Keratinocyte cancer

8.2 Radiotherapy for basal cell carcinoma

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Guideline contents > In which patients with basal cell carcinoma does a radiotherapy modality achieve equal or better outcomes than conventional surgery?

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Prof Gerald Fogarty, Howard Liu, Cancer Council Australia Keratinocyte Cancers Guideline Working Party. Clinical question:Patient outcomes of RT modality vs conventional surgery for BCC . In: Clinical practice guidelines for keratinocyte cancer. Sydney: Cancer Council Australia. [Version URL: https://wiki.cancer.org.au/australiawiki/index.php?oldid=208361, cited 2023 Mar 30]. Available from: https://wiki.cancer.org.au/australia/Guidelines:Keratinocyte_carcinoma.


Last modified:
25 November 2019 20:49:36

Unless stated otherwise, tumour stage is according to the American Joint Committee on Cancer (AJCC) cancer staging manual 8th edition [1] and Union for International Cancer Control (UICC) TNM classification of malignant tumours 8th edition.[2]

Background[edit source]

Radiotherapy (RT) has been used for treating basal cell carcinoma (BCC) for over a century. It is an efficacious alternative treatment for primary untreated BCC in a minority of patients when surgery is disadvantageous:

  • when surgery is not feasible (e.g. in patients unfit for surgery, including those with significant coagulation risk)
  • when the patient declines surgery
  • when surgery will cause cosmetic or functional morbidity unacceptable to the patient (e.g. nasectomy, loss of function of lips or eyelids, large tissue deficits, multiple lesions).

Radiotherapy is also used in the management of metastatic BCC.

Unlike topical therapies, RT is not limited to certain BCC histological subtypes.[3]

The availability of new office-based portable systems is increasing the availability of RT for BCC.[4][5]


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Evidence[edit source]

Systematic review evidence[edit source]

In which patients with basal cell carcinoma does a radiotherapy modality achieve equal or better outcomes than conventional surgery?

A systematic review was undertaken to evaluate in which patients with basal cell carcinoma a radiotherapy modality achieves equal or better outcomes than conventional surgery.

The search strategy, inclusion and exclusion criteria, and quality assessment are described in detail in the Technical report.

Twenty studies were identified that assessed outcomes in patients treated with RT for BCC and met the inclusion criteria,[6][7][8][9][10][11][12][13][14][15][3][16][17][18][19][20][21][22][23][24] including five representing level III-2 evidence [11][21][22][23][24] and 15 level IV.[14][3][17][19][20][8][9][7][12][13][15][16][18][6][10]

There were no randomised controlled trials. Three prospective studies were identified,[10][20][13] and the remainder were retrospective studies. All studies were at high risk of bias.

Participants were mainly patients for whom surgery was unsuitable. Many different RT techniques were used, including different types of external-beam radiotherapy (EBRT) and brachytherapy.

Survival[edit source]

Seven studies reported survival outcomes in patients treated with EBRT or brachytherapy.[14][8][11][12][19][6]

Four studies[14][9][11][6] reported overall survival rates, which ranged from 61% after 1 year follow-up, to 97% after 5 years follow-up.

Six studies[14][9][11][12][19] reported disease-free survival, which ranged from 57% after 13 months follow-up to 90% after 5 years follow-up.

Response rates[edit source]

Four studies reported response rates for patients with BCC treated with RT or brachytherapy. Three reported complete response rates greater than 95% following treatment by EBRT or brachytherapy, in a combined total of 231 patients, with follow-up ranging from 3 months to 4 years.[14][20][13] Another small study[18] reported a complete response rate of 97.9% for those treated with 40 Gy radiotherapy, and 88.9% response rate for those treated with 50 Gy (n=9).

Recurrence rates[edit source]

Nine studies reported recurrence or relapse rates for patients treated by EBRT or brachytherapy.[14][17][11][21][7][23][25][10][24]

Recurrence rates ranged from 2% to 10% in a combined total of 2987 patients, with a follow-up of up to 5 years.

