To establish prediction models to predict 2-year overall survival (OS) and stratify patients with different risks based on radiomics features extracted from magnetic resonance imaging (MRI) and computed tomography (CT) before definite chemoradiotherapy (dCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). Patients with locally advanced ESCC were recruited. We extracted 547 radiomics features from MRI and CT images. The least absolute shrinkage and selection operator (LASSO) for COX algorithm was used to obtain features highly correlated with survival outcomes in the training cohort. Based on MRI, CT, and the hybrid image data, three prediction models were built. The predictive performance of the radiomics models was evaluated in the training cohort and verified in the validation cohort using AUC values. A total of 192 patients were included and randomized into the training and validation cohorts. In predicting 2-year OS, the AUCs of the CT-based model were 0.733 and 0.654 for the training and validation sets. The MRI radiomics-based model was observed with similar AUCs of 0.750 and 0.686 in the training and validation sets. The AUC values of hybrid model combining MRI and CT radiomics features in predicting 2-year OS were 0.792 and 0.715 in the training and validation cohorts. It showed significant differences in 2-year OS in the high-risk and low-risk groups divided by the best cutoff value in the hybrid radiomics-based model. The hybrid radiomics-based model demontrated the best performance of predicting 2-year OS and can differentiate the high-risk and low-risk patients.

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer. Despite initial responses, the majority of patients with limited-stage SCLC experience relapse, and long-term survival remains unsatisfactory. Novel treatment strategies are in need to enhance therapeutic outcomes. With the inspiring results of PACIFIC trial in non-small cell lung cancer (NSCLC), and CAPIAN and IMpower133 trial in extensive-stage SCLC, immunotherapy has increasingly gained attention. Serplulimab, a PD-1 inhibitor, showed great antitumor activity in ASTRUM-005 trial and has been recommended as first-line therapy in extensive-stage SCLC. Hypofractionation radiotherapy has emerged as a promising approach in the management of limited-stage SCLC, offering the advantage of shorter treatment duration and potential benefits combining with subsequent immunotherapy. This clinical trial aims to address whether serplulimab following hypofractionation radiotherapy and chemotherapy could bring better outcomes in limited-stage SCLC. This single-arm, phase II trial will enroll fifty-five eligible patients diagnosed with limited-stage SCLC. All patients will receive four cycles chemotherapy. Recommended regimens are etoposide in combination with cisplatin or carboplatin. Thoracic radiation should initiate no later than the third cycle of chemotherapy. It is planned to target the primary tumor and involved mediastinal lymph node regions. For simulation, 4D-CT simulation positioning and enhanced CT positioning image scanning should be performed as far as possible. A total of 45Gy in 15 fractions over 3 weeks will be delivered. Prophylactic cranial irradiation(PCI) is routinely scheduled for patients without progression after chemoradiotherapy, and hippocampal avoidance is highly recommended. 25Gy in 10 fractions over 2 weeks to the brain will be prescribed. Patients without disease progression will receive intravenous infusion of serplulimab 300mg every 3 weeks for up to one year. Regular follow-up assessments will be conducted to monitor treatment responses, survival outcomes, and potential adverse events. NCT05443646. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Shanghai Henlius Biotech, Inc.

The PACIFIC subgroup analysis indicates that immune consolidation therapy may not be beneficial for patients (pts) harboring EGFR mutations. Our prior large retrospective multicenter study showed that combining radiotherapy with targeted therapy outperformed chemoradiotherapy (CRT). Here, we firstly conduct a multicenter randomized controlled phase III study to evaluate the benefits of AUM, a third-generation EGFR-TKI, and radiotherapy instead of cCRT for unresectable stage III EGFR-mutant NSCLC. Eligible pts were aged 18-75 years old, histologically confirmed as unresectable stage III EGFR-mutant NSCLC, who were randomized into experimental group (Group A) and control group (Group B). Group A: AUM (110mg PO QD) for 9 weeks as induction therapy, followed by radiotherapy (60 Gy) +AUM, and AUM maintenance therapy. Group B: Radiotherapy (60Gy)+Cisplatin (75 mg/m2) + Pemetrexed (500 mg/m2) Q3W for 2 cycles, followed by Pemetrexed+ Cisplatin Q3W for 1-2 cycles. After progression in Group B, crossover to Group A was allowed. The primary endpoint was PFS. Partial secondary endpoints included OS, safety and quality of life. 40 pts (ITT) were enrolled, with 24 pts in Group A and 16 pts in Group B. At data cut-off (Dec,2023), the hazard ratio (HR) for PFS was 0.152 [95%CI 0.040-0.0579; p=0.0002]. The mPFS was NR for Group A vs 6.2 months for Group B, with the median follow-up time 11.2m vs 5.7m. The 12-months PFS rate was 87.0% in Group A. In Group B, eight pts had progressed. Of these pts, 4/8 (50%) had crossed over, while 3/8 (37.5%) of the pts did not, and 1/8 (12.5%) had died. OS was not reached. Grade 3 or higher (G3+) AEs occurred in 4.2% of Group A and as high as 25% of Group B. The most common TRAEs were muscular pain (12.5%; grade 1/2) and cough (8.3%; grade1), versus myelosuppression (27%; grade 3, 13%) and vomiting (13%, grade 2), respectively. For pts with unresectable EGFR-mutated stage III NSCLC, the combination of AUM and radiotherapy provides better PFS benefit versus cCRT with fewer symptomatic AEs. Our study is still ongoing to extend the follow-up period to determine longer-term outcomes.

