Endocrine therapy remains one of the primary treatment modalities for estrogen receptor (ER) positive breast cancer, serving a pivotal role in improving patient outcomes and extending survival. Nevertheless, the gradual emergence of endocrine resistance continues to limit its clinical efficacy. In recent years, advances in molecular biology and genomics have driven the development of innovative technologies and therapeutic strategies in this field. The present review highlights the latest progress in endocrine therapy for breast cancer, including the introduction of next-generation selective ER degraders (SERDs), ER antagonists/degraders and selective ER modulators (SERMs). In addition, combination strategies integrating endocrine therapy with small-molecule inhibitors of critical signaling pathways, such as PI3K/AKT/mTOR and CDK4/6, have demonstrated promising potential in overcoming resistance. Cutting-edge technologies, such as single-cell sequencing and organoid models, are providing novel insights into treatment monitoring and the implementation of personalized therapy. Looking ahead, precision medicine platforms powered by artificial intelligence and big data are expected to further refine therapeutic strategies and ultimately improve patient prognosis. Collectively, endocrine therapy for breast cancer is evolving toward a more diversified, precise and individualized approach, offering patients broader treatment options and enhanced survival benefits.

Background:We aimed to explore the efficacy and safety of neoadjuvant toripalimab plus chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). Methods:This phase II, non-randomized, 2-cohort study enrolled patients with unresectable, stage T1-4N0-3M0-1 ESCC (M1 only includes patients with lymph node metastasis in the supraclavicular region). Patients received neoadjuvant therapy comprised of albumin-bound paclitaxel, nedaplatin and toripalimab every 3 weeks, for 2 cycles, followed by CCRT (total dose 60Gy in cohort A, 50Gy in cohort B, combined with oral capecitabine). The primary endpoint was progression-free survival (PFS). The trial is registered with ClinicalTrials.gov, NCT04844385. Findings:Between February 26, 2021 and June 20, 2023, 124 patients were enrolled, and 118 (95.2%) patients completed treatment. The objective response rate to neoadjuvant chemo-immunotherapy was 91.9% overall, and was 93.7% in cohort A-60Gy and 93.4% in cohort B-50Gy after CCRT. With a median follow-up of 30.8 months, the 18-month PFS rates were 65.0% (95% CI, 53.9-78.3%) in cohort A-60Gy and 65.1% (95% CI, 53.7-78.8%) in cohort B-50Gy. Grade (G) 3 and G5 pneumonitis occurred in two (3.2%) and one patient (1.6%) in cohort A-60Gy, respectively, with no ≥G3 pneumonitis in cohort B-50Gy. Improvements on patient reported outcomes from baseline to 12 months post-CCRT were observed overall. Interpretation:Neoadjuvant chemo-immunotherapy, radiotherapy and concurrent capecitabine achieved promising efficacy in locally advanced ESCC. Further investigation is warranted. Funding:None.

Synergistic antitumor effects of thoracic radiotherapy (TRT) are still debated due to conflicting clinical evidence. The aim of the present meta-analysis was to evaluate the efficacy and safety of chemo-immunotherapy combined with TRT in extensive-stage small cell lung cancer (ES-SCLC). CNKI, Wanfang, VIP, Pubmed, Embase and the Cochrane library were searched for published literature on chemo-immunotherapy combined with TRT for ES-SCLC between January 1, 2018, and March 4, 2024. After screening the studies and extracting data according to the inclusion criteria, Review Manager 5.4 and Stata 15 were used to assess the risk of bias of the studies and perform a meta-analysis of the data. A total of 19 relevant prospective and retrospective clinical research articles were included, involving 1,557 patients. The results of the meta-analysis demonstrated that, in terms of efficacy, chemo-immunotherapy combined with TRT significantly improves overall survival [OS; hazard ratio (HR)=0.49; 95% confidence interval, (CI), 0.34-0.71; P<0.05] and progression-free survival (PFS; HR=0.62; 95% CI, 0.51-0.76; P<0.05) of patients with ES-SCLC. Sub-group analysis indicated that primary liver metastasis was an independent predictor of poor OS (HR=2.45; 95% CI, 1.84-3.25; P<0.05), and TRT was a favorable predictor of OS (HR=0.44; 95% CI, 0.21-0.96; P<0.05) and PFS (HR=0.59; 95% CI, 0.47-0.76; P<0.05). In terms of safety, the incidence of grade ≥3 adverse reactions in the chemo-immunotherapy/TRT combination group was significantly higher than that in the chemo-immunotherapy group (risk ratio=1.30; 95% CI, 1.02-1.66; P<0.05). The most common adverse reactions in the chemo-immunotherapy/TRT combination group were radiation pneumonitis (27%; 95% CI, 14-41%), radiation esophagitis (17%; 95% CI, 9-25%) and thrombocytopenia (9%; 95% CI, 5-14%). In conclusion, chemo-immunotherapy combined with TRT demonstrated improved survival outcomes in patients with ES-SCLC, with acceptable toxicity profiles. However, further validation through prospective clinical trials is warranted.

