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.

Objective:To evaluate the safety and efficacy of thoracic radiotherapy (TRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy.Methods:Medical records of 56 patients with ES-SCLC who received thoracic radiotherapy after first-line platinum-based chemotherapy plus immunotherapy in Cancer Hospital Chinese Academy of Medical Sciences from January 2018 to December 2021 were retrospectively analyzed. The control group was not established for clinical causes. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were employed to identify prognostic factors using the Cox proportional hazards model. The cumulative incidence of local regional recurrence (LRR) was estimated using the Fine-Grey competing risks regression model.Results:Among 56 patients in our cohort, 47 patients received consolidative TRT (cTRT) before progression and 9 patients received salvage TRT after progression. The median follow-up time was 21 months (95% CI=19.8-22.2 months), the median OS was not reached, the median PFS was 9 months (95% CI=7.0-13.0 months), and the 1-year and 18-month OS rates were 84.9%, 62.1%. In the cTRT group, the 1-year and 18-month OS rates were 84.1%, 64.5%, with the median PFS of 10 months; 1-year and 18-month LRFS rates were 73.6% and 66.0%, respectively; the cumulative incidence of LRR at 1-year and 2-year were 24.9% and 30.8%, respectively. No other 4-5 grade adverse events (AE) were reported except 6 patients presenting with 4 grade hematologic toxicities. Three grade radiation esophagitis occurred in 3 patients (5%). Ten patients (18%) developed 1-2 grade treatment-related pneumonitis, including 5 (9%) patients with immune related pneumonitis and 5 (9%) patients with radiation pneumonitis. Conclusion:The application of TRT after first-line chemoimmunotherapy is safe and may has potential survival benefit for patients with ES-SCLC.

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Objective:To establish the first Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale in China and evaluate its preliminary application value in the standardized training for radiation oncology resident physicians.Methods:Based on the educational curriculum and examination requirements for the standardized training for radiation oncology resident physicians, as well as the standardized Mini-Clinical Evaluation Exercise (Mini-CEX) scale commonly used in clinical practice, the Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale was developed to facilitate the standardized training for resident physicians in the field of radiation oncology. In this prospective study, a randomization method using a random number table was employed to select a cohort of 26 resident physicians who completed their rotations in Department of Radiation Oncology at the Cancer Hospital, Chinese Academy of Medical Sciences from March 1, 2021 to December 31, 2021. The Mini-FERO scale was administered in the initial, middle, and final stages during the rotation period. The differences in evaluation scores before and after the assessments were analyzed by paired t-test. Furthermore, participating resident physicians and supervising teachers provided satisfaction ratings, and a comprehensive evaluation of the Mini-FERO scale was conducted. Results:The average scores of the three examinations of 26 resident physicians demonstrated a successive improvement, with individual performance in each assessed category also showing progressive enhancement. The second evaluation exhibited a more pronounced score increase compared to the first evaluation, with a mean improvement of (1.43±1.02) points ( t=7.13, P<0.001); while the third evaluation had a mean improvement of (0.41±0.50) points ( t=4.07, P<0.001) compaired to the second evaluation, with a mean difference of (1.02±1.15) points between the two ( t=4.53, P<0.001). The average time required for the assessments was (34.31±24.46) min. Overall satisfaction ratings from the evaluated resident physicians for the Mini-FERO scale were (8.42±0.85) points, and supervising teachers reported an overall satisfaction rating of (8.45±0.85) points. The satisfaction rate was 96% (25/26). Conclusions:In this study, the Mini-FERO scale was successfully developed and validated in the context of clinical teaching practice for radiation oncology resident physicians. The Mini-FERO scale is proven to be a feasible tool for assessing the gradual improvement of resident physicians throughout their learning process in the field of radiation oncology. Importantly, it offers the advantages of short assessment time, thereby avoiding additional burden on supervising teachers. The adoption of the Mini-FERO scale addresses current limitations of lacking of formative evaluation in the standardized training for radiation oncology resident physicians.

Objective:To explore the effect of pretreatment body mass index (BMI) on the prognosis of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) after chemoradiotherapy.Methods:The clinical data of 711 patients with locally advanced NSCLC treated with radiotherapy, sequential chemoradiotherapy or concurrent chemoradiotherapy from January 2013 to December 2017 in Cancer Hospital of Chinese Academy of Medical Science and Peking Union Medical College were retrospectively analyzed. Radiotherapy was performed with intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT), and the chemotherapy regimens were paclitaxel+carboplatin, pemetrexed+cisplatin or etoposide+cisplatin. The effects of pretreatment BMI and other clinical factors on overall survival (OS) of patients were analyzed. Survival analysis was performed by using Kaplan-Meier method; univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:According to the World Health Organization (WHO) recommended BMI grouping method for Asian, the median OS time of low BMI group (<18.5 kg/m 2, 23 cases), normal BMI group (18.5-23.9 kg/m 2, 293 cases) and high BMI group (≥24.0 kg/m 2, 395 cases) was 17 months (95% CI 11-29 months), 29 months (95% CI 22-36 months) and 30 months (95% CI 27-34 months), respectively. OS in the low BMI group was poorer than that in the normal BMI group and high BMI group ( χ2 = 11.20, P = 0.004). Maximally selected rank statistics was used to determine the optimal cut-off value of BMI for prediction of survival as 21.31 kg/m 2, according to which patients were divided into low BMI group (BMI<21.31 kg/m 2, 130 cases) and high BMI group (BMI≥21.31 kg/m 2, 581 cases), the median OS time of the two groups was 20 months (95% CI 17-27 months) and 32 months (95% CI 28-35 months), respectively. OS in the low BMI group was poorer than that in the high BMI group ( χ2 = 12.30, P < 0.001). Multivariate analysis showed that age ≥ 65 years old, male, Karnofsky score < 80 points, low BMI, smoking, histological type of squamous cell carcinoma and radiotherapy alone were independent risk factors for OS (all P < 0.05). Conclusions:For patients with unresectable locally advanced NSCLC who received chemoradiotherapy, those with low pretreatment BMI have poor prognosis.

Objective:To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer (ES-SCLC) after induction systemic therapy.Methods:ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment (chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors) and consolidated with PD-1/PD-L1 inhibitors. These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital (Clinical Trials.gov number, NCT03971214, NCT04947774).Results:Between January 2019 and March 2021, a total of 11 patients with ES-SCLC were analyzed, aged 52-73 years, with a median age of 62 years. Among them, five patients (45.5%) received induction chemotherapy and six patients (54.5%) received chemotherapy combined with PD-1/PD-L1 inhibitor, and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy. Two patients developed treatment-related grade G3-5 toxicity (18.2%, 1 treatment-related pneumonitis and 1 radiation esophagitis). G 1-G 2 hematologic toxicity, pneumonia, and anorexia were common mild toxicities. Only one patient (9.1%) terminated immunotherapy due to immune-related pneumonitis. During a median follow-up time of 12.5 months (range: 3.5-16.4 months), the median disease progression-free survival and overall survival was 7.4 months (95% CI: 6.9-8.0 months) and 14.6 months (95% CI: 9.0-20.2 months), respectively. Conclusions:Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy. Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival, this comprehensive treatment modality warrants further investigation.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

Objective:To explore the motion and influencing factors of implanted gold markers in guiding liver stereotactic body radiation therapy (SBRT) using abdominal compression.Methods:Twenty patients with oligometastatic colorectal cancer or primary hepatocellular carcinoma from January 2016 to December 2019 were included. All patients were treated with SBRT under abdominal compression, with 1-3 gold markers were implanted within 2 cm from the lesion before positioning. Four-dimensional computed tomography (4DCT) scan was used for treatment planning. The respiratory cycle was divided into 0-90% respiratory phase images based on the respiratory signal, which were reconstructed by the system (Pinnacle 3 version 9.1; Philips Medical System, Madison, WI, USA), and cone beam CT validation images before radiation exposure were obtained. The liver volume was divided into 3 parts: within 2 cm from the main hepatic portal vein, 2-5 cm from the main hepatic portal vein, and>5 cm from the main hepatic portal vein. The motion of different tumor locations was evaluated. Results:The average intrafractional motion amplitude was (2.63±2.81) mm in the cranial-caudal (CC) direction, (1.35±1.23) mm in the anterior-posterior (AP) direction, and (0.76±0.88) mm in the left-right (LR) direction, respectively. The average interfractional motion amplitude was (3.45±3.06) mm, (2.64±2.60) mm, and (2.23±2.07) mm, respectively. Both the intra-or inter-fractional motion amplitudes in the CC direction were the highest, followed by those in the AP and LR direction (all P<0.001). The motion varied at different tumor locations. The longer distance from the main hepatic portal vein, the larger the intrafractional motion (all P<0.05). To cover the 95% population-based confidence interval, the internal target volume (ITV) was suggested to include the expansion of 3.9 mm, 5.2 mm and 7.9 mm in the LR, AP and CC direction. The expansion of 4.3 mm, 4.4 mm and 6.1 mm was delivered within 2 cm from the main hepatic portal vein, and 3.5 mm, 7.3 mm and 9.7 mm>5 cm from the main hepatic portal vein, respectively. The expansion varied significantly depending on the tumor location, whereas the motion in the CC direction was the largest regardless of the tumor location. The longer distance of the tumor from the main portal vein, the larger expansion in the CC direction. The expansion of tumor > 5 cm from the main portal vein in the AP direction was larger than that of inner parts. Conclusion:Liver tumors at different locations require individual external expansion of ITV.

Oligometastasis is an intermediate status between the locally advanced and wide spread disease. Patients with oligometastasis may obtain long-term survival after local treatment. Stereotactic body radiation therapy (SBRT) can deliver radical ablative doses in a small number of fractions, which is a highly precise local ablation therapy. Approximately half of patients diagnosed with colorectal cancer (CRC) will develop metastases, with the liver and lung as the most common site of involvement. In this article, the safety, local efficacy and prognostic factors of SBRT for liver and lung oligometastases from CRC were illustrated. The highlights of SBRT implementation were also discussed. SBRT is safe and effective for oligometastases from CRC under respiratory motion management and robust quality assurance.