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Backgrounds: The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non–small cell lung cancer (LA‐NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation‐related parameters in patients with LA‐NSCLC treated with CCRT plus durvalumab. Methods: We recruited 76 LA‐NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil‐to‐lymphocyte ratio (NLR), C‐reactive protein‐to‐albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre‐treatment) and 2 months after (post‐treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression‐free survival (PFS) after durvalumab therapy. Results: The median follow‐up time was 17 (range, 3.3–35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non‐infectious pneumonitis being the most common reason. Post‐treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not‐reached vs. 9.6 months. Log‐rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post‐treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003). Conclusions: This study suggests that post‐treatment CAR has predictive value for LA‐NSCLC patients treated with CCRT plus durvalumab consolidation therapy. [ABSTRACT FROM AUTHOR]

Background: The prognostic implications of palliative chemotherapy for advanced or recurrent thymic carcinomas require full elucidation. The lung immune prognostic index (LIPI) is a novel prognostic index whose effectiveness has recently been reported in lung cancer patients. This study aimed to evaluate the clinical value of the LIPI in advanced or recurrent thymic carcinoma patients. Methods: We retrospectively analyzed 41 advanced or recurrent thymic carcinoma patients undergoing palliative chemotherapy between January 2001 and December 2020. Survival‐time analysis was conducted using the Kaplan–Meier method and log‐rank test. Multivariate analysis using the Cox proportional hazards model was performed to investigate the predictive and/or prognostic value of the LIPI. Results: Median progression‐free survival (PFS) for first‐line chemotherapy and overall survival (OS) were significantly longer in the good‐LIPI group (LIPI: 0) than in the intermediate/poor‐LIPI group (LIPI: 1 or 2) (PFS: 13.4 vs. 6.8 months, p = 0.025; OS: 48.2 vs. 28.9 months, p = 0.00506). Multivariate analysis revealed that intermediate/poor LIPI was the adverse prognostic factor for PFS. With regard to OS, serum albumin <3.5 g/dl and an intermediate/poor LIPI were identified as independent adverse prognostic factors. Conclusions: Our study indicates that the LIPI is a potential prognostic marker in patients with advanced or recurrent thymic carcinoma undergoing palliative chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Nivolumab, a programmed death-1 antibody, is an immune checkpoint inhibitor approved in Japan in March 2017 for the treatment of recurrent or metastatic head and neck cancers (RM-HNCs) after platinum drug administration. This study aimed to evaluate the effectiveness and safety of nivolumab and to determine the prognostic factors affecting the treatment outcome, in a real-world setting in Japanese RM-HNCs. Methods: Forty-six patients with RM-HNCs treated with nivolumab between April 2017 and April 2021 at Shinshu University Hospital were retrospectively assessed in this cohort study. Results: The overall response rate was 17.4%, and the disease control rate was 41.3%. The median first and second progression-free survival (PFS1 and PFS2) were 2.6 and 10.3 months, respectively. The median overall survival (OS) was 14.8 months. Multivariate analysis showed that performance status (PS) (p = 0.003) and a decrease in neutrophil-lymphocyte ratio (NLR) (p = 0.02) were significantly associated with a better OS, and a decrease in NLR (p = 0.035) was associated with a better PFS2. Conclusions: This study is the first report of PFS2 in RM-HNCs treated with nivolumab; the long PFS2 may contribute to prolonged OS. We propose that the PS and a decrease in NLR could be useful clinical prognostic markers of nivolumab therapy, which can easily be evaluated in the clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. Methods: In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. Results: Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (p = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; p = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; p = 0.022). Conclusions: Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: The development of immune-related adverse events (irAEs) in patients undergoing immunotherapy has been reported to be a favorable prognostic factor in several studies. We aimed to examine the correlation between irAEs and prognosis in patients with non-small cell lung cancer (NSCLC) and further reveal the patient characteristics associated with response to immunotherapy among treatment responders who developed irAEs. Methods: We retrospectively enrolled 80 patients with NSCLC who received immunotherapy at Shinshu University Hospital between February 2016 and February 2020. Progression-free survival (PFS) and overall survival (OS) were compared between patients with and those without irAEs. We examined the prognostic factors associated with PFS and OS using univariate and multivariate Cox proportional-hazards models. We further analyzed the patients who developed irAEs by classifying them into responders and non-responders. Results: Twenty-five patients developed irAEs. The median PFS and OS of the patients with irAEs were significantly longer than those of the patients without irAEs (6.8 vs. 1.9 months, p < 0.001, and 37.8 vs. 8.1 months, p < 0.001, respectively). Multivariate analysis associated with PFS and OS indicated that the development of irAEs was an independent favorable prognostic factor. Among the patients developing irAEs, the responder group had a significantly higher incidence of multiple irAEs than the non-responder group (41.7 vs. 0.0%, p = 0.009). Conclusion: Our findings revealed that the development of irAEs was associated with clinical benefits in NSCLC patients who received immunotherapy. In particular, patients with multiple irAEs might have good prognoses. [ABSTRACT FROM AUTHOR]