Purpose/Objective(s) We aim to evaluate dynamic survival of limited-stage small cell lung cancer (LS-SCLC) treated with intensity-modulate radiation therapy (IMRT) in the first-line chemoradiotherapy (CRT) era. Materials/Methods This retrospective cohort study reviewed 821 LS-SCLC patients who underwent chemoradiotherapy with IMRT. Conditional survival and annual hazard rates were used to evaluate the dynamic survival. The clinical prognostic factors were estimated by Cox regression proportional analysis. The corresponding conditional survival of each factor was calculated, with IPTW used to balance other confounding factors. The differences of conditional survival were evaluated by standardized differences (D value). Sensitivity analysis was also conducted. Results The median follow-up of the entire cohort was 66 months (95% CI：62.20-69.80). 3-year survival rates raised from 45.47% (95% CI: 42.1%-48.9%) at diagnosis to 93.01% (95% CI: 88.4%-97.7%) at year five for conditional overall survival and from 30.31% (95% CI: 27.2%-33.5%) to 90.71% (95% CI: 83.9%-97.5%) at year five for conditional progression-free survival. The annual hazard rates for patients reach the highest point between year 1 to year 2 for death and drop continuously for progression. Supraclavicular metastasis, smoking history, sequence of chemoradiotherapy were clinical prognostic factors at diagnosis, while the difference remained or disappeared in the follow-up for OS and PFS. Results in subgroup of patients achieved CR and PR was consistent. Conclusion In the first-line chemoradiotherapy era, the survival probability for LS-SCLC increased and progression probability decreased over time. The influence of prognostic factors at initial diagnosis may change in the long-term follow-up.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Purpose/Objective(s) We aimed to investigate the timing of once-daily thoracic radiotherapy (TTRT) in patients with limited-stage small cell lung cancer (LS-SCLC) in the first-line concurrent chemoradiotherapy era. Materials/Methods A total of 445 patients with LS-SCLC receiving concurrent chemoradiotherapy were reviewed. Nonlinear analysis by restricted cubic splines was used to determine the relationship between timing of TRT (TTRT) and PFS or OS. OS and PFS in different TTRT groups were compared using log-rank tests and multivariable analyses. The cumulative incidence of locoregional recurrence (LRR), brain metastases (BM), and extracranial distant metastases (EDM) were investigated using competing risk analyses. Adverse events were also compared. Results The median duration of follow-up was 64 months. There was a non-linear relationship between TTRT and PFS (P = 0.002) or OS (P < 0.001). When TRT started from 31 days to 63 days, improved 5-year PFS (37.0%; P = 0.001) and OS (49.7%; P < 0.001) and decreased 5-year EDM (27.9%; P = 0.009) were achieved compared with the ≤30-day group (19.5%; 32.0%; 43.3%) and >63-day group (23.7%; 24.2%; 43.5%). However, no significant difference in overall survival was observed in groups divided by actual chemotherapy cycle. A downward trend was seen in the incidence of myelosuppression of grade 3–4 in different TTRT groups (P = 0.04). Conclusion Appropriate treatment timing window might exist in once-daily TRT with concurrent chemotherapy. Delaying in combination of TRT and prescribed chemotherapy cycle may impair the survival outcomes.

EDRIC was an independent prognostic factor for survival. Higher doses of radiation to the immune system were associated with tumor progression and death after the PORT of NSCLC. The organ at risk for the immune system should be considered during radiotherapy planning.

GTV contouring variability was seen between T1c, T2f and T2 sequences. The coincidence of T1+c and T2f was better than T1+c and T2 in BMs. Since reductions in volume and changes of lesion center was observed during HFRT, the use of MR-guided radiation therapy (RT) and treatment adaptation is needed. The optimal timing for treatment plan modification might be when the course of treatment reaches 2/3 for most large BMs. Further research to find out patients who may benefit form MR-guided adaptive RT is ongoing.