A single study[24] reported comparative recurrence rates in patients treated by surgery, adjuvant RT, or RT alone. After a median follow-up of 33 months, patients treated by surgery alone (n=244) had a recurrence rate of 5.3%. The recurrence rate rose to 10% in those treated by surgery and RT (n=20), and to 20% in those treated by RT alone (n=19).[24]

Recurrence can occur at any time after RT, but 88–90% of recurrences were reported to occur within the first 5 years.[26][27] Among patients treated with a curative dose, reported 5-year recurrence rates were approximately 5%.[14][3][17][11][21][7][23][25][10][24]

Control[edit source]

Five studies reported control rates for patients treated with EBRT or brachytherapy only.[14][20][21][22][6]

Control rates at 5 years and 10 years post treatment were greater than 85% across all studies (reported for 974 patients).

Toxicity[edit source]

Six studies[20][7][13][16][18][10] reported acute toxicity outcomes. Approximately 75% or more of patient reported grade 0 or 1 acute toxicities, in a cumulative total of 503 patients.

Only two studies.[12][18] reported late toxicity outcomes. Grade 0 or 1 late toxicity was reported in 78–91% of patients (n=127). There were no cases of necrosis.[12][18]

Cosmetic outcomes[edit source]

Six studies[3][20][23][13][16][18] reported cosmetic outcomes for patients treated with EBRT or brachytherapy.

Good or excellent outcomes were reported in 62–100% of the 308 patients included.

Cosmetic outcomes for brachytherapy were generally inferior to those reported for EBRT[3][20][23][13][16][18]


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Overview of additional evidence (non-systematic literature review)[edit source]

Outcomes of RT series and other relevant clinical findings were reported in additional studies that did not meet inclusion criteria.

Control rates[edit source]

For BCC ≤2cm treated with RT, control rates of 95–99% at 5 years and 93–95% at 10 years have been reported (Table 7).[28][29][26][30][27][31][32][33]


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Table 7. Control rates for BCC treated with radiotherapy, according to AJCC/UICC stage (6th edition)[34][35][36][37][38][39][40][41]

Lesion size T Stage 5 years 10 years
<2cm T1 97% 95%
2–5cm T2 92% 89%
>5cm T3 60% 50%
T4 lesions T4
Note: Staging according to American Joint Committee on Cancer and International Union Against Cancer classification (AJCC/UICC) 6th edition,[42] which was the edition current at the time the cited studies were conducted.
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Basal cell carcinoma of medial canthus[edit source]

Radiotherapy has comparable control rates to surgery[26] but results in superior tissue conservation.

A small case series reported good cancer outcomes and cosmetic outcomes for high-dose-rate brachytherapy in the treatment of tumours of the medial canthus of the eyelid, the majority of which were BCCs.[43] At median follow-up of 40 months investigators reported a local control rate of 94% and good or excellent cosmetic outcomes in 70% of patients.

Recurrent tumours of the medial canthus require surgical salvage.[44]

Recurrence of basal cell carcinoma following radiotherapy[edit source]

Recurrent BCC should be treated with excisional surgery, including excision of the irradiated tissues, by a specialist surgeon.

Salvage re-irradiation can be considered In some circumstances (e.g. a long disease-free interval[45]) when surgery cannot be performed.[46][47] Surgery may be preferred to re-irradiation, as there is increased risk of more serious late RT-related sequelae (radionecrosis of skin and other underlying tissues).

Residual basal cell carcinoma following radiotherapy[edit source]

Complete clinical resolution of a BCC following curative radiotherapy can occasionally take up to 4 months.[48] Most small BCC resolve by the time the acute radiation reaction has resolved (4–6 weeks after finishing radiotherapy).[48]

Postoperative radiotherapy for aggressive tumours[edit source]

Postoperative RT has been reported to increase local control rates for extensive, locally advanced BCCs where complete surgical excision cannot be achieved,[49] and for head-and-neck BCCs with aggressive features on histopathology.[50]

A small case series reported a 5-year cure rate of 55.13% with definitive RT for extensive and recurrent BCC.[49]

Postoperative radiotherapy for residual tumours following incomplete excision[edit source]

The observed recurrence rate of incompletely excised BCC is approximately 33% on average.[51][52][53][54][55][56][57][58][59][47][60]

Re-excision following incomplete excision of BCC is controversial (Protocol to manage incomplete resected basal cell carcinoma). Approximately two-thirds of incompletely excised BCCs do not recur. Some authors have reported similar rates for salvage of recurrent lesions. However, a Canadian case series of incompletely resected BCCs reported that 6% were eventually not controlled after salvage.[58] Numerically higher rates of recurrence have been reported when the deep margin is involved, compared with a lateral margin, and higher again when both are involved.[57][58]

Following incomplete excision, re-excision surgery is usually performed as complete excisional surgery is more accessible, expedient and convenient, and has optimal cancer outcomes and cosmetic outcomes. However, RT is an option following incomplete excision of primary BCCs when surgery is declined, likely to be associated with unacceptable function and cosmetic outcomes, or is not feasible (e.g. due to comorbidity). Margins added for RT fields depend on tumour size and histology.[61]

Salvage radiotherapy[edit source]

Control rates after salvage therapy are lower than those for primary treatment and are associated with size of the recurrent tumour, number of recurrences and invasion of skeletal muscle, cartilage or bone.[32]

Radiotherapy has been reported to increase local control in advanced BCC.[62]

Radiotherapy has been reported to be successful as a salvage treatment for recurrence of BCC post Mohs micrographic surgery.[63]

Following recurrence of BCC after RT managed by salvage surgery, further recurrence rates of 14–18% have been reported.[27][51][64][65]
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Evidence summary and recommendations[edit source]

Evidence summary Level References
Recurrence and control

Recurrence rate were relatively low (≤10%) across all reported studies, and were comparable for surgery only and RT only. Short-term recurrence rates were variable across studies, and were dependent on patient-related factors. Control rates after approximately 10 years of follow-up were >90% in all studies.

III-2, IV [14], [20], [13], [18], [3], [17], [11], [21], [7], [23], [25], [10], [24], [22], [6]
Survival

Overall survival and disease-free survival were high, but variable across the included studies, ranging from 57% to 97%, depending on follow-up time.

Survival outcomes were likely to have been influenced by patients’ ages, disease characteristics, and comorbidities.

III-2, IV [14], [8], [9], [11], [12], [19], [6]
Toxicity

Substantial acute and late toxicities were reported in <25% of treated patients following RT or brachytherapy.

IV [20], [7], [13], [66], [18], [10], [12]
Cosmetic outcomes and complications

Treatment by RT or brachytherapy resulted in good or excellent cosmetic outcomes in most, if not all patients.

Fewer than half of patients experienced treatment-related complications or side effects. Adverse effects were more pronounced in patients treated with higher RT doses and higher dose per fraction.

III-2, IV [3], [20], [23], [13], [66], [18], [22], [25], [19]
Evidence-based recommendationQuestion mark transparent.png Grade
EBR 8.2.1. Radiotherapy using curative doses can be considered as an alternative to surgical excision in the definitive treatment of basal cell carcinoma if surgery is either declined by the patient or surgery is inappropriate. 		D


Consensus-based recommendationQuestion mark transparent.png

CBR 8.2.1. For patients with T3/T4 primary persistent or recurrent basal cell carcinoma, consideration should be given to obtaining an opinion from a radiation oncologist as part of multidisciplinary care.


Practice pointQuestion mark transparent.png

PP 8.2.1. Clinical persistence or progression of a basal cell carcinoma after a standard curative dose of radiotherapy should be confirmed in consultation with the treating radiation oncologist. The lesion should be biopsied and managed with salvage excisional surgery.