Background: This study was performed to clarify the treatment outcome of patients with primary mediastinal germ cell tumors (PMGCTs), focusing on the clinical manifestations and management during definitive therapy and long‐term follow‐up. Methods: In this study, we retrospectively reviewed the medical records of patients with PMGCTs treated at Shinshu University School of Medicine, and examined the clinical profiles and treatment outcomes of 22 patients (mean age of 29 years) with primary mediastinal GCTs treated at our hospital between 1983 and 2019. Results: Five patients were diagnosed with pure seminoma and 17 had nonseminomatous GCT. A total of 21 patients were treated with cisplatin‐based chemotherapy and 15 patients (68.2%) underwent thoracic surgery after chemotherapy. Although all cases of nonseminomatous GCT were negative for tumor markers after cisplatin‐based chemotherapy, two cases showed variable GCT cells and two had somatic components (angiosarcoma and rhabdomyosarcoma) in resected specimens. Three relapsed soon after surgery. Growing teratoma syndrome developed during chemotherapy in four cases. Urgent thoracic surgery was performed in three patients, but one case was inoperable. The calculated 10‐year overall survival rates were 100% in mediastinal seminoma and 64.7% in NSGCT. During follow‐up, second non‐GCT malignancies developed in three patients (colon cancer, 190 months; thyroid cancer, 260 months; non‐small cell lung cancer, 250 months after the initial chemotherapy) and one patient with primary mediastinal seminoma was associated with multiple type I endocrine tumors. Conclusions: Our experiences demonstrated that long‐term survival and/or cure can be achieved with adequate chemotherapy followed by local surgical treatment even in patients with mediastinal GCTs. However, the clinical manifestations and biological behaviors during and/or after chemotherapy were complex and varied. In addition, the development of secondary malignancies should be taken into consideration for long‐term follow‐up. Clinicians should be aware of the various clinical features and secondary malignancies in primary mediastinal GCTs. [ABSTRACT FROM AUTHOR]

Background: Nivolumab is a second‐line chemotherapy for non‐small cell lung cancer (NSCLC). This study explored the impact of clinical biomarkers such as neutrophil:lymphocyte ratio (NLR), C‐reactive protein:albumin ratio (CAR), and modified Glasgow prognostic score on the efficacy and outcome of nivolumab monotherapy in previously treated NSCLC patients. Methods: We retrospectively analyzed advanced or postoperative recurrence of NSCLC in 113 patients in two Japanese facilities from January 2015 to December 2019. Optimal cutoff values of NLR and CAR were assessed by the area under the receiver operating characteristic curves predicting death events to conduct regression analysis. Baseline values and values collected eight weeks after nivolumab treatment were measured to investigate time‐series changes of these markers. Results: The patients showed median overall survival (OS) and progression‐free survival (PFS) of 14.0 months and 2.3 months, respectively, with both being significantly longer in patients with partial response (PR) than in patients with progressive disease (PD). Optimal cutoff levels for NLR and CAR were 5.8 and 0.83, with significant decrease in CAR (P = 0.002) from baseline levels in PR patients and significant increase in PD patients. Baseline CAR ≥0.83 was significantly associated with one‐year mortality events and overall survival (OS), and multivariate analysis showed significant association of age ≤70 years, an Eastern Cooperative Oncology Group performance status score of 2 or 3, and a baseline CAR ≥0.83 with inferior OS. Conclusions: For second‐line nivolumab therapy, evaluation of baseline CAR and subsequent changes in CAR may be predictive of therapeutic response to nivolumab and long‐term survival in NSCLC patients. Key points: Significant findings of the study The baseline value of C‐reactive protein:albumin ratio was significantly associated with one‐year mortality and overall survival in non‐small cell lung cancer patients treated with nivolumab. What this study adds Time‐series change of C‐reactive protein:albumin ratio may be useful for predicting the treatment efficacy in patients treated with nivolumab. [ABSTRACT FROM AUTHOR]

