Radiation Pneumonitis Research Articles

A multiomics approach-based prediction of radiation pneumonia in lung cancer patients: impact on survival outcome.

To predict the risk of radiation pneumonitis (RP), a multiomics model was built to stratify lung cancer patients. Our study also investigated the impact of RP on survival. This study retrospectively collected 100 RP and 99 matched non-RP lung cancer patients treated with radiotherapy from two independent centres. They were divided into training (n = 175) and validation cohorts (n = 24). The radiomics, dosiomics and clinical features were extracted from planning CT and electronic medical records and were analysed by LASSO Cox regression. A multiomics prediction model was developed by the optimal algorithm. Overall survival (OS) between the RP, non-RP, mild RP, and severe RP groups was analysed by the Kaplan‒Meier method. Sixteen radiomics features, two dosiomics features, and one clinical feature were selected to build the best multiomics model. The optimal performance for predicting RP was the area under the receiver operating characteristic curve (AUC) of the testing set (0.94) and validation set (0.92). The RP patients were divided into mild (≤ 2 grade) and severe (> 2 grade) RP groups. The median OS was 31months for the non-RP group compared with 49months for the RP group (HR = 0.53, p = 0.0022). Among the RP subgroup, the median OS was 57months for the mild RP group and 25months for the severe RP group (HR = 3.72, p < 0.0001). The multiomics model contributed to improving the accuracy of RP prediction. Compared with the non-RP patients, the RP patients displayed longer OS, especially the mild RP patients.

ACT001 Ameliorates ionizing radiation-induced lung injury by inhibiting NLRP3 inflammasome pathway

Radiotherapy is a prevalent treatment modality for thoracic tumors; however, it can lead to radiation-induced lung injury (RILI), which currently lacks effective interventions. ACT001, a prodrug of micheliolide, has demonstrated promising clinical application potential, yet its impact on RILI requires further validation. This study aims to investigate the radioprotective effects of ACT001 on RILI and elucidate its underlying mechanism. Sprague-Dawley rats were utilized to induce RILI following 20 Gy X-ray chest irradiation, and lung tissue inflammation and fibrosis were assessed using hematoxylin and eosin (H&E) and Masson staining. Lung injury, inflammation, and oxidative stress markers were evaluated employing commercial kits. Pyroptosis-related differentially expressed genes (DEGs) were analyzed using a microarray dataset from the Gene Expression Omnibus (GEO) database, and their functions and hub genes were identified through protein-protein interaction networks. Pyroptosis-related genes were detected via RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. The results demonstrated that ACT001 ameliorated RILI, diminished pro-inflammatory cytokine release and fibrosis, and mitigated the activation of the NLRP3 inflammasome while inhibiting pyroptosis in lung tissue. In conclusion, our study reveals that ACT001 can suppress NLRP3 inflammasome-mediated pyroptosis and improve RILI, suggesting its potential as a novel protective agent for RILI.

Clinical results of proton beam radiotherapy for inoperable stage III non-small cell lung cancer: a Japanese national registry study.

This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.

Downregulation of β-Catenin Contributes to type II Alveolar Epithelial Stem Cell Resistance to Epithelial-Mesenchymal Transition by Lowing Lin28/let-7 Ratios in Fibrosis-Resistant Mice after Thoracic Irradiation.

Transdifferentiation of type II alveolar cells (AECII) is a major cause for radiation-induced lung fibrosis (RILF). Cell differentiation phenotype is determined by Lin28 (undifferentiated marker) and let-7 (differentiated marker) in a see-saw-pattern. Therefore, differentiation phenotype can be extrapolated based on Lin28/let-7 ratio. Lin28 is activated by β-catenin. To the best of our knowledge this study was the first to use the single primary AECII freshly isolated from irradiated lungs of fibrosis-resistant C3H/HeNHsd strain to further confirm RILF mechanism by comparing its differences in AECII phenotype status/state and cell differentiation regulators to fibrosis-prone C57BL/6j mice. Results showed that radiation pneumonitis and fibrotic lesions were seen in C3H/HeNHsd and C57BL/6j mouse strains, respectively. mRNAs of E-cadherin, EpCAM, HOPX and proSP-C (epithelial phenotype biomarkers) were significantly downregulated in single primary AECII isolated from irradiated lungs of both strains. Unlike C57BL/6j, α-SMA and Vimentin (mesenchymal phenotype biomarkers) were not upregulated in single AECII from irradiated C3H/HeNHsd. Profibrotic molecules, TGF-β1 mRNA was upregulated and β-catenin was significantly downregulated in AECII after irradiation (both P < 0.01). In contrast, transcriptions for GSK-3β, TGF-β1 and β-catenin were enhanced in isolated single AECII from irradiated C57BL/6j (P < 0.01-P < 0.001). The Lin28/let-7 ratios were much lower in single primary AECII from C3H/HeNHsd after irradiation vs. C57BL/6j. In conclusion, AECII from irradiated C3H/HeNHsd did not undergo epithelial-mesenchymal transition (EMT) and lower ratios of Lin28/let-7 contributed to AECII relatively higher differentiated status, leading to increased susceptibility to radiation stress and a failure in transdifferentiation in the absence of β-catenin. Reducing β-catenin expression and the ratios of Lin28/let-7 may be a promising strategy to prevent radiation fibrosis.

PO-2322 A novel tool to evaluate and quantify radiation induced lung injury(RILI): volume of pneumonia patch

PO-2322 A novel tool to evaluate and quantify radiation induced lung injury(RILI): volume of pneumonia patch

PO-2203 Generation of synthetic radiation pneumonitis images using deep learning

PO-2203 Generation of synthetic radiation pneumonitis images using deep learning

PO-2115 federated learning of decentralized AI for predicting radiation pneumonitis in lung cancer patients

PO-2115 federated learning of decentralized AI for predicting radiation pneumonitis in lung cancer patients

Effectiveness of Stereotactic Ablative Radiotherapy for Systemic Therapy Respondents with Inoperable Pulmonary Oligometastases and Oligoprogression.

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Early Detection of Radiation Pneumonitis on Cone-Beam CT Images During a Course of Radiotherapy: A Case Series Report.

Background and aim Radiation pneumonitis (RP) is a critical pulmonary toxicity following dose delivery to the lung, and it is usually diagnosed after radiotherapy courses are completed. Because RP may result in a lethal complication, a practical method for detecting early-phase RP is awaited. In this article, we describe our experience through a variety of clinical cases and discuss treatment decisions and lessons we have made and learned. Materials and methods A daily cone-beam computed tomography (CBCT) scan was employed with a lung window setting to detect the early-phase RP during treatment courses. For the past five years, thirty patients were diagnosed with RP, and eight patients were detected during radiotherapy courses on the CBCT images. Our best efforts were made in detecting early ground-glass opacity and early RP on CBCT images prior to symptoms. The eight cases were described in more detail with CBCT or CT images. Results and discussion Initially, RP was detected at 50 Gy or greater. However, more careful CBCT observation resulted in earlier detection at around 40 Gy. Then, a new problem arose whether the treatment should be terminated. It was reported that early RP development was associated with higher-grade complications, and therefore it is preferable to terminate radiotherapy once we detect even early-phase RP. However, termination in the middle of the treatment coursemay significantly reduce the therapeutic effect. In our experience, patients with favorable clinical status may continue to receive radiotherapy with careful observation of lung parenchyma on CBCT images and clinical data, such as Krebs Von den Lungen-6(KL-6) and C-reactive protein (CRP). Conclusion We have shown that early detection of RP may be feasible during radiotherapy courses by daily monitoring of CBCT lung images. Further studies are awaited to proceed.

An interactive murine single-cell atlas of the lung responses to radiation injury

Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the latter being a life-threatening condition. The order of cellular and molecular events in the progression towards fibrosis is key to the physiopathogenesis of the disease, yet their coordination in space and time remains largely unexplored. Here, we present an interactive murine single cell atlas of the lung response to irradiation, generated from C57BL6/J female mice. This tool opens the door for exploration of the spatio-temporal dynamics of the mechanisms that lead to radiation-induced pulmonary fibrosis. It depicts with unprecedented detail cell type-specific radiation-induced responses associated with either lung regeneration or the failure thereof. A better understanding of the mechanisms leading to lung fibrosis will help finding new therapeutic options that could improve patients’ quality of life.

Long-term Outcomes After Moderate Hypofractionated Proton Therapy for Centrally Located Non-small Cell Lung Cancer.

