CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Eruptive cutaneous squamous cell carcinoma and psoriasis: response to cetuximab M. Kamaria,1 C. R. Shea,1 R. K. Chin,2 E. E. Cohen,3 R. Maggiore3 and D. Bolotin1 1
Section of Dermatology, 2Department of Radiation Oncology, and 3Section of Hematology-Oncology, University of Chicago, Chicago, IL, USA
doi:10.1111/ced.12341
Summary
Cutaneous squamous cell carcinomas (CSCCs) comprise 20–30% of nonmelanoma skin cancers (NMSCs), and continue to increase in incidence. We report a case of a patient with severe psoriasis who had recurrent and eruptive CSCCs on her leg, which were successfully treated with cetuximab and radiotherapy. The patient had successful long-term clearance of her skin tumours, with the additional finding of resolution of psoriasis while on cetuximab therapy.
Nonmelanoma skin cancers (NMSCs) are the most common malignancy worldwide, and 20–30% of these are cutaneous squamous cell carcinomas (CSCCs). With early detection and surgical treatment, CSCCs have an excellent prognosis. In patients not amenable to surgical treatment, limited data exist regarding optimal therapeutic solutions. We report a case of a patient with multiple comorbidities precluding surgical treatment of eruptive CSCCs, and resolution with cetuximab and radiotherapy.
Report A 93-year old white woman presented with large nodule and several smaller nodules on her right leg. She had a history of cellulitis on her right leg, along with erythrodermic and plaque psoriasis and NMSC. On physical examination, a keratotic nodule 15 mm in size was seen within a scar from a prior CSCC excision (Fig. 1a; arrow) on the patient’s right leg, as well as 10 smaller (5–10 mm) keratotic nodules on the same leg (Fig. 1a, b; arrowheads).
Correspondence: Dr Diana Bolotin, 5841 S. Maryland Ave, MC 5067, Chicago, IL 60637-1470, USA E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 17 January 2014
604
Clinical and Experimental Dermatology (2014) 39, pp604–607
Histological examination of biopsies taken from the large central nodule and two smaller lesions showed invasive SCCs (Fig. 1c). The dermatopathology findings were not consistent with keratoacanthomas. The aetiology of these eruptive CSCCs was unclear but was probably related to a combination of field cancerization because of her history of extensive phototherapy [narrowband ultraviolet (UV)B and psoralen UVA] and her treatment with etanercept and methotrexate for her psoriasis.1 The patient’s age, her poorly controlled psoriasis and the presence of multiple tumours below the knee and recent cellulitis in the same leg increased the likelihood of healing complications and precluded surgical treatment. The patient had a strong preference against extensive surgical procedures. Nonsurgical approaches were considered, including systemic therapy and radiotherapy (RT). Previous intolerance of acitretin for psoriasis precluded its use. A multidisciplinary approach of electron beam radiation to the central recurrent CSCC and intravenous cetuximab for the eruptive CSCCs was pursued. The patient received a total radiation dose of 66 Gy over 6 weeks delivered in 3 Gy fractions, with concomitant cetuximab (loading dose 400 mg/m2 and four subsequent weekly infusions of 250 mg/m2 each). By week 4, all lesions had resolved, and a shallow erosion remained in the area of the recurrent CSCC (Fig. 2a; arrow). The patient had complete clinical response after 6 weeks of therapy. Remarkably, the psoriatic lesions
ª 2014 British Association of Dermatologists
Eruptive CSCC and psoriasis: response to cetuximab M. Kamaria et al.
(a)
(b)
(c) Figure 1 (a) Diffuse erythema with coarse yellow scale on the right leg. A keratotic nodule 15 mm in size with central hemorrhagic
crust within a linear scar (arrow) and 10 smaller (5–10 mm) dome-shaped nodules with central keratotic crusts (arrowheads). (b) Right lateral shin with eruptive keratotic nodules (arrowheads). (c) Keratinocytes with full thickness severe cytological atypia extending from the epidermis into the dermis, consistent with invasive cutaneous squamous cell carcinomas. Hematoxylin and eosin stain, original magnifications as marked.
also completely responded within 2 weeks of starting cetuximab therapy (Fig. 2a), although they recurred within 3 months of cetuximab discontinuation and
ª 2014 British Association of Dermatologists
were treated topically (Fig. 2b). Adverse effects of the treatment included fatigue, shortness of breath, and residual erosion at the radiated site. The pulmonary
Clinical and Experimental Dermatology (2014) 39, pp604–607
605
Eruptive CSCC and psoriasis: response to cetuximab M. Kamaria et al.
Figure 2 (a) Complete clinical resolution
(a)
(b)
symptoms were deemed secondary to chronic obstructive pulmonary disease. No acneiform eruption developed while the patient was on cetuximab. The patient’s CSCCs showed continued response, with lack of recurrence for 9 months (Fig. 2b; arrowhead). At the 9-month follow-up, a new nodule was noted on her right lateral calf, outside the radiation field, and biopsy confirmed invasive CSCC. This was thought to be a de novo CSCC or a recurrent satellite lesion, and was treated with radiation (51 Gy total dose in 3 Gy fractions) with complete resolution. No other concerning growths were noted on the right leg at 13 months posttreatment, when she died from a stroke. Therapeutic options for nonresectable CSCC include local, field and systemic therapy. Identification of tumours at risk for recurrence or metastasis is important for optimizing outcomes. Although no universal guidelines for risk categorization exist, the American Joint Committee on Cancer (AJCC) considers the following factors as high risk (for noneyelid carcinoma): ≥ 2 mm Breslow thickness, Clark level ≥ 4, perineural invasion, location on ear or hair-bearing lip, and poorly differentiated or undifferentiated histological type.2 Eruptive CSCCs represent a therapeutic challenge, regardless of risk level. For high-risk nonresectable CSCC, treatment options include RT, combined chemotherapy and RT, or systemic chemotherapy. RT may be used when tumour size, location or comorbidities preclude surgery. RT has higher recurrence rates than surgical resection as
606
Clinical and Experimental Dermatology (2014) 39, pp604–607
of all of the satellite lesions at 4 weeks into the treatment course; a shallow erosion (arrow) in the area of the central recurrent squamous cell carcinoma (SCC) lesion being treated with radiotherapy. Note resolution of diffuse erythema and scaling on the shin. (b) At 3 months post-treatment, there was complete clinical response of the eruptive cutaneous SCC lesions as well as the recurrent SCC (arrowhead). Note the recurrence of the psoriatic plaques.
monotherapy, but is an excellent adjuvant to surgical excision or chemotherapy. However, RT cannot be used at previously irradiated sites because of the risk of tissue necrosis. Various chemotherapy agents for high-risk tumours have been reported, including cytotoxic agents (cisplatin, 5-fluorouracil, capecitabine, bleomycin and doxyrubicin), 13-cis-retinoic acid and interferon, and epidermal growth factor receptor (EGFR)-blocking agents. Clinical efficacy data is limited by small study populations and lack of randomization. The choice of agent is conditional upon comorbidities, toxicities and side-effect profiles.3 Utility in eruptive CSCCs has not been reported. Cetuximab is a monoclonal antibody that competitively inhibits EGFR. It is approved for head and neck SCC (HNSCC) and colorectal cancer. A phase II trial4 in patients (n = 36) with unresectable CSCC demonstrated disease control in 69% of patients at 6 weeks. Several case reports have also shown efficacy for refractory or unresectable CSCC.5,6 Evidence from patients with HNSCC demonstrates synergy between cetuximab and RT in improving locoregional control and survival, without increasing RT-associated toxicity.7 Cetuximab has a favourable side effect profile, with folliculitis as the most common adverse effect. These studies, combined with our case, suggest that cetuximab is a viable option for eruptive CSCCs, especially in elderly patients. We chose a combination approach of RT for the higher-risk recurrent lesion, and cetuximab to treat the
ª 2014 British Association of Dermatologists
Eruptive CSCC and psoriasis: response to cetuximab M. Kamaria et al.
surrounding CSCCs and provide a radiosensitizing effect. Concerns about poor healing and extensive tissue necrosis precluded irradiation of the entire leg. No cases of eruptive CSCCs treated with radiation and cetuximab have been reported previously, to our knowledge. Remarkably, complete response of both the eruptive CSCCs and psoriasis were observed. Previous case reports demonstrated similar dual response to cetuximab in psoriasis and colon carcinoma.8,9 Dual efficacy in epithelial tumours and psoriasis probably relates to increased cell proliferation and EGFR activity, which is downregulated by cetuximab. This case highlights a role for cetuximab in the treatment of eruptive CSCCs, as an adjunct to RT in high-risk SCC, and as a potential therapy for psoriasis. Our patient had an excellent response to treatment of multiple CSCCs, with only one recurrent lesion posttreatment and complete clearance of psoriasis within 3 months after therapy. Further studies are needed to better elucidate the therapeutic role of cetuximab in CSCCs and psoriasis.
Learning points ● Around 20–30% of NMSCs are CSCCs. ● Limited data exist, and there are no standard
guidelines on optimal treatment for nonresectable tumours, particularly eruptive CSCCs. ● Treatment may involve RT, chemotherapy, or combination chemotherapy and RT, and outcomes are highly variable. ● Cetuximab is a viable and efficacious option in nonresectable and multiply eruptive CSCCs, particularly in elderly patients. ● Cetuximab synergizes with RT to improve locoregional control and survival, without increasing RT-associated toxicity. ● EGFR inhibitors may have a potential therapeutic role in psoriasis.
ª 2014 British Association of Dermatologists
References 1 Bangash SJ, Green WH, Dolson DJ et al. Eruptive postoperative squamous cell carcinomas exhibiting a pathergy-like reaction around surgical wound sites. J Am Acad Dermatol 2009; 61: 892–7. 2 Edge S, Byrd DR, Compton CC et al. AJCC Cancer Staging Manual, 7th edn. New York: Springer, 2010. 3 Cranmer LD, Engelhardg C, Morgan SS. Treatment of unresectable and metastatic cutaneous squamous cell carcinoma. Oncologist 2010; 15: 1320–8. 4 Maubec E, Petrow P, Scheer-Senyarich I et al. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol 2011: 29: 3419–26. 5 Kalapurakal SJ, Malone J, Robbins KT et al. Cetuximab in refractory skin cancer treatment. J Cancer 2012; 3: 357–61. 6 Goppner D, Nekwasil S, Franke I et al. Successful combination therapy of a locally advanced squamous cell carcinoma of the skin with cetuximab and c-radiation. J Dtsch Dermatol Ges 2010; 8: 826–8. 7 Bernier J, Schneider D. Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squmaous cell carcinoma of the head and neck? Eur J Can 2007; 43: 35–45. 8 Neyns B, Meert V, Vandenbroucke F. Cetuximab treatment in a patient with metastatic colorectal cancer and psoriasis. Curr Oncol 2008; 15: 196–7. 9 Trivin F, Boucher E, Raoul J. Complete sustained regression of extensive psoriasis with cetuximab combination chemotherapy. Acta Oncol 2004; 43: 592–3.
Clinical and Experimental Dermatology (2014) 39, pp604–607
607
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Eruptive cutaneous squamous cell carcinoma and psoriasis: response to cetuximab M. Kamaria,1 C. R. Shea,1 R. K. Chin,2 E. E. Cohen,3 R. Maggiore3 and D. Bolotin1 1
Section of Dermatology, 2Department of Radiation Oncology, and 3Section of Hematology-Oncology, University of Chicago, Chicago, IL, USA
doi:10.1111/ced.12341
Summary
Cutaneous squamous cell carcinomas (CSCCs) comprise 20–30% of nonmelanoma skin cancers (NMSCs), and continue to increase in incidence. We report a case of a patient with severe psoriasis who had recurrent and eruptive CSCCs on her leg, which were successfully treated with cetuximab and radiotherapy. The patient had successful long-term clearance of her skin tumours, with the additional finding of resolution of psoriasis while on cetuximab therapy.
Nonmelanoma skin cancers (NMSCs) are the most common malignancy worldwide, and 20–30% of these are cutaneous squamous cell carcinomas (CSCCs). With early detection and surgical treatment, CSCCs have an excellent prognosis. In patients not amenable to surgical treatment, limited data exist regarding optimal therapeutic solutions. We report a case of a patient with multiple comorbidities precluding surgical treatment of eruptive CSCCs, and resolution with cetuximab and radiotherapy.
Report A 93-year old white woman presented with large nodule and several smaller nodules on her right leg. She had a history of cellulitis on her right leg, along with erythrodermic and plaque psoriasis and NMSC. On physical examination, a keratotic nodule 15 mm in size was seen within a scar from a prior CSCC excision (Fig. 1a; arrow) on the patient’s right leg, as well as 10 smaller (5–10 mm) keratotic nodules on the same leg (Fig. 1a, b; arrowheads).
Correspondence: Dr Diana Bolotin, 5841 S. Maryland Ave, MC 5067, Chicago, IL 60637-1470, USA E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 17 January 2014
604
Clinical and Experimental Dermatology (2014) 39, pp604–607
Histological examination of biopsies taken from the large central nodule and two smaller lesions showed invasive SCCs (Fig. 1c). The dermatopathology findings were not consistent with keratoacanthomas. The aetