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Combined chemotherapy plus programmed death-1 (PD-1) blockade is an established treatment against patients with advanced non-small cell lung cancer (NSCLC). However, a promising predictor besides programmed death ligand-1 expression remains uncertain. We examined the prognostic significance of baseline 18 F-FDG-positron emission tomography for predicting first-line combined chemotherapy plus PD-1 blockade in NSCLC patients. Forty-five patients with advanced NSCLC who received 18 F-FDG-positron emission tomography immediately before combined platinum-based chemotherapy with PD-1 blockade as first-line setting were eligible for this study, and assessment of maximum of standard uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18 F-FDG uptake was performed. The objective response rate, median progression-free survival, and overall survival were 51.2%, 206 days, and 681 days, respectively. High SUV max , TLG, and MTV significantly correlated with age and performance status (PS), C-reactive protein (CRP), and PS, CRP, albumin, and baseline tumor size, respectively. Univariate analysis identified albumin, TLG and MTV as significant predictors of progression-free survival, and CRP, albumin, TLG and MTV as significant factors for predicting overall survival. High TLG was confirmed as an independent factor associated with poor prognosis in multivariate analysis. In particular, TLG is identified as the most powerful predictor in patients with good PS, adenocarcinoma, programmed death ligand-1≥1%, and low baseline tumor size. The tumor metabolic volume by MTV and TLG at pretreatment was clarified as a significant predictor for combined chemotherapy with PD-1 blockade, but not maximal glycolytic level by SUV max ., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Cardiotoxicity related to osimertinib, including cardiac failure, QT prolongation, and atrial fibrillation, has been reported as an extremely rare incidence in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the occurrence of osimertinib-induced cardiomyopathy., Patient Concerns: A 76-year old woman was treated with afatinib (40 mg/day) as the 1st line treatment due to recurrence after surgical resection for pulmonary adenocarcinoma. However, she experienced recurrence with positive T790 M, and osimertinib (80 mg/day) was administered as the 2nd line therapy., Diagnosis: Four months after osimertinib initiation, she complained of fever and progressive dyspnea, and a diagnostic endomyocardial biopsy confirmed non-specific cardiomyopathy, indicating osimertinib-induced cardiomyopathy., Interventions and Outcomes: She was treated with furosemide, carvedilol, and enalapril, and her cardiac function, her symptoms, and condition improved 3 weeks after the withdrawal of osimertinib., Lessons: Physicians should be alert of the cardiomyopathy-causing potential of osimertinib in advanced NSCLC patients.

Nivolumab, a monoclonal antibody targeting programmed cell death-1, significantly prolongs survival for patients with advanced non-small-cell lung cancer (NSCLC). However, little is known about the value of predictive biomarkers. Hence, we investigated the impact of skeletal muscle (SM) mass loss on clinical outcomes in NSCLC patients undergoing nivolumab treatment. Thirty patients with histologically confirmed NSCLC treated with nivolumab were included in this study. Computed tomography was used to determine SM loss based on the SM index (SMI). The SMI is the cross-sectional area of the bilateral psoas muscles at the third lumbar vertebra, divided by height squared. The cut-off values were defined as 6.36 cm/m for men and 3.92 cm/m for women. Among the 30 patients, 13 (43%) had SM loss. There was no significant association between SM loss and immune-related adverse events. The SM loss group had undergone significantly more prior chemotherapy cycles (P = .04). SM loss was significantly associated with fewer nivolumab cycles (P = .01). No patients in the SM loss group achieved a partial response. Patients with SM loss had a significantly shorter progression-free survival period (P = .008) and median overall survival than those with normal SM mass (10 vs 25 months, respectively, P = .03). SM loss was an independent prognostic factor of poor survival. In conclusion, SM loss may be a predictive factor of poor outcomes in NSCLS patients undergoing nivolumab therapy.

Class III β-tubulin (TUBB3) has been recognized as being associated with resistance to taxane-based regimens in several cancers. However, little is known about the clinicopathological significance of TUBB3 expression in patients with cutaneous malignant melanoma. The aim of this study was to examine the prognostic significance of TUBB3 expression in cutaneous malignant melanoma. A total of 106 patients with surgically resected cutaneous malignant melanoma were assessed. Tumour sections were immunohistochemically stained for TUBB3, Ki-67 and microvessel density with CD34. TUBB3 was highly expressed in 80% (85/106) of patients. No statistically significant relationship was observed between the high expression of TUBB3 and any variables. On univariate analysis, ulceration, disease stage, TUBB3 and CD34 revealed a significant relationship with overall survival and progression-free survival. Multivariate analysis confirmed that a low TUBB3 expression was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The decreased expression of TUBB3 could be a significant marker for predicting unfavourable prognosis in patients with cutaneous malignant melanoma.

