Recent therapeutic strategies for metastatic melanoma: introduction to invited articles

Considering bone health in the treatment of prostate cancer bone metastasis based on the results of the ERA-223 trial

List of reviewers 2018–2019

Prognostic analysis of surgically treated clear cell sarcoma: an analysis of a rare tumor from a single center Abstract Background The objective of this retrospective study was to evaluate the prognostic value of various factors in clear cell sarcoma patients after radical surgery. Methods Forty-two clear cell sarcoma patients from August 2006 to March 2018 were included in the study. Curves of disease-free survival and overall survival were calculated using the Kaplan–Meier method, and univariate and multivariate analyses of various prognostic factors were performed using a Cox proportional hazard regression model. Laboratory test of peripheral blood was recorded before surgery. The optimal cutoff value of systemic inflammatory markers was defined by receiver-operating curve analysis. Results The 5-year DFS and 5-year OS rate were 22% and 46%, respectively. The median DFS and OS times were 12 and 41.5 months, respectively. In univariate analysis, there was a significant association between shorter DFS and tumor size larger than 5 cm (p = 0.0043), positive surgical margin (p = 0.0233), and the neutrophil-to-lymphocyte ratio (NLR) higher than 2.73 (p = 0.0009). Furthermore, we observed a significant association between shorter OS and tumor size larger than 5 cm (p = 0.0075), positive surgical margin (p = 0.0101), NLR higher than 2.73 (p = 0.0126), the platelet-to-lymphocyte ratio (PLR) higher than 103.89 (p = 0.0147) and the lymphocyte-to-monocyte ratio (LMR) lower than 4.2 (p = 0.0445). A multivariate analysis demonstrated that the surgical margin (p = 0.013) and NLR (p = 0.001) were significantly associated with DFS. Tumor size (p = 0.010) and NLR (p = 0.013) were independent prognostic factors for OS. Conclusions This study had the second largest sample around the world and preoperative NLR may be a useful prognostic factor in CCS patients after radical surgery.

Peri-operative efficacy and long-term survival benefit of robotic-assisted radical cystectomy in septuagenarian patients compared with younger patients: a nationwide multi-institutional study in Japan Abstract Background To determine the peri-operative safety and oncological value of robotic-assisted radical cystectomy (RARC) for older and younger patients in an initial Japanese RARC series. Methods We retrospectively analyzed the demographics, complications, peri-operative and oncological outcomes of 253 consecutive patients with bladder cancer who underwent RARC at 34 institutions in Japan between April 2009 and March 2017. The patients were assigned to groups according to ages at surgery of < 70 (younger; n = 125) and ≥ 70 (older; n = 128) years. Results Mean Charlson comorbidity index (p = 0.045) and the incidence of a history of previous abdominal surgery (p = 0.002) were significantly higher, whereas a history of neoadjuvant chemotherapy (p = 0.028) and neobladder (p < 0.001) were significantly lower in the older group. Mean total operative time was significantly shorter (p = 0.019) and mean estimated blood loss (p = 0.013) was significantly lower in the older group. Post-operative Grade ≥ II complications were comparable at 0–30, 31–90 and 91 days after surgery despite urinary tract associations. Rates of positive surgical margins and mean numbers of removed lymph nodes were comparable between the two groups. Although 5-year overall survival rates were significantly lower (p = 0.03) for older patients, 5-year cancer-specific (p = 0.10) and recurrence-free survival rates were comparable (p = 0.20) between the groups. Conclusion Using RARC potentially allows the application of less invasive procedures and cancer control for septuagenarian patients that are equivalent to those for younger patients.

Recent advances in therapeutic strategies for unresectable or metastatic melanoma and real-world data in Japan Abstract New therapeutic strategies including immunotherapy and selective molecular target inhibitors have brought about a new era in the treatment of patients with advanced melanoma. In Japan, the immune checkpoint inhibitors ipilimumab, nivolumab and pembrolizumab, the BRAF inhibitor (BRAFi) vemurafenib, dabrafenib and MEK inhibitor (MEKi) trametinib have been available for the treatment of unresectable and metastatic melanoma. The BRAFi + MEKi combination shows high response rates (60–70%) and rapid response induction associated with symptom control, with a progression-free survival of 12 months. Nivolumab and pembrolizumab offer moderate response rates (30–40%) and long survival (3- to 5-year survival: 30–50%). In Japan, treatment options for the first-line setting frequently include nivolumab or pembrolizumab monotherapy and BRAFi + MEKi combinations (for patients with BRAF-mutant melanoma). Ipilimumab is included in the second-line setting, and the nivolumab + ipilimumab combination has not been approved yet in Japan. Although these medications have demonstrated impressive efficacy, the clinical trials and real-world data have shown that the clinical benefit is not fully satisfactory. We have to carefully manage a new class of adverse events due to these medicines. Moreover, biomarkers are emerging with which we can identify a population that would experience more benefits without severe adverse events.

A clinical trial to assess the feasibility and efficacy of nab -paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer Abstract Background The efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) in elderly Japanese patients with pancreatic cancer remain unclear. Therefore, we prospectively investigated the tolerability and efficacy of nab-PTX + GEM in Japanese patients aged ≥ 75 years with non-curatively resectable pancreatic cancer. Methods We treated eligible patients (n = 27) with nab-PTX + GEM until disease progression, appearance of adverse events, or withdrawal of consent. The primary endpoints included adverse events as well as dosing- and survival-related parameters. Results The rates of 2-cycle completion were 48.1% for nab-PTX and 55.6% for GEM; the relative dose intensities for the 7th (median) treatment cycle were 65.1% and 74.1%, respectively, whereas the dose-reduction rates were 81.5% and 48.1%, respectively. Grade 3 or higher hemotoxicity was observed in 14 of 27 subjects (51.9%); moreover, 22% experienced grade ≥ 3 peripheral nerve disorder and 1 patient (3.7%) died owing to chemotherapy-related interstitial pneumonia. The disease control rate was 92.6% (25/27), while the median progression-free and overall survival times were 7 and 10.3 months, respectively. Conclusion The nab-PTX + GEM regimen is as efficacious in elderly patients who meet certain criteria as it is in previously reported non-elderly patients. The regimen is feasible with appropriate dose adjustments and attention to adverse events. Trial registration Clinical trial registration number: UMIN000018907.

Validation of prognostic impact of number of extrathoracic metastases according to the eighth TNM classification: a single-institution retrospective study in Japan Abstract Background In the eighth edition of the TNM classification of lung cancer, the M1b and M1c descriptors are newly defined by the number of extrathoracic metastases. To verify the prognostic value of these descriptors in Japan, we reclassified our cases and re-evaluated prognosis in M1b and M1c patients. Methods All non-small cell lung cancer (NSCLC) patients with extrathoracic metastases who visited Saitama Medical Center from 2010 to 2016 were evaluated, divided according to the eighth edition of the TNM classification criteria into two groups (M1b, patients with single extrathoracic metastasis, and M1c, patients with multiple extrathoracic metastases), and followed up until December 31, 2017. Survival time analysis was performed using the Kaplan–Meier method, and between-group differences in overall survival time (OS) were evaluated by the log-rank test. Results A total of 231 NSCLC patients were divided into 57 patients with M1b and 174 with M1c. Median OS was 15.2 months (95% confidence interval [CI]: 9.3–19.9) and 7.3 months (95% CI 5.7–10.7) for M1b and M1c, respectively, with no significant between-group difference (P = 0.239). However, after excluding patients with epidermal growth factor receptor (EGFR) mutation or echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4–ALK) fusion gene, median OS was 12.9 months (95% CI 7.2–19.9) for M1b and 5.4 months (95% CI 3.8–6.3) for M1c, respectively, showing a significant difference (P = 0.029). Conclusions The effect of therapy directed toward EGFR mutation or EML4–ALK fusion gene might obscure the significant prognostic difference between M1b and M1c.

Outcomes of non-metastatic colon cancer patients in relationship to socioeconomic status: an analysis of SEER census tract-level socioeconomic database Abstract Objective To evaluate the outcomes of non-metastatic colon cancer patients in relation to the socioeconomic status (SES) at diagnosis based on the Surveillance, Epidemiology, and End Results (SEER) census tract level-SES database. Methods SEER SES census tract level database represents a specially designed database to integrate different aspects of SES among cancer patients. It reports a composite SES index for each patient. Patients were then stratified into three SES groups. Patients with a non-metastatic colon cancer diagnosis, diagnosed (2004–2015), and who were included in this specialized database were included in the current study. Multivariate Cox regression analysis was used to assess the impact of SES index on colon cancer-specific survival. Results A total of 80,121 patients with non-metastatic colon cancer were included in the current study. Comparing patients in the lower SES group with patients in the higher SES group, patients with lower SES were more likely to have a younger age at presentation (P < 0.001), black race (P < 0.001) and more advanced stage at presentation (P < 0.001). The impact of the SES on colon cancer-specific survival was evaluated through multivariate Cox regression analysis adjusted for age, sex, race, stage, and colon cancer side. Lower SES was associated with worse colon cancer-specific survival (hazard ratio for group 1 versus group 3: 1.257; 1.190–1.328; P < 0.001). Interaction testing between race (black race versus white race) and SES was non-significant (P = 0.932). Conclusions Lower SES is associated with worse colon cancer-specific survival among non-metastatic colon cancer patients.