Skin cancer Merkel cell carcinoma definitive EBRT

• Merkel cell carcinoma (MCC).

• T1-4, any N, M0.

• Patients not suitable for upfront surgery (either due to feasibility or morbidity of surgery) following multidisciplinary team discussion.

• ECOG 0-2.

Cautions

• Pregnancy.

• Cardiac implantable electronic devices (CIEDs).

• Non-rheumatoid collagen vascular disorders.

• Cartilage, tendon or bone involvement.

• Sites of poor vascularity or healing, and wear and tear sites e.g.
  • regions below elbow or knee (including the pretibial region and dorsum of the hand)
  • bony prominences
  • cartilage.

• Tumours located on:
  • freely mobile skin suitable for simple excision
  • upper eye lid
  • top of a burn
  • hair bearing areas
  • areas overlying lacrimal glands
  • periorbital lesions
  • exposed bone or cartilage.

Exclusions

• Previous high dose radiation therapy to the same site.

• Staging PET/CT scan should be performed.

• Current smokers should be referred to a smoking cessation program.

Simulation notes

• To document the treatment set-up, take clinical photographs of the scar and/or lesion and markings such as field placement.

Prescription notes

• For PTV_HR  doses in the 54-60 Gy range are appropriate and have been utilised in published reports. Consider using higher doses (60-66 Gy) for larger lesions. However, for small T1 lesions,  54 Gy can be considered.

• Patients should be compensated (e.g. bi-daily, treatment acceleration and/or hypofractionation) for non-treatment days i.e. public holidays or service days or for unavoidable treatment delays.

• Definitive hypofractionated schedules to consider include:
  • 50-55 Gy in 20# over 4 weeks
  • 36 Gy in 6# over 3 weeks.

Margin ranges have been agreed by the Radiation Oncology reference committee and reflect safe clinical practice.

Target volume notes

• For limb lesions, a strip of skin and subcutaneous tissue should be spared where practical.

Target volume guides

• Resources are available for contouring head and neck nodal target volumes:
  • Lymph node target volumes for definitive head and neck radiation therapy: a 2019 Update.^r
  • Delineation of the neck node levels for head and neck tumors: A 2013 update. DAHANCA,EORTC, HKNPCS, NCICCTG, NCRI, RTOG, TROG consensus guidelines. opens in a new tab or window^r

Head and neck region organs at risk

Axilla region organs at risk

Inguinal region organs at risk

OAR notes

• Where no referenced dose constraints are available, the listed constraints are the consensus of the reference committee.

Target verification recommendations reflect the minimum imaging required for the safe delivery of this protocol.

• Departments should have a system in place to monitor change in patient contour due to weight loss or tumour shrinkage. For example, regular CBCT or repeat planning CT may be performed to check dose distribution. Repeat simulation and planning may be required if changes are not within departmental tolerances.

Efficacy

There is limited randomised evidence to support the role of definitive radiation therapy in the treatment of patients with Merkel cell carcinoma (MCC). The Radiation Oncology reference committee (RC) supported the use of this protocol on the basis of the information summarised below. The RC was most strongly influenced by Gunaratne et al.,^r Veness et al.,^r Poulsen et al.,^r Mortier et al.^r and Pape et al.^r

There is a paucity of evidence on treating patients with MCC with definitive radiation therapy. Surgery followed by adjuvant radiation therapy remains the standard of care for most patients with MCC. However, the majority of lesions present in the head and neck and resection is often contra-indicated because of the proximity of nearby structures and the inability to achieve adequate excision margins without compromising form or function. In this group of patients, definitive radiation therapy has been shown by small institutional studies to provide similar locoregional control rates as surgery plus adjuvant radiation therapy.^rr

The study by Veness et al^r of 43 patients with MCC, included patients receiving radiation therapy alone at initial diagnosis (56%) and in the relapse setting (44%). The reported in-field control rate was 75% and overall survival at 2 and 5 years were 58% and 37% respectively. The median relapse free survival (RFS) was significantly better for patients without nodal metastases present at the time of treatment (38.1 months vs 10.7 months).

The dose response of MCC to radiation has been reported in 112 patients treated with curative intent. This data suggests that surgical margins do not greatly affect locoregional control if doses greater than 50 Gy are used. For microscopic disease, doses of 50 Gy are effective and for gross disease doses >55 Gy should be considered as illustrated in the table below.

© Int J Radiat Oncol Biol Physics^r

Management of draining lymph nodes is an essential component of treatment. There is level 2 evidence to show that elective nodal radiation therapy improves regional control rates. Sentinel lymph node biopsy/mapping may be useful to guide either elective lymph node dissection or delineation of radiation therapy fields and provides prognostic information. Patients with positive sentinel lymph node biopsy require nodal treatment. False negative sentinel lymph node biopsies may occur in up to 20% of cases.^r Based on this, and the proclivity of MCC to spread via dermal lymphatics to locoregional nodes, we recommend that radiation therapy fields encompass the primary with a wide-field, in transit lymphatics and the first echelon of draining lymph nodes.^r

Dose escalation

There is limited data on dose response in MCC. One study has specifically tried to address this and has indicated that doses of 50 Gy (2 Gy per fx) to microscopic disease, and >55 Gy (2 Gy per fx) to gross disease result in excellent in-field local control.^r Multiple series have suggested that doses >54 Gy (2 Gy per fx) to gross local and regional disease may result in improved in field control. There is no evidence to suggest doses of >60 Gy are required, but it is reasonable to consider dose escalation in the setting of bulky and/or recurrent loco-regional disease.^rrrrr

Toxicity

• Late radiation changes include atrophy, telangiectasia, sclerosis and a small risk of induction of malignancy.
• Rare late toxicity includes <5% risk of soft tissue and cartilage necrosis. Toxicity is related to increasing tumour size and larger doses per fraction.^r
• Lymphoedema.
• Grade 3-4 (64%) significant skin mucosal reactions may occur when treating head and neck MCC.^r