Amino acid transporters play a crucial role in the development and invasiveness of cancer cells. However, it remains unclear whether or not the expression of L-type amino acid transporter 1 (LAT1) has prognostic significance in patients with cutaneous melanoma. A total of 128 patients with cutaneous melanoma were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, CD98, Ki-67, and microvessel density determined by CD34 and p53. We also analyzed 30 specimens of patients with melanocytic nevi as negative controls. LAT1 and CD98 were highly expressed in 58% (75/128) and 75% (97/128), respectively. The rates of positivity for LAT1 in the melanocytic nevi were 0% (0/30). The expression of LAT1 was associated significantly with tumor thickness, T factor, CD98 expression, cell proliferation (Ki-67), and microvessel density (CD34). By Spearman's rank test, LAT1 expression was correlated with CD98, Ki-67, and CD34. By univariate analysis, tumor thickness, ulceration, disease staging, LAT1, and CD34 showed a significant relationship with overall survival and disease-free survival. Furthermore, a multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting a poor prognosis. This study had a small sample size. LAT1 can serve as a significant prognostic factor to predict a poor outcome and it may therefore play an important role in the aggressiveness of cutaneous melanoma.

Objectives: Among patients with locally advanced lung adenocarcinoma, the frequency of epidermal growth factor receptor (EGFR) and KRAS mutations was unknown. In addition, it has not been fully evaluated about the role of these mutations treated with concurrent chemoradiotherapy (CCR)., Methods: The clinical records of locally advanced lung adenocarcinoma patients treated with CCR at Shizuoka Cancer Center between September 2002 and December 2009 were reviewed., Results: Forty-four patients were eligible for this study. EGFR mutation was detected in 13 (29.5%) of 44 patients, and KRAS mutation was detected in 2 (6.5%) of 31 patients. Among EGFR mutation status known patients, overall response rate, median progression-free survival (PFS), and median survival time were 52.3%, 11.5 months, and 35.8 months, respectively. Overall response rate was significantly higher in EGFR mutant group than in EGFR wild-type group (76.9% vs. 41.9%, P=0.02), but this difference did not translate into a significant PFS benefit (9.6 vs. 13.2 mo, P=0.78). Locoregional relapse occured less frequently in patients with EGFR mutation than those with EGFR wild-type, but not significant (15.4% vs. 32.3%, P=0.46). Brain was the most frequent metastatic site of relapse in EGFR mutant group., Conclusions: Among locally advanced lung adenocarcinoma, EGFR mutation was detected in 29.5% and KRAS mutation was detected in 6.5%. We were not able to detect a difference in PFS or overall survival between EGFR mutant and wild-type patients treated with conventional CCR. Locoregional relapse was approximately half in the EGFR mutant group compared with the EGFR wild-type group; however, this finding did not reach statistical significance.

Purpose: The aim of this study was to investigate the feasibility of separately evaluating bronchial (BAP) and pulmonary arterial perfusion (PAP) of lung cancers using dual-input perfusion computed tomography., Materials and Methods: Twenty-nine lesions from 28 patients [19 men and 9 women; age, 65.8±11.3 y (mean±SD); range, 39 to 85 y] were included in this study (1 patient had 2 tumors). From computed tomography data, quantitative maps of PAP and BAP were created using the dual-input maximum-slope method. Total blood perfusion (TBP) was defined as the sum of PAP and BAP, and the percentage of PAP to TBP was defined as %PAP. Correlation of these values with tumor size, location, and pathologic type was statistically analyzed., Results: PAP ranged from 2.0 to 93.1 mL/min/100 mL (mean±SD, 26.8±26.4), BAP was 0 to 65.4 (25.1±19.12), TBP was 20.7 to 132.0 (52.0±29.0), and %PAP was 4% to 100% (48.8%±31.9%). PAP, TBP, and %PAP correlated negatively with tumor size (P<0.05). PAP and %PAP were higher in the peripheral zone than in the central zone (P<0.05). There was significant correlation between pathologic type and the respective perfusion parameters (P>0.05)., Conclusions: We were successful in separating the dual vascular supply to assess dual-input perfusion of lung cancer. We found perfusion of lung cancers to depend on tumor size and location. Acknowledging and assessing the dual vascular supply in lung perfusion may have clinical implications in the management of lung cancer treatment.

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and gemcitabine combination regimen in the treatment of elderly patients (> or = 70 years) with advanced nonsmall cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC were treated with S-1 and gemcitabine. S-1 was administered orally twice daily for 14 days and gemcitabine on days 1 and 15 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 800/60; level 2, 1000/60; level 3, 1000/70; and level 4, 1000/80 [gemcitabine (mg/m2/ day)/S-1 (mg/m2/day)]. The dose-limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle. Sixteen patients were enrolled in this study. The main grade 3 toxicities observed during the first cycle were neutropenia (43.7%), leukopenia (18.7%), and hyperglycemia. One of six patients in level 3 had DLT. Although no patients in level 4 experienced DLT, this level was considered the maximum tolerated dose. Level 4 was selected as the recommended dose. Objective responses were seen in four patients (response rate, 42.9%). The combination of S-1 plus gemcitabine is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC.

