Virginia Caliendo

Expression of p63 is the sole independent marker of aggressiveness in localised (stage I–II) Merkel cell carcinomas

Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria are a matter of dispute. Specifically, no predictor is presently available in stage I–II tumours. We collected clinical and follow-up data from 70 Merkel cell carcinomas of the skin. The same cases were studied for p63 expression by immunohistochemistry, by reverse-transcription PCR (RT-PCR) and TP63 gene status by FISH and for presence of Merkel cell polyomavirus by PCR. Stage emerged as a significant prognostic parameter (P=0.008). p63 expression, detected in 61% (43/70) of cases by immunohistochemistry, was associated with both decreased overall survival (P<0.0001) and disease-free survival (P<0.0001). Variable expression patterns of the different p63 isoforms were found only in cases immunoreactive for p63. In these latter lesions, at least one of the N-terminal p63 isoforms was detected and TAp63α was the most frequently expressed isoform. TP63 gene amplification was observed by FISH in only one case. Presence of Merkel cell polyomavirus DNA sequences was detected in 86% (60/70) of Merkel cell carcinomas and did not emerge as a significant prognostic parameter. Merkel cell carcinoma cases at low stage (stage I-II) represented over half (40/70 cases, 57%) of cases, and the clinical course was uneventful in 25 of 40 cases while 15 cases died of tumour (10/40 cases) within 34 months or were alive with disease (5/40 cases) within 20 months. Interestingly, a very strict correlation was found between evolution and p63 expression (P<0.0001). The present data indicate that p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma, and in localised tumours it represents the single independent predictor of clinical evolution.

Efficacy and Skin Toxicity Management with Cetuximab in Metastatic Colorectal Cancer: Outcomes from an Oncologic/Dermatologic Cooperation

PURPOSE The aim of this study was to investigate the efficacy of the combination of irinotecan/cetuximab and to plan related skin toxicity management with an oncologic/dermatologic team. PATIENTS AND METHODS Thirty-four patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer received cetuximab 400 mg/m2 as an initial dose and 250 mg/m2 weekly thereafter. In addition, patients received irinotecan 180 mg/m2 every 2 weeks. RESULTS Thirty-two patients were evaluated for response rate (RR) and skin toxicity to establish the best management. In our study, the responses observed with cetuximab treatment were complete response in 1 patient (3%), partial response in 11 patients (34%), disease stabilization in 6 patients (19%), and progressive disease in 14 patients (44%). Of 34 patients evaluable for cutaneous toxicity, 10 patients (29%) presented with grade 1 eruption, 13 (38%) with grade 2 eruption, and 4 (12%) with grade 3 eruption. Allergic reactions such as flushing and urticaria (grade 2) were seen in 2 patients (6%). CONCLUSION Cutaneous reactions consisted of follicular rash, xerosis, painful fissures in palms and soles, alterations in hair growth, and mucositis. In the majority of patients (80%-90%), the worst recorded skin effects were mild (grade 1) to moderate (grade 2). The incidence of severe cases (grade 3) was approximately 15%. All dermatologic effects were reversible and generally without sequelae within 4 weeks after treatment discontinuation. We observed significant correlations between degree of cutaneous toxicity and increased RR. Correct identification and treatment by oncologic/dermatologic cooperation of EGFR cutaneous side effects help to improve quality of life.

Complete response of metastatic cutaneous squamous cell carcinoma to cetuximab plus paclitaxel

BACKGROUND AND METHODS Cetuximab therapy results strongly active in advanced cutaneous squamous cell carcinoma (cSCC). A patient affected by a rapidly progressing, already irradiated and cisplatin-refractory cSCC, with lung, pleura and thoracic lymph nodes metastasis, was treated with weekly cetuximab and paclitaxel. RESULTS Treatment was well tolerated and a partial response was obtained after four months of cetuximab plus paclitaxel therapy. Then we continued maintenance cetuximab for another seven months with tumor shrinkage until complete response, maintained after six months. CONCLUSIONS Cetuximab was safely associated with paclitaxel, obtaining a rapid tumor response in cisplatin-refractory metastatic cSCC. Single-agent cetuximab maintenance sustained tumor shrinkage until complete response.

