Skin Cancer

What’s new in treatment of cutaneous T cell lymphoma

Rudolf Stadler (Germany)

Basal cell carcinoma (BCC) is the most common cancer among Caucasians. It generally occurs on sun-exposed areas of the body, mostly on the head and neck (80%), trunk (15%), but rarely on arms and legs. Skin phototypes 1 and 2, male sex, old age and a history of previous sun burns are all considered significant risk factors in developing BCC.

The majority of BCCs can be treated by surgical excision, destructive procedures, or topical products. Advanced BCC is divided into two groups: metastatic and locally advanced BCC. The term locally advanced BCC refers to the tumors in which surgery is contraindicated or failed, radiotherapy is contraindicated or failed, or surgery is not possible or appropriate. Hedgehog inhibitors provide substantial clinical benefit for patients with locally advanced and metastatic BCC, and they are a first option in the treatment of locally advanced BCC. Since BCC has one of the highest tumor mutation burdens it is a good candidate for immunotherapy. The mechanism of action of immune checkpoint inhibitors includes blocking of PD-L1 or PD-1, allowing T cells to kill the tumor cells. Cemiplimab is indicated in the USA and Europe for the treatment of locally advanced BCC and metastatic BCC in patients previously treated with Hedgehog inhibitors, or for whom Hedgehog inhibitors are not appropriate.

The role of multidisciplinary management in high-risk SCC

Jessica Hassel (Germany)

A high risk of cutaneous Squamous cell carcinoma (SCC) recurrence is characterized by different features including a vertical tumor thickness above 6mm, a low differentiation, perineural invasion, localisation on the lip/ears or immunosuppression.

The gold standard for high-risk SCC is micrographically controlled surgery. In tumors excised with scarce margins, perineural invasion or extensive lymph node metastases, adjuvant radiotherapy can be discussed. However, in advanced local disease, primary radiation or even systemic therapy can be indicated.

To facilitate treatment decision for a patient with advanced local disease a decision aid is developed and presented. Moreover, new treatment strategies such as local injections with oncolytic viruses might be a promising new treatment option. In patients with resected high-risk SCC, adjuvant systemic therapy might be considered in the future.

Update on management of Merkel cell carcinoma

Claudia Pföhler (Germany)

Merkel cell carcinoma (MCC) is a rare, but highly aggressive tumor of the skin that tends to metastasize at an early stage. Although MCC is still a rare tumor mostly in elderly persons, its incidences seem to be on the rise worldwide. Sun exposure, impairment of the immune system and Merkel cell polyoma virus play an important role in its development. MCCs arise mostly in chronic sun exposed areas such as the head and neck area, but also on the extremities. They usually present as reddish, pink or purple nodules that are painless and grow very fast. Due to early metastases in locoregional lymph nodes, sentinel-node biopsy is indicated after exclusion of locoregional macro-metastases. In primary tumors without evidence of organ metastases, complete surgical excision with an adequate safety margin is indicated. Radiation therapy should be considered at all stages of the disease. 

In advanced MCCs that can no longer be treated by surgery or radiotherapy, there is still no established systemic therapy for which an improvement in recurrence-free survival or overall survival has been demonstrated in a prospective randomized study. However, the use of PD-1 or PDL-1-antibodies such as avelumab, nivolumab or pembrolizumab has become standard in these cases. Chemotherapy regimens are no longer used as a first line treatment, but can be considered after progression under systemic therapy with checkpoint inhibitors.

All therapeutic decisions concerning surgical, radiotherapeutic or systemic treatment of MCC should be discussed in an interdisciplinary tumor board.

Management of nonmelanoma skin cancer in immunosuppressed patients

Mahtab Samimi (France)

Immunosuppressed patients, especially organ transplant recipients, are at big risk of keratinocyte cancers. Indeed, the incidence and aggressiveness of squamous cell carcinoma (SCC) and Merkel cell Carcinoma (MCC) dramatically increase in these patients. As the risk of recurrent and metastatic disease is significantly increased in these patients, there are specific recommendations for appropriate management, with management of both early and late stages of the disease discussed on multidisciplinary tumor boards.  

This presentation will be based on clinical cases to focus on the following points: the characteristics of keratinocyte cancers in organ transplant recipients, in terms of behavior and prognosis; how to treat these patients at early stages of the disease; how to handle their immunosuppressive regimens; which preventive measures should be implemented and when; how to treat locally advanced/recurrent/metastatic disease at the era of immune checkpoint inhibitors, and which carry the risk of graft loss in these patients.

What’s new in treatment of cutaneous T cell lymphoma

Rudolf Stadler (Germany)

In advanced-stage cutaneous T-cell lymphoma (CTCL), the current therapeutic options rarely provide long-lasting responses, leaving allogenic stem-cell transplantation the only potentially curative option for highly selected patients. It is therefore important to take all available measures in good time. An individual therapeutic concept should be established and taken into account whether it is an early advanced or late advanced cutaneous T-cell Lymphoma.

The traditionally used recombinant Interferon alpha has been replaced by pegylated Interferon, which seems to induce favorable results in combination with UV phototherapy or radiotherapy.

The pillars of modern targeted therapy are the CCR4 receptor-targeting mogamulizumab, as well as the CD30-targeting brentuximab vedotin. 

The therapeutic option for future therapy is Lacutamab, a first-in-class cytotoxic–inducing antibody, currently in clinical evaluation. Atezolizumab (anti-PD-L1) showed moderate activity in pre-treated advanced cutaneous T-cell Lymphoma. Among single agent chemotherapeutics, Gemcitabine is an effective single-agent used in advanced stages of CTCL.  Low dose regimens have recently been shown to induce high and long-lasting remission rates. Moreover, Ifosfamid and Etoposid is a valuable therapeutic option in patients with advanced, refractory CTCL.

Management of stage I and II melanoma

Zsuzsanna Lengyel (Hungary)

Melanoma represents 5% of malignant skin cancers. The incidence of melanoma is increasing worldwide, especially in fair skinned people with excessive sun exposure. In Europe, the incidence rate counts between 10 to 25 new melanoma cases per 100,000 inhabitants. The majority of new cases are in early stages (I and II) (70%) and have a favorable outcome. 

The eighth edition of American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma has been implemented in everyday care since 2018.  

According to the AJCC stages of primary tumor staging, examinations and further surgical interventions are needed.  This lecture highlights when to perform sentinel lymph node biopsy, as it is an important component of melanoma staging to identify occult regional lymph node disease among patients with clinical stage I or II diseases.   

Patient surveillance is also an important part of patient care. Today there is no available data from randomised clinical trials regarding an optimal follow-up scheme. There are various recommended schemes, and I will cover the latest recommendations by the European consensus-based interdisciplinary guideline. 

Patients with stage II disease, especially IIB and IIC, have worse prognosis than AJCC 8th stages III A and III B. 

The higher incidence of distant/regional metastases in these stages led to clinical trials to assess the efficacy of adjuvant therapies already approved in stage III diseases in completely resected high-risk stage II melanoma. 

Management of BRAF-mutant melanoma

Pietro Quaglino (Italy)

The introduction in the clinical practice of new drug compounds, both targeted therapies anti-BRAF and check point inhibitors, has largely improved our potential to manage advanced metastatic melanoma patients, inducing a significant improvement in terms of response rates and particularly overall survival (OS). The long-term results of trials with follow-up data of patients treated with targeted or immunotherapies reported median OS rates around 24 months, with 5-year survival rates around 35-40%. 

As to the drugs currently available and reimbursed by the Italian National Health System, three combinations of anti-BRAF/anti-MEK inhibitors are available (dabrafenib/trametinib, vemurafenib/cobimetinib and the most recently introduced encorafenib/binimetinib). 

As to check point inhibitors, first line immunotherapy is represented by anti-PD1 blockers (nivolumab and pembrolizumab), whilst the anti-CTLA-4 ipilimumab can be used as second line. The decision-making factors to define the best treatment approach in a patient with stage IV metastatic melanoma are represented by: mutation pattern, performance status, high/low tumour load, brain metastases, progression pattern (low/fast) and availability of clinical trials.

This presentation will analyse the therapeutic tools available for the treatment of patients with BRAF-mutant metastatic melanoma and will focus on an update of results obtained by the new treatments (check-point inhibitors and targeted therapies) which can be used in the clinical daily practice.

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