Sequential or concomitant chemotherapy with hypofractionated radiotherapy for locally advanced non-small cell lung cancer: a meta-analysis of randomized trials

BackgroundFor patients with locally advanced non-small cell lung cancer (NSCLC), the standard treatment is concurrent or sequential chemotherapy with radiotherapy. Most treatment schedules use radiotherapy with conventional fractionation; however, the application of hypofractionated radiotherapy (HYPO-RT) regimens is rising. A meta-analysis was performed to assess the efficacy and safety of chemotherapy combined with HYPO-RT and indirectly compare with the outcomes from previous studies employing concomitant conventional radiotherapy (CONV-RT).MethodsRandomized controlled trials (RCTs) were identified on the electronic database sources through June 2020. Following the PRISMA guidelines, a meta-analysis was performed to assess if there were significant differences in the overall mortality (OM), local failure (LF), and disease progression (DP), comparing HYPO-RT-C vs. sequential chemotherapy followed HYPO-RT (HYPO-RT-S). To establish an indirect comparison with the current standard treatment, we calculate the risk ratio (RR) of the OM from RCTs using conventional chemoradiation, concurrent (CONV-RT-C), and sequential (CONV-RT-S), and compared with HYPO-RT. A P value <0.05 was considered significant.ResultsTwo RCTs with a total of 288 patients were included. The RR for the OM, DP and LF at 3 year comparing HYPO-RT-C vs. HYPO-RT-S were 1.09 (95% CI: 0.96–1.28, P=0.17), 1.06 (95% CI: 0.82–1.23, P=0.610), and 1.06 (95% CI: 0.86–1.29, P=0.490), respectively. The late grade 3 pneumonitis and esophagitis had no significant difference between HYPO-RT groups. In the indirect comparison of RCTs using CONV-RT, the RR for the OM at 3 years was 1.03 (95% CI: 0.96–1.10, P=0.36) with no significant difference for the HYPO-RT arms 1.09 (95% CI: 0.96–1.28, P=0.17).DiscussionHYPO-RT given with chemotherapy provides satisfactory OM, LF, and DP in locally advanced NSCLC with similar rates to the CONV-RT. These findings support HYPO-RT inclusion in future clinical trials as an experimental arm in addition to the incorporation of new strategies, such as immunotherapy.     

Clinical efficacy and safety of Huachansu injection combination with platinum-based chemotherapy for advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials

Background:Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy.Objective:To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC.Methods:A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence.Results:A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia.Conclusions:Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.     

Efficacy and safety of pembrolizumab/carrelizumab,alone or in combination with chemotherapy in treatment of patients with non-small cell lung cancer: A protocol for evidence-based systematic review and Bayesian network meta-analysis

Background:To date, there have been no reported trials that directly compare pembrolizumab/carrelizumab monotherapy versus pembrolizumab/carrelizumab and chemotherapy in the first-line treatment setting of advanced/metastatic non-small cell lung cancer (NSCLC). We performed a Bayesian network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of pembrolizumab/carrelizumab versus pembrolizumab/carrelizumab and chemotherapy in previously treated patients with NSCLC.Methods:The following search terms would be used in PUBMED, Scopus, EMBASE, and Cochrane Library databases on July 20, 2021, as the search algorithm: (pembrolizumab) OR (carrelizumab) OR (programmed death-1) AND (non-small cell lung cancer) OR (NSCLC). All RCTs that reported the outcomes of pembrolizumab/carrelizumab with or without chemotherapy compared with those of pembrolizumab/carrelizumab alone for patients with NSCLC were considered eligible for inclusion in this meta-analysis. The primary outcomes of interest were overall survival, progression-free survival, objective response rate based on the Response Evaluation Criteria in Solid Tumors for complete and partial responses, and treatment-related adverse events including immune-related adverse events. Secondary outcomes included overall survival, progression-free survival, objective response rate, and treatment-related adverse events for the FDA-approved doses.Conclusions:The results of our review will be reported strictly following the PRISMA criteria and the review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.Ethical approval:As this study is on the basis of published or registered previous studies, ethical approval and informed consent of patients are not required.     

