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Background: Thymic carcinoma is a rare disease with an incidence of around 0.5 cases per million with a poor prognosis. The aim of this study was to assess patient outcomes with advanced thymic carcinoma receiving first-line chemotherapy., Methods: In our retrospective cohort study, we included patients who underwent treatment for metastatic thymic carcinoma between January 2013 to December 2019 in our hospital. Overall survival, progression-free survival (PFS), objective response rates (ORR) and chemotherapy regimens were assessed and analyzed., Results: A total of 27 patients were retrospectively analyzed. All patients received a platinum (cisplatin or carboplatin) based regimen as first-line chemotherapy (29.6% received ADOC, 11.1% received PE, 40.7% received CP, 14.8% received CAP). The median PFS on first-line chemotherapy was 199 days. The response rate was 40.7%. Median overall survival (OS) was 585 days. Positive CD5 staining was associated with better PFS., Conclusion: We highlight the critical role of platinum-based chemotherapy agents as a primary treatment modality in advanced thymic carcinoma, underscoring the efficacy of platinum as a first-line option for recurrent disease, even in cases previously treated with platinum. Additionally, our findings indicate that CD5 positivity could be associated with improved PFS, suggesting its potential as a prognostic marker., (© 2023 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: There is no well-established late-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel-carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late-line therapy in a clinical setting., Methods: Thirty patients with nonsquamous NSCLC who received paclitaxel-carboplatin with bevacizumab therapy as a late-line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated., Results: The median progression-free survival (PFS) was 6.3 (range, 4.9-6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2-17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported., Conclusions: With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel-carboplatin and bevacizumab, a late-line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: As the outcome of immunotherapy can be improved when concurrently or sequentially combined with cytotoxic chemotherapy or radiotherapy, we investigated the efficacy of immunotherapy maintenance following platinum-based chemotherapy in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (EGFR-TKI) failure., Methods: In this prospective, open-label, single arm phase 2 trial, we enrolled patients aged 18 years or older with EGFR-mutant NSCLC, which progressed after first- or second-line EGFR-TKI. Patients received platinum-based chemotherapy followed by nivolumab maintenance therapy. They were intravenously administered 240 mg of nivolumab every 2 weeks for 3 months followed by 480 mg every 4 weeks until disease progression or unacceptable toxic effects occurred. The primary endpoint was progression-free survival (PFS). Secondary outcomes were overall survival (OS) and incidence of grade 3-4 treatment-related adverse events (AEs)., Results: We enrolled 26 patients between May 2020 and July 2021. The median PFS was 1.7 months (95% CI: 0.401-2.999 months). The median OS was 21.4 months (95% CI: 18.790-24.010 months) with 6- and 12-month OS rates of 96.2% and 76.9%, respectively. The objective response rate was 7.7% (2/26) and disease control rate, 11.5% (3/26). The tumor mutational burden by next-generation sequencing in blood was not related to the treatment outcomes. Grade 3-4 treatment-related AEs occurred in four (15.4%) patients; the most frequent AE was increased alanine aminotransferase (7.7%)., Conclusion: Nivolumab maintenance following platinum-based chemotherapy did not show clinical benefits after EGFR-TKI failure in patients with EGFR-mutant NSCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: Combined treatment using anti-programmed death-ligand 1 antibody (anti-PD-L1) and platinum-etoposide is the current standard first-line treatment for patients with extensive-stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES-SCLC after the first-line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES-SCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second- or later-line setting for patients with ES-SCLC who have been previously treated with combined treatment., Methods: Our study will enroll total 30 patients who are diagnosed with ES-SCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m 2 ) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression-free survival, and safety., Discussion: Since the present first-line treatment has been changed to the combined treatment, the second- or later-line treatment should be re-evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and re-evaluates the clinical benefits of irinotecan after combined treatment with anti-PD-L1 and platinum-etoposide for patients with ES-SCLC., Registration Details: This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Rechallenge with platinum-combination chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) after disease progression on platinum-combination chemotherapy occasionally leads to a favorable response. The