Psychological characteristics of early-stage melanoma patients: a cross-sectional study on 204 patients

The presence of psychological distress has a negative impact not only on cancer patients’ quality of life but also on the course of the disease, with slower recovery and increased morbidity. These issues are of particular importance in melanoma patients (MP), who remain at risk of disease progression for many years after diagnosis. This study aimed to investigate psychological distress, coping strategies, and their possible relationships with demographic–clinical features in patients with early-stage melanoma in follow-up. The investigation focused in particular on whether the psychological profile differed between patients at different melanoma stages. Data of 118 patients with melanoma in the Tis-Ia stages (MP_Tis-Ia) and 86 patients with melanoma in the Ib–IIa–IIb stages (MP_Ib–II) were gathered through a self-administered survey and compared using a cross-sectional design. The results evidenced a high percentage of anxiety (25%) and distress symptoms (44%), whereas depressive symptoms seemed less frequent (8%). Psychological distress was higher in women than in men, and in patients with a higher educational level. Nevertheless, no significant differences were found between MP_Tis-Ia and MP_Ib–II. With respect to coping style, the patients in this sample adopted predominantly positive and active strategies. Correlational analyses showed that maladaptive coping strategies such as behavioral disengagement, denial, self-distraction, and self-blame were most strongly related to increased levels of psychological distress. The high presence of anxiety and distress symptoms, their relationship, and the use of negative coping strategies underline the importance of psychological distress screening also in early-stage MP, including at long-term follow-up.

Treatment of metastatic melanoma: A multidisciplinary approach

The prognosis of stage IV metastatic melanoma is poor. An overall 1-year survival of 25.5% and a median survival of 6.2 months were reported without any significant improvement during the last 30 years before the introduction of new drugs (immune checkpoint inhibitors and targeted therapies) which completely modified the therapeutic approach and induced an overwhelming improvement on the survival rates of these patients. This review will analyze the therapeutic tools available for the treatment of patients with metastatic melanoma, including adjuvant interferon and locoregional therapies (surgery, radiotherapy and electrochemotherapy) and will mainly focus on the presentation of results obtained by the new treatments (checkpoint inhibitors and targeted therapies).

Role of perioperative dynamic sentinel node biopsy for cN0 penile cancer management: experience from an Italian tertiary referral center

Purpose: Inguinal lymphadenectomy (iLAD) reduces mortality in patients with cN0 penile cancer but yields high complication rates. Thus, its prophylactic role has been questioned and dynamic sentinel node biopsy (DSNB) was introduced to select men who should undergo the procedure. Our aim was to investigate the accuracy of a contemporary DSNB cohort. Methods: We performed a retrospective analysis of ≥T1 or ≥G2 cN0 penile cancer undergoing perioperative DSNB from June 2009 to June 2015 at a tertiary referral center. We excluded men with <18 months follow-up or with local recurrence after primary curative treatment. Complications were graded according to the Clavien-Dindo classification. Results: Thirty-five men underwent DSNB; 85.71% had ≤T2 penile cancer with ≤G2a histology. Per groin detection rate was 80% (scintigraphy being positive bilaterally in 60% and unilaterally in 20.0%). In no cases did DSNB prolong the postoperative course compared to primary surgery. Nine men (n = 15/109 nodes removed) had positive results, 8 of whom underwent iLAD. Among negative DSNB patients, 2 developed nodal penile cancer recurrence; none of them had node biopsy due to inconclusive scintigraphy. At a median follow-up of 42 months (interquartile range 30-78 months), if considering only men with scintigraphy detected inguinal nodes, per-patient sensitivity and specificity were 50% and 80% whereas positive predictive value and negative predictive value were 25% and 92.3%, respectively. Conclusions: Perioperative DSNB is a safe procedure, yielding promising results when performed at a tertiary referral center. Future prospective large studies are needed to investigate how to optimize detection rate and reduce false-negative rates.

Emotional distress and health-related quality of life among cutaneous melanoma follow-up outpatients: the role of self-perception of body image and surgical scarring

Figure 1. Nail modifications during chemotherapy treatment. A) Beau lines, onycholysis and subungual hyperkeratosis with fingertip scaling (Grade 2). B) Severe onycholysis with marked thinning and fragility of the nail plate associated with eczematoid changes of the dorsum of the finger (Grade 2). C) Painful haemorrhagic onycholysis and nail plate abnormalities (Grade 2). D) Multiple bands of longitudinal melanonychia in several fingernails. Note the associated bands of transverse leukonychia (Grade 1). E) Paronychia associated with pyogenic granulomas of the proximal and lateral nail folds of the toenails (Grade 2). F) Paronychia and pyogenic granulomas of several fingernails (Grade 3).