Practice pointQuestion mark transparent.png

PP 8.2.2. Patients who have undergone complete excision of basal cell carcinomas should be offered referral to a specialist skin cancer clinic (or head and neck clinic) for individual assessment and consideration of postoperative radiotherapy or additional treatment if any of the following are present:

  • bone invasion
  • rapidly growing tumour
  • tumour recurrence (including multifocal recurrence or multiple recurrences)
  • inadequate margins on excision when further surgery is problematic
  • perineural invasion (major and minor nerves)
  • lymphovascular invasion
  • in-transit metastases
  • regional nodal involvement
  • histological subtype associated with poor prognosis (micronodular, infiltrative or metatypical).
Key point(s)
  • Radiotherapy can be considered an alternative to re-excision in the management of incompletely excised basal cell carcinoma if further treatment is deemed advisable and re-excision is disadvantageous or not feasible.
  • Radiotherapy can be considered as an alternative to excision surgery as a definitive treatment for T1 and T2 BCC when surgery is difficult due to patient-related factors (e.g. frailty), tumour-related factors (e.g. where tissue conservation or cosmesis is a high priority, such as in BCC of the eyelid), or treatment-related factors (e.g. concurrent anticoagulant therapy).

Notes on the recommendations[edit source]

Radiotherapy may be considered in some cases when function and/or cosmesis are a high priority, as RT is tissue-conserving when compared with surgery.


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Appendices[edit source]

Jutta's magnifying glass icon.png PICO question RT2 View Evidence statement form RT2 Evidence statement form RT2

View Systematic review report RT2 Systematic review report RT2

References[edit source]

