Skin cancer squamous cell carcinoma adjuvant EBRT post-operative

Cautions

• Pregnancy.

• Previous radiation therapy to the same site.

• Concurrent systemic therapy.

• Non-rheumatoid collagen vascular disorders.

• 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.

• Cardiac implantable electronic devices (CIEDs).

• In general, radiation therapy is not recommended for younger patients due to worsening functional and cosmetic results with time and the risk of developing a secondary cancer in the treatment field. Other treatment options should be considered.

• Radiation therapy to commence as soon as post-surgical wound healing is complete (ideally within 4-6 weeks of surgery).
• In the presence of a skin graft for wound coverage post-surgery, radiation therapy should be delayed until the graft has fully taken.^r

Simulation notes

• For electron and superficial therapy, consider internal shielding and surface shielding with a lead mask/cut-out to define the treatment field.

• Use good light and magnification to assess skin lesion/scar for clinical mark-up.

• To document the treatment set-up, take clinical photographs of the lesion (pre-operation), scar and markings such as field placement.

OAR notes

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

MV photons

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

Target verification notes

• Consideration should be given to dose delivered from verification imaging and whether this needs to be accounted for in treatment planning, particularly with respect to critical OARs.

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

Efficacy

Local recurrence

Incomplete excision of squamous cell carcinoma (SCC) is the strongest factor predicting recurrence, and local recurrence increases the risk of nodal metastases. If margins of excision are <2 mm, re-excision should be performed if function is not compromised. If re-excision cannot be performed, or if other adverse features present after re-excision, adjuvant RT should be considered to reduce local recurrence.^r

Approach to the regional lymph nodes in cN0 patients

Most patients with cutaneous SCC will not develop metastases. Certain high risk pathological features can identify a subgroup of primary tumours with a higher risk (>5%) of having subclinical metastases to regional lymph nodes. However, accurately predicting patients at high risk, and therefore justifying the elective treatment of the first echelon, lymph nodes is difficult. Patients with more than one high risk factor should be considered at high risk of developing nodal metastases and in these patients the regional lymph nodes should be addressed.^r

Approach to the regional lymph node bed following dissection in patients with nodal metastases

There is no prospective randomised controlled data to support the use of adjuvant radiation therapy in this setting for cutaneous SCC. Extrapolation from historical case series in cutaneous SCC and prospective trials of PORT in mucosal head and neck SCC supports the use of a dose of 60Gy EQD2 to reduce the risk of locoregional recurrence. A recent meta-analysis of retrospective studies has reported that the receipt of PORT improves the probability of overall survival (OS) and disease specific survival (DSS).^r

Timing of PORT

There is a paucity of published information on the effect of treatment package time (TPT) in cutaneous SCC. Extrapolation from prospective randomised trials in mucosal head and neck SCC showed an OS detriment with prolongation of treatment package time and PORT should be commenced as soon as possible following surgery and any unnecessary treatment delays should be avoided.^r This is supported by a recent case series in cutaneous head and neck SCC which reported worse OS and freedom from locoregional failure with TPT prolongation beyond 14 weeks.^r

Identification of a low-risk patient with cervical nodal metastasis

Patients with established nodal metastases should have surgery and adjuvant RT to optimise regional control (extent of nodal dissection should be discussed at a multidisciplinary meeting).^rrrrr For patients with a single cervical node <3 cm who have had an adequate neck dissection without other high risk features, it may be possible to omit radiotherapy providing that close surveillance is performed to allow for salvage neck dissection and PORT.^rr

Approach to the neck with parotid-only nodal metastases

The treatment of the clinically negative neck in patients with parotid metastases remains unresolved, but commonly selective neck dissection with parotidectomy is performed. An alternative approach which avoids neck dissection is to treat the deep cervical nodes electively in addition to the parotid bed.^r

Utility of concurrent or adjuvant systemic therapy

The prospective randomised controlled POST trial (TROG 05.01) has not demonstrated a locoregional control, disease specific survival or OS advantage to the addition of concurrent carboplatin chemotherapy to postoperative RT for patients with high risk cutaneous head and neck SCC.^r

Significance of perineural invasion and perineural spread

Microscopic perineural invasion (PNI) of nerves greater than 0.1 mm calibre extending beyond the tumour is a recognised adverse feature and increases the risk of recurrence. It is a relative indication for adjuvant radiotherapy, particularly if it occurs in the trigeminal or facial nerve distribution. Clinical PNI or large nerve perineural spread (PNS) affecting cranial nerves i.e. symptomatic with palsy, pain, formication, visible perineural spread on MRI, or histological involvement of a named nerve should be referred to a multidisciplinary head and neck service (with skull base surgical expertise where possible) because long term disease control can be obtained by maximal safe resection followed by PORT.^rrrr

The presence of symptomatic PNI or PNS may portend a poorer prognosis. The 5-year outcomes after treatment for pathological compared with clinical PNI are: local control, 80% and 55%; cause specific survival, 75% and 65%; and overall survival 55% and 50%, respectively.^r Another Australian series showed a better 5 year local control rate of 90% with pathological PNI compared to 57% with clinical PNI, when treated with surgery and adjuvant RT.^r

Axilla and groin metastases

There is a paucity of data on the management of cutaneous SCC nodal metastases in the axilla and groin. In general, these patients have a poor prognosis.^rr PORT may be offered for high risk nodal features as in the neck and may improve local control.^r Careful consideration should be given to the risk of toxicity when delivering PORT to the groin as demonstrated in the TROG 02.01 melanoma adjuvant lymph node radiotherapy trial.^r

Toxicity

A summary of the most clinically significant toxicities associated with this protocol are included in the tables below.

Head and neck

Axilla

Groin

• Cosmesis outcomes may alter over time due to the development of late radiation changes including atrophy, telangiectasias and sclerosis. These late skin changes, and the increased possibility of developing secondary cancers, is a cause for concern and treatment of patients < 50 years should be carefully considered.
• In the study by Locke et al. 92% of patients reported a good to excellent cosmetic outcome. The quality of the cosmetic results were dependent on the size of the carcinoma, 99% in tumours <1 cm, 92% in tumours 1-3 cm.^r
• A reduction in late cosmetic changes may result after continued unprotected skin exposure post radiation therapy in patients treated with large doses (>3 to 4 Gy) per fraction.^r
• There is a small risk (<5%) of late soft tissue and cartilage necrosis which is related to increasing tumour size and larger doses per fraction.^r
• Radiation induced malignancies following small field superficial radiation therapy for skin cancers are rare, but must be considered when discussing radiation therapy as a treatment option in younger patients.^r