To investigate the outcomes of patients with centrally located non-small-cell lung cancer (NSCLC) treated with proton beam therapy (PBT) using moderate hypofractionation. Between 2006 and 2019, 34 patients with centrally located T1-T4N0M0 NSCLC who received moderate hypofractionated PBT were retrospectively reviewed. The median follow-up was 50.8 months (range=5.8-100.4 months). The 3-year overall survival, progression-free survival (PFS), and local control rates were 70.4%, 55.5% and 80.5%, respectively. Grade 2 or 3 lung adverse events (AEs) after PBT were observed in five (14.7%) patients; however, grade 3 radiation pneumonitis was observed in one (2.9%) patient. Notably, no grade 4 or higher AEs were observed. Regarding the correlation between the lung dose and proximal bronchial tree maximum dose and grade 2 or higher lung AEs, a weak correlation was observed between the mean lung dose and AEs (p=0.035). Although the clinical target volume (CTV) was a risk factor for poor PFS, no significant correlation was found between the CTV and lung AEs after PBT. Moderate hypofractionated PBT may be a useful radiotherapy method for centrally located cT1-T4N0M0 NSCLC.

Ipsilateral lung dose as a correlative measure for radiation pneumonitis in patients treated with definitive concurrent radiochemotherapy.

Mean lung dose (MLD) and percent of total lung (TL) volume that receive a dose greater than 20 Gy (V20) have been the most validated parameters in the prediction of radiation pneumonitis (RP). However, these parameters present mean values of TL parenchyma and predict the right and the left lung as a unique functional organ unit, not take into account the difference in function and dose density between the lungs. Furthermore, there have been very limited data evaluating ipsilateral lung dosimetric constraints in addition to TL parameters to predict RP in non-small cell lung cancer (NSCLC) patients treated with radiochemotherapy (RCT). Between 2010 and 2017, clinical-radiological findings of NSCLC patients treated with RCT were evaluated in terms of RP, retrospectively. MLD, V20, and V30 values of ipsilateral lung were assessed from dose-volume histogram and registered. The primary endpoint was to assess the relation between ipsilateral lung dose constraints and RP risk. There were 75 patients. There was ≥Grade 2 RP in 33 cases (%44). In univariate analysis, ipsilateral MLD, ipsilateral V20, ipsilateral V30, and TL V30 were found to be significant. Ipsilateral MLD and PTV were found to be the independent risk factors for RP. Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL. In NSCLC patients treated with RCT, MLD, V20, and V30 values of ipsilateral lung parameters might increase the predictability of RP risk in addition to TL parameters. Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL.

Subpleural fibrotic interstitial lung abnormalities are implicated in non-small cell lung cancer radiotherapy outcomes.

The relationship between interstitial lung abnormalities (ILAs) and the outcomes of lung cancer radiotherapy is unclear. This study investigated whether specific ILA subtypes are risk factors for radiation pneumonitis (RP). This retrospective study analysed patients with non-small cell lung cancer treated with radical-intent or salvage radiotherapy. Patients were categorised into normal (no abnormalities), ILA, and interstitial lung disease (ILD) groups. The ILA group was further subclassified into non-subpleural (NS), subpleural non-fibrotic (SNF), and subpleural fibrotic (SF) types. The Kaplan-Meier and Cox regression methods were used to determine RP and survival rates and compare these outcomes between groups, respectively. Overall, 175 patients (normal, n = 105; ILA-NS, n = 5; ILA-SNF, n = 28; ILA-SF, n = 31; ILD, n = 6) were enrolled. Grade ≥2 RP was observed in 71 (41%) patients. ILAs (hazard ratio [HR]: 2.33, p = 0.008), intensity-modulated radiotherapy (HR: 0.38, p = 0.03), and lung volume receiving 20 Gy (HR: 54.8, p = 0.03) contributed to the cumulative incidence of RP. Eight patients with grade 5 RP were in the ILA group, seven of whom had ILA-SF. Among radically treated patients, the ILA group had worse 2-year overall survival (OS) than the normal group (35.3% vs 54.6%, p = 0.005). Multivariate analysis revealed that the ILA-SF group contributed to poor OS (HR: 3.07, p =0.02). ILAs, particularly ILA-SF, may be important risk factors for RP, which can worsen prognosis. These findings may aid in making decisions regarding radiotherapy.

