Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Clinical benefit of gemcitabine plus cisplatin 3-week regimen for patients with advanced non-small cell lung cancer: a prospective observational study

Background Platinum-based chemotherapy has been proved effective in patients with advanced non-small cell lung cancer (NSCLC). This study evaluated the effectiveness and safety of first-line chemotherapy with gemcitabine plus cisplatin (GEM-Cis) 3-week regimen in routine care of Chinese patients with advanced NSCLC. Methods Two hundred and twenty-one patients with NSCLC stage IIIb or IV were enrolled and 209 were eligible for effectiveness and safety analysis. The median age was 58 (range 29 to 79) years. The percents of cases in stage Ⅳ and stage Ⅲb were 52.2% and 47.8%; of Karnofsky performance score (KPS) less than 80 and 80-100 were 37.3% and 62.7% and of adeno-cancer and non-adeno-cancer were 59.8% and 40.2%. The average number of completed chemotherapy cycles was three. Measures of effectiveness included clinical benefit, significant clinical response (SCR) and adverse effects of GEM-Cis in the treatment of NSCLC at stages Ⅲb/Ⅳ.Results KPS increased from 79±9 at baseline to 86±10 after chemotherapy (P<0.01). Lung cancer symptom scale (LCSS) score of pain, dyspnea and cough increased from 77±24, 74±22 and 63±19 to 92±15, 90±14 and 86± 15, respectively (P<0.01). The clinical benefit rate was 85.2% [95% confidence interval (CI) 80.3%-90.0%]. The SCR was 89.5% (95% CI 85.3%-93.7%). Median survival time was 7.8 months (95% CI 7.1 months-9.1 months). Sixty-four patients (30.6%) experienced an adverse effect that was deemed clinically significant. Only one patient (0.5%) was hospitalized due to chemotherapy related adverse effects. Life-threatening toxicity was observed in two patients (1.0%).Conclusion First-line chemotherapy with GEM-Cis in the routine care of Chinese patients with advanced NSCLC is effective and safe.

Prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer

Background The prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer （NSCLC） remains unclear.This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions.Methods The data of 124 NSCLC patients who underwent R1-resection at the bronchial stump was reviewed.There were 41 patients in the surgery group （S）,21 in the postoperative radiotherapy （PORT） group （S＋R）,30 in the postoperative chemotherapy （POCT） group （S＋C）,and 32 in the PORT plus POCT group （S＋R＋C）.The constitute proportion in different groups was tested using the X2 method,univariate analysis was performed using the Kaplan-Meier and log-rank method,and multivariate analysis was done using the Cox hazard regression with entry factors including age,sex,pathological type and stage,classification of the residual disease,and treatment procedure.The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step.Results In univariate analysis,survival was more favorable for patients with squamous cell carcinoma,early pathological T or N stage,and chemotherapy or radiotherapy.There was no significant difference in the survival for patients with different types of the residual disease,except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa （P=0.030）.The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone （P=0.016）.In multivariate analysis,the pathological type （HR 2.51,95% CI 1.59 to 3.96,P=0.000）,pathological T （HR 1.29,95% CI 1.04 to 1.60,P=-0.021） or N stage （HR 2.04,95% CI 1.40 to 2.98,P=0.000）,and chemotherapy （HR 0.24,95% CI 0.13 to 0.43,P=0.000） were independent prognostic factors.Conclusion Patients with squamous cell carcinoma,early pathological T or N stage,or receiving chemotherapy had a more favorable prognosis.

Tolerability and toxicity of adjuvant cisplatin and gemcitabine for treating non-small cell lung cancer

Background The combination of cisplatin and vinorelbine is an evidence-supported regimen for adjuvant chemotherapy for treating non-small cell lung cancer （NSCLC）. But this doublet has considerable toxicity and unfavorable tolerability, and results in poor compliance. The cisplatin and gemcitabine regimen is one of the most active and well-tolerated regimens against advanced NSCLC, but its toxicity and tolerability has not been adequately evaluated in the adjuvant setting. Methods From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin （75 mg/m2） and gemcitabine （1250 mg/m2） between January 2005 and December 2011. Postoperative demographics, compliance to adjuvant therapy and toxicity were retrieved from medical records. Results A total of 132 patients met the criteria and were included in the study, 96 were male （72.7%） and 36 were female （27.3%）. Median age was 60.5 years old, range 29-75 years, and 41.7% of patients were 〉65 years old. Overall, 68.2% patients received all four planned cycles, and the cumulative dose delivered for gemcitabine was 8333 mg （83.3% of the planned dose） and cisplatin 248 mg （82.7% of the planned dose）. There were no treatment-related deaths. Grade 3/4 neutropenia developed in 47 patients （35.6%） and was the predominant hematologic toxicity. Common grade 3/4 non- hematologic toxicities were nausea/vomiting （22.0%）, infection （12.3%）, and febrile neutropenia （11.4%）. Conclusion Cisplatin and gemcitabine are feasible for use in the adjuvant setting with a favorable toxicity profile and superior tolerabilitv compared with Dublished data on cisDlatin and vinorelbine.

Emerging insights to lung cancer drug resistance

Lung cancer remains the malignant tumor with the highest morbidity and mortality in China,with non-small cell lung cancer(NSCLC)accounting for 80%-85% of cases.Nowadays,the treatment pattern of NSCLC has evolved toward precision management with the development of molecular targeted therapy and immunotherapy.However,the median overall survival for patients with metastatic NSCLC,unfortunately,remains less than three years.Drug resistance is the bottleneck to preventing drugs from playing a further role,and the mechanistic study of drug resistance is the prerequisite for new regimen development.This Special Issue pays special attention to drug resistance in the treatment of NSCLC.We received and published several excellent articles regarding this topic.We hope that,through this Special Issue,we can have a deep understanding of the existing problems,the underlying mechanism,and the future solutions and that the publication of this Special Issue can bring some inspiration to readers.

MVP方案治疗非小细胞肺癌21例临床分析

[目的]评价以VDB为主的MVP方案治疗非小细胞肺癌（NSCIC）的疗效和毒副反应。[方法]每一病人给予2周期MVP方案进行化疗，每周期用VDB3mg/m2静注第1、8天；DDP30mg/m2静滴第1－3天；MMC6mg/m2静注第1天。[结果]3例完全缓解，8例部分缓解，总有效率52．38%。不同病期之间、不同组织类型之间的疗效差别无显著性差异（P＞0．05）。本方案主要毒副反应为骨髓抑制。[结论]MVP方案对NSCLC疗效是好的，其骨髓抑制的毒副作用应引起重视。