efficacy and safety of platinum-combination chemotherapy with or without immune-checkpoint inhibitor (ICI) for patients with recurrent NSCLC after surgery followed by adjuvant platinum-doublet chemotherapy remains uncertain., Methods: Patients who relapsed after surgery plus adjuvant platinum-doublet chemotherapy and received platinum-combination chemotherapy with or without ICI between April 2011 and March 2021 at four Nippon Medical School hospitals were retrospectively analyzed., Results: Among 177 patients who received adjuvant platinum-doublet chemotherapy after surgery, a total of 30 patients who received platinum-combination rechemotherapy with or without ICI after relapse were included in this study. Seven patients received ICI-combined chemotherapy. The median disease-free survival (DFS) after surgery was 13.6 months. The objective response rate and disease-control rate were 46.7% and 80.0%, respectively. The median progression-free survival and overall survival were 10.2 and 37.5 months, respectively. Patients with longer DFS (≥12 months) had a better prognosis than others. The most common grade ≥3 toxicity associated with this treatment was neutropenia (33%). Grade ≥3 immune-related adverse events were pneumonitis (14%) and colitis (14%). Treatment-related deaths did not occur in this study., Conclusion: Platinum-combination chemotherapy with or without ICI for patients with postoperative recurrent NSCLC who previously received adjuvant platinum-doublet chemotherapy was effective and safe. In particular, this therapy may be promising for patients with longer DFS., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Previous trials suggest that older adults with non-small cell lung cancer (NSCLC) derive benefit from platinum doublet combination therapy, but its superiority is controversial. Although geriatric assessment variables are used to assess the individual risk of severe toxicity and clinical outcomes in older patients, the standard first-line treatment is still debated. Therefore, we aimed to identify the risk factors for clinical outcomes in older patients with NSCLC., Methods: Patients aged ≥75 years with advanced NSCLC treated at any of 24 National Hospital Organization institutions completed a pre-first-line chemotherapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. We evaluated whether these variables were the risk factors for progression-free survival (PFS) and overall survival (OS)., Results: A total of 148 patients with advanced NSCLC were treated with combination therapy (n = 90) or monotherapy (n = 58). Median PFS was 5.3 months and OS was 13.6 months. We identified that hypoalbuminemia (hazard ratio [HR] 2.570, 95% confidence interval [CI]: 1.117-5.913, p = 0.0264) was a risk factor for PFS and monotherapy (HR 1.590, 95% CI: 1.070-2.361, p = 0.0217), lactate dehydrogenase (HR 3.682, 95% CI: 1.013-13.39, p = 0.0478), and high C-reactive protein (HR 2.038, 95% CI: 1.141-3.642, p = 0.0161) were risk factors for OS. The median OS was significantly longer in patients treated with combination therapy than in those who received monotherapy (16.5 months vs. 10.3 months; HR 0.684, 95% CI: 0.470-0.995, p = 0.0453)., Discussion: Platinum doublet combination therapy may be beneficial in older patients with NSCLC. Identification of risk factors will assist in the development of a personalized treatment strategy., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: Immune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild-type non-small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first-line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second-line therapy options. Plinabulin is a selective immunomodulating microtubule-binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD-1) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance., Methods: In this investigator-initiated, single-arm, open-label, phase II trial, metastatic NSCLC patients who acquired resistance to first-line immunotherapy-based therapy will be enrolled. Participants will receive pembrolizumab 200 mg D1, plinabulin 30 mg/m 2 D1 and D8, and docetaxel 75 mg/m 2 D1 intravenously for a 21-day cycle. The study intervention will be given until disease progression, intolerable toxicity, informed consent withdrawal or investigator decision. The primary endpoint is investigator-based objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary endpoints are progression-free survival, overall survival, duration of response, and safety., Discussion: This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first-line PD-1/PD-L1 inhibitor either as monotherapy or in combination with chemotherapy., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: The PACIFIC study demonstrated that durvalumab consolidation therapy significantly improved progression-free survival (PFS) and overall survival (OS) in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). However, there was no clinical benefit in both PFS and OS in epidermal growth factor receptor (EGFR) mutation-positive patient groups in a post hoc exploratory analysis. Moreover, the clinical effects of immune checkpoint inhibitors (ICIs) in EGFR mutation-positive stage IV NSCLC were demonstrated to be poor. Personalized treatment according to the mutation status is also required