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment landscape for advanced non-small cell lung cancer (NSCLC) in previous years. However, not all patients achieve a satisfactory objective response and long-term benefits, leading to growing interest in combining immunotherapy with radiotherapy (RT) to enhance therapeutic outcomes. The present review explored the rationale, efficacy and safety of combining RT with immunotherapy in advanced NSCLC. RT can potentiate immune responses through various mechanisms, such as immunogenic cell death and modification of the tumor microenvironment. The addition of RT to immunotherapy has notable synergistic antitumor effects to improve systemic control as RT can induce diverse immunomodulatory effects. The present review assessed the efficacy and safety of combining ICIs with RT and examined the optimal timing, dose and fraction strategies of RT for enhancing immune activation while minimizing toxicity. Additionally, the potential of RT to overcome primary and acquired resistance to immunotherapy was discussed. Despite encouraging findings, challenges such as optimal patient selection and biomarkers, treatment-related toxicity and precise timing of interventions remain unresolved. The present review aimed to provide a comprehensive analysis of current evidence, as well as the key considerations for integrating RT and immunotherapy into clinical practice.

e16035 Background: The efficacy of programmed death receptor 1(PD-1) inhibitors combined with chemotherapy for advanced and metastatic ESCC has been recognized. However, there is limited evidence on the use of PD-1 inhibitors combined with chemotherapy for local Primary-recurrent ESCC after definitive chemoradiotherapy or radiotherapy, and further exploration is needed. Methods: This is a prospective clinical study. The study will focus on those who have attained a complete response (CR) subsequent to definitive chemoradiotherapy or radiotherapy and have a histologically proven in-field recurrence, with no distant metastases. These patients will receive treatment with a PD-1 inhibitor (sintilimab or camrelizumab 200mg, d1, q3w) combined with monotherapy chemotherapy (paclitaxel 175mg/m 2 or irinotecan 250mg/m 2 , d1, q3w) for 4 cycles, followed by a 2-year maintenance treatment with PD-1 inhibitors. During this period, patients diagnosed with esophageal wall thickening and identified as having progressive disease (PD) have the option to undergo salvage radiotherapy (45-50.4 Gy/25-28/F/5-5.5 weeks) in conjunction with a dual-agent chemotherapy (paclitaxel 50 mg/m 2 , d1 + carboplatin AUC 2, d1, qw) for 5 cycles. The primary endpoint of is after recurrence survival (ARS). The secondary endpoints include the progression-free survival (PFS) and safety. Results: From July 2023 to January 2025, a total of 35 patients were enrolled in the study. The median age was 65 years (range, 53-76 years). Among the enrolled patients, 27 completed a 4-cycle treatment regimen of PD-1 inhibitor combined with monotherapy chemotherapy, 14 patients are currently in the PD-1 inhibitor maintenance phase, and only 2 patients have received salvage chemoradiotherapy. To date, the disease control rate (DCR) is 65.7%(23/35). The median ARS and PFS were 27.3 months (95% CI : 9.7-44.8 months) and 15.0 months (95% CI : 4.9-21.2 months). The 1-year and 2-year ARS rates were 76.0% and 66.4%, respectively. Besides, the 1-year and 2-year PFS rates were 59.1% and 38.7%. In terms of safety, adverse events were mostly grade 1-2, with no severe adverse events occurring. The common adverse events included anemia(22 ; none with grade≥3), Leukopenia (12 ;4 with grade≥3), thrombocytopenia(9 ; 2 with grade≥3) and alopecia(9 ; none with grade≥3).The common immune-related adverse events were hypothyroidism(14 ; none with grade≥3) and elevated troponin T(12 ; none with grade≥3). Conclusions: The combination of PD-1 with chemotherapy for the treatment of locally primary-recurrent of ESCC following definitive chemoradiotherapy or radiotherapy represents a safe and efficacious therapeutic strategy. This approach not only improve ARS but also ensures safety and manageable outcomes.

