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Table. Summary of Results
Table. Summary of Results
1.
Holt PJ. Cryotherapy for skin cancer: results over a 5-year period using liquid nitrogen spray cryosurgery.  Br J Dermatol. 1988;119(2):231-240PubMedArticle
2.
Kokoszka A, Scheinfeld N. Evidence-based review of the use of cryosurgery in treatment of basal cell carcinoma.  Dermatol Surg. 2003;29(6):566-571PubMed
3.
Quirk C, Gebauer K, De ’Ambrosis B, Slade HB, Meng TC. Sustained clearance of superficial basal cell carcinomas treated with imiquimod cream 5%: results of a prospective 5-year study.  Cutis. 2010;85(6):318-324PubMed
4.
Gollnick H, Barona CG, Frank RG,  et al.  Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe.  Eur J Dermatol. 2008;18(6):677-682PubMed
5.
Rosen T, Harting M, Gibson M. Treatment of Bowen's disease with topical 5% imiquimod cream: retrospective study.  Dermatol Surg. 2007;33(4):427-432PubMedArticle
6.
Patel GK, Goodwin R, Chawla M,  et al.  Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen's disease): a randomized, double-blind, placebo-controlled trial.  J Am Acad Dermatol. 2006;54(6):1025-1032PubMedArticle
Research Letter
Nov 2011

Cryoimmunotherapy: Superficial Basal Cell Cancer and Squamous Cell Carcinoma In Situ Treated With Liquid Nitrogen Followed by Imiquimod

Author Affiliations

Author Affiliations: Department of Dermatology, Division of Internal Medicine (Drs MacFarlane and El Tal), and Department of Plastic Surgery, Division of Surgery (Dr MacFarlane), The University of Texas MD Anderson Cancer Center, Houston.

Arch Dermatol. 2011;147(11):1326-1327. doi:10.1001/archdermatol.2011.334

Superficial basal cell cancer (sBCC) and squamous cell carcinoma in situ (SCCIS) are common skin cancers limited to the epidermis and traditionally treated with liquid nitrogen with success rates of approximately 90%.1,2 Other treatments include electrodessication and curettage, 5-fluorouracil, topical tretinoin, photodynamic therapy, imiquimod cream, and excision.

In a multicenter study of 169 patients with sBCC treated daily with imiquimod for 6 weeks, high initial (94.1%) and 5-year sustained (85.4%) clearance rates were observed.3 Others report similar findings.4 Of 49 patients with SCCIS treated with imiquimod, 5%, cream, 86% had a complete clearance.5 Patel et al6 report similar results.

Herein, we report the results of a study examining the efficacy of combining liquid nitrogen and imiquimod therapy to treat superficial skin cancers.

Methods

Immunocompetent patients with histologically confirmed sBCC and/or SCCIS who were treated with liquid nitrogen followed by a 6-week course of imiquimod, 5%, cream were eligible for this retrospective study approved by our institutional review board. Only immunocompetent patients with untreated, biopsy-proven sBCC or SCCIS who were observed for a period of 24 months or more were included. Patients were excluded if they (1) could not tolerate the treatment; (2) did not continue follow up for at least 24 months after treatment; or (3) were noncompliant with the regimen. Diagnosis of efficacy of treatment was based on the findings of clinical examination and/or histologic evaluation, when available. Informed consent was obtained from all patients.

Lesions were treated by one of us (D.F.M.) using a CRY-AC container (Brymill Cryogenic Systems, Ellington, Connecticut) with an aperture C (0.022 inches) at a distance of 8 to 10 cm for a period of approximately 5 seconds for 2 cycles, obtaining a 2-mm margin around the lesion. One week following the spray with liquid nitrogen, patients were instructed to apply a thin coat of imiquimod for 5 consecutive nights, to take 2 days off, and repeat for a total of 6 weeks. Patients were seen halfway through this course and 2 weeks following the course. Records were reviewed from February 1, 2003, until June 1, 2011. If there was clinical suspicion of recurrence, a punch biopsy was performed.