  1. ↑ Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, et al. (Eds.). AJCC Cancer Staging Manual (8th edition). Springer International Publishing: American Joint Commission on Cancer; 2017 [cited 2016 Dec 28].
  2. ↑ Brierley JD, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours, 8th Edition. Wiley-Blackwell; 2017.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Caccialanza M, Piccinno R, Cuka E, Alberti Violetti S, Rozza M. Radiotherapy of morphea-type basal cell carcinoma: results in 127 cases. J Eur Acad Dermatol Venereol 2014 Dec;28(12):1751-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25564683.
  4. ↑ Ballester-Sánchez R, Pons-Llanas O, Candela-Juan C, Celada-Alvarez FJ, de Unamuno-Bustos B, Llavador-Ros M, et al. Efficacy and safety of electronic brachytherapy for superficial and nodular basal cell carcinoma. J Contemp Brachytherapy 2015 Jun;7(3):231-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26207112.
  5. ↑ Ballester-Sánchez R, Pons-Llanas O, Candela-Juan C, Celada-Álvarez FJ, Barker CA, Tormo-Micó A, et al. Electronic brachytherapy for superficial and nodular basal cell carcinoma: a report of two prospective pilot trials using different doses. J Contemp Brachytherapy 2016 Feb;8(1):48-55 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26985197.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Haseltine JM, Parker M, Wernicke AG, Nori D, Wu X, Parashar B. Clinical comparison of brachytherapy versus hypofractionated external beam radiation versus standard fractionation external beam radiation for non-melanomatous skin cancers. J Contemp Brachytherapy 2016 Jun;8(3):191-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27504127.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Maroñas M, Guinot JL, Arribas L, Carrascosa M, Tortajada MI, Carmona R, et al. Treatment of facial cutaneous carcinoma with high-dose rate contact brachytherapy with customized molds. Brachytherapy 2011 May;10(3):221-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20932808.
  8. ↑ 8.0 8.1 8.2 8.3 Matthiesen C, Thompson JS, Forest C, Ahmad S, Herman T, Bogardus C Jr. The role of radiotherapy for T4 non-melanoma skin carcinoma. J Med Imaging Radiat Oncol 2011 Aug;55(4):407-16 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21843177.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Matthiesen C, Forest C, Spencer Thompson J, Ahmad S, Herman T, Bogardus C. The role of radiotherapy for large and locally advanced non-melanoma skin carcinoma. Journal of Radiotherapy in Practice 2013;12(1):56-65.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 Olek D Jr, El-Ghamry MN, Deb N, Thawani N, Shaver C, Mutyala S. Custom mold applicator high-dose-rate brachytherapy for nonmelanoma skin cancer-An analysis of 273 lesions. Brachytherapy 2018 May;17(3):601-608 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29398593.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 Pampena R, Palmieri T, Kyrgidis A, Ramundo D, Iotti C, Lallas A, et al. Orthovoltage radiotherapy for nonmelanoma skin cancer (NMSC): Comparison between 2 different schedules. J Am Acad Dermatol 2016 Feb;74(2):341-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26589877.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7 Arenas M, Arguís M, Díez-Presa L, Henríquez I, Murcia-Mejía M, Gascón M, et al. Hypofractionated high-dose-rate plesiotherapy in nonmelanoma skin cancer treatment. Brachytherapy 2015 Nov;14(6):859-65 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26489922.
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 13.9 Ballester-Sánchez R, Pons-Llanas O, Candela-Juan C, de Unamuno-Bustos B, Celada-Alvarez FJ, Tormo-Mico A, et al. Two years results of electronic brachytherapy for basal cell carcinoma. J Contemp Brachytherapy 2017 Jun;9(3):251-255 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28725249.
  14. ↑ 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 Belaid A, Nasr C, Benna M, Cherif A, Jmour O, Bouguila H, et al. Radiation Therapy for Primary Eyelid Cancers in Tunisia. Asian Pac J Cancer Prev 2016;17(7):3643-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27510024.
  15. ↑ 15.0 15.1 Bhatnagar A. Electronic brachytherapy for the treatment of non-melanoma skin cancer: Results up to 5 years. International Journal of Radiation Oncology Biology Physics 2015;1:E637-E638.
