In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of ...oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial.
Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC.
Forty-two patients (33 men; median age 77 years) were treated. Most (86%) received previous treatments consisting in surgery (86%), RT (50%) and CT (14%). RR was 28% (2% complete response; 26% partial response), disease control rate was 86%. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93%) experienced at least one adverse event (AE): diarrhoea, skin rash (71% each), fatigue (36%) and mucositis (31%); AEs grade 3–4 occurred in 36% of pts. In 16% of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup.
In sSCC, dacomitinib showed activity similar to what was observed with anti–epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.
•Dacomitinib obtained a 28% response rate in recurrent metastatic skin squamous cell cancer.•Safety profile of dacomitinib is similar to other epidermal growth factor receptor inhibitors.•BRAF/NRAS/HRAS mutations can be possible markers to ameliorate patient selection.
Summary
Background
The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM).
Objectives
To investigate whether the extent of ulceration (EoU) ...predicts relapse‐free survival (RFS) and overall survival (OS) in PCM.
Materials and methods
We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU.
Results
A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS hazard ratio (HR) (1‐mm increase) 1·26, 95% confidence interval (CI) 1·08–1·48, P = 0·0047 and OS HR (1‐mm increase) 1·25, 95% CI 1·05–1·48, P = 0·0120 was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour‐infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01–4 mm and > 4 mm BT.
Conclusions
This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports.
What is already known about this topic?
Ulceration is a well‐known prognostic factor in melanoma.
There are conflicting results on the prognostic value of the extent of ulceration.
What does this study add?
The extent of ulceration is an independent prognostic factor in primary cutaneous melanoma with Breslow thickness (BT) ≤ 2 mm.
The extent of ulceration should be incorporated into the pathology report as a required, core element.
Patients with extensive ulceration with a BT ≤ 2 mm are at high risk of recurrence and should be included in prospective adjuvant trials.
Linked Comment: Wilkinson and Gyorki. Br J Dermatol 2021; 184:192–193.
Although the number of excised LNs has been associated with patient prognosis in many solid tumors, this association has not been widely investigated in cutaneous melanoma. This study aims to ...evaluate the association between the number of excised regional lymph nodes (LNs) and melanoma-specific survival.
Clinico-pathological data from 2507 patients with LN metastasis treated at nine Italian centers were retrospectively collected.
The number of excised LNs correlated with younger age (P < 0.001), male sex (P < 0.001), neck LN field (P < 0.001), LN micrometastasis (P < 0.001) and number of positive LNs (P < 0.001).
The number of excised LNs was an independent prognostic factor (HR = 0.85; P = 0.002) after adjustment for other staging features. Upon subgroup analysis, the number of excised LNs had a significant prognostic value in patients bearing 1.01–2.00mm (HR = 0.79; P = 0.032) and 2.01–4.00mm (HR = 0.71; P < 0.001) thick melanomas, primary tumors showing ulceration (HR = 0.86; P = 0.033) and Clark level V of invasion (HR = 0.86; P = 0.010), LN micrometastasis (HR = 0.83; P = 0.014) and two to three positive LNs (HR = 0.71; P = 0.001). Finally, this study investigated the influence of the number of excised LNs on patient staging: only when ≥11 nodes were excised the AJCC N stage could stratify prognosis (P < 0.001). Considering the number of excised LNs for each lymphatic field, at least 14, 11, 10 and 12 LNs were needed to stage patients according to the AJCC N stage after a lymphadenectomy of the neck, axilla, inguinal and ilioinguinal LN fields, respectively.
The number of excised LNs can be considered for risk stratification of patients with regional LN metastasis from cutaneous melanoma. We demonstrated that a minimum number of LNs is required for the correct staging of patients. Further research is needed to evaluate the effectiveness of the minimum number of LNs to be dissected.
ABSTRACT Introduction Debate remains about prognostic factors in primary Merkel cell carcinoma (MCC). We investigated clinicopathological factors as determinants of survival in patients with MCC ...submitted to sentinel node biopsy. Methods Sixty-four consecutive patients treated for a primary MCC were identified from a prospectively maintained database at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Time to events outcome were described by product limit estimators and proportional hazards model was used to investigate the association between outcome and potential predictors. Results The most common site of primary tumor was lower limbs (56.3%). The size of primary lesion was ≤ 2 cm in 67.2% of cases. Presence of residual disease after the diagnostic surgical excision was observed in 28% of cases. All patients received sentinel node biopsy (SNB) and a SN positivity was detected in 26.6%. The median follow up was 78 months. Disease recurrence occurred in 17 patients (26.6%). In the SN negative group 10 recurrences occurred (21.3%), whereas 7 (41.2%) were found in SN positive one. Nine patients SN negative (19.1%) died of disease and 3 (17.6%) among SN positive. SN status was not associated with survival (p=0.78). Neither age, gender, size and site of primary tumor resulted predictors of patients’ outcome. The presence of residual tumor in the specimen of the wide local excision, after the diagnostic surgical excision, was the only variable associated with survival (p= 0.03). Conclusions Presence of residual tumor in the specimen of the wide local excision is the main prognostic factor in MCC patients.
Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if ...lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.
•This AIOM Guideline on BCC provides key recommendations for managing basal cell carcinoma.•It covers clinical and pathological diagnosis, treatment and follow-up.•Addressing systemic treatments for BCC unresponsive to surgery/radiotherapy.•GRADE approach: transparent, evidence-based and comprehensive guidelines.•Expert consensus: panel of experts selected by AIOM contribute to priority aspects of BCC management.
Cutaneous squamous cell carcinoma (CSCC) accounts for ∼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal ...forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.
•This AIOM guideline on CSCC provides key recommendations for managing CSCC.•It covers clinical and pathological diagnosis, treatment, and follow-up.•Addressing systemic treatments, like cemiplimab, for CSCC unresponsive to surgery/radiotherapy.•GRADE approach: transparent, evidence-based, and comprehensive guidelines.•Expert consensus: panel of experts selected by AIOM contribute to priority aspects of CSCC management.
In the American Joint Committee on Cancer (AJCC) classification, acral lentiginous melanoma (ALM) histotype ALM is not included as an independent prognostic factor; in small series its negative ...prognostic impact on disease-free survival (DFS) and overall survival (OS) has been linked to the greater Breslow thickness (BT).
The study was carried out at four referral melanoma centers (three Italian and one Polish). Clinical consecutive patients with stage I-II melanoma, who were diagnosed, treated, and followed up between January 1998 and March 2018 in annotated specific databases were included.
Overall, 6734 were evaluable, 4349 with superficial spreading melanoma (SSM), 2132 with nodular melanoma (NM), and 253 with ALM. At univariable analysis, a statistically significant worse DFS hazard ratio (HR) 2.72, 95% confidence interval (CI) 2.24-3.30; P < 0.001 and OS (HR 2.67, 95% CI 2.15-3.32; P < 0.001) were found in patients with ALM compared with SSM. Similarly, the NM histotype was associated with a worse prognosis compared with the SSM histotype (DFS: HR 2.29, 95% CI 2.08-2.52; P < 0.001 and OS: HR 2.21, 95% CI 1.99-2.46; P < 0.001). At multivariable analysis, after adjusting for age, sex, BT, ulceration, and the sentinel lymph node status, a statistically significant worse DFS adjusted HR (aHR; ALM versus SSM) 1.25, 95% CI 1.02-1.52; P = 0.028 was confirmed for patients with ALM. For patients with NM, instead, no impact of histology was found in terms of DFS aHR (NM versus SSM) 1.04, 95% CI 0.93-1.15; P = 0.513 and OS aHR (NM versus SSM) 0.96, 95% CI 0.86-1.08; P = 0.548.
ALM is associated with a worse long-term DFS. Our results could have important clinical implications for patients' stratification in future clinical trials and the incorporation of ALM histotype in the new AJCC classification as an independent prognostic factor.
Abstract Introduction The optimal extent of the groin lymph node (LN) dissection for melanoma patients with positive sentinel LN biopsy is still debated and no agreement exist on dissection of pelvic ...LN. This study aimed at investigating predictors of pelvic LN metastasis and prognostic significance of having metastasis in the pelvic LNs. Methods Clinicopathologic data of 740 patients with positive groin sentinel LN who underwent ilioinguinal completion LN dissection at four Italian centre were analysed. Multivariable logistic and Cox regression analysis was used to identify independent predictors of pelvic LN metastasis and to adjust prognostic significance of pelvic LN metastasis. Results More than a quarter (26%) of patients had positive non-SLNs after inguinal and pelvic lymphadenectomy, which were located in their pelvis in the 12% of cases. Older patients (OR) 1.69; 95% confidence interval (CI) 1.02–2.78 having thick primary (OR 1.6; 95% CI, 1.01–2.53) and ≥ 2 positive SLNs (OR 2.5; 95% CI, 1.4–4.47) were more likely to harbour pelvic LN metastasis. Interestingly, 4% of all patients (34% of patients with positive pelvic LNs) had pelvic LN metastasis with negative inguinal LNs. Pelvic LN metastasis was independently associated with higher risk of recurrence and lower survival. 5-year disease free and overall survival was 30% and 50%, respectively, for patients with pelvic LN metastasis. Conclusions Pelvic LNs are frequently positive after ilioinguinal lymphadenectomy and it should be considered for all patients, especially those who are older, have thick primary and ≥ 2 positive SLN. Patients with pelvic LN metastasis have worse prognosis.
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