BACKGROUND:To evaluate the efficacy and safety of magnetic resonance (MR)-guided split-course hypo-fractionated radiotherapy (hypo-RT) with concurrent chemotherapy followed by consolidative immunotherapy (CIT) in locally advanced non-small cell lung cancer (LA-NSCLC). METHODS:In this phase 2 trial, patients with unresectable stage IIIA-C NSCLC (18-75 years old, Eastern Cooperative Oncology Group 0-1) received MR-guided split-course hypo-RT (30 Gy in six fractions, repeated after 4 weeks for a total of 60 Gy) with concurrent weekly docetaxel (25 mg/m2) and cisplatin (25 mg/m2). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), objective response rate (ORR), and toxicities. RESULTS:Between July 2020 and January 2023, 104 patients were enrolled with a median follow-up of 34.4 months. Split-course hypo-concurrent chemoradiotherapy (CCRT) was completed in 101 (97.1%) patients, and 74 (71.2%) received CIT. The median PFS was 27.5 months (95% confidence interval [CI], 18.9-36.0 months), and the 1- and 2-year PFS rates were 76.9% (95% CI, 69.2%-85.5%) and 54.7% (95% CI, 45.9%-65.1%), respectively. The 1- and 2-year OS were 87.5% (95% CI, 81.4%-94.1%) and 65.3% (95% CI, 56.8%-75.2%), respectively. The most common grade 3-4 adverse event was lymphopenia (35.6%). Grade 2-3 pneumonitis was observed in eight patients (7.7%) during hypo-CCRT and in seven patients (6.7%) during CIT. Grade 3 esophagitis occurred in three patients (2.8%), and one grade 5 hemoptysis was reported (0.9%). CONCLUSION:The MR-guided split-course hypo-CCRT delivered at 5 Gy per fraction to a total dose of 60 Gy followed by CIT yielded encouraging survival outcomes with manageable toxicities in patients with LA-NSCLC.

CDK2 is a principal mediator of CDK4/6 resistance. Concurrent CDK2/4/6 blockade may be effective in treating HR-positive, HER2-negative advanced breast cancer (ABC). This randomized, double-blind, parallel-controlled, phase 3 trial (ClinicalTrials.gov, NCT05375461) assessed the efficacy of culmerciclib, a CDK2/4/6 inhibitor, plus fulvestrant in ABC. Patients with HR-positive, HER2-negative, locally recurrent or metastatic breast cancer were randomized (2:1) to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant. Between March 18, 2022 and March 3, 2023, 293 pretreated patients (median age 53.0 years; pre- or perimenopausal 42.3%; bone metastasis 65.2%) were randomized to assigned treatments. At this prespecified interim analysis, culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival (PFS) significantly, the primary endpoint, as compared with placebo plus fulvestrant (16.6 months, 95% CI 13.8 to not evaluable versus 7.5 months, 95% CI 5.3 to 11.0; hazard ratio 0.36, 95% CI 0.26–0.51; stratified log rank test P < 0.001). Consistent effects were observed across diverse subgroups of patients. At a median follow-up duration of 13.8 months, overall survival was immature. The investigators-assessed objective response rate was 40.2% (95% CI, 33.3–47.5) for culmerciclib compared to 12.1% (95% CI 6.4–20.2) for placebo (stratified Mantel-Haenszel χ2 test P < 0.001). Diarrhea (87.1%) and neutropenia (80.4%) were the most common toxicities with culmerciclib plus fulvestrant. In conclusion, this randomized clinical trial met its primary outcome. Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.