in stage III NSCLC. Lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is newly developed and approved for use in Korea., Methods: This prospective, open, single-arm, multicenter, phase II clinical trial aims to evaluate the efficacy and safety of lazertinib as a consolidative therapy after CCRT treatment in unresectable, EGFR mutation-positive NSCLC stage III patients. The primary endpoint of this study is PFS, and the secondary endpoints are OS, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), and safety profiles., Discussion: Our study may extend the indications for third-generation EGFR-TKIs to treat patients with stage III NSCLC. Moreover, using this drug to treat stage III NSCLC would emphasize the value of mutation analysis and personalized medicine., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free-survival (PFS) when compared to the placebo group in treatment-naïve extensive stage (ES) small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy have become mainstay treatment modalities as first-line treatment in ES-SCLC. Nevertheless, real-world data are still lacking and the search for potential biomarkers is essential. This study aimed to evaluate potential predictive biomarkers applicable in ES-SCLC under combination therapy., Methods: Patients with ES-SCLC under etoposide-platinum-atezolizumab enrolled from seven university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. p-values below 0.05 were considered statistically significant., Results: A total of 41 patients were evaluated. Six-month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, nine (22.0%) showed stable disease, and four (9.8%) showed progressive disease. During the induction phase, grade I-II AEs occurred in 22 (53.7%) patients, and grade III-IV AEs occurred in 26 (63.4%) patients. During the maintenance phase, nine out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase (LDH), c-reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant., Conclusion: In ES-SCLC under etoposide-platinum-atezolizumab, pretreatment CRP, LDH and FVC (%) were independent predictive factors., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: This multicenter phase 1b/2 trial aimed to explore the maximum tolerated dose (MTD), activity, and safety of anlotinib plus chemotherapy in patients with T790M-negative epidermal growth factor receptor (EGFR)-mutant advanced nonsquamous non-small cell lung cancer (NSCLC) after resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs)., Methods: In the phase 1b stage, patients received anlotinib (8/10/12 mg, days 1-14) combined with cisplatin (75 mg/m 2 , day 1) or carboplatin (AUC = 5, day 1) plus pemetrexed (500 mg/m 2 , day 1) for a 3-week cycle based on a 3 + 3 dose-escalation design. In the phase 2 single-arm stage, anlotinib was administered at MTD combined with platinum plus pemetrexed for four cycles, followed by anlotinib maintenance therapy. The primary endpoint of the phase 2 stage was progression-free survival (PFS)., Results: The study was prematurely terminated due to slow accrual after 19 patients had been enrolled between January 18, 2019, and March 21, 2021. The MTD of anlotinib was 12 mg. The median PFS was 5.75 (95% confidence interval, 4.37-7.52) months. The objective response rate was 47.4% (95% confidence interval, 24.5%-71.1%). In the 12 mg group, seven (58.3%) patients experienced grade 3-4 treatment-related adverse events, and the most common ones were hypertension (6 [50.0%]), decreased platelet count (2 [16.7%]), and hypertriglyceridemia (1 [8.3%]). No treatment-related deaths occurred., Conclusion: Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M-negative EGFR-mutant advanced nonsquamous NSCLC after progression on first- or second-generation EGFR TKIs., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The effect of first-line chemotherapy on overall survival (OS) may be significantly influenced by subsequent therapy for patients with extensive disease small cell lung cancer (ED-SCLC). Therefore, we evaluated the relationship between progression-free survival (PFS), post-progression survival (PPS), and OS of ED-SCLC patients treated with atezolizumab plus carboplatin and etoposide as first-line therapy., Methods: We analyzed the data of 57 patients with relapsed ED-SCLC treated with atezolizumab plus carboplatin and etoposide (AteCE) as first-line chemotherapy between August 2019 and September 2020. The respective correlations between PFS-OS and PPS-OS following first-line AteCE treatment were examined at the individual patient level., Results: Spearman's rank correlation analysis and linear regression analysis showed that PPS strongly correlated with OS (r = 0.93, p < 0.05, R 2  = 0.85) and that PFS moderately correlated with OS (r = 0.55, p < 0.05, R 2  = 0.28). Performance status at relapse (0-1/≥2), number of cycles of atezolizumab maintenance therapy (<3/≥3), and platinum rechallenge chemotherapy all significantly positively correlated with PPS (p < 0.05)., Conclusions: Upon comparing OS-PFS and OS-PPS in this patient population, OS and PPS were found to have a stronger correlation. These results suggest that performance status at relapse, atezolizumab maintenance, or chemotherapy rechallenge could affect PPS., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The