Facial basal cell carcinoma
Cite this as: BMJ 2012;345:e5342
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I read with great interest the clinical review on facial basal-cell carcinoma (BCC) by Baxter et al.1 Indeed BCC grows locally with invasion and destruction of local tissues and rarely metastasizes. Therefore treatment mainly consists of surgery for high-risk BCC, but other options are available for low-risk BCC.1 However locally advanced BCC can be inoperable because of multiple postsurgical recurrences or risk of significant deformity or loss of function, and radiotherapy can be contraindicated. Furthermore chemotherapy for metastatic disease is poorly effective.
Surprisingly, the authors only mention-–at the end of the “Questions for future research” section--the inhibitors of Hedgehog signalling pathway for advanced BCC.1 Indeed, alterations in this pathway are observed in most BCC resulting in aberrant pathway activation and uncontrolled proliferation of basal cells.2 Vismodegib is the first Hedgehog pathway inhibitor approved in the US for the treatment of metastatic BCC or locally advanced BCC with contraindications to surgery or radiation therapy.2 This oral drug seems to be a promising alternative treatment. Its interest was suggested in a phase I study including 33 patients with advanced BCC with a 58% response rate and a median duration of response of 12.8 months.3 In a recent non-randomized phase II study the response rate was 30% in 33 patients with metastatic BCC, 43% in 63 patients with locally advanced BCC with complete responses in 21%, and the median duration of response was 7.6 months in both groups.4 The tolerability was acceptable with adverse events consisting of muscle spasms, fatigue, alopecia, dysgueusia, and weight loss.3,4 However, in 28 patients with vismodegid-responsive tumor and still continuing therapy, tumor regrowth has been reported in 21% of them within or immediately adjacent to the prior tumor bed with disputed pathogenetic mechanisms.5
In conclusion, vismodegib is a real new treatment option for advanced BCC, but further studies with larger numbers of patients and longer periods of follow-up are still required.
1. Baxter JM, Patel AN, Varma S. Facial basal cell carcinoma. BMJ 2012;345:e5342.
2. Keating GM. Vismodegib: in locally advanced or metastatic Basal cell carcinoma. Drugs 2012;72:1535-41.
3. LoRusso PM, Rudin CM, Reddy JC, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res 2011;17:2502-11.
4. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012;366:2171-9.
5. Chang AL, Oro AE. Initial assessment of tumor regrowth after vismodegib in advanced basal cell carcinoma. Arch Dermatol 2012 Aug 20:1-2 [Epub ahead of print].
Competing interests: None declared
Hôpital Tenon (AP-HP), Paris, France
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We read with great interest the review on Facial basal cell carcinoma by Julia M. Baxter et al.(1) published on the 21st of August 2012 and we found both the overview and the synopsis very accurate and interesting. Our Clinic of Plastic Surgery has grown an extensive experience in the management of basal cell carcinoma and, serving a large population of patients from the North-eastern Italy, we strongly agree that the issue is of primary medical and social importance. Baxter et al. have correctly outlined current therapeutic alternative and possible therapeutic strategies: even so, we may partially disagree with the indication of authors to avoid any treatment in a subset of elderly patients affected by serious comorbidities, which in our experience may represent a considerable amount of cases. In this light we would like to briefly comment on the chance to adopt novel therapeutic approaches which have provided valuable results in recent literature, such as electrochemotherapy.
Gargiulo et al.(2) have recently reported the effective adoption of electrochemotherapy using bleomycin in a series of patients affected by non-melanoma head and neck cancers, among which nine having a facial basal cell carcinoma. Similarly to other reports, patients were addressed to the treatment mostly due to their age and poor general conditions, both of which remarkably limiting other therapeutic approaches. Almost all patients (8/9) achieved a complete response after one treatment with no recurrences up to twenty months. Indeed, the therapeutic strategy account for a cost-effective low-invasive treatment since it may be performed under sedation and local anesthesia in dedicated outpatient surgeries without the need for hospitalization.
These outcomes confirm those of previous series reported by Glass et al.(3) (20 patients showing totally 54 lesions treated, achieving a complete response in 98% of cases, mostly after a single treatment) and others (4) also for complex ulcerated lesions.(5) Testori et al.(4) resumed main advantages of the procedure in the high rate of success after a single session and in the excellent safety profile with an advantageous cost/benefit ratio. Notably, all these features contribute to a reasonable improvement of quality of life, physical and psychological wellness, life expectancy. Furthermore, the treatment has also been proposed as ideal palliative care in critical patients.(6)
In conclusion, in our opinion it may be precipitous to extend, as some authors have suggested, the adoption of electrochemotherapy as first-line treatment in less severe patients: even so, we suggest that this valuable novel therapeutic strategy should be reported and taken in consideration in order to provide a more comprehensive discussion on therapeutic decision-making and currently available alternatives for complex patients.
1. Baxter JM, Patel AN, Varma S. Facial basal cell carcinoma. BMJ. 2012;345:e5342.
2. Gargiulo M, Papa A, Capasso P, Moio M, Cubicciotti E, Parascandolo S. Electrochemotherapy for non-melanoma head and neck cancers: clinical outcomes in 25 patients. Ann Surg. 2012;255(6):1158-1164.
3. Glass LF, Jaroszeski M, Gilbert R, Reintgen DS, Heller R. Intralesional bleomycin-mediated electrochemotherapy in 20 patients with basal cell carcinoma. J Am Acad Dermatol. 1997;37(4):596-599.
4. Testori A, Tosti G, Martinoli C, Spadola G, Cataldo F, Verrecchia F, Baldini F, Mosconi M, Soteldo J, Tedeschi I, Passoni C, Pari C, Di Pietro A, Ferrucci PF. Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach. Dermatol Ther. 2010;23(6):651-661
5. Richetta AG, Curatolo P, D'Epiro S, Mancini M, Mattozzi C, Giancristoforo S, Rotunno R, Calvieri S. Efficacy of electrochemotherapy in ulcerated basal cell carcinoma. Clin Ter. 2011;162(5):443-445.
6. Fantini F, Gualdi G, Cimitan A, Giannetti A. Metastatic basal cell carcinoma with squamous differentiation: report of a case with response of cutaneous metastases to electrochemotherapy. Arch Dermatol. 2008;144(9):1186-1188.
Competing interests: None declared
Clinic of Plastic Surgery, Padua University Hospital, V floor Monoblocco Ospedaliero, Via Giustiniani, 2 I-35100 Padua (Italy)
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This article gives an excellent overview of BCC management but a number of points need to be raised: Mohs micrographic surgery (MMS), a technique developed by Frederic Mohs a general surgeon in the 1930’s is currently limited in the UK, a fact that is recognised by the British Society of Dermatological Surgery and British Association of Dermatologists in their 2011 report 1. The authors state that this is the treatment of choice for lesions of the central face, high risk and recurrent lesions however, issues of access to MMS need to be addressed. Currently in the UK it is anticipated that most Moh’s surgeons on average undertake 3 – 5 cases a weeks1 with access to Mohs currently limited to specialist regional units. Given that 75,000 of the UK population develop BCC’s, one must consider whether training programmes should be widened to include specialities such as Plastic, Oculoplastic and ENT surgery who are commonly involved in post-Mohreconstruction of complex defects. Whilst fellowships in Mohs micrographic surgery are available, these tend to be for the minority and geared to dermatology trainees, improving exposure to this important technique at an early stage may prove pivotal in increasing public access to MMS and allowing simultaneous excisional and reconstructive surgery at the same site. Perhaps the time has come to consider MMS as an interface specialty in itself, taking note from the success of other areas such as hand and breast surgery in bringing together clinicians from different specialist training pathways to provide a common resource in treating patients.
With regards to the mentioned use of photodynamic therapy (PDT), current guidance is that it should not be used for infiltrative or recurrent lesions 2. Guidance on both BCC management and PDT from the British association of Dermatologist suggests its use in patients with primary superficial BCC’s and low-risk nodular BCC’s though in the later situation it is less efficacious than surgery 2,3. Another factor in using PDT that was not mentioned in it that it can be a time consuming process requiring the application of the photosensitising agent for a number of hours before treatment.
Whilst this article presented an excellent overview of common modalities employed in treating basal cell carcinomas, more novel techniques such as vismodegib, the hedgehog signalling pathway inhibitor, were not considered. Approved by the US FDA in January 2012, phase II data has shown promising results in treating patients with both locally-advanced (43% response) and metastatic (30% response) basal cell carcinoma4. However, significant adverse events were noted, of which seven were patient deaths. Furthermore, the cost of implementing vismodegib at an estimated $7,500 (£4700) or $75,000 (£47,000) for a ten-month course (Genentech, Roche Group, USA) may well be prohibitive in allowing widespread use5. Regardless, these areas remain important avenues for exploration, particularly in the specific target group with inoperable disease or those for whom surgery is inappropriate due to the anticipated surgical disfigurement or low cure rate.
Mr Kavan S Johal+, Mr Saif Ramman+, Mr Chidi Ekwobi*
+Core Trainees in Plastic Surgery, *Specialist Registrar (SpR) in Plastic Surgery
1. BSDS Mohs Setting Standards Working Group. British Association of Dermatologists working party report on setting standards for Mohs Micrographic Surgery Services. Recommendations of The British Society for Dermatological Surgery and British Association of Dermatologists. November 2011 (final revision 4a AC).
2. Telfer NR, Colver GB, Morton CA; British Association of Dermatologists. Guidelines for the management of basal cell carcinoma. Br J Dermatol. 2008 Jul;159(1):35-48.
3. Morton CA, McKenna KE, Rhodes LE; British Association of Dermatologists. Therapy Guidelines and Audit Subcommittee and the British Photodermatology Group. Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008 Dec;159(6):1245-66.
4. Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366(23):2171-9.
Competing interests: None declared
Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Fulwood, Preston, Lancashire, PR2 9HT
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