Korean Real-World Data on Patients With Unresectable Stage III NSCLC Treated With Durvalumab After Chemoradiotherapy: PACIFIC-KR

IntroductionThis study aimed to investigate real-world evidence for efficacy and safety of durvalumab consolidation (DC) after chemoradiotherapy (CRT) in patients with unresectable stage III NSCLC. MethodsPatients with stage III NSCLC who started DC after CRT between September 2018 and December 2020 and were treated at five tertiary hospitals in the Republic of Korea were included. The primary end point was real-world progression-free survival (rwPFS). Secondary end points were overall survival, objective response rate, and adverse events including radiation pneumonitis (RP) and immune-related adverse events (irAEs). ResultsA total of 157 patients were enrolled. At the median follow-up of 19.1 months, median rwPFS of DC was 25.9 months (95% confidence interval: 16.5–35.4) and the 1-, 2-, and 3-year rwPFS rates were 59.4%, 51.8%, and 43.5%, respectively. The median overall survival was not mature, and objective response rate of DC was 51.0%. High programmed death-ligand 1 expression (≥50%) and development of RP requiring steroid treatment were significantly associated with longer (p = 0.043) and shorter rwPFS (p = 0.036), respectively. RP, RP requiring steroid treatment, and irAEs developed in 57 (36.3%), 42 (26.8%), and 53 (33.8%) patients, respectively. Among peripheral blood cell counts at the initiation of DC, a high derived monocyte-to-lymphocyte ratio was the most significant risk factor for the development of RP requiring steroid treatment (OR 44.76, 95% CI: 8.89–225.43, p < 0.001) and irAEs (OR 2.85, 95% CI: 1.27–6.41, p = 0.011). ConclusionsCompared with the outcome of the PACIFIC trial, these real-world data revealed favorable survival benefits of DC after CRT in patients with unresectable stage III NSCLC. Blood-based biomarkers could predict higher-grade RP and irAEs before the initiation of DC.

Concurrent sintilimab with sequential chemoradiotherapy for unresectable, stage III non-small cell lung cancer: a retrospective study.

Concurrent programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors with sequential chemoradiotherapy (SCRT) have been reported in only a limited number of studies involving patients with unresectable stage III non-small-cell lung cancer (NSCLC). A retrospective study was conducted to systematically analyze the efficacy and safety of the emerging therapy among Chinese patients. We included patients with unresectable, stage III NSCLC who received concurrent sintilimab with chemotherapy or chemotherapy alone for 3-6 cycles, followed by radical radiotherapy at the First Hospital of Jilin University from Dec 15, 2019, to Jul 15, 2022. The primary end point was the objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), 12-month and 18-month PFS rates, the duration of response (DoR), and safety. The retrospective study involved 77 patients, of which 49 receiving concurrent sintilimab with SCRT were assigned to cohort A, and 28 receiving SCRT alone were assigned to cohort B. The ORR was significantly higher in cohort A (79.6%, 95% CI 65.7-89.8) than in cohort B (35.7%, 95% CI 18.6-55.9) (p<0.001). Median PFS was significantly longer in cohort A than in cohort B (NR [95% CI 21.4-NR] vs. 16.0 months [13.0-22.5]; HR 0.375, 95% CI 0.192-0.735; p=0.003). The PFS rates at 12 and 18 months were 84.8% (95% CI 75.0-95.9) and 71.3% (95% CI 58.7-86.7) in cohort A and 75.0% (95% CI 60.6-92.9) and 38.3% (95% CI 23.7-61.7) in cohort B, respectively. Grade 3 or 4 adverse events (AEs) were reported in 19 patients (38.8%) and seven patients (25.0%) in two cohorts, respectively. Grade 3 or 4 pneumonitis or immune-mediated pneumonitis, radiation pneumonitis, and pneumonia occurred in five (10.2%), four (8.2%), and two (4.1%) cohort A patients, and zero, two (7.1%), and two (7.1%) cohort B patients, respectively. Only cohort A reported AE leading to death in one (2.0%) patient (immune-mediated pneumonitis). Concurrent sintilimab with SCRT resulted in a significantly better ORR and longer PFS than SCRT alone, with manageable safety profiles in Chinese patients with unresectable stage III NSCLC.

