Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients

BackgroundAnti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF.Patients and methodsThe study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsThirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p < 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups.ConclusionNivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma

A retrospective study of sentinel lymph node biopsy for skin cancer in Japan: Comparison with breast cancer and evaluation of factors related to its use

Abstract Background Sentinel lymph node biopsy (SLNB) underuse has been reported for skin cancers; however, actual performance rates have not been compared. The objective of this study was to investigate the SLNB performance rate in skin cancers covered by health insurance in Japan and compare it with that in breast cancer. Methods This was a retrospective study of the SLNB performance rate in SLNB‐eligible patients with breast or skin cancer from 2018 to 2019, utilizing a database linked to the Hospital‐Based Cancer Registry and Diagnosis Procedure Combination survey. Demographic and tumor characteristics were analyzed using logistic regression. Results A total of 71,652 patients were included in this study. SLNB was performed in 86.4% (57,904/67,036) of the patients with breast cancer, 44.7% (694/1552) with melanomas, 3.1% (89/2849) with squamous cell carcinomas (SCCs), and 13.5% (29/215) with Merkel cell carcinomas (MCCs). The performance rate of SLNB was significantly lower for skin cancers than for breast cancers (odds ratio [OR], 0.03; p < 0.001). In addition, the performance rates of SLNB were significantly lower for SCCs and MCCs than for melanomas (SCC: OR, 0.04; p < 0.001; MCC: OR, 0.19; p < 0.001). Factors associated with SLNB performance included age, sex, year of incidence, primary tumor site, T stage, and number of hospital beds. Conclusions SLNB is underutilized for skin cancer. Further investigation is required to explore the reasons for its underutilization so that it may be implemented more universally

A single‐center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan

Abstract Background Melanoma brain metastasis (MBM) has a poor prognosis, although recent treatments, including immune checkpoint inhibitors and targeted therapy, have improved the prognosis. However, these systemic therapies have been reported to be less efficient for Asian patients. We investigated the survival of Asian patients with MBM and the effectiveness of systemic therapies. Methods We retrospectively reviewed the survival rates of patients diagnosed with MBM between January 2011 and December 2021 at the National Cancer Center Hospital in Tokyo, Japan. In addition, we identified factors associated with survival using Cox regression analysis. Results A total of 135 patients were included. The median overall survival (OS) after an MBM diagnosis was 7.8 months (95% confidence interval [CI] 6.1–9.6). The 6‐month and 1‐year survival rates were 60.7% and 34.8%, respectively. We identified the prognostic factors of MBM, including non‐acral primary location, low serum LDH levels, systemic therapy of single‐agent immune checkpoint inhibitors (ICIs) or targeted therapies (TTs), and radiotherapy of stereotactic irradiation (STI). We found no significant difference in effectiveness between single‐agent ICIs, the combination of Nivolumab and Ipilimumab (COMBI‐ICI), and TTs (COMBI‐ICI vs. single‐agent ICI, hazard ratio 0.71, 95% confidence interval 0.27–1.88, p = 0.49; COMBI‐ICI vs. TT: hazard ratio 0.46, 95% confidence interval 0.14–1.55, p = 0.21). Conclusions Systemic therapy and radiotherapy have improved the survival of MBM patients, but the survival of Asian patients remains poor. Our findings suggest that COMBI‐ICIs are not significantly more effective than single‐agent ICI or TT in treating MBM

Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics

Cutaneous adnexal tumors are neoplasms that arise from skin appendages. Their morphologic diversity and phenotypic variability with rare progression to malignancy make them difficult to diagnose and classify, and there is currently no established treatment strategy. To overcome these difficulties, this study investigated the transcription factor SOX9 expression, morphology, and genetics of skin adnexal tumors for understanding their biology, especially their histogenesis. We showed that cutaneous adnexal tumors and their nontumor counterparts of skin and appendages exhibit expression patterns similar to that of SOX9. Its expression intensity and pattern, as well as histopathologic evaluation of tumors, were analyzed using digital images of 69 normal skin adnexal 9-type organs and 185 skin adnexal 29-type tumors as references. It was possible to distinguish basal cell carcinoma from squamous cell carcinoma, sebaceous carcinoma, and pilomatrixoma with significant differences, along with porocarcinoma from squamous cell carcinoma. Furthermore, unsupervised machine learning “computational pathology” was used to derive a multiregion whole-exome sequencing fusion method termed “genocomputed pathology.” The genocomputed pathology of three representable adnexal carcinomas (porocarcinoma, hidradenocarcinoma, and spiradenocarcinoma) was evaluated for total nine cases. We showed that there was more heterogeneity than expected within the tumors as well as the coexistence of components lacking driver fusion genes. The presence or absence of potential driver genes, such as PIK3CA, YAP1, and PTEN, in each region was identified, highlighting a therapeutic strategy for cutaneous adnexal carcinoma encompassing heterogeneous tumors