Different Response to Immunotherapy According to Melanoma Histologic Subtype.

Superficial spreading melanoma (SSM) and nodular melanoma (NM) are the most common melanoma histologic subtypes and are characterized by different biological features. We retrospectively analyzed all consecutive patients with advanced melanoma, treated with anti-PD-1 and/or anti-CTLA-4 at our center, with data available on primary tumor subtype. The primary objective was to assess the association between histologic subtype and patients' outcomes. In addition, we analyzed whole-exome and whole-transcriptome sequencing data of a cohort of advanced melanoma to identify genes and related pathways, characterized by significant differences between NMs and SSMs. Twenty-one patients with NM and 39 with SSM, treated with anti-PD-1(53/60) as monotherapy or combined with anti-CTLA-4 (7/60), were analyzed. All known clinical-pathologic prognostic factors were well balanced between NM and SSM groups, except for the ECOG-PS score. The overall response rate was 52.4% (95% confidence interval, 29.8-74.3) in the NMs group versus 20.5% (9.3-36.5) in the SSMs group (P-value=0.02). The median progression-free survival and overall survival were, respectively, 13.9 and 44.5 months in the NMs group versus only 3.2 and 12 months in SSMs group (progression-free survival P-value=0.032; overall survival P-value=0.002). Multivariable analysis adjusting for the ECOG-PS, confirmed similar results. Whole-exome and whole-transcriptome data of 28 NMs and 21 SSMs were analyzed. No significant differences were observed in terms of both TMB and frequency of mutation in any gene. A total of 266 genes were overexpressed in NMs as compared with SSMs, and enrichment-analysis revealed a significant enrichment (false discovery rate<0.05) of genes belonging to immune-related pathways involved in antigens presentation mechanisms, response to interferon gamma and neutrophil activation. We provided clinical evidences suggesting a relevant association between melanoma histologic subtype and response to immunotherapy.

Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series.

Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 to 2020, among patients with histologically confirmed MCC managed at a neuroendocrine neoplasm-referral center, we selected those with an exclusive nodal basin, no distant metastasis, and an unknown primary site defined by cross-sectional and physical examination. A total of 55 out of 310 patients fulfilled the selection criteria. The median age was 64 years and the majority were males. Inguinal lymph-nodes were the most common anatomic site. With a median follow-up of 4.3 years, the 5-year relapse-free survival (RFS) rate was 56.6 (95% CI 42.0-68.8%) and the 5-year cancer specific survival (CSS) rate was 68.5 (95% CI 52.8-79.9%) for the whole population. The 36 patients (65.5%) undergoing lymphadenectomy (LND) + radiotherapy (RT) ± chemotherapy had a 5-year RFS rate of 87.2% (95% CI 65.5-95.7%) and a 5-year CSS rate of 90.5% (95% CI 67.0-97.5), which were better than those receiving LND alone. In a multivariable analysis, the survival benefit for LND + RT remained significant. Results from one of the largest single-center series of nMCC-UP suggest that a curative approach including RT can be effective, similar to what is observed for stage IIIB MCC. Multicentric studies with homogenous populations should be carried out in this controversial clinical entity, to minimize the risk of biases and provide robust data.

Multidisciplinary team approach for Merkel cell carcinoma: the European Institute of Oncology experience with focus on radiotherapy.

OBJECTIVE: To review the therapeutic strategy in Merkel cell carcinoma (MCC) treated with radiotherapy (RT) discussed in a multidisciplinary tumour board. METHODS: Clinical records of patients with a diagnosis of MCC and with an indication to undergo RT at the European Institute of Oncology between 2003 and 2018 were reviewed retrospectively. RESULTS: Twenty-six patients were included in the analysis (median age 65 years, range 42-87). Nineteen received adjuvant RT, 4 exclusive RT, and the remainder palliative RT. Intensity-modulated RT was used in 13 cases, a 3D conformal technique in 11 cases, and stereotactic RT in 2 cases. No major toxicities were recorded. The median relapse-free survival (RFS) after adjuvant RT was 20.5 months, while for unknown primary MCC, it was 23 months. In the adjuvant setting, median polyomavirus-positive RFS was 21.5 months (range 1-49) and median polyomavirus-negative RFS was only 14 months (range 4-45). Overall, RFS of polyomavirus-positive and polyomavirus-negative patients was 10.5 and 8 months, respectively. After adjuvant RT, only 1 out of 10 patients had a recurrence in the RT field. At the time of data collection, 16 patients were alive with no evidence of disease, 1 patient was alive with advanced status of disease, 8 patients died of disease progression, and 1 patient died of other causes. CONCLUSIONS: The management of unknown primary and polyomavirus-positive cases, which had a better prognosis in our series, may benefit from a multidisciplinary approach, given the limited data available regarding optimal treatment.

Adjuvant high-dose-rate interstitial brachytherapy for malignant peripheral nerve sheath tumor of the foot: a case report.

Soft tissue sarcomas of the foot are extremely rare and can therefore be misdiagnosed as benign diseases, and be prematurely removed with an unplanned excision. The standard treatment is a wide local excision with an addition of radiotherapy as an alternative to a radical resection (e.g., below-knee or foot amputation). We report on a patient with primary malignant peripheral nerve sheath tumor in the foot plantar soft tissue, who had no evidence of the disease and no severe late toxicity higher than grade 2, 40 months after receiving amputation of toes and adjuvant interstitial high-dose-rate brachytherapy (HDR-BT). To the best of our knowledge, only a few cases were treated with HDR-BT with this scenario. From our findings, HDR-BT could be a safe and quick treatment option for these types of lesions.

Robot-assisted inguinal lymphadenectomy: preliminary experience and perioperative outcomes from an Italian referral center.

BACKGROUND: Inguinal lymphadenectomy remains the gold standard for the treatment of inguinal lymph node metastases from penile carcinoma, melanoma, Merkel cell carcinoma, and squamous cell carcinoma (SCC). This procedure is associated with significant complications. In order to reduce morbidity, minimally invasive approaches have been described. We report our preliminary experience with robot-assisted inguinal lymphadenectomies (RAIL). METHODS: RAIL was performed according to the Sotelo technique. When indicated, a robot-assisted pelvic lymphadenectomy (RAPLND) was performed. We recorded age, sex, comorbidities, baseline oncologic diagnosis, operative time, hospital stay, lymph node yield, complications, time to drain removal, and oncologic outcomes. RESULTS: From December 2016 to February 2019, 13 patients underwent RAIL. Median age was 65 years (range: 31-85 years). Primary malignancy was melanoma in five patients, Merkel cell carcinoma in four, dermal duct tumor in one, penile cancer in two, and SCC in one. RAIL was monolateral in 12 cases and bilateral in 1 case. A total of 10 monolateral RAPLNDs were performed; median operative time was 279 min (range: 169-320). Median lymph nodes yield was 11 (range: 2-24) for monolateral RAIL and 9 for monolateral RAPLND (range 2-24). Median hospital stay was 4 days (range: 2-5). No procedure was converted to open. Median follow up was 16 months (range: 5-31). Five Clavien-Dindo grade I complications were recorded. Median time to drain removal was 32.5 days (range 7-65). Three recurrences and two cancer-related deaths were recorded. CONCLUSIONS: RAIL is feasible and associated with a short hospital stay, with little incidence of perioperative complications.

Metastasis of sigmoid colon cancer in cryptorchid testis: report of a case.

Isolated testicular metastasis from colorectal cancer is considered an unusual event. In this case report we describe for the first time a metastasis from an adenocarcinoma of the sigmoid colon to a cryptorchid testis. The patient developed a painless testicular nodule three years after the diagnosis of primary sigmoid colon cancer. Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased over the past 50 years; in particular, cryptorchid testes increase the clinical risk factors for primary or metastatic testicular cancer. In conclusion, there should be awareness of the risk of metastasis of colorectal cancer to the testis in the workup of patients with testicular symptoms. Furthermore, patients with colorectal cancer and cryptorchidism should be managed with a single surgical intervention: when the primary colorectal tumor is removed, the cryptorchid testicle should also be removed to reduce the risk of late metastases.