The role of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) remains controversial in the era of magnetic resonance imaging (MRI). The present study aimed to evaluate the effectiveness of PCI in the treatment of LS-SCLC in the era of MRI. The PubMed, EMBASE and Cochrane Library databases were searched from the time of database creation until May 24, 2023, to identify clinical studies that evaluated the effectiveness of PCI in patients with LS-SCLC in the MRI era. The references of the obtained studies were also reviewed to identify clinical studies that were not discovered in the initial search. All studies were screened in accordance with the inclusion criteria, and the data were extracted and subjected to meta-analysis using STATA17.0. In total, 21 studies were included in the analysis. Notably, 10 studies only used brain MRI at baseline to confirm the absence of brain metastases (BMs; pre-chemoradiotherapy MRI group), 7 studies used brain MRI prior to PCI to confirm the absence of BMs (pre-PCI MRI group) and 4 studies used active surveillance in the form of brain MRI following PCI (MRI surveillance group). The results of the meta-analysis demonstrated that for all included patients, PCI was associated with a significant improvement in overall survival time [OS; hazard ratio (HR), 0.61; confidence interval (CI), 0.53-0.70] and progression-free survival (HR, 0.69; CI, 0.61-0.79), as well as a significant decrease in the rate of BM (HR, 0.59; CI, 0.50-0.70). Subgroup analyses revealed that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who did not have BMs confirmed via brain MRI performed at baseline or prior to PCI. However, in the MRI surveillance group, PCI failed to significantly improve the OS (HR, 0.65; CI, 0.41-1.05), despite significantly reducing the BM rate (HR, 0.6; CI, 0.45-0.8) of LS-SCLC. Collectively, the results of the present study demonstrated that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who had the absence of BM confirmed via brain MRI at baseline or prior to PCI. Additionally, in patients with LS-SCLC who had undergone active surveillance using brain MRI following PCI, the incidence of BM was reduced, while the OS was not significantly improved. However, additional randomized controlled clinical studies are required to verify these findings.

PURPOSE:A preclinical model found that elective nodal irradiation attenuated the efficacy of radiotherapy (RT) and radio-immunotherapy. However, limited clinical studies have explored the correlation between radiation dose-volume parameters of negative tumor-draining lymph nodes (TDLN) and T-cell activation/prognosis for patients with cancer treated with definitive radiochemotherapy. EXPERIMENTAL DESIGN:Patients with locally advanced esophageal cancer undergoing definitive chemoradiotherapy (CRT) were selected from two prospective trials. Dose-volume parameters of TDLN as well as other lymphocyte-related organs at risk and lymphocyte subsets such as CD3-CD19+ B cells, CD8+CD28+ T cells, and activated T cells (CD3+CD8+HLA-DR+) before and at the end of RT were collected. Logistic analysis was utilized to correlate dose-volume parameters with reductions in lymphocyte subsets. Prognosis of TDLN irradiation was investigated through Kaplan-Meier analysis and Cox hazards models. RESULTS:Among 512 patients, the median mean dose of TDLN and negative non-TDLN was 25.6 and 15.1 Gy, respectively. Multivariable analyses indicated that TDLN V15 >50% was an independent predictor of poorer local recurrence-free survival (HR, 1.31; P = 0.029) and distant metastasis-free survival (HR, 1.39; P < 0.001), as well as greater reductions in CD3-CD19+ B cells (OR, 1.98; P = 0.002), CD8+CD28+ T cells (OR, 3.42; P < 0.001), and CD3+CD8+HLA-DR+ T cells (OR, 4.67; P = 0.002) after RT. CONCLUSIONS:A higher radiation dose-volume parameter of TDLNs in patients with esophageal cancer undergoing CRT was significantly associated with suppression of T-cell activation and a worse prognosis. Limiting the percentage of TDLN V15 may be beneficial for improving the prognosis of CRT with or without PD-1 inhibitors.