  16. ↑ 16.0 16.1 16.2 16.3 16.4 Campos A, Perez H, Lora D, Cabezas AM, Rodriguez V, Gascon N. Non-melanoma skin cancer treated with HDR Brachytherapy: Acute toxicity and cosmesis outcomes. Brachytherapy 2016;1:S67.
  17. ↑ 17.0 17.1 17.2 17.3 17.4 Cognetta AB, Howard BM, Heaton HP, Stoddard ER, Hong HG, Green WH. Superficial x-ray in the treatment of basal and squamous cell carcinomas: a viable option in select patients. J Am Acad Dermatol 2012 Dec;67(6):1235-41 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22818756.
  18. ↑ 18.00 18.01 18.02 18.03 18.04 18.05 18.06 18.07 18.08 18.09 18.10 Delishaj D, Laliscia C, Manfredi B, Ursino S, Pasqualetti F, Lombardo E, et al. Non-melanoma skin cancer treated with high-dose-rate brachytherapy and Valencia applicator in elderly patients: a retrospective case series. J Contemp Brachytherapy 2015 Dec;7(6):437-44 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26816500.
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 Ducassou A, David I, Filleron T, Rives M, Bonnet J, Delannes M. Retrospective analysis of local control and cosmetic outcome of 147 periorificial carcinomas of the face treated with low-dose rate interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2011 Nov 1;81(3):726-31 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21435798.
  20. ↑ 20.00 20.01 20.02 20.03 20.04 20.05 20.06 20.07 20.08 20.09 20.10 Ferro M, Deodato F, Macchia G, Gentileschi S, Cilla S, Torre G, et al. Short-course radiotherapy in elderly patients with early stage non-melanoma skin cancer: a phase II study. Cancer Invest 2015 Mar;33(2):34-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25608635.
  21. ↑ 21.0 21.1 21.2 21.3 21.4 21.5 Grossi Marconi D, da Costa Resende B, Rauber E, de Cassia Soares P, Fernandes JM Junior, Mehta N, et al. Head and Neck Non-Melanoma Skin Cancer Treated By Superficial X-Ray Therapy: An Analysis of 1021 Cases. PLoS One 2016;11(7):e0156544 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27367229.
  22. ↑ 22.0 22.1 22.2 22.3 22.4 Krema H, Herrmann E, Albert-Green A, Payne D, Laperriere N, Chung C. Orthovoltage radiotherapy in the management of medial canthal basal cell carcinoma. Br J Ophthalmol 2013 Jun;97(6):730-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23532618.
  23. ↑ 23.0 23.1 23.2 23.3 23.4 23.5 23.6 23.7 van Hezewijk M, Creutzberg CL, Putter H, Chin A, Schneider I, Hoogeveen M, et al. Efficacy of a hypofractionated schedule in electron beam radiotherapy for epithelial skin cancer: Analysis of 434 cases. Radiother Oncol 2010 May;95(2):245-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20334941.
  24. ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 Soysal HG, Soysal E, Markoç F, Ardiç F. Basal cell carcinoma of the eyelids and periorbital region in a Turkish population. Ophthalmic Plast Reconstr Surg 2008 May;24(3):201-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18520835.
  25. ↑ 25.0 25.1 25.2 25.3 Bhatnagar R, Kahan BC, Morley AJ, Keenan EK, Miller RF, Rahman NM, et al. The efficacy of indwelling pleural catheter placement versus placement plus talc sclerosant in patients with malignant pleural effusions managed exclusively as outpatients (IPC-PLUS): study protocol for a randomised controlled trial. Trials 2015 Feb 12;16:48 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25880969.
  26. ↑ 26.0 26.1 26.2 Ashby MA, Smith J, Ainslie J, McEwan L. Treatment of nonmelanoma skin cancer at a large Australian center. Cancer 1989 May 1;63(9):1863-71 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2702595.
  27. ↑ 27.0 27.1 27.2 CHURCHILL-DAVIDSON I, JOHNSON E. Rodent ulcers: an analysis of 711 lesions treated by radiotherapy. Br Med J 1954 Jun 26;1(4877):1465-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/13160499.
  28. ↑ Petrovich Z, Parker RG, Luxton G, Kuisk H, Jepson J. Carcinoma of the lip and selected sites of head and neck skin. A clinical study of 896 patients. Radiother Oncol 1987 Jan;8(1):11-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3809597.
  29. ↑ Lovett RD, Perez CA, Shapiro SJ, Garcia DM. External irradiation of epithelial skin cancer. Int J Radiat Oncol Biol Phys 1990 Aug;19(2):235-42 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2394605.