Effects of irradiation with different fractionations on radioresistant esophageal cancer cells and lung tissues

BackgroundLocal recurrence is the main cause of treatment failure for esophageal cancer and a large part of them require re-irradiation which needs to face the two major challenges of radioresistance and radiation-induced lung injury (RILI). This study aimed to evaluate the effects of irradiation with different fractionations on inhibition in radioresistant esophageal cancer cells in vitro and RILI in vivo. MethodsEC109R was selected from the human esophageal squamous carcinoma cell line EC109 by multiple exposures and verified to be radioresistant through colony forming assay and cell proliferation assay. EC109R was irradiated with different fractionations (conventional radiotherapy, CR: 2 Gy/d, 5 d; pulsed low dose-rate radiotherapy, PLDR: 0.2 Gy x 10 pulses with 3-min intervals/d, 5 d; hypo-fractionated radiotherapy, HR: 5 Gy/d, 2 d) to verify their inhibition by CCK-8. The protection of PLDR on RILI was assessed by H&E-staining paraffin sections and mice serum TGF-β1 levels. ResultsEC109R exhibited much better radioresistance (p < 0.0001) than EC109 in colony forming and cell proliferation assays. For EC109R, PLDR showed slightly lower inhibition by detection of optical density than HR (p = 0.0025) but similar to CR (p = 0.1155). In addition, pathological sections of lung tissues from PLDR group showed less alveolar structural damage and inflammatory cells infiltration, and serum TGF-β1 levels were significantly lower than those in the other two fractionations (vs CR: p = 0.0092; vs HR: p = 0.0045). ConclusionPLDR could effectively inhibit the proliferation of radioresistant esophageal cancer cells in vitro and mitigate RILI in vivo.

METTL3 Mediates Epithelial-Mesenchymal Transition by Modulating FOXO1 mRNA N6 -Methyladenosine-Dependent YTHDF2 Binding: A Novel Mechanism of Radiation-Induced Lung Injury.

The biological roles of epithelial-mesenchymal transition (EMT) in the pathogenesis of radiation-induced lung injury (RILI) have been widely demonstrated, but the mechanisms involved have been incompletely elucidated. N6 -methyladenosine (m6 A) modification, the most abundant reversible methylation modification in eukaryotic mRNAs, plays vital roles in multiple biological processes. Whether and how m6 A modification participates in ionizing radiation (IR)-induced EMT and RILI remain unclear. Here, significantly increased m6 A levels upon IR-induced EMT are detected both in vivo and in vitro. Furthermore, upregulated methyltransferase-like 3 (METTL3) expression and downregulated α-ketoglutarate-dependent dioxygenase AlkB homolog 5 (ALKBH5) expression are detected. In addition, blocking METTL3-mediated m6 A modification suppresses IR-induced EMT both in vivo and in vitro. Mechanistically, forkhead box O1 (FOXO1) is identified as a key target of METTL3 by a methylated RNA immunoprecipitation (MeRIP) assay. FOXO1 expression is downregulated by METTL3-mediated mRNA m6 A modification in a YTH-domain family 2 (YTHDF2)-dependent manner, which subsequently activates the AKT and ERK signaling pathways. Overall, the present study shows that IR-responsive METTL3 is involved in IR-induced EMT, probably by activating the AKT and ERK signaling pathways via YTHDF2-dependent FOXO1 m6 A modification, which may be a novel mechanism involved in the occurrence and development of RILI.

Acute Post-Radiation Pneumonitis: A Case Report

Acute radiation pneumonitis is a rare cause of pneumonitis. The diagnosis is considered in the presence of respiratory symptoms that appear with recent thoracic exposure. We report the case of a 67-year-old patient followed for mediastinal lymphoma who presented an acute pneumonitis when she started her radiotherapy sessions. Two diagnostics were suspected: radiotherapy toxicity or metastatic origin. Acute post-radiation pneumonitis can be very serious if the diagnostic is delayed. The diagnosis of acute post-radiation pneumonitis constitutes a diagnosis of elimination of any pneumonitis with an unfavorable evolution under antibiotic therapy, in the context of semi-recent thoracic radiotherapy.