非小细胞肺癌脑转移的预后因素分析

目的探讨影响非小细胞肺癌脑转移治疗效果的预后因素。方法收集2006年3月-2009年3月在我科接受全脑放射治疗的57例非小细胞肺癌脑转移患者的临床资料,分析影响生存预后的各种因素。结果平均生存期可达到(9.7±2.8)个月。脑转移放疗后复发再次放疗组生存期(11.5月)优于复发后未放疗组(8.7月),无肺、骨转移组生存期(10.1月)优于有肺、骨转移组(8.5月),有显著统计学差异(P0.05)。多因素分析结果显示:脑转移放疗后复发再次放疗,同步放化疗和无肺、骨转移是肺癌脑转移患者的独立预后因素(P0.05)。结论影响非小细胞肺癌脑转移患者预后的主要因素是有无肺内、骨转移、是否采用同步放化疗,脑转移复发后是否再次放疗,选择同步放化疗以及对于脑转移放疗后复发的患者选择再次放疗的治疗方式,可以延长生存。     

放疗联合长春瑞滨加顺铂同步治疗Ⅲ期非小细胞肺癌的临床研究

目的为了比较放射治疗联合长春瑞滨(NVB)加顺铂(DDP)同步与序贯放化疗治疗Ⅲ期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及毒副反应。方法将64例Ⅲ期NSCLC患者随机分成2组,同步放化疗组(32例):放疗第1天起即同时开始化疗。序贯放化疗组(32例):入组后先予化疗2个疗程,再单独予放疗。结果近期有效率(CR+PR)同步放化疗组为68.7%,序贯放化疗组为43.7%,P=0.03。1、2、3年生存率同步放化疗组为75%、40%、21%。序贯放化疗组为50%、25%、12%。3年生存率差异有统计学意义,P=0.041。两组患者的毒副反应主要为可逆性骨髓抑制、放射性食管炎,两组发生率相似(χ2=1.65,P0.05),患者大多能耐受。结论初步研究结果提示,放射治疗联合长春瑞滨(NVB)加顺铂(DDP)同步放化疗治疗Ⅲ期NSCLC的疗效优于序贯放化疗,不良反应可耐受,值得进一步研究。     

Prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery

The aim of this study was to retrospectively analyze and assess the outcomes and prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. One hundred twenty-six patients with node-positive thoracic esophageal squamous cell carcinoma who had undergone adjuvant therapy (postoperative radiotherapy alone or postoperative sequential chemoradiotherapy without receiving postoperative concurrent chemoradiotherapy) after radical surgery, were retrospectively reviewed from January 1996 to December 2003. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves were estimated using the Kaplan-Meier method. The 1-, 3- and 5-year overall survival rates of all 126 patients were 71.4, 39.1, and 22.0%, and disease-free survival rates were 64.3, 36.4, and 21.5%, respectively. Lymph node ratio (the ratio of the number of metastatic lymph nodes to the number of lymph nodes removed, LNR) ≥0.2 ( P = 0.006), pT3 + pT4 ( P = 0.06) and sequential chemoradiotherapy ( P = 0.08) were associated with a poorer survival by univariate analysis. In multivariate analysis, LNR ( P = 0.01, hazard ratio = 0.57, 95% confidence interval, 0.37–0.87) and tumor depth of invasion ( P = 0.03, hazard ratio = 0.62, 95% confidence interval, 0.41–0.96) were the independent predictors of survival. Sequential chemoradiotherapy receded survival tendency without significant difference ( P = 0.09, hazard ratio = 0.64, 95% confidence interval, 0.37–1.08). Therefore, LNR and tumor depth of invasion were the independent prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. The addition of chemotherapy does not seem to confer a survival benefit.     