Background: Owing to the rarity of this tumor, there is limited information about second‐line chemotherapy for patients with previously treated advanced thymic carcinoma. Material and Methods: We performed a multi‐institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma. Patients without indications for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions in the North East Japan Study Group. Demographic and clinicopathologic characteristics, data on treatment methods, and outcomes of second‐line chemotherapy were obtained from medical records. Results: In total, 191 patients were enrolled in this study. Second‐line chemotherapy included platinum‐based doublets in 57.6% of patients, other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide) in 13.6%, and monotherapy in 28.8%. The median follow‐up time was 50.5 months, and the median overall survival (OS) from the start of second‐line chemotherapy was 22.4 (95% confidence interval, 17.5‐26.7) months. The average response rate (RR) was 20.0% overall; it was 21.6% for patients treated with platinum‐based doublet chemotherapy, 13.6% for those treated with other multidrug chemotherapy, and 19.6% for those treated with single agent chemotherapy. There was no significant difference in OS between platinum‐based doublet chemotherapy, other multidrug chemotherapy, and monotherapy (the median OS was 22.4, 25.7, and 21.4 months, respectively). Conclusion: The median OS was 22.4 months in patients with advanced thymic carcinoma treated with second‐line chemotherapy. There were no significant differences in RR and OS between monotherapy and multidrug chemotherapy in this study. Implications for Practice: Owing to the rarity of this tumor, there is limited information about second‐line chemotherapy for patients with previously treated advanced thymic carcinoma. This is the largest data for those patients treated with second‐line chemotherapy. This study suggests there is no significant difference in efficacy between monotherapy and multidrug chemotherapy for previously treated advanced thymic carcinoma. This result can support the adequacy to select monotherapy as treatment of those patients. Thymic carcinoma is rare and highly progressive. This study aimed to evaluate the efficacy of second‐line chemotherapy for patients previously treated for advanced thymic carcinoma and to identify promising chemotherapeutic regimens for clinical practice and further investigation. [ABSTRACT FROM AUTHOR]

Background: The efficacy of amrubicin for relapsed small‐cell lung cancer (SCLC) has been reported in previous studies. Few reports, however, describe the efficacy and survival benefit of third‐line amrubicin chemotherapy in patients with extensive disease (ED)‐SCLC. Methods: We retrospectively analyzed the clinical records of ED‐SCLC patients treated with amrubicin salvage chemotherapy as a third‐line chemotherapy between January 2005 and July 2016 (salvage amrubicin group). The efficacy and toxicities of amrubicin were evaluated. Overall survival (OS) in the amrubicin salvage group was compared with OS among ED‐SCLC patients treated with at least second‐line chemotherapy between May 2000 and July 2016 and without subsequent amrubicin salvage chemotherapy. Results: A total of 18 patients with a median age of 70 years were analyzed in the amrubicin salvage group. The median number of treatment cycles of amrubicin was four. The response rate was 27.8% (95% confidence interval (CI), 7.1%–48.5%), and the disease control rate (DCR) was 66.7% (95% CI, 44.9%–88.4%). Median progression‐free survival was 2.9 months (95% CI, 1.0–4.9 months), and median OS after an initial chemotherapy was 18.1 months (95% CI, 10.2–26.0 months). OS in the amrubicin salvage group was significantly longer than in the no‐amrubicin group (n = 19; 12.6 months, 95% CI, 11.5–13.8 months, P = 0.005). The frequency of neutropenia greater than grade 3 was 72.2%, with febrile neutropenia developing in 38.9% of patients in the amrubicin salvage group. Conclusions: Despite a high frequency of febrile neutropenia, amrubicin salvage chemotherapy may improve OS in patients with relapsed ED‐SCLC. [ABSTRACT FROM AUTHOR]