BACKGROUND:Radiation-induced lung injury is a major dose-limiting toxicity in thoracic radiotherapy. Pirfenidone, an oral antifibrotic drug that is often used to treat idiopathic pulmonary fibrosis, could offer therapeutic benefits for patients with radiation-induced lung injury. We evaluated the efficacy and safety of pirfenidone in patients with grade 2 or grade 3 radiation-induced lung injury. METHODS:This multicentre, open-label, randomised, phase 2 clinical trial enrolled patients with grade 2 or grade 3 radiation-induced lung injury diagnosed according to Common Terminology Criteria for Adverse Events version 5.0 from ten medical centres across China. Eligible patients were aged 18-75 years with an Eastern Cooperative Oncology Group performance status of 0-2 and had grade 2 or grade 3 radiation-induced lung injury. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either pirfenidone plus glucocorticoids or glucocorticoids alone. Pirfenidone was given orally three times daily at doses of 200 mg in week 1, 300 mg in week 2, and 400 mg in weeks 3-24. Glucocorticoids were administered concurrently at the equivalent dose of prednisone 40 mg/day, divided into two oral doses, and maintained for 2 weeks, followed by a tapering schedule of 10 mg every 2 weeks over a period of 6 to 8 weeks. The control group received glucocorticoids only. The primary endpoint, evaluated in the modified intention-to-treat population, was the change in the percentage of carbon monoxide diffusing capacity (DLCO%) from baseline to week 24. Safety was assessed in all participants who received at least one dose of treatment. The trial is registered with ClinicalTrials.gov, NCT03902509, and has completed enrolment. FINDINGS:Between Nov 29, 2021, and Dec 4, 2023, 134 patients were enrolled and randomly assigned, with 67 patients in each group study group. 105 (78%) of 134 patients were male and 29 (22%) were female. The median follow-up was 9·2 months (IQR 6·3-16·0). At week 24, the pirfenidone group showed an 8·0% improvement from baseline in DLCO%, whereas the control group showed a 2·4% reduction (least squares mean difference 10·4%, 95% CI 4·3-16·5; p=0·0010). The most common grade 3 or worse adverse events included pneumonia (four [6%] of 67 patients in the pirfenidone group vs eight [12%] of 67 patients in the control group), and rash (two [3%] of 67 patients in the pirfenidone group vs none in the control group). Serious adverse events occurred in 12 (18%) of 67 patients in the pirfenidone group and 11 (16%) of 67 patients in the control group. There were no treatment related deaths. INTERPRETATION:Pirfenidone in combination with glucocorticoids provides a potential therapeutic strategy for grade 2 or grade 3 radiation-induced lung injury, addressing the unmet clinical need for effective antifibrotic therapy in patients receiving thoracic radiotherapy. Further investigation is needed to validate these findings in patients with worse radiation-induced lung injury than was studied here. FUNDING:Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, National Natural Science Foundation of China, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center.

Objective:To evaluate the efficacy and safety of QL1206 (a denosumab biosimilar to Xgeva®) in breast cancer patients with bone metastasis (BM) through subgroup analysis of a randomized, double-blind phase III trial (No. NCT04550949). Methods:This subgroup analysis included patients with BM from breast cancer enrolled in a phase III trial. Patients were randomized (1:1) to receive either three cycles of QL1206 or denosumab (120 mg subcutaneously every 4 weeks). Subsequently, they received 10 cycles of QL1206 (120 mg) over 40 weeks, followed by a 20-week safety follow-up. The primary endpoint was the percentage changes from baseline to week 13 in urinary N-telopeptide corrected for creatinine (uNTx/Cr). Results:The breast cancer cohort consisted of 311 patients. Vertebral involvement (66.4%) was the most prevalent BM site at enrollment, while 27.7% of patients presented with ≥3 metastatic bone lesions. At week 13, QL1206 demonstrated a median uNTx/Cr reduction of -69.9% (range: -98.1%-568.0%) vs. -74.3% (range: -97.7%-386.3%) for denosumab. The analysis of covariance revealed comparable least-square means for log-transformed changes: -1.416 [95% confidence interval (95% CI): -1.736 to -1.096] vs. -1.501 (95% CI: -1.824 to -1.178), yielding an between-group difference of 0.085 (90% CI: -0.062-0.232; P=0.343). After a 53-week treatment period, 83.6% achieved bone density improvement/disease stabilization. Safety profiles were comparable between groups. Conclusions:QL1206 demonstrated similar efficacy and safety to the reference denosumab in patients with BM from breast cancer, supporting QL1206 as a new option for management of BM from breast cancer.