适形放疗联合化疗治疗非小细胞肺癌的疗效观察

目的观察适形放疗联合化疗同步与序贯治疗中晚期非小细胞肺癌的临床疗效。方法选择不能手术的中晚期非小细胞肺癌（NSCLC）患者100例,随机分成同步组和序贯组各50例。适形放疗采用三维适形放疗（3D—CRT）和调强放疗（IM—RT）方法,化疗方案为盖诺＋顺铂（NP方案）。结果治疗总有效率比较（CR＋PR）：同步组78％,序贯组46％,两组比较差异有显著性（P〈0．05）;生存率（Kaplan—Meier法）比较：同步组1年生存率为71．2％,序贯组为50．3％,两组比较差异有显著性（P〈0.05）;两组病人均能耐受治疗中的不良反应。结论同步组的近期疗效明显优于序贯组,能提高患者的一年生存率。该方法是治疗中晚期非小细胞肺癌较好的方案。     

Impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation for hepatocellular carcinoma: a meta-analysis

Objective: To evaluate the impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation for hepatocellular carcinoma (HCC).

Methods: We searched medical literature databases to identify appropriate studies assessing the impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation from January 1962 to April 2014. Study inclusion criteria were the existence of a control group, a sufficiently long follow-up period and reporting of survival outcomes. We then performed a meta-analysis of these studies.

Results: Our search identified 12 studies from among a possible 1105. A total of 1504 patients were included in our analysis. There was no significant heterogeneity among the studies. In the meta-analysis, preoperative locoregional therapy was not statistically significant in affecting five-year survival rates following liver transplantation (hazard ratio [HR]?=?1.06; 95% confidence interval [CI]?=?0.82–1.38). For patients meeting the Milan criteria, preoperative locoregional therapy did not affect survival rates following liver transplantation (HR =1.04, 95% CI =0.74–1.45). The recurrence-free survival rate also had no association with preoperative locoregional therapy (HR =1.02, 95% CI =0.70–1.50).

Conclusion: Our meta-analysis suggests that preoperative locoregional therapy has no impact on survival following liver transplantation for HCC.     

Esophageal cancer patients' survival after complete response to definitive chemoradiotherapy: a retrospective analysis

Background

Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow.

Methods

We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking.

Results

At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n?=?58), regional lymph nodes (n?=?36), or distant disease (n?=?34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n?=?22), endoscopic treatment (n?=?23), and lymphadenectomy (n?=?9) was 47.4%, 70.9%, and 33.3%, respectively.

Conclusions

A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.

     

Invasive Anal Squamous-Cell Carcinoma in the HIV-Positive Patient: Outcome in the Era of Highly Active Antiretroviral Therapy

Introduction The incidence of invasive anal squamous-cell carcinoma in patients with HIV is increasing. We report the outcome after combined chemoradiotherapy for anal squamous-cell carcinoma in HIV-infected individuals. Methods Thirty-two HIV-positive patients treated at the St. Vincent’s Cancer Care Center for anal squamous-cell carcinoma from 1997 through mid 2005 were reviewed retrospectively. All patients also received highly active antiretroviral therapy. Treatment consisted of radiotherapy concurrent with 5-fluorouracil and mitomycin C in most patients. Overall survival, anal cancer-specific survival, local recurrence, and toxicity were assessed. Results Median time from completion of radiotherapy to last follow-up of surviving patients was 35 months. Five-year locoregional relapse, anal cancer-specific survival, and overall survival were 16 , 75, and 65 percent, respectively. In multivariate analysis, locoregional recurrence, cancer-specific survival, and overall survival were all significantly associated with tumor size. Overall survival was independently associated with high viral load and low CD4 count. Acute toxicity included: Grade 3 skin in 25 percent of patients, Grade 3 diarrhea: 28 percent, and Grade 3 or 4 hematologic toxicity in 21 and 48 percent, respectively. More than two-thirds of patients required radiotherapy interruption. There was no negative impact of chemoradiotherapy on viral load. Conclusions Outcome after chemoradiotherapy for HIV-related anal squamous-cell carcinoma in the era of highly active antiretroviral therapy is comparable to outcome in patients without HIV. However, significant toxicity is seen with standard treatment regimens. Earlier diagnosis and risk-adapted therapy could lead to improved survival and decreased treatment-related morbidity. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Patterns of recurrence after intracranial stereotactic radiosurgery for brain-only metastases from non-small cell lung cancer and the impact of upfront thoracic therapy with synchronous presentation