Background: In the LUX‐Lung 3 and LUX‐Lung 6 trials, afatinib improved overall survival in previously untreated patients with EGFR 19del mutated non‐small cell lung cancer (NSCLC) compared to chemotherapy. The appropriate management of adverse events and dose reduction of afatinib are important for EGFR‐positive NSCLC patients. We conducted a retrospective and observational study of patients treated with first‐line afatinib for EGFR‐positive NSCLC in Nagano prefecture, Japan, focusing on efficacy and toxicities. Methods: We retrospectively collected the medical records of NSCLC patients initially treated with afatinib between May 2014 and March 2018. Results: A total of 62 patients with a median age of 67 years and a median body surface area (BSA) of 1.57 m2 were included. The overall response rate was 87.7% and median progression‐free survival (PFS) was 15.7 months. The median PFS was similar between standard initial dose (40 mg) and reduced initial doses (30 and 20 mg) (15.7 vs. 14.2 months; P = 0.978). The frequency of dose reduction and the discontinuation rate in the 40 mg daily dose group was higher in patients with BSA < 1.58 m2 (100%) compared to BSA ≥ 1.58 m2 (68.2%) (P = 0.014). The frequency of diarrhea was higher in patients with BSA < 1.58 m2 (93.5%) compared to BSA ≥ 1.58 m2 (71.0%) (P = 0.02). Conclusion: In real‐world clinical practice, first‐line afatinib was well managed and was equally as effective as in previous clinical trials of EGFR‐positive NSCLC. BSA is considered a predictive marker for appropriate afatinib dose reduction. [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced thymic carcinoma (ATC) is rare. Owing to its rarity, there is limited information on the prognostic factors, and the optimal serum tumor markers are also unknown. We conducted a multi-institutional retrospective study of patients with ATC. In this study, we collected data on patient characteristics, progression-free survival (PFS), overall survival (OS), and tumor marker values, and investigated the relationship between tumor marker values and PFS/OS. We found that the neuron-specific enolase (NSE) level may be a useful prognostic tumor marker for ATC, regardless of histology. The findings of the analysis limited to squamous cell carcinoma suggested that the NSE and squamous cell carcinoma antigen levels may be useful prognostic factors. The optimal tumor marker for predicting the prognosis of advanced thymic carcinoma (ATC) remains unclear. We conducted a multi-institutional retrospective study of patients with ATC. A total of 286 patients were treated with chemotherapy. Clinicopathological information, including serum tumor markers, was evaluated to determine the overall survival (OS) and progression-free survival (PFS). The carcinoembryonic antigen, cytokeratin-19 fragment, squamous cell carcinoma (SCC) antigen, progastrin-releasing peptide, neuron-specific enolase (NSE), and alpha-fetoprotein levels were evaluated. In the Kaplan–Meier analysis, the OS was significantly shorter in the patients with elevated NSE levels than in those with normal NSE levels (median, 20.3 vs. 36.8 months; log-rank test p = 0.029; hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05–2.31 (Cox proportional hazard model)); a similar tendency regarding the PFS was observed (median, 6.4 vs. 11.0 months; log-rank test p = 0.001; HR, 2.04; 95% CI, 1.31–3.18). No significant differences in the OS and PFS were observed among the other tumor markers. In both univariate and multivariate analyses of the patients with SCC only, the NSE level was associated with the OS and PFS. Thus, the NSE level may be a prognostic tumor marker for thymic carcinoma, regardless of histology. [ABSTRACT FROM AUTHOR]

Background Primary mediastinal seminoma is a rare neoplasm. Cisplatin-based chemotherapy is the standard treatment, but management of post-chemotherapy seminoma residuals is still controversial. We encountered four cases of primary mediastinal seminoma and reviewed the clinical characteristics and outcomes, focusing on tumor size and F-18 fluorodeoxyglucose positron emission tomography ( FDG-PET) findings after chemotherapy. Methods A retrospective review was performed of four consecutive patients with primary mediastinal seminoma treated in our institution between 2006 and 2010. All patients were young adult males with a median age of 31.3 years (range: 20-46 years). All patients were treated with three to four cycles of a combination of cisplatin, bleomycin, and etoposide, and FDG-PET was performed after chemotherapy. Results The response to chemotherapy was good in all patients. After chemotherapy, the findings of the FDG-PET were negative in three subjects. Two of the patients, with tumors measuring over 30 mm, underwent surgical resection for the residual mass and revealed necrotic tissues and no viable cells. A third patient remained stable without salvage surgery. The size of the residual mass in the remaining patient was less than 30 mm, but the FDP-PET result was positive and the mass considered inoperable because of the involvement of large vessels. Subsequently, radiotherapy was added for the residual tumor, but disease progression was seen seven months after the initiation of chemotherapy. Conclusions FDG-PET findings after chemotherapy could be useful as a tool for the prediction of viable residual tumor in post chemotherapy residual mediastinal seminoma. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Cases of lung cancer with pure ground-glass nodules (GGNs) have been detected with increasing frequency since the advent of computed tomography (CT), and growth is sometimes noted during follow-up. The objective of this study was to evaluate the potential predictive factors for pure GGN growth. Materials and methods: We retrospectively examined 124 cases involving pure GGNs. Patients were monitored for >2 years using high-resolution CT. After a median follow-up period of 57.0 months, GGNs showed growth in 64 of the 124 cases. We compared the patient characteristics and tumor properties of cases with and without growth. The predictive value of the mean CT attenuation for GGN growth was evaluated using receiver operating characteristic curve analysis. Results: Univariate analysis revealed significant differences between mean CT attenuation values in patients with and without growth (−602.9±90.7 Hounsfield units [HU] vs −705.7±77.7HU, P <0.0001). The final incidence of growth was estimated to be significantly higher for lesions with a mean CT attenuation value of ≥−670HU (n =62; 93.2%) than for lesions with values of <−670HU (n =62; 31.6%; P <0.0001). The sensitivity and specificity for predicting tumor growth using this cutoff value were 78.1% and 80.0%, respectively (area under the curve, 0.81). Conclusion: The mean CT attenuation value could be useful in predicting the growth of GGNs. [Copyright &y& Elsevier]