Abstract CT219: Efficacy and safety of Low dose radiotherapy (LDRT) concurrent Atezolizumab (Atezo) plus chemotherapy as first line (1L) therapy for ES-SCLC: Primary analysis of Phase II MATCH study

Abstract Background: The IMpower133 represented the current standard of care in the 1L setting for patients (pts) with ES-SCLC (extensive-stage small cell lung cancer). However, there are still unmet needs for ES-SCLC treatment. LDRT could play a key role in the priming effect of immune system by acting as an immune adjuvant and having sensitive cytotoxic activity to SCLC. The interim analysis of MATCH study after stage I showed promising benefit and tolerability of combination of Atezo + chemotherapy + LDRT in pts with ES-SCLC. Here we report the primary efficacy and safety results of this study. Methods: The MATCH study was a single-arm phase II trial conducted in 8 centers across China. Previously untreated ES-SCLC pts with measureable disease per RECIST v1.1 at baseline, age≥18, ECOG 0-1 were eligible. Atezo (1200 mg IV, D1) + Cisplatin (75 mg/m2 IV, D1)/Carboplatin (AUC = 5 IV, D1) +Etoposide (100 mg/m2 IV, D1-D3) were administrated on a 21-day cycle for four cycles. Concurrent LDRT (15 Gy/5f) were conducted from D1-D5 in the first cycle. Then pts received Atezo maintenance until loss of clinical benefit or unacceptable toxicity. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with a complete response or partial response on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. A Simon’s minimax 2-stage design was adopted. Results: As the cutoff date of 30th Nov. 2022, 56 pts have been enrolled. 49 (87.5%) were males; mean age was 58.9 years with 78.6% pts had ECOG PS of 1. 80.4% pts had smoking history. Most pts were staged T4 (n = 33, 58.9%), N3 (n = 37, 66.1%) and M1(n = 40, 71.4%). Median follow-up was 14.8 months (range: 11.6-17.8 m). The confirmed ORR was 87.5% (95% CI: 75.9%-94.8%), all partial response. DCR was 94.6% (95% CI: 85.1%-98.9%). Median PFS was 6.9 m (95% CI: 5.4-9.3 m). The 6-month and 12-month PFS rate were 56.5% and 27.7%. Median OS was not reached (NR, 95% CI: 13.3m, NR). The 12-month OS rate was 71.9%. The safety profile, analyzed in all 56 pts, was consistent with the previous reports. Neutrophil count decreased (60.7%), white blood cell count decreased (58.9%) and platelet count decreased (23.2%) were the most common grade (G) 3-4 adverse events (AE). G5 AE occurred in 1 pt (pneumonia and pulmonary embolism). 4 pts experienced AEs leading to treatment discontinuation. IrAEs were reported in 21 (37.5%) pts, most common irAEs were hyperthyroidism (5.4%) and rash (5.4%). Radiation pneumonitis (G1) was observed in 1 pt. Conclusions: Adding LDRT to Atezo + chemotherapy shows impressive antitumor activity, potential survival benefit and well tolerability in 1L treatment of ES-SCLC. Clinical registration: NCT04622228. Citation Format: Lin Zhou, Jianguo Sun, Conghua Xie, Youling Gong, Meijuan Huang, Zhiyong Yuan, Lin Wu, Hui Wang, Nan Bi, Yaping Xu, Jiang Zhu, Yongmei Liu, Yan Zhang, Min Fan, Bingwen Zou, Min Yu, Yanying Li, Feifei Na, Weigang Xiu, Yong Xu, Jin Wang, Xuanwei Zhang, Jianxin Xue, You Lu. Efficacy and safety of Low dose radiotherapy (LDRT) concurrent Atezolizumab (Atezo) plus chemotherapy as first line (1L) therapy for ES-SCLC: Primary analysis of Phase II MATCH study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT219.

Measurements of target volumes and organs at risk using DW‑MRI in patients with central lung cancer accompanied with atelectasis.

Accurate imaging-based tumor delineation is crucial for guiding the radiotherapy treatments of various solid tumors. Currently, several imaging procedures, including diffusion-weighted magnetic resonance imaging (DW-MRI), intensified computed tomography and positron emission tomography are routinely used for targeted tumor delineation. However, the performance of these imaging procedures has not yet been comprehensively evaluated. In order to address this matter, the present study was conducted in an aim to assess the use of DW-MRI in guiding radiotherapy treatments, by comparing its performance to that of other imaging procedures. Specifically, the exposure dosages to organs at risk, including the lungs, heart and spinal mencord, were evaluated using various radiotherapy regimes. The findings of the present study demonstrated that DW-MRI is a non-invasive and cost-effective imaging procedure that can be used to reduce lung exposure doses, minimizing the risk of radiation pneumonitis. The data further demonstrate the immense potential of the DW-MRI procedure in the precision radiotherapy of lung cancers.