BackgroundWe characterized long-term organ-specific patterns of recurrence, time to progression (TTP) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) with brain-only metastases treated with single-fraction stereotactic radiosurgery (SRS) and analyzed the impact of upfront thoracic therapy (UTT) in those with synchronous presentation of primary NSCLC and brain metastases.MethodsThe clinical records of 137 patients with brain metastases from NSCLC treated with intracranial SRS, and no other metastatic sites, were retrospectively reviewed. Patients with available follow-up imaging (n=124) were analyzed for patterns of recurrence; all were analyzed for OS.ResultsThe majority of first distant recurrences were in brain and thoracic sites, while extra-thoracic sites were relatively uncommon. After median follow-up of 16.0 months, 24.8% did not develop recurrence outside of brain and/or thoracic sites and 43.5% were free of distant extracranial recurrence. Whole brain radiotherapy (WBRT) and UTT, but not systemic therapy, altered patterns of recurrence and intracranial or extracranial TTP. Multivariable analysis revealed UTT, but not systemic therapy or WBRT, was associated with more favorable OS [hazard ratio (HR) 0.515, P=0.029] among 88 patients with synchronous presentation. Within the subgroup of thoracic stage III patients (n=69), those treated with UTT experienced remarkable median extracranial TTP and OS of 19.3 and 22.7 months, respectively.ConclusionsFirst and cumulative recurrences in patients treated with intracranial SRS for NSCLC metastases limited to brain are most often in the brain and thorax. Long-term survival is possible, regardless of thoracic stage, and is dependent on UTT among other factors.     

Gastric and colonic metastasis from NSCLC: A very unusual case report

Rationale:Lung cancer is the most common cause of cancer-related deaths worldwide. Approximately 50% of patients is metastatic at diagnosis and the most common metastatic sites are bone, lungs, brain, adrenal glands, liver, and extra thoracic lymph nodes. The occurrence of gastrointestinal metastasis from lung carcinoma is rare and seems more commonly related to small cell lung cancer compared to non-small cell lung cancer (NSCLC).Patient information and diagnosis:A 78-year-old man with completely surgically resected NSCLC and no initial evidence of distant metastases developed colon and gastric metastases 7 months after diagnosis, confirmed by serial radiological examinations and endoscopic biopsies.Interventions:The patient was subjected to total gastrectomy with D2 lymph node dissection plus partial colectomy for intraoperative detection of a transverse colon neoformation. Subsequent instrumental imaging showed bilateral lung tumor recurrence, treated with gemcitabine monotherapy for 8 months as first line chemotherapy for lung adenocarcinoma.Results:The patient presented complete response to therapy and was disease-free for 4 years.Lessons:Colonic and gastric metastasis are very infrequent in NSCLC. The resection of gastrointestinal metastasis may provide benefits in terms of both symptom control and survival in patients properly selected.     

EP方案与超分割放疗同步治疗小细胞肺癌的临床观察

目的观察EP化疗方案与超分割放疗同步治疗局限期小细胞肺癌的近远期疗效及不良反应。方法足叶乙苷（VP-16）100mg静脉滴注（第1-5天）；顺铂（PDD）70mg／mg／（第1天）；21d为1个周期，完成至少2个周期的化疗。同步组患者的放疗与第1个周期化疗同步进行。1．2Gy／次，2次／d，总量45Gy；序贯组患者的放疗在2个周期化疗完成后开始，方法及剂量同前。结果同步治疗组患者的肿瘤进展时间与序贯组患者比较有显著性差异，但总生存期、1-3年生存率及平均生存期两组相似。同步组患者发生向细胞、血小板下降及严重放射性食管炎的比例高于序贯组，但无显著性差异。结论EP方案与超分割放疗同步进行治疗局限期小细胞肺癌较序贯治疗有一定优势且不良反应可耐受。     

Efficacy and safety of apatinib combined with whole-brain radiation therapy with a simultaneous integrated boost for brain metastases from non-small cell lung cancer: a multicenter retrospective study

