Post-operative Concurrent Chemo-radiotherapy Versus Post-operative Radiotherapy in High-risk Cutaneous Squamous Cell Carcinoma of the Head and Neck
Two in every 3 Australians will be affected by skin cancer over their lifetime. The
prevalence of skin cancer will continue to increase due to the ageing population and
represents a significant problem in our community. Cure of early (T1-2) de novo cutaneous
squamous cell carcinoma (CSCC) treated with either curative intent surgery or radiotherapy
is 85-100%. However, the cure rate for locally advanced, recurrent, or metastatic disease to
regional nodes following surgery alone are much lower, in the order of 20-70%. Metastatic
CSCC is the most common malignancy of the parotid region in Australia. The 5 year
loco-regional control with surgery alone is in the order of 40%-45%. The addition of
post-operative radiotherapy improves loco-regional control by 15-20%, and is therefore
considered the standard of care in this group of patients.
Recent data have shown that synchronous post-operative chemo-radiotherapy is superior to
post-operative radiotherapy alone in "high-risk" mucosal head and neck squamous cell
carcinoma (HNSCC). However, to date, there is no evidence from randomised trials that such a
benefit exists in CSCC of the head and neck. At present there is little consensus amongst
clinicians in Australia as to who should receive post-operative chemo-radiotherapy in CSCC.
Although tumour control rates may be improved, the addition of chemotherapy may also
significantly increase treatment related toxicity. Nonetheless, some centres have adopted
the use of post-operative chemo-radiotherapy in selected patients with CSCC based on
extrapolation from mucosal sites. This has resulted in a wide variability in practice for
Australia is uniquely placed to perform such a trial comparing post-operative
chemo-radiotherapy to post-operative radiotherapy alone in high-risk CSCC due to the high
rate of skin cancer. Currently there are limited data to guide management of patients with
resected CSCC who are at high risk for recurrence. While it is reasonable to hypothesize
that concurrent chemotherapy in this setting will confer a similar benefit to that seen in
mucosal HNSCC, this can only be established by a randomized trial as proposed. If the
addition of chemotherapy is shown to be beneficial and safe, then these results are likely
to be translated into standard practice both nationally and internationally quite rapidly.
On the other hand, if the treatment is found to be ineffective then patients will be spared
the unnecessary toxicity and inconvenience associated with the addition of chemotherapy. A
further important aspect of this trial will be the assessment of patient-related outcomes
using a validated quality of life questionnaire. It will be important to ascertain whether
any improvement in locoregional control due to the addition of chemotherapy, is also
associated with improvement in quality of life compared to the control arm.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
The date of primary outcome analysis will occur when the final patient has reached a minimum 2 years follow-up.
Princess Alexandra Hospital
Australia: Department of Health and Ageing Therapeutic Goods Administration
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