aim of this prospective, pilot, single-arm phase II trial was to evaluate the safety and efficacy of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC)., Methods: This phase II study was conducted at Fudan University Shanghai Cancer Center between December 2018 and December 2020. All patients received standard chemotherapy (etoposide plus cisplatin/carboplatin) consisting of four courses and anlotinib at 12 mg once per day for 2 weeks followed by a one-week rest. Anlotinib administration was continued until disease progression, intolerable adverse events (AEs) or patient withdrawal from the study. The primary outcome measure was progression-free survival (PFS). The secondary outcome measures were overall survival (OS), objective control rate (ORR), disease control rate (DCR) and AEs., Results: Thirty-seven patients were included in this study, and 30 patients were eligible for efficacy analysis. ORR and DCR were 90.0% and 96.7%, respectively. The estimated PFS and OS were 6.0 months (95% CI: 1.1-11.9 months) and 14.0 months (95% CI: 8.6-19.4 months), respectively. No unexpected adverse effects were reported. Hypertension (20/37, 54.1%), anemia (16/37, 43.2%), alopecia (15/37, 40.5%), elevated transaminases (9/37, 24.3%) and alkaline phosphatase (9/37, 24.3%) were the most commonly reported AEs. Thirteen patients (35.1%) reported grade 3-5 AEs. No treatment-related deaths occurred during this study., Conclusion: The addition of anlotinib to standard etoposide/platinum chemotherapy achieved encouraging PFS and OS in previously untreated ES-SCLC patients, with an acceptable tolerability profile and no new safety signals observed., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: This study analyzed the efficacy and safety of neoadjuvant chemotherapy with liposomal paclitaxel plus platinum in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC)., Methods: The data of patients with locally advanced resectable ESCC (staging cT2N + M0, cT3-4aNanyM0, IA-IVA) who received preoperative chemotherapy with liposomal paclitaxel plus platinum (cisplatin, nedaplatin or carboplatin) in HuanXing Cancer Hospital from July 2018 to October 2019 were collected. The primary endpoint of this study was R0 resection rate, and secondary endpoints were pathological complete response (pCR) rate, 1- and 2-year overall survival (OS) rate, 1-year and 18-month disease-free survival (DFS) rate, and safety., Results: A total of 32 eligible patients were included in this study. All patients received neoadjuvant chemotherapy and surgery. The R0 resection rate was 93.8%, the pCR rate was 12.5%, and down-staging was achieved in 14 patients (47.8%). Median follow-up was 31.0 months (95% confidence interval [CI] 30.1-31.9 months). The 1- and 2-year OS rates were 96.9% and 78.1%, and the 1-year and 18-month DFS rates were 86.7% and 76.7%, respectively. The median DFS and OS were not reached. The incidence rate of neoadjuvant chemotherapy related grade 3-4 adverse events was 21.9%, including neutropenia (21.9%) and leukopenia (9.4%)., Conclusions: The results of this study suggest that liposomal paclitaxel combined with platinum as neoadjuvant chemotherapy can provide satisfactory R0 resection rate and survival rate, and significant tumor down-staging effect for patients with locally advanced resectable ESCC, with safety profile., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. It is advisable to select the appropriate treatment based on characteristics of the cancer such as pathology, mutations, and programmed death-ligand 1 (PD-L1) levels. In this study, by remarking squamous NSCLC with low PD-L1 expression without mutations, we investigated the efficacy and safety of regimens that included molecularly targeted drugs such as immune checkpoint inhibitors (ICIs) through a network meta-analysis., Methods: Databases were searched systematically to identify appropriate articles, in which randomized trials with incurable squamous NSCLC were described. Suitable studies were manually checked by two reviewers. A random model network meta-analysis was conducted, in which the primary outcome was the overall survival rate., Results: We identified 48 studies, which included 16 391 patients. When a platinum + third-generation cytotoxic agent regimen (platinum regimen) was a reference, the platinum regimen + pembrolizumab (Pemb) yielded the best results in regard to the overall survival rate when compared with chemotherapy (hazard ratio [HR] = 0.57, 95% confidence interval [CI] = 0.36-0.90, p = 0.016) followed by the platinum regimen + nivolumab (Niv) + ipilimumab (Ipi) (HR = 0.61, 95% CI = 0.44-0.84, p = 0.003). However, the efficacy of ICI monotherapy was not statistically different from that of the platinum regimen., Conclusions: The combination therapies, which were the platinum regimen + Pemb and the platinum regimen + Niv + Ipi, rather than ICI monotherapy were effective first-line agents for treating squamous NSCLC with low PD-L1 levels., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Lung cancer has the highest mortality rate among malignant tumors, with non-small cell lung cancer (NSCLC) being the most common type. As the main component of the human microflora, the intestinal flora interacts with the human body to affect immunity, metabolism, and