BackgroundBrain metastases (BMs) develop in 20–65% of non-small cell lung cancer (NSCLC) patients and are associated with a poor prognosis. Apatinib, a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor 2, is safe and significantly prolongs the survival of chemotherapy-refractory gastric cancer patients. This retrospective study evaluated the safety and efficacy of apatinib combined with concurrent brain radiotherapy in NSCLC patients with BMs.MethodsThis trial enrolled patients with non-recurrent BM from histologically-confirmed NSCLC without any limits regarding the BM size/quantity. Eligibility criteria were patients 18–75 years old with measurable BM from histologically-confirmed NSCLC (including both newly-diagnosed and previously treated NSCLC) and expected survival time greater than 3 months. Oral apatinib (500 or 250 mg/day) was started within 1 week prior to commencing whole brain radiotherapy with simultaneous integrated boost (WBRT-SIB) and continued until one week after radiotherapy completion. In addition to toxicities, analyzed outcomes included intracranial overall response rate (iORR), intracranial disease control rate (iDCR), intracranial progression free survival (iPFS), and overall survival (OS).ResultsFrom July 2016 to January 2020, 16 patients were enrolled in this retrospective study. After 3 months of brain radiotherapy, the iORR was 75%, the iDCR was 100%, and the brain edema index (EI) was significantly reduced compared to that before brain radiation therapy (4.2 vs. 1.9; P=0.02). The median iPFS was 16.5 months [95% confidence interval (CI): 15.1–37.4 months]. The median OS was 26 months (95% CI: 17.0–54.0 months). Most of the patients tolerated apatinib well, but 7 patients had side effects, most commonly grade 1 or 2. Only 2 patients experienced grade 3 adverse events (hypertension and oral mucositis), and no grade 4 or 5 toxicities were observed.ConclusionsApatinib combined with WBRT-SIB appears to be safe and effective in treating BMs in NSCLC patients.     

Effect analysis of chemoradiotherapy after operation in patients with stage III A non-small cell lung cancer

ObjectiveTo investigate the effect of chemoradiotherapy after surgery on III A stage non-small cell lung cancer (NSCLC).MethodsA total of 156 NSCLC patients undergoing total pneumonectomy or pulmonary lobectomy were included in this study. The chemotherapy group (n=75) received the protocol of cisplatin (DDP) + gemcitabine (GEM) / docetaxel (DOC) / vinorelbine (NVB); the radiotherapy + chemotherapy group (n=81) received sequential chemoradiotherapy. The response rate, local control rate in 1 to 2 years, overall survival (OS), progression-free survival (PFS) and adverse reactions were evaluated.ResultsThe overall response rate was obviously higher in radiotherapy + chemotherapy group (79.4%) than in chemotherapy group (56.8%) (P<0.01). The 1 year local control rates for chemotherapy group and radiotherapy + chemotherapy group were (69.1±7.9)% and (77.8±8.2)% respectively and the difference reached statistical significance (P<0.001). The 2 year local control rates were (42.1±6.1)% and (61.5±6.9)% respectively (P<0.001). The difference in median follow-up time between the two groups did not reach statistical meaning (P>0.05), while the median PFS of two groups were 10.8 months and 16.9 months respectively (P<0.001). 1-year and 3-year survival rates were obviously higher in radiotherapy + chemotherapy group than in chemotherapy group, and the difference reached statistical significance (P<0.05 or P<0.01). The adverse reactions manifested as hematological toxicity and digestive tract reaction in the two groups. In the radiotherapy + chemotherapy group, incidences of radiation-induced esophagus injury and lung injury were 24.7% and 34.6% respectively, all occurring within 2 to 6 weeks after the start of radiation and both below grade 2.ConclusionsChemoradiotherapy after surgery can improve local control rate and reduce or prevent distant metastasis, but there are still many controversies. In clinical work, we should carefully evaluate each patient's age, lung function, basic physical condition scoring and complications to choose a therapeutic schedule that is suitable for the patient.     

Is There a Survival Benefit in Patients With Stage IIIA (N2) Non-small Cell Lung Cancer Receiving Neoadjuvant Chemotherapy and/or Radiotherapy Prior to Surgical Resection: A Systematic Review and Meta-analysis

Optimal management of clinical stage IIIA (N2) non-small cell lung cancer (NSCLC) is controversial. This study is a systematic review and meta-analysis of published randomized control trials of multimodality management strategies for NSCLC.We conducted a comprehensive literature search of the Pubmed, Embase, Medline, and CENTRAL databases for relevant studies comparing patients with stage IIIA (N2) NSCLC undergoing surgery alone, chemotherapy and/or radiotherapy alone, or surgical resection after neoadjuvant treatment with chemotherapy and/or radiotherapy. We estimated hazard ratios, odds ratios (ORs), and 95% confidence intervals (CIs) for survival data.Seven trials involving 1049 patients were included in this study. There was no significant difference in overall survival (OS) or progression-free survival (PFS) in stage IIIA (N2) NSCLC patients who received neoadjuvant chemotherapy or chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy or chemoradiotherapy prior to radical radiotherapy. There was a significant increase in pathological complete remission in the mediastinal lymph nodes in stage IIIA (N2) NSCLC patients who received neoadjuvant chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy (OR 3.61; 95% CI 1.07–12.15; P = 0.04), but no difference in tumor downstaging, OS, or PFS.Neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection do not appear to be clinically superior to neoadjuvant chemotherapy and/or radiotherapy prior to definitive radiotherapy in IIIA (N2) NSCLC patients. Neoadjuvant chemoradiotherapy does not improve survival compared to neoadjuvant chemotherapy alone.     

Non-surgical treatment of advanced non-small cell lung cancer in Japan

Abstract The cisplatin-based conventional combination chemotherapy has been shown to prolong survival of patients with advanced non-small cell lung cancer (NSCLC), but the treatment effect is only modest and of little clinical significance. Several promising 'new-generation' anti-cancer drugs, such as taxanes, vinorelbine, gemcitabine and irinotecan, have offered both chance and challenge to develop effective chemotherapy against NSCLC. In Japan, large-scale phase III trials of cisplatin-irinotecan combination regimen vs. conventional chemotherapy have been conducted; patient accrual has been completed and the final results will be presented in a couple of years. Other new agents will also be available by the end of 1999, and it will be our important task to evaluate those drugs efficiently.
The current standard treatment strategy against unresectable stage III NSCLC is chemoradiotherapy. However, there remain many questions to be answered through well-designed clinical trials. Those include optimal timing and schedule of the chemoradiotherapy, dose and fractionation of radiation and best chemotherapy regimen. An important randomized trial of concurrent vs. sequential chemoradiotherapy has been conducted in Japan, which has suggested that the concurrent schedule has survival benefit. Many trials of concurrent chemoradiotherapy with the new agents are currently performed or planned, but potential toxicity of the concurrent chemoradiotherapy must be carefully evaluated.     

Patients with unresectable stage III non-small cell lung cancer eligible to receive consolidation therapy with durvalumab in clinical practice based on PACIFIC study criteria

BackgroundCompared to a placebo, durvalumab has been reported to significantly prolong progression-free and overall survival in patients with stage III unresectable non-small cell lung cancer (NSCLC) after chemoradiotherapy. The aim of this retrospective study was to evaluate the eligibility of patients with unresectable stage III NSCLC able to receive consolidation therapy with durvalumab in clinical practice based on the PACIFIC study criteria.MethodsFrom January 2011 to May 2018, electronic data were collected from patients diagnosed with unresectable stage III NSCLC treated with definitive chemoradiotherapy. A total of 81 patients were identified. Of these, 73 were treated with platinum-based chemotherapy based on the PACIFIC study criteria.ResultsRadiation pneumonitis of any grade occurred in 54 patients (73.9%) who received definitive chemoradiotherapy. Of these, 12 (16.4%) developed radiation pneumonitis of grade 2 or more within 42 days after chemoradiotherapy and were excluded from durvalumab treatment. Two patients (2.7%) developed other pneumonitis, seven patients (9.6%) showed poor performance status, and three patients (4.1%) displayed disease progression at the initial assessment. After considering overlapping cases mentioned above, 22 patients (30.1%) were ineligible to receive durvalumab by the criteria utilized in the PACIFIC study.ConclusionIn clinical practice, approximately 70% of patients with unresectable stage III NSCLC would be eligible to receive consolidation therapy with durvalumab.     

Efficacy of immune checkpoint inhibitors in the treatment of non-small cell lung cancer patients with different genes mutation: A meta-analysis

Background:Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in non-small cell lung cancer (NSCLC) patients. However, we still have no clear ideas of the factors which could affect the efficacy of immune checkpoint inhibitors. Cancer, essentially, is a disease related to genes mutation. Therefore, we conducted a systematic review and meta-analysis to compare efficacy of immune checkpoint inhibitors for NSCLC patients with different genes mutation.Methods:PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched for all clinical trials in NSCLC until December 16, 2019. The hazard ratio (HR) and 95% confidence intervals (CIs) of OS or progression-free survival (PFS) were used.Results:A total of 4453 patients from 7 randomized controlled trials (RCTs) were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.67; 95% CI, 0.60–0.67) in NSCLC patients having epidermal growth factor receptor (EGFR) wild-type versus chemotherapy. Meanwhile, they prolonged the OS (HR, 0.61; 95% CI, 0.39–0.94) in NSCLC patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. No matter PD-L1 tumor proportion scores were >1% or <1%, immune checkpoint inhibitors were more effective than chemotherapy (HR, 0.64; 95% CI, 0.55–0.75).Conclusion:Immune checkpoint inhibitors are more efficacious than chemotherapy in NSCLC patients with EGFR wild-type, KRAS mutation, and any PD-L1 tumor proportion scores.     

Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma

AIM: To investigate the role of neoadjuvant chemoradiotherapy in prognosis and surgery for esophageal carcinoma by a meta-analysis.METHODS: PubMed and manual searches were done to identify all published randomized controlled trials (RCTs) that compared neoadjuvant chemoradiotherapy plus surgery (CRTS) with surgery alone (S) for esophageal cancer. According to the test of heterogeneity, a fixed-effect model or a random effect model was used and the odds ratio (OR) was the principal measure of effects.RESULTS: Fourteen RCTs that included 1737 patients were selected with quality assessment ranging from A to C (Cochrane Reviewers' Handbook 4.2.2). OR (95% CI, P value), expressed as CRTS vs S (values > 1 favor CRTS arm), was 1.19 (0.94-1.48, P = 0.28) for 1-year survival, 1.33 (1.07-1.65, P = 0.69) for 2-year survival, 1.76 (1.42-2.19, P = 0.11) for 3-year survival, 1.41 (1.06-1.87, P = 0.11) for 4-year survival, 1.64 (1.28-2.12, P = 0.40) for 5-year survival, 0.82 (0.39-1.73, P < 0.0001) for rate of resection, 1.53 (1.33-2.84, P = 0.007) for rate of complete resection, 1.78 (1.14-2.78, P = 0.79) for operative mortality, 1.12 (0.89-2.48, P = 0.503) for all treatment mortality, 1.33 (0.94-1.88, P = 0.04) for the rate of adverse treatment, 1.38 (1.23-1.63, P = 0.0002) for local-regional cancer recurrence, 1.28 (0.85-1.58, P = 0.60) for distant cancer recurrence, and 1.27 (0.86-1.65, P = 0.19) for all cancer recurrence. A complete pathological response to chemoradiotherapy occurred in 10%-45.5% of patients. The 5-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR: 1.45, 95% CI: 1.26-1.79, P = 0.015) instead of sequentially (OR: 0.85, 95% CI: 0.64-1.35, P = 0.26).CONCLUSION: Compared with surgery alone, neoadjuvant chemoradiotherapy can improve the long-term survival and reduce local-regional cancer recurrence. Concurrent administration of neoadjuvant chemoradiotherapy was superior to sequential chemoradiotherapy.