  30. ↑ Avril MF, Auperin A, Margulis A, Gerbaulet A, Duvillard P, Benhamou E, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer 1997;76(1):100-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9218740.
  31. ↑ Fitzpatrick PJ, Thompson GA, Easterbrook WM, Gallie BL, Payne DG. Basal and squamous cell carcinoma of the eyelids and their treatment by radiotherapy. Int J Radiat Oncol Biol Phys 1984 Apr;10(4):449-54 Available from: http://www.ncbi.nlm.nih.gov/pubmed/6725035.
  32. ↑ 32.0 32.1 Wilder RB, Kittelson JM, Shimm DS. Basal cell carcinoma treated with radiation therapy. Cancer 1991 Nov 15;68(10):2134-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1913451.
  33. ↑ Cho M, Gordon L, Rembielak A, Woo TC. Utility of radiotherapy for treatment of basal cell carcinoma: a review. Br J Dermatol 2014 Nov;171(5):968-73 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25041560.
  34. ↑ Mathers C, Penn R, Sanson-Fisher R, Carter R, Campbell E. Health system costs of cancer in Australia 1993-94. Canberra: Australian Institute of Health & Welfare.; 1998. Report No.: Cat No. HWE4..
  35. ↑ Carter R, Marks R, Hill D.. Could a national skin cancer primary prevention campaign in Australia be worthwhile?: an economic perspective. Health Promotion International 1999.
  36. ↑ Staples M, Marks R, Giles G. Trends in the incidence of non-melanocytic skin cancer (NMSC) treated in Australia 1985-1995: are primary prevention programs starting to have an effect? Int J Cancer 1998 Oct 5;78(2):144-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9754642.
  37. ↑ Swerdlow AJ, English JS, Qiao Z. The risk of melanoma in patients with congenital nevi: a cohort study. J Am Acad Dermatol 1995 Apr;32(4):595-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7896948.
  38. ↑ Karagas MR, McDonald JA, Greenberg ER, Stukel TA, Weiss JE, Baron JA, et al. Risk of basal cell and squamous cell skin cancers after ionizing radiation therapy. For The Skin Cancer Prevention Study Group. J Natl Cancer Inst 1996 Dec 18;88(24):1848-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8961975.
  39. ↑ Ewing MR.. The significance of a single injury in the causation of basal cell carcinoma of the skin. Aust N Z J Surg 1971;41:140-147.
  40. ↑ Castrow FF, Williams TE. Basal-cell epithelioma occurring in a smallpox vaccination scar. J Dermatol Surg 1976 May;2(2):151-2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/932293.
  41. ↑ Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol 1992 Mar;26(3 Pt 2):467-84 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1564155.
  42. ↑ (AJCCC) AJCoC. Cancer staging manual. Philadelphia, USA: Lippincott-Raven; 2002 [cited 2016 Dec 16].
  43. ↑ Mareco V, Bujor L, Abrunhosa-Branquinho AN, Ferreira MR, Ribeiro T, Vasconcelos AL, et al. Interstitial high-dose-rate brachytherapy in eyelid cancer. Brachytherapy 2015 Jul;14(4):554-64 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25959364.
  44. ↑ Swanson EL, Amdur RJ, Mendenhall WM, Morris CG, Kirwan JM, Flowers F. Radiotherapy for basal cell carcinoma of the medial canthus region. Laryngoscope 2009 Dec;119(12):2366-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19780029.
  45. ↑ Abbatucci JS, Boulier N, Laforge T, Lozier JC. Radiation therapy of skin carcinomas: results of a hypofractionated irradiation schedule in 675 cases followed more than 2 years. Radiother Oncol 1989 Feb;14(2):113-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2710943.
  46. ↑ Mendenhall WM, Parsons JT, Mendenhall NP, Million RR. T2-T4 carcinoma of the skin of the head and neck treated with radical irradiation. Int J Radiat Oncol Biol Phys 1987 Jul;13(7):975-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3597161.
  47. ↑ 47.0 47.1 Sussman LA, Liggins DF. Incompletely excised basal cell carcinoma: a management dilemma? Aust N Z J Surg 1996 May;66(5):276-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8634041.
  48. ↑ 48.0 48.1 McKay MJ. Advanced skin squamous cell carcinoma: role of radiotherapy. Aust Fam Physician 2014 Jan;43(1):33-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24563891.
