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase II Prospective Clinical Trial (GASTO1011)

PurposeWe aimed to explore the efficacy and toxicity of split-course hypofractionated radiation therapy with concurrent chemotherapy (HRT-CHT) in patients with locally advanced non-small cell lung cancer (LANSCLC) in this single-arm, phase II study. Methods and MaterialsPatients with LANSCLC were considered eligible if their forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC%) and carbon monoxide diffusing capacity (DLCO%) were ≥40% and ≥45%, respectively. HRT-CHT using the intensity modulated radiation therapy technique was administered with 51 Gy in 17 fractions as the first course followed by a break. Patients without disease progression or persistent ≥grade 2 toxicities had an HRT-CHT of 15 to 18 Gy in 5 to 6 fractions as a boost. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival (OS). ResultsEighty-nine patients were enrolled and analyzed. The median follow-up was 29.5 months for all patients and 35.3 months for the survivors. The objective response rate was 97.8%; the median progression-free survival and OS were 11.0 and 27.0 months, respectively. Grade 3 acute esophagitis/pneumonitis occurred in 15 (16.9%)/7 (7.9%) patients. Grade 3/5 late pneumonitis occurred in 2 (2.2%)/1 (1.1%) patients. Of the 78 (87.6%) who completed the split-course HRT-CHT per protocol, patients with better FEV1/FVC% and DLCO% after the break had significantly better OS (for the FEV/FVC1% ≥ 80% vs 60%-79% vs 41%-59% groups, 2-year OS values were 57.2% vs 56.9% vs 0%, respectively, P = .024; for the DLCO% ≥ 80% vs 60%-79% vs 45%-59% groups, 2-year OS values were 70.4% vs 48.4% vs 37.5%, respectively, P = .049). ConclusionsSplit-course HRT-CHT achieved a promising response rate and survival with tolerable toxicity in LANSCLC. Pulmonary function tests are necessary indicators for radiation treatment planning and dose escalation.

Radiation Therapy in Non-Small-Cell Lung Cancer.

The management of non-small-cell lung cancer (NSCLC) varies according to stage. Surgical resection is reserved for operable patients with early-stage NSCLC, while high-dose target radiation-stereotactic body radiation therapy (SBRT)-is reserved for patients whose comorbidities prohibit them from a major surgical procedure. The treatment of locally advanced NSCLC (LA-NSCLC) is stratified according to resectability. Those with resectable disease may require additional treatments such as chemotherapy and radiation, while patients with unresectable disease will require definitive chemoradiation therapy with adjuvant durvalumab. Patients with limited metastatic disease benefit from the combination of SBRT and systemic therapy.

Gefitinib With Concurrent Thoracic Radiotherapy in Unresectable Locally Advanced NSCLC With EGFR Mutation; West Japan Oncology Group 6911L

IntroductionAbout 10% of patients with locally advanced NSCLC (LA-NSCLC) harbor EGFR mutation and recent reports suggested the declined benefit with an immune checkpoint inhibitor in this population. The attempt that introduces EGFR tyrosine kinase inhibitor into the treatment of LA-NSCLC with EGFR mutation has been warranted. MethodsChemotherapy-naive patients with unresectable LA-NSCLC with sensitive EGFR mutation (exon 19 deletion or exon 21 L858R point mutation) were enrolled. Patients were treated with gefitinib (250 mg/d for 2 y) plus concurrent thoracic radiotherapy (64 Gy/32 fractions). The primary end point was progression-free survival (PFS) at 2 years (trial identifier, UMIN000008366). ResultsBetween August 2012 and November 2017, a total of 28 patients were enrolled and 27 were eligible. The median age was 67 years (range: 45–74); never/current or former smoker in 15/12 patients, respectively; Eastern Cooperative Oncology Group performance status of 0/1 in 19/8; EGFR exon 19 deletion/exon 21 L858R in 13/14; and c-stage IIIA/IIIB in 14/13. The PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%–). The overall response rate was 81.5% (95% CI: 63.3%–91.3%), median PFS was 18.6 months (95% CI: 12.0–24.5 mo), and median overall survival was 61.1 months (95% CI: 38.1 mo–not reached). Approximately half of the patients exhibited solitary brain metastasis as their first site of relapse. Adverse events greater than or equal to grade 3 were fatigue, skin reaction, and appetite loss (3.7% each). ConclusionsThis prospective study revealed the tolerability and the possible efficacy of gefitinib plus concurrent thoracic radiotherapy in patients with LA-NSCLC having EGFR mutation.

Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer

BackgroundWe have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC).Materials and methodsBaseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy).ResultsFollowing re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values.ConclusionsCardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.

The Prognostic Value of Programmed Death-ligand 1 (PD-L1) in Patients who Received Neoadjuvant Chemoradiation Therapy Followed by Surgery for Locally Advanced Non-small Cell Lung Cancer.

