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

Abstract

This case series analyzes the outcomes of patients with primary cutaneous squamous cell carcinoma treated with limited-field irradiation for microscopic residual disease after surgery.

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.

Table. Characteristics and Outcomes of Patients With Tumors Treated With Salvage Radiation Therapy.

Patient No.	Immunosuppression	Tumor Location	Tumor Stage (BWH/AJCC8)	High-Risk Factors	Primary Tumor Treatment	Radiation Treatment Year	Reason Reexcision Not Performed	Outcomes	Disease-Free Survival, mo
1	None	Nose	T2a/T1	Poor differentiation, PNI (unknown nerve caliber)	Excision with positive margins, salvage XRT with electrons (60 Gy in 30 fractions)	2006	Reexcision would be disfiguring	LR, NM, DSD	7
2	None	Nose	T2b/T3	Tumor diameter (4.0 cm), depth of invasion (nasal mucosa)	Rhinectomy with positive margins, salvage XRT	2007	Rhinectomy already performed	LR, NM, DSD	30
3	Chronic lymphocytic leukemia	Cutaneous lip	T2b/T3	Poor differentiation, depth of invasion (muscle), neurotropism	MMS with positive margins, salvage XRT with brachytherapy (56.1 Gy in 17 fractions)	2006	Patient declined reexcision	NM, DSD	5
4	None	Neck	T2a/T3	Poor differentiation, depth of invasion (7.6 mm), PNI (unknown nerve caliber)	Excision with positive margins, salvage XRT with IMRT (66 Gy in 30 fractions)	2005	Advised to pursue radiation instead of reexcision	Parotid metastasis, NM	29
5	Systemic lupus erythematosus, RTR	Hand	T2b/NA	Poor differentiation, tumor diameter (2.0 cm)	Excision with positive margins, salvage XRT with electrons (54 Gy in 30 fractions)	2012	Advised to pursue radiation instead of reexcision	NM, DM, DSD	0
6	Dermatomyositis, psoriasis, scleroderma	Elbow	T2b/NA	Poor differentiation, depth of invasion (fascia), PNI (0.2 mm)	MMS with focal positive deep margin, salvage XRT with brachytherapy (25 fractions)	2017	Patient declined reexcision	In transit metastasis, NM	3
7	None	Scalp	T2b/T3	Tumor diameter (2.0 cm), depth of invasion (9.0 mm, muscle)	MMS with positive margins, salvage XRT with electrons (50 Gy in 20 fractions)	2015	Positive deep margin	Parotid metastasis	10
8	None	Scalp	T2b/T3	Poor differentiation, depth of invasion (12 mm, galea)	Excision with positive margins, salvage XRT with electrons (52.50 Gy in 29 fractions)	2009	Positive deep margin	LR	21
9	RTR	Cheek	T2b/T3	Poor differentiation, tumor diameter (4.0 cm), PNI (unknown nerve caliber)	Excision with focal positive margins, salvage XRT with electrons (60 Gy in 30 fractions)	2010	Multiple excisions already performed	LR, NM, DM	34
10	None	Cheek	T2b/T2	Poor differentiation, tumor diameter (2.0 cm), PNI (multifocal, unknown nerve caliber)	Excision with positive margins, salvage XRT with brachytherapy (60 Gy in 24 fractions)	2013	Reexcision would not clear residual disease	NED	60
11	Follicular lymphoma	Neck	T2b/T3	Poor differentiation, tumor diameter (2.9 cm), PNI (diameter 0.1 mm)	MMS with positive margins, salvage XRT with electrons (59 Gy in 29 fractions)	2015	Patient declined reexcision	NED	8

Abbreviations: BWH, Brigham and Women’s Hospital tumor staging system; AJCC8, American Joint Committee on Cancer 8th edition tumor staging system; DM, distant metastasis; DSD, disease-specific death; IMRT, intensity-modulated radiation therapy; LR, local recurrence; MMS, Mohs micrographic surgery; NA, not available; NED, no evidence of disease; NM, nodal metastasis; PNI, perineural invasion; RTR, renal transplant recipient; XRT, radiation therapy.

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.