Abstract Purpose: Multiple brain metastases (BMs) remain a therapeutic challenge. Helical tomotherapy (HT) is a novel equipment which has shown favorable dosimetric properties in previous studies. The aim of this single institutional phase II trial was to investigate the feasibility and toxicity of hypofractionated radiotherapy (HFRT) with or without simultaneous whole brain radiotherapy (WBRT) by HT in treating patients with multiple BMs. Methods:Patients with at least 3 BMs were enrolled. All the patients were treated with HT. The prescribed dose was 40 Gy in 20 fractions for WBRT and 60 Gy in 20 fractions for BMs simultaneously. For patients who had prior WBRT or refusing WBRT, focal HFRT for the lesions with optimized doses based on tumor volumes and locations were given. The primary endpoint was 1y-intracranial progression free survival (IPFS). Results: Between September 2014 and June 2017, 69 patients were enrolled and finally been analyzed. The median follow-up time was 40.1 months. The 1-year IPFS rate was 80.5%. The median survival time was 18.1 months (95% CI, 15.5- 20.7). The 1-year local control, overall survival and brain metastasis-specific survival rates were 96.4%, 71.0% and 94.6%, respectively. The 2-year rates were 87.6%, 51.1% and 39.1%, respectively. Only 1 patient (1.4%) had Grade 3 hematological toxicity and the radiation necrosis rate was 2.9%. Conclusion: Helical tomotherapy was well tolerated and could significantly extend IPFS compared with historical controls in multiple BMs.

A machine learning model based on clinicohematological markers and MR radiomics to predict pCR after nCRT for patients with esophageal cancer was developed and validated, providing a novel tool for personalized treatment. It is necessary to further validate in more large datasets.

TRT is well-tolerated and effective for selected ES-SCLC patients in the modern era of immunotherapy. Prospective trials are still needed to further evaluate the combination of TRT and immunotherapy for patients with ES-SCLC.

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer (LS-SCLC), but the optimal radiotherapy schedule and dose remains controversial. Recently, characterized by the improved dose conformality to tumor target and reduced normal tissue exposure, intensity-modulated radiation therapy (IMRT) has been used widely, making hypo-fractionated radiotherapy (HypoRT) for LS-SCLC feasible. The aim of this study was to determine whether a 3-week schedule of HypoRT is as efficacious and safe as a 6-week schedule of conventional fractionated radiotherapy (ConvRT) with concurrent chemotherapy in LS-SCLC.

Post-CRT residual ctDNA predicted worse survival in LA-NSCLC, but indicated more benefit from further ICIs therapy and thereby could facilitate personalization of consolidation immunotherapy. Further prospected studies with large sample size are warranted to validated these findings.

Dynamic bTMB (∆bTMB) combined with post-CRT ctDNA status is a novel and effective biomarker model of predicting survival outcomes in LA-NSCLC patients treated with CRT ± ICIs, and outperforms each individual feature.

PORT significantly improved the DFS and LRFS in patients with N2a2 and significantly improved the DFS, LRFS, and OS in patients with N2b. Patients with N2a1 could not benefit from PORT.

This randomized trial did not find a higher probability of survival improvement in patients with ES-SCLC receiving cTRT of 45 Gy in 15 fractions compared with 30 Gy in 10 fractions. In contrast, there was an increase in toxicity, especially radiation pneumonitis. Additional randomized studies investigating the role of cTRT in ES-SCLC after a response to chemoimmunotherapy are warranted.

Purpose/Objective(s)Previous studies showed that prophylactic cranial irradiation (PCI) reduced brain metastases and improved overall survival of patients with limited-stage small-cell lung cancer (LS-SCLC). However, brain magnetic resonance imaging (MRI), currently recognized as the preferred modality for brain metastases detection, was not routinely used for staging and reassessment in previous trials. This retrospective study aimed to reevaluate the role of PCI for LS-SCLC patients in the modern MRI era.Materials/MethodsWe retrospectively reviewed LS-SCLC patients treated with definitive chemoradiotherapy (≥4 cycles of chemotherapy and thoracic intensity-modulated radiotherapy [IMRT]) between 2006 and 2014 in our center. Patients who responded to initial therapy were included and subsequently reassessed for brain metastases by MRI. The cumulative incidence of brain metastases was estimated using the Fine-Grey competing risks regression model. The overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model.ResultsWe enrolled 177 patients in this study, of which 79 were treated by PCI and 98 were not (non-PCI). The median follow-up was 76.0 months (95% confidence interval, 71.2-80.8 months). All patients achieved complete response (n = 50, 28.2%) or partial response (n = 127, 71.8%) to initial chemoradiotherapy. The cumulative incidence of brain metastases in the PCI group was lower than in the non-PCI group (6.6% vs. 30.0% at 2 years, 12.2% vs. 31.0% at 5 years, P = 0.004). 5-year PFS in the PCI group was significantly higher than in the non-PCI group (45.3% vs. 26.5%, P = 0.002). However, 5-year OS of 48.8% and 39.2% in the PCI and non-PCI groups, respectively, were similar (P = 0.255). In the multivariate analysis, treatment response (P<0.001) and PCI (P = 0.038) were independent prognostic factors for PFS. Stratification analysis revealed that PCI did not improve 5-year PFS for patients with partial response to initial therapy (26.6% vs. 19.7%, P = 0.234).ConclusionIn the Modern Era with MRI Surveillance, PCI is associated with a lower incidence of brain metastases and improved PFS while OS benefit wasn't observed. Patients achieving partial response to initial therapy did not gain PFS benefit from PCI. Prospective trials are still needed to further evaluate the utility of PCI for patients with LS-SCLC.