Background The efficacy of local therapy for patients with oligometastatic oesophageal squamous cell carcinoma is unclear. We aimed to assess the efficacy of local plus systemic therapy compared with systemic therapy alone in patients with oligometastatic oesophageal squamous cell carcinoma. Methods The ESO-Shanghai 13 trial was a randomised, open-label, multicentre, phase 2 trial. Patients (aged >= 18 years) were recruited from six hospitals in China with histological confirmation of oligometastatic oesophageal squamous cell carcinoma with a controlled primary tumour and one to four metastatic lesions. Eligible patients were randomly assigned via a computer-generated schedule in a 1:1 ratio to receive either systemic therapy alone (ie, systemic therapy only group) or combined systemic and local therapy (ie, systemic and local therapy group). The systemic therapy regimens in both groups were at the discretion of the investigator and included chemotherapy alone, anti-PD-1 antibodies alone, or chemotherapy plus anti-PD-1 antibodies. Local therapy-radiotherapy, surgery, or thermal ablation-was delivered to all metastatic lesions for patients in the systemic and local therapy group. Randomisation was balanced dynamically on three factors: the number of disease sites, the lines of systemic therapy, and the location of the metastases. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, defined as the time from randomisation to progression or death from any cause in the intention-to-treat population. The safety population included all patients who had undergone random assignment and at least one of the intended therapies. This trial is registered with ClinicalTrials.gov, NCT03904927. The trial is ongoing but closed to new participants. Findings 116 patients were screened for enrolment between March 5, 2019, and Sept 16, 2021, and 104 patients who met the eligibility criteria were randomly assigned to the systemic and local therapy group (n=53) or the systemic therapy only group (n=51). 20 (38%) patients in the systemic plus local therapy group and 23 (45%) patients in the systemic therapy only group received anti-PD-1 antibody-based systemic therapy; three patients in the systemic and local therapy group did not receive systemic therapy. At a median follow-up of 305 months (IQR 247-378), median progression-free survival was 153 months (95% CI 101-205) in the systemic and local therapy group versus 64 months (52-76) in the systemic therapy only group (stratified hazard ratio 026 [95% CI 016-042]; stratified log rank p<00001). Grade 1-2 acute oesophagitis was more common in the systemic and local therapy group than in the systemic therapy only group (10 [19%] vs one [2%] patients; p=0036). The number of patients who had grade 3 or worse treatment-related adverse events was similar between groups (25 [47%] vs 21 [41%]; p=0538), with the most common adverse events being leukocytopenia (17 [32%] vs 18 [35%]) and neutropenia (19 [36%] vs 20 [39%]). Treatment-related deaths occurred in two patients in the systemic and local therapy group and one patient in the systemic therapy only group. Interpretation The addition of local treatment for metastases could significantly improve progression-free survival among patients with oligometastatic oesophageal squamous cell carcinoma being treated with systemic therapy. Our findings suggest that combining local and systemic therapy could be a treatment option for patients with oligometastatic oesophageal squamous cell carcinoma, but further support from phase 3 trials is required.