the formation of diseases., Methods: Forty-five patients with advanced NSCLC who received platinum-containing dual-drug chemotherapy were enrolled in a prospective exploratory cohort study. The intestinal flora was dynamically collected at baseline and after two chemotherapy cycles. Next-generation sequencing and metagenomics were then used to analyze the species and function of the intestinal flora at all levels., Results: Significant differences in the intestinal flora of patients with NSCLC were found according to sex and age. At the family level, the abundances of Streptococcaceae, Lactobacillaceae, and Leuconostocaceae after platinum-containing dual-drug chemotherapy were significantly higher compared to those before chemotherapy. At the family level, patients with chemotherapy-induced gastrointestinal reactions had a significantly higher abundance of Leuconostocaceae than those without gastrointestinal responses. Meanwhile, patients with gastrointestinal reactions had higher metabolism, human diseases, cellular processes, and environmental information processing than those who did not. At the genus level, responders had higher abundances of Bacteroides compared to nonresponders. Moreover, nonresponders had higher levels of the six major metabolic pathways compared to responders., Conclusions: The intestinal flora of Chinese patients with advanced NSCLC differed according to sex and age. Moreover, significant differences in the intestinal flora were noted after chemotherapy, which could be associated with chemotherapy-induced gastrointestinal reactions and the efficacy of chemotherapy., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: A heterogeneous radiological response is frequently observed in cancer patients and could reflect tumor heterogeneity. We investigated the prognostic impact of heterogeneous radiological responses in patients with advanced non-small-cell lung cancer (NSCLC) who received platinum-based chemotherapy., Methods: The treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria was evaluated in 212 patients with advanced NSCLC who received platinum-based chemotherapy. Patients with partial response (PR) or stable disease (SD) were classified into "PR homo," "PR hetero," "SD homo," and "SD hetero" by the presence of a heterogeneous radiological response, and survival was compared between groups. We also compared survival based on the presence of metabolic responses in lesions with heterogeneous radiological responses., Results: Fifty-two patients (24.5%) were classified as PR, 112 patients (52.8%) as SD, and 48 patients (22.7%) as progressive disease (PD). There was no significant difference in progression-free survival (PFS) and overall survival (OS) between the PR homo and PR hetero groups. The SD homo group had a longer PFS and OS than the SD hetero group. In the SD hetero group, patients with increased maximum standardized uptake value (SUVmax) in lesions with heterogeneous radiological responses had a shorter PFS than those with a stable SUVmax., Conclusions: The presence of lesions with radiological heterogeneity was associated with disease progression and poor prognosis in the SD group. Patients with heterogeneous radiological responses require careful monitoring., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: NJLCG1402 was a phase I/II trial investigating biweekly nanoparticle albumin-bound paclitaxel (nab-PTX) in patients with advanced non-small cell lung cancer (NSCLC)., Methods: The study included patients aged ≥20 years with previously treated NSCLC. Nab-PTX (100-150 mg/m 2 ) was administered biweekly in a 28-day cycle. The phase I portion was performed to determine the recommended phase II dose of nab-PTX. In the phase II portion, the primary endpoint was the objective response rate. Secondary endpoints were disease control rate, progression-free survival, overall survival, and safety., Results: A total of 15 patients received biweekly nab-PTX (100-150 mg/m 2 ) and 12 patients in phase II were treated with 150 mg/m 2 . In the phase I portion, 150 mg/m 2 was determined as the recommended dose. Among those treated with 150 mg/m 2 , the objective response rate was 22%, and the median progression-free and overall survival was 3.6 and 11.2 months, respectively. Adverse events grade ≥3 were observed in 39% of patients., Conclusions: Biweekly nab-PTX monotherapy was well tolerated and exhibited favorable antitumor activity in patients with previously treated NSCLC., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Pulmonary sarcomatoid carcinoma (SC) is an aggressive subtype of lung cancer that exhibits resistance to cytotoxic chemotherapy. Although programmed cell death 1 (PD-1) inhibitors have been reported to show antitumor effects in patients with high programmed death-ligand 1 (PD-L1) expressing SC, the efficacy of combined therapy with PD-1 inhibitor plus cytotoxic chemotherapy has not previously been clarified. We herein report a case of SC with low expression of PD-L1 and few pre-existing tumor-infiltrating lymphocytes which showed a remarkable response to pembrolizumab plus cytotoxic chemotherapy as first-line treatment. Our findings suggest that combined treatment might enhance the immunogenic response, even in immunologically ignored SCs., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: Platinum-based chemotherapy is currently the most frequently applied first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) without targetable mutations or high PD-L1 expression. Unfortunately, chemotherapy-induced toxicity is prevalent and may affect patients' quality of life to a considerable extent. Presumably, genetic variants of genes, coding for proteins involved in the processes of the development of toxicity, may be of interest as predictors of benefits and harms of platinum-based chemotherapy. The primary objective of the study is to investigate the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy. The main secondary objectives are to study the association between genetic variants and treatment response and to study the association between skeletal muscle mass (SMM) as well as patient-reported health-related quality of life (HRQOL) and treatment response and toxicity., Methods: In this multicenter prospective follow-up study, a total of 350 patients with NSCLC (stage II-IV) undergoing first-line platinum-based chemotherapy will be included. Blood samples for DNA isolation and genotyping, questionnaires and data on patients risk factors and disease stage will be recorded. The primary endpoint is chemotherapy-induced (non-)hematological toxicity, comprising; nephrotoxicity, neuropathy, esophagitis, ototoxicity, pneumonitis, gastrointestinal toxicity, anemia, leukocytopenia, neutropenia and thrombocytopenia. Secondary endpoints include dose-limiting toxicity, HRQOL, and treatment response (radiological response [RECIST 1.1] and overall survival [OS])., Discussion: Results of the PGxLUNG study will be primarily used to determine the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population., Methods: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients., Results: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders., Conclusion: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced pan-negative non-squamous (non-Sq) non-small cell lung cancer (NSCLC). However, it is unknown which chemotherapy regimen confers the greatest benefit in such patients. This study explored which chemotherapy regimens were advantageous in non-Sq NSCLC patients., Methods: A retrospective study was conducted on 114 patients with advanced non-Sq NSCLC using platinum-based chemotherapy in a first-line setting between January 2013 and December 2015. The study evaluated the most common first-line regimens including pemetrexed/platinum (PP), paclitaxel/carboplatin, gemcitabine/platinum, and vinorelbine/cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were the objective response rate and disease control rate (DCR). Univariate and multivariate logistic analysis was carried out., Results: Sixty of the 114 patients were administered PP regimens and 54 non-pemetrexed plus platinum (NPP) regimens. The median PFS was significantly longer in the PP than in the NPP group (7.2 months, 95% confidence interval [CI] 5.3-9.1 vs. 4.9 months, 95% CI 3.2-6.6; P = 0.031). The DCR of the PP regimen was better than that of the NPP regimen (90.0% vs. 74.1%; P = 0.026). Smoking status was an independent predictor of PFS (hazard ratio 2.1, 95% CI 1.4-3.3; P = 0.001) in a final multivariate Cox regression model., Conclusions: A PP regimen tends to be more beneficial than an NPP regimen for patients with pan-negative advanced non-Sq NSCLC. Smoking status may be a valuable predictor for the selection of a chemotherapy regimen in such patients., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The safety of front-line chemotherapies for the treatment of extensive stage small-cell lung cancer (ED-SCLC) is uncertain. We carried out a network meta-analysis to compare the toxicity of different therapies for ED-SCLC., Methods: We searched EMBASE, PubMed, CENTRAL and clinicaltrials.gov. We performed network meta-analysis on hematological (anemia, leukopenia, neutropenia, and thrombocytopenia) and non-hematological toxicities (diarrhea, infection, and nausea and vomiting)., Results: Nine studies with 2317 patients were included. Etoposide with carboplatin (EC) was associated with a higher incidence of anemia (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.13-3.63), leukopenia (OR 2.67, 95% CI 1.25-5.72), neutropenia (OR 12.08, 95% CI 2.13-68.66), and thrombocytopenia (OR 2.73, 95% CI 1.27-5.85) compared with irinotecan with carboplatin (IC). Similarly, etoposide with cisplatin (EP) was associated with a higher incidence of anemia (OR 1.70, 95% CI 1.13-2.56), leukopenia (OR 2.65, 95% CI 1.34-5.28), neutropenia (OR 5.70, 95% CI 2.93-11.10), and thrombocytopenia (OR 3.26, 95% CI 1.66-6.38) compared with irinotecan with cisplatin (IP). EC was associated with a lower incidence of diarrhea (OR 0.26, 95% CI 0.10-0.68) compared with IC, and EP was associated with a lower incidence of diarrhea (OR 0.09, 95% CI 0.03-0.25) and nausea and vomiting (OR 0.53, 95% CI 0.33-0.84) than IP., Conclusions: Hematological toxicities were most common in EC-treated patients, while the lowest incidence occurred with IP treatment. The IP regimen was associated with the highest incidence of toxicities of the digestive tract, while the lowest incidence occurred with EC treatment., (© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)