  49. ↑ 49.0 49.1 Piccinno R, Benardon S, Gaiani FM, Rozza M, Caccialanza M. Dermatologic radiotherapy in the treatment of extensive basal cell carcinomas: a retrospective study. J Dermatolog Treat 2017 Aug;28(5):426-430 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28132575.
  50. ↑ Rishi KS, Alva RC, Kadam AR, Sharma S. Outcomes of Computed Tomography-Guided Image-Based Interstitial Brachytherapy for Cancer of the Cervix Using GEC-ESTRO Guidelines. Indian J Surg Oncol 2018 Jun;9(2):181-186 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29887698.
  51. ↑ 51.0 51.1 HAYES H. Basal cell carcinoma: the East Grinstead experience. Plast Reconstr Surg Transplant Bull 1962 Aug;30:273-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/13905648.
  52. ↑ Gooding CA, White G, Yatsuhashi M. Significance of marginal extension in excised basal-cell carcinoma. N Engl J Med 1965 Oct 21;273(17):923-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/5832875.
  53. ↑ Shanoff LB, Spira M, Hardy SB. Basal cell carcinoma: a statistical approach to rational management. Plast Reconstr Surg 1967 Jun;39(6):619-24 Available from: http://www.ncbi.nlm.nih.gov/pubmed/6026420.
  54. ↑ Pascal RR, Hobby LW, Lattes R, Crikelair GF. Prognosis of "incompletely excised" versus "completely excised" basal cell carcinoma. Plast Reconstr Surg 1968 Apr;41(4):328-32 Available from: http://www.ncbi.nlm.nih.gov/pubmed/5647401.
  55. ↑ Taylor GA, Barisoni D. Ten years' experience in the surgical treatment of basal-cell carcinoma. A study of factors associated with recurrence. Br J Surg 1973 Jul;60(7):522-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/4577594.
  56. ↑ De Silva SP, Dellon AL. Recurrence rate of positive margin basal cell carcinoma: results of a five-year prospective study. J Surg Oncol 1985 Jan;28(1):72-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3968892.
  57. ↑ 57.0 57.1 Richmond JD, Davie RM. The significance of incomplete excision in patients with basal cell carcinoma. Br J Plast Surg 1987 Jan;40(1):63-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3814899.
  58. ↑ 58.0 58.1 58.2 Liu FF, Maki E, Warde P, Payne D, Fitzpatrick P. A management approach to incompletely excised basal cell carcinomas of skin. Int J Radiat Oncol Biol Phys 1991 Mar;20(3):423-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1899855.
  59. ↑ Park AJ, Strick M, Watson JD. Basal cell carcinomas: do they need to be followed up? J R Coll Surg Edinb 1994 Apr;39(2):109-11 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7520063.
  60. ↑ Rippey JJ, Rippey E. Characteristics of incompletely excised basal cell carcinomas of the skin. Med J Aust 1997 Jun 2;166(11):581-3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9201177.
  61. ↑ Khan L, Choo R, Breen D, Assaad D, Fialkov J, Antonyshyn O, et al. Recommendations for CTV margins in radiotherapy planning for non melanoma skin cancer. Radiother Oncol 2012 Aug;104(2):263-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22857860.
  62. ↑ Tang S, Thompson S, Smee R. Metastatic basal cell carcinoma: case series and review of the literature. Australas J Dermatol 2017 May;58(2):e40-e43 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26916335.
  63. ↑ Wee E, Goh MS, Estall V, Tiong A, Webb A, Mitchell C, et al. Retrospective audit of patients referred for further treatment following Mohs surgery for non-melanoma skin cancer. Australas J Dermatol 2018 Jan 18 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29349770.
  64. ↑ RANK BK, WAKEFIELD AR. Surgery of basal-cell carcinoma. Br J Surg 1958 Mar 18;45(193):531-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/13536360.
  65. ↑ Emmett AJ. Surgical analysis and biological behaviour of 2277 basal cell carcinomas. Aust N Z J Surg 1990 Nov;60(11):855-63 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2241644.
  66. ↑ 66.0 66.1 Campos A, Perez H, Lora D, Cabezas AM, Rodrigues V, Gascon N, Guardado S, Perez-Regadera JF. Non-Melanoma Skin Cancer Treated with HDR-Brachytherapy: Acute Toxicity and Cosmesis Outcomes. Volume 15, S67 2016.


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Medical practitioners who through training, experience and peer opinion specialise in the management of keratinocyte cancers

showing evidence of squamatisation (descriptor applicable to basaloid tumours and indicating aggressive subtype)

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