We analyzed the prognostic efficacy of programmed death-ligand 1 (PD-L1) in locally advanced non-small cell lung cancer (LA-NSCLC) patients. During 2005-2016, 211 patients underwent neoadjuvant concurrent chemoradiation therapy (CCRT) followed by surgical resection for LA-NSCLC at Asan Medical Center. PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TIL) were measured pre- and post-neoadjuvant CCRT and analyzed using immuno - histochemical staining. In total, 39 patients were enrolled. Overall survival (OS) and disease-free survival (DFS) were significantly longer in patients with increased PD-L1 expression and increased CD8+ TIL density post-neoadjuvant CCRT. Univariate Cox regression analysis confirmed that increased levels of PD-L1 and increased CD8+ TIL density were prognostic factors for OS and DFS. Multivariate Cox regression analysis confirmed that increased levels of PD-L1 was a prognostic factor for OS and increased CD8+ TIL density for DFS. Relative changes in PD-L1 expression post-neoadjuvant CCRT can be utilized to predict the prognosis of LA-NSCLC patients.

Intensity‐modulated radiotherapy combined with intensity‐modulated radiotherapy CT–guided iodine 125 seed brachytherapy for non‐small cell lung cancer: A case report

AbstractIntensity‐modulated radiotherapy (IMRT) has been used to treat locally advanced non‐small cell lung cancer (LA‐NSCLC) disseminated to primary gross tumor volume (pGTV) and mediastinal lymph nodes (LNs). However, it is challenging to deliver definitive doses to the pGTV and regional LNs without exceeding the tolerance of the organs at risk (OAR). Iodine‐125 (I‐125) brachytherapy has recently been applied in clinical practice for the treatment of malignant tumors. Its merits include a higher dose to the primary tumor lesion and lower dose surrounding the tumor mass. Using brachytherapy in these settings may maximize the dose delivered to the pGTV while minimizing the dose delivered to the OAR. I‐125 brachytherapy combined with IMRT for the treatment of LA‐NSCLC has rarely been reported. Here we report a patient with peripheral squamous cell carcinoma of the lung who received I‐125 brachytherapy for pulmonary lung lesions and IMRT for metastatic mediastinal LNs. The patient received 16 months of follow‐up care with no evidence of complications or disease recurrence. Moreover, we compared brachytherapy plus IMRT to theoretically planned IMRT dosimetry to evaluate the merits of each approach. This treatment modality resulted in a higher target dose escalation and lower doses delivered to the OAR.

Treatment strategies for locally advanced non-small cell lung cancer in elderly patients: Translating scientific evidence into clinical practice.

Treatment of locally advanced NSCLC (LA-NSCLC) is focused on multimodal strategy, including chemotherapy and radiotherapy (in combination or as alternative treatments), followed by surgery in selected cases. Recently, durvalumab consolidation after definitive chemo-radiation has shown a meaningful overall survival benefit. However, it is important to note that elderly patients represent a high proportion of NSCLC population and frailty and comorbidities can significantly limit treatment options. Indeed, elderly patients are under-represented in clinical trials and data to drive treatment selection in this category of patients are scanty. Available data, main issues and controversies on multimodal treatment in elderly LA-NSCLC patients will be reviewed in this paper.

Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study

Background and purposeIntensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. Materials and methodsWe retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. ResultsMedian follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. ConclusionCCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.

MSOR06 Presentation Time: 10:15 AM: The 3-Year Outcomes of 3D High-Dose-Rate Brachytherapy in Combination with Regional Metastatic Lymph Nodes Intensity-Modulated Radiotherapy in Peripheral Locally Advanced Non-Small Cell Lung Cancer: A Phase I/II Clinical Trial

Purpose: To determine the safety, late toxicities, and locoregional control of three-dimensional(3D) high-dose-rate(HDR) brachytherapy in combination with regional metastatic lymph nodes intensity-modulated radiotherapy(IMRT) in patients with peripheral locally advanced non-small cell lung cancer(LA-NSCLC).

PO50: Iodine-125 Brachytherapy Plus Intensity-Modulated Radiotherapy in Peripheral Local Advanced Non-Small Cell Lung Cancer

Purpose: Intensity-modulated radiotherapy (IMRT) has been used to treat local advanced local advanced non-small cell lung cancer (LA-NSCLC) disseminated to primary gross tumor volume (pGTV) and mediastinal lymph nodes (pGTVnd). However, it is a challenge to deliver definitive doses to pGTV and pGTVnd in the definitive setting without exceeding the tolerance of organs at risk (OAR). Using Iodine-125 (I-125) brachytherapy in these settings may maximize dose to the pGTV while minimizing dose to OAR.