Objective To explore the short-and long-term efficacy and toxic and side effects of hyperfractionated radiotherapy with different fractionated doses in patients with limited stage small cell lung cancer(SCLC).Methods From August 2017 to August 2019,70 patients with limited stage SCLC admitted to Zhangye People's Hospital were selected and divided into control group(n=35)and observation group(n=35)according to the random number table method.Conventional chemotherapy and hyperfractionated radiotherapy were used in both groups,with a total dose of 45 Gy in the control group and 60 Gy in the observation group.A three-year follow-up was carried out to compare the short-and long-term efficacy(survival and local control rate),and the occurrence of toxic and side effects between the two groups.Results The total effective rate in the observation group was obviously higher than that in the control group(91.43％vs 71.43％,x2=4.629,P=0.031).The 1-,2-,and 3-year local control rates and survival rates of patients in the observation group were significantly higher than those in the control group(P＜0.05).There was no statistically significant difference in the total incidence of adverse reactions between the two groups(P＞0.05),and most of adverse reactions were grade Ⅰ-Ⅱ,which did not affect the course of treatment.After treatment,the scores of life quality in both groups increased significantly(P＜0.01),and the observation group showed a significant increase compared to the control group(P＜0.01).Conclusion Hyperfractionnated radiotherapy with appropriately increased fractionated dose for patients with limited stage SCLC has better short-and long-term efficacy,higher local control rate and survival,and no significant increase in toxic and side effects,which is safe and can improve the quality of patients'life.

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607. In this triple-arm, placebo-controlled phase 3 trial, first-line treatment of patients with extensive-stage small-cell lung cancer with the anti-PD-L1 benmelstobart, tyrosine kinase inhibitor anlotinib and chemotherapy (CT) showed improved survival outcomes compared with anlotinib and CT or CT alone.

Objective:To investigate the risk factors for lung infection in lung cancer patients undergoing radiotherapy. Methods:We selected 142 patients with lung cancer who underwent radiotherapy at our hospital from January 2020 to June 2021. The patients were divided into groups according to whether they had pulmonary infection during radiotherapy in our hospital, which was infected group (n=44) and the uninfected group (n=98), respectively. To observe the incidence of lung infection in lung cancer patients during radiotherapy. The distribution of pathogenic bacteria in patients with pulmonary infection was observed. Clinical data of the two groups were collected and compared. The risk factors of lung cancer patients complicated with lung infection were analyzed by binary Logistic regression. Results:All patients with lung cancer complicated with lung infection underwent relevant examination, and the results showed that they were all complicated infections, and the composition ratio of Klebsiella pneumoniae was the highest (31.82%), followed by Staphylococcus, Pseudomonas, and fungi, which accounted for 27.27%, 22.73%, and 18.18%, respectively. Binary Logistic regression analysis showed that age ≥60 years old, smoking history ≥30 years, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L were risk factors for lung cancer patients during radiotherapy. Conclusion:Age ≥60 years old, smoking history ≥30 years old, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L are the risk factors for lung cancer patients during radiotherapy. Clinical prevention and intervention should be based on the aforementioned independent risk factors to decrease the incidence of lung infections, thereby enhancing patient prognosis.

PURPOSEThis multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival.MATERIALS AND METHODSThe patients in the TKI plus TRT group received 60 Gy to primary lung tumor and positive regional lymph nodes. Radiotherapy for metastases to other sites was determined by clinicians. The primary end point was the progression-free survival (PFS). Secondary end points included overall survival (OS) and treatment-related adverse events (TRAEs). The first and second interim analyses were performed in March 2021 and March 2022.RESULTSBetween April 14, 2016, and February 25, 2022, a total of 118 patients were enrolled. Compared with the TKI alone group, the TKI plus TRT group achieved significantly better PFS (hazard ratio [HR], 0.57; P = .004) and OS (HR, 0.62; P = .029). The median PFS was 10.6 months in the TKI alone group and 17.1 months in the TKI plus TRT group. The median OS was 26.2 months and 34.4 months in the TKI alone group and TKI plus TRT group, respectively. The TKI plus TRT group showed better local control but was associated with a higher incidence of severe TRAEs (11.9% v 5.1%).CONCLUSIONFor patients with EGFR-mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent TRT improves the PFS and OS, and TRAEs are acceptable and tolerable.

Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a phase III trial. This phase III trial aims to compare the efficacy, safety, and pharmacokinetics between QL1206 and denosumab in patients with bone metastases from solid tumors. This randomized, double-blind, phase III trial was conducted in 51 centers in China. Patients aged 18–80 years, with solid tumors and bone metastases, and an Eastern Cooperative Oncology Group performance status of 0–2 were eligible. This study was divided into a 13-week double-blind period, a 40-week open-label period, and a 20-week safety follow-up period. In the double-blind period, patients were randomly assigned (1:1) to receive three doses of QL1206 or denosumab (120 mg subcutaneously every 4 weeks, each). Randomization was stratified by tumor types, previous skeletal-related events, and current systemic anti-tumor therapy. In the open-label period, up to ten doses of QL1206 could be given in both groups. The primary endpoint was percentage change in urinary N-telopeptide/creatinine ratio (uNTX/uCr) from baseline to Week 13. Equivalence margins were ± 0.135. Secondary endpoints included percentage change in uNTX/uCr at Week 25 and 53, percentage change in serum bone-specific alkaline phosphatase at Week 13, 25, and 53, and time to on-study skeletal-related events. The safety profile was evaluated based on adverse events and immunogenicity. From September 2019 to January 2021, in the full analysis set, 717 patients were randomly assigned to receive QL1206 (n = 357) or denosumab (n = 360). Median percentage changes in uNTX/uCr at Week 13 in two groups were − 75.2

目的:探究图像引导放射治疗技术中宫颈癌调强放射治疗的摆位误差特征及原因分析.方法:回顾性分析2019年1月至2021年12月在我院应用调强放射治疗的92例宫颈癌患者资料.应用锥形束CT评价X、Y、Z轴向的误差及不同误差范围内,X、Y、Z轴向摆位误差绝对值发生率.以(BMI=23kg/m2)作为临界值,将患者分为肥胖(n=40)和正常组(n=52),比较两组患者不同轴向的误差情况.结果:①对1063次锥形束CT验证图像的摆位误差进行分析发现,在X、Y、Z轴向上呈"正态分布".其中X、Y、Z轴的摆位误差分别为(-0.32±3.61)mm、(0.01±4.52)mm和(-0.13±2.82)mm.②从不同误差范围来看,误差范围≤5mm患者不同轴向摆位误差绝对值发生率高于>10mm和5～10mm,差异均具有统计学意义(P<0.05).误差范围>10mm和5～10mm的患者不同轴向摆位误差绝对值发生率无统计学差异(P>0.05).③从不同BMI来看,在X轴向肥胖组摆位误差大于正常组(P<0.05),在Y、Z轴向两组摆位误差比较无统计学差异(P>0.05).结论:在宫颈癌调强放射治疗中,整体摆位效果能够较好满足治疗需求,但对于不同BMI患者,肥胖会对X轴向形成较大的误差影响,在调强放射治疗中应注重摆位误差问题,实现精准放疗.

目的:仰卧位乳腺托架和俯卧位乳腺托架两种放疗固定模式在早期乳腺癌保乳术后容积旋转调强放疗(VMAT)中摆位误差的对比研究.方法:选取2021年1月至2021年12月在我院需要放疗的早期乳腺癌保乳术后女性患者40例,固定方式分别为仰卧位乳腺托架和俯卧位乳腺托架,然后根据两组CT定位图像及靶区的情况分别来设计VMAT计划,最后按照放疗计划实施放疗.结果:早期乳腺癌保乳术后使用VMAT中仰卧位乳腺托架的数据:左右(X轴)、头脚(Y轴)、腹背(Z轴)分别为(0.48±4.86)mm、(0.55±5.48)mm、(0.36±3.62)mm;用俯卧位乳腺托架的数据:左右(X轴)、头脚(Y轴)、腹背(Z轴)分别为(0.53±5.29)mm、(0.68±6.83)mm、(0.41±4.08)mm.早期乳腺癌保乳术后使用VMAT中仰卧位乳腺托架和俯卧位乳腺托架两组数据左右(X轴)、腹背(Z轴)方向误差数据比较,差异无统计学意义(P>0.05);但从头脚(Y轴)方向误差数据比较,差异有统计学意义(P<0.05).结论:早期乳腺癌保乳术后放疗,仰卧位可保证摆位的重复性和稳定性,放疗摆位精度上更优于俯卧位,在临床应用中具有一定的优势.