Surgery and Salvage Limited-Field Irradiation for Control of Cutaneous Squamous Cell Carcinoma With Microscopic Residual Disease | Dermatology | JAMA Dermatology | JAMA Network
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Table.  Characteristics and Outcomes of Patients With Tumors Treated With Salvage Radiation Therapy
Characteristics and Outcomes of Patients With Tumors Treated With Salvage Radiation Therapy
1.
Rogers  HW, Weinstock  MA, Feldman  SR, Coldiron  BM.  Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012.  JAMA Dermatol. 2015;151(10):1081-1086. doi:10.1001/jamadermatol.2015.1187PubMedGoogle ScholarCrossref
2.
Jambusaria-Pahlajani  A, Miller  CJ, Quon  H, Smith  N, Klein  RQ, Schmults  CD.  Surgical monotherapy versus surgery plus adjuvant radiotherapy in high-risk cutaneous squamous cell carcinoma: a systematic review of outcomes.  Dermatol Surg. 2009;35(4):574-585. doi:10.1111/j.1524-4725.2009.01095.xPubMedGoogle ScholarCrossref
3.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. squamous cell skin cancer. version 2. 2019. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed December 13, 2018.
4.
Karia  PS, Jambusaria-Pahlajani  A, Harrington  DP, Murphy  GF, Qureshi  AA, Schmults  CD.  Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women’s Hospital tumor staging for cutaneous squamous cell carcinoma.  J Clin Oncol. 2014;32(4):327-334. doi:10.1200/JCO.2012.48.5326PubMedGoogle ScholarCrossref
Research Letter
August 21, 2019

Surgery and Salvage Limited-Field Irradiation for Control of Cutaneous Squamous Cell Carcinoma With Microscopic Residual Disease

Author Affiliations
  • 1Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio
  • 3Department of Otolaryngology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
JAMA Dermatol. 2019;155(10):1193-1195. doi:10.1001/jamadermatol.2019.2190

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant neoplasm in the United States, with an estimated 1 million cases diagnosed annually.1 Most patients have an excellent prognosis with surgery alone, but a small subset have poor outcomes. Margin status following surgery greatly affects outcomes.2 Complete circumferential peripheral and deep margin assessment, which involves en face sectioning to allow for nearly 100% histologic margin assessment, is associated with lower recurrence rates compared with standard assessment, in which approximately 1% of the margin is evaluated (A. Waldman, MD, written communication, January 2019). National Comprehensive Cancer Network guidelines for CSCC include salvage radiation therapy as an option for positive histologic margins after surgical excision.3 However, there are limited data evaluating outcomes after salvage radiation therapy. Herein we review outcomes of patients with primary CSCCs treated with salvage limited-field irradiation for microscopic residual disease after surgery.

Methods

The study was approved by Partners Human Research Committee, which waived patient written informed consent because all data were deidentified. Patients with CSCC diagnosed at Brigham and Women’s Hospital (BWH) from January 1, 2000, through December 31, 2017, were identified via the Department of Pathology’s electronic database. Pathology reports were reviewed, and patients with noncutaneous SCC, in situ CSCC, and recurrent CSCC were excluded. Patients with surgically treated primary tumors with histologic positive margins without gross residual disease after salvage irradiation were included in the study. Tumors were staged using the BWH staging system4 and the American Joint Committee on Cancer 8th edition staging (AJCC8) system for head and neck CSCC. Tumors categorized as BWH stage T3 or AJCC8 T4a/T4b were excluded because these tumors have a high risk of poor outcomes regardless of treatment modality.4 Medical records of eligible patients were reviewed for clinical information, primary tumor characteristics, outcomes (including local recurrence [LR], nodal metastasis, distant metastasis [DM], and disease-specific death [DSD]), types of treatment (including surgical method and adjuvant therapy), and information on radiation treatment (ie, radiation modality, dose, and fractions). Descriptive statistics were performed in October 2018.

Results

A total of 11 patients (8 men and 3 women; mean [SD] age, 70 [11] years) with CSCCs who underwent salvage irradiation for positive histologic margins were identified. Patient and tumor characteristics, treatments, and outcomes are summarized in the Table. Most patients (10 [91%]) had high-stage tumors based on the AJCC8 (ie, T3) and/or BWH (ie, T2b) staging systems. All patients received salvage radiation therapy to the primary tumor only. Nine of 11 patients (82%) had a CSCC-related poor outcomes. Four patients (36%) had a LR, 7 (64%) developed nodal metastasis, 2 (18%) developed DM, and 3 (36%) died of CSCC. Of the 9 patients who had a poor outcome, the disease-free interval ranged from 0 to 34 months (mean, 19 months). One of 2 patients who had no evidence of disease died from follicular lymphoma 8 months after treatment. The other patient with no evidence of disease was alive and had no evidence of recurrence at 60 months.

Discussion

Prior adjuvant radiation studies2 for CSCC have included clear and positive histologic margins in the same analysis, making it difficult to evaluate the association between microscopic residual disease and outcomes. The data presented herein indicate that salvage limited-field irradiation for aggressive CSCCs with microscopic residual disease resulted in a progression rate of more than 80%, although only 4 patients developed LR within the radiated field. This rate is much higher than the usual failure rate for high-risk CSCC. In patients with BWH T2b stage CSCC, the usual LR rate is 26% (71 of 273), and the overall CSCC failure rate is 33% (90 of 273) (BWH, unpublished data, January 2000 to December 2016). Thus, radiation therapy can aide in local control of tumors when histologic negative margins cannot be achieved, but may be limited in overall disease control in those with AJCC or BWH high-stage tumors given the high risk of out-of-field progression. This small series underscores the importance of aggressive surgery to achieve negative margins whenever feasible, and the need to intensify radiation volume and consider incorporating systemic therapies. Additional studies are needed to optimize management of CSCCs with positive margins.

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Article Information

Accepted for Publication: June 9, 2019.

Corresponding Author: Chrysalyne D. Schmults, MD, MSCE, Department of Dermatology, Brigham and Women’s Hospital, 1153 Centre St, Ste 4J, Boston, MA 02130 (cschmults@bwh.harvard.edu).

Published Online: August 21, 2019. doi:10.1001/jamadermatol.2019.2190

Author Contributions: Drs Ruiz and Schmults 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: Ruiz, Schmults.

Acquisition, analysis, or interpretation of data: Ruiz, Koyfman, Kass.

Drafting of the manuscript: Ruiz.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Ruiz.

Study supervision: Koyfman, Schmults.

Conflict of Interest Disclosures: Dr Koyfman reported research support from Merck and honoraria from UpToDate and Varian Medical Systems outside the submitted work. No other disclosures were reported.

Funding/Support: Dr Ruiz is supported by a Dermatology Foundation Career Development Award.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Jonathan D. Schoenfeld, MD, MPhil, MPH, from the Department of Radiation Oncology, Dana-Farber Cancer Institute, for assisting us with the radiation treatment content. He received no compensation for his contribution.

References
1.
Rogers  HW, Weinstock  MA, Feldman  SR, Coldiron  BM.  Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012.  JAMA Dermatol. 2015;151(10):1081-1086. doi:10.1001/jamadermatol.2015.1187PubMedGoogle ScholarCrossref
2.
Jambusaria-Pahlajani  A, Miller  CJ, Quon  H, Smith  N, Klein  RQ, Schmults  CD.  Surgical monotherapy versus surgery plus adjuvant radiotherapy in high-risk cutaneous squamous cell carcinoma: a systematic review of outcomes.  Dermatol Surg. 2009;35(4):574-585. doi:10.1111/j.1524-4725.2009.01095.xPubMedGoogle ScholarCrossref
3.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. squamous cell skin cancer. version 2. 2019. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed December 13, 2018.
4.
Karia  PS, Jambusaria-Pahlajani  A, Harrington  DP, Murphy  GF, Qureshi  AA, Schmults  CD.  Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women’s Hospital tumor staging for cutaneous squamous cell carcinoma.  J Clin Oncol. 2014;32(4):327-334. doi:10.1200/JCO.2012.48.5326PubMedGoogle ScholarCrossref
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