Synovial sarcoma is the third most common histological type of extremity soft tissue sarcoma. However, primary mediastinal synovial sarcoma is extremely rare. We present 2 cases of unresectable primary mediastinal synovial sarcoma. The radiographic imaging of our present cases was characteristic of a heterogeneously enhancing mass. They were treated with radiotherapy and chemotherapy. However, there was complete obstruction of esophagus resulting from progressive diseases. The radiographic findings and treatment were discussed.

Objective: The aim of this phase I study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity of the biweekly paclitaxel and carboplatin combination chemotherapy in frail patients with advanced non-small cell lung cancer (NSCLC)., Method: Seventeen unresectable and previously untreated NSCLC patients participated in this study. Frail patients (>80 years old with PS 0-1 and adequate organ functions, or <80 years old with PS 2 or <80 with PS 0-1 and one inadequate organ function of bone marrow, liver, or kidney) of NSCLC were enrolled in this study. Both paclitaxel and carboplatin were administered on day 1 and repeated biweekly. The starting dose of paclitaxel 120 mg/m2 and carboplatin was AUC 3 /d on day 1 every 2 weeks for 4 to 8 cycles., Results: Seventeen frail patients received a total of 1 to 10 cycles. The major hematologic toxicity was neutropenia. Nonhematologic toxicities, including numbness and constipation, were generally mild and reversible. The MTD of paclitaxel were determined as 140 mg/m2. The recommended phase II study dose of paclitaxel was determined as 120 mg/m2 with area under the curve 3 biweekly for 1 day. An objective response was observed in 8 of 17 patients (47%) with frail patients., Conclusion: The combination chemotherapy of biweekly paclitaxel and carboplatin appears to be tolerable and sufficiently effective in frail patients with NSCLC. A phase II trial is underway.

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin on day 1 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 5/65; level 2, 5/80; level 3, 6/80 [carboplatin (area under the curve, mg/ml/min)/S-1 (mg/m/day)]. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle. Twelve patients were enrolled in this study. The main grade 3 or grade 4 toxicities observed during the first cycle were neutropenia (41%), thrombocytopenia (41%) and transaminase elevation. Two of three patients in level 2 had dose-limiting toxicity and this level was considered the maximum tolerated dose. Level 1 was selected as the recommended dose. Objective responses were seen in four patients (response rate 33%). The combination of S-1 plus carboplatin is a feasible and well-tolerated regimen for the treatment of patients with advanced non-small-cell lung cancer.

Objective: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD), and the safety profile of a weekly docetaxel and carboplatin combination regimen in the treatment of elderly patients with advanced nonsmall cell lung cancer (NSCLC)., Patients and Methods: Chemotherapy-naive patients with stage IIIB and IV NSCLC, >70 years of age, performance status (ECOG) 0-2, with adequate bone marrow, renal, liver and cardiac function, were treated with docetaxel and carboplatin. Docetaxel was given at escalated doses starting from 20 mg/m2/wk on days 1, 8, and 15, with an increment of 5 mg/m2 followed by carboplatin also administered at escalated doses starting from AUC 4 to 6 (mg/ml/min); the regimen was administered every 4 weeks. The dose limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle., Results: There were 25 patients enrolled in this study and assessed for safety. Neutropenia was the main DLT of the regimen; grade 3/4 neutropenia occurred in 5 patients (20%). Hematologic toxicities were mild, and included grade 3 thrombocytopenia in 1 patient (4%) and grade 3 anemia in 1 patient (4%). Nonhematologic toxicities were generally mild, and included grade 3 constipation in 1 patient (4%) and grade 3 renal disorder in 1 patient (4%). Objective responses were seen in 9 patients (response rate 36%)., Conclusions: The MTD was carboplatin AUC 5 on day 1 and docetaxel 30 mg/m2 on days 1, 8, and 15; therefore, the RD for the phase II study is carboplatin AUC 5 and docetaxel 30 mg/m2. The combination of docetaxel and carboplatin is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC. This regimen merits further investigation in phase II trials.

We conducted a phase II study to examine the efficacy and safety of weekly docetaxel and cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC). Forty chemotherapy-naive patients (10 with stage IIIB and 30 with stage IV NSCLC) with an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ functions were enrolled. Chemotherapy consisted of cisplatin (80 mg/m2) on day 1, and docetaxel (35 mg/m2) on days 1, 8 and 15, delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. There were 18 partial responses, with an overall response rate of 45% (95% confidence interval 29.6-60.4%) in 40 treated patients. The median survival period was 19.9 months, median progression-free survival was 5.5 months and 1-year survival rate was 69.4%. Hematologic toxicities were mild and included grade 3 or 4 neutropenia in 37.5%. There were no severe infections or septic deaths. Non-hematologic toxicities were generally mild. Grade 3 or 4 transaminase elevations were observed in two patients. Grade 3 events included two cases each of vomiting, and one case each of hypokalemia, diarrhea and creatinine elevations. Weekly docetaxel and cisplatin is an effective and safe combination in the treatment of patients with advanced NSCLC.