Results

A total of 152 patients with SCCIS or sBCC treated with cryoimmunotherapy were identified; 73 had to be excluded owing to lack of a 24-month follow-up, and 5 owing to a severe reaction to the cream.

sBCC Findings

Fifty patients (27 men and 23 women) with 57 sBCC lesions were treated. No patients were lost to follow-up. Twelve cancers were located on the head or neck, 45 on the trunk and/or extremities. Seventeen patients underwent posttreatment biopsies; all results were negative. Biopsies were performed on patient request for confirmation purposes. Of the 17 patients biopsied, 14 showed scarring, and 3 showed solar elastosis. Sixteen patients were biopsied at 3 to 5 months, and 1 patient at 10 months following treatment. Disease recurred at the same site in 1 patient, giving a recurrence rate of 2% for sBCC. Three patients had a severe reaction and had to be withdrawn from the study. Another seven patients were not compliant with treatment and were excluded. Mean follow-up was 46.4 months (range, 24-88 months) (Table). Seven patients required application of tretinoin, 0.025%, cream to enhance the imiquimod penetration and incite a reaction.

SCCIS Findings

Twenty-nine patients (14 men and 15 women) with 31 SCCIS lesions were treated. No patients were lost to follow-up. Nine cancers were located on the head or neck, 22 on the trunk and/or extremities. Five patients underwent posttreatment biopsies; all biopsy findings were negative. No recurrences were noted. Two patients experienced a severe reaction (ulcerations, severe erythema, constitutional symptoms) and were withdrawn from the study. Four patients were noncompliant. Mean follow-up was 43.5 months (range, 24-83 months) (Table). Four patients required application of tretinoin, 0.025%, cream to incite a skin reaction.

Comment

The recurrence rate was 2% for sBCC and 0% for SCCIS. In the 1 sBCC recurrence, the patient failed to apply the cream to a sufficiently wide area. An excellent cosmetic outcome was noted in all cases. In those cases in which a severe reaction occurred, eventual cosmetic outcome was also acceptable.

The combination treatment of liquid nitrogen followed by the application of imiquimod, for which the term cryoimmunotherapy is proposed, was more effective than either treatment alone and would appear to be more effective than other nonsurgical treatments for superficial skin cancers. We believe that liquid nitrogen damages the integrity of the stratum corneum, thereby facilitating penetration of the cream. Larger randomized studies are needed to assess the efficacy of this combination treatment.

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Article Information

Correspondence: Dr MacFarlane, The University of Texas MD Anderson Cancer Center, 1400 Pressler, Unit 1452, Houston, TX 77030 (dmacfarl@mdanderson.org).

Accepted for Publication: July 1, 2011.

Author Contributions: Both authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: MacFarlane. Acquisition of data: MacFarlane and El Tal. Analysis and interpretation of data: MacFarlane and El Tal. Drafting of the manuscript: MacFarlane. Critical revision of the manuscript for important intellectual content: MacFarlane and El Tal. Statistical analysis: MacFarlane and El Tal. Administrative, technical, and material support: El Tal. Study supervision: MacFarlane.

Financial Disclosure: None reported.

References
1.
Holt PJ. Cryotherapy for skin cancer: results over a 5-year period using liquid nitrogen spray cryosurgery.  Br J Dermatol. 1988;119(2):231-240PubMedArticle
2.
Kokoszka A, Scheinfeld N. Evidence-based review of the use of cryosurgery in treatment of basal cell carcinoma.  Dermatol Surg. 2003;29(6):566-571PubMed
3.
Quirk C, Gebauer K, De ’Ambrosis B, Slade HB, Meng TC. Sustained clearance of superficial basal cell carcinomas treated with imiquimod cream 5%: results of a prospective 5-year study.  Cutis. 2010;85(6):318-324PubMed
4.
Gollnick H, Barona CG, Frank RG,  et al.  Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe.  Eur J Dermatol. 2008;18(6):677-682PubMed
5.
Rosen T, Harting M, Gibson M. Treatment of Bowen's disease with topical 5% imiquimod cream: retrospective study.  Dermatol Surg. 2007;33(4):427-432PubMedArticle
6.
Patel GK, Goodwin R, Chawla M,  et al.  Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen's disease): a randomized, double-blind, placebo-controlled trial.  J Am Acad Dermatol. 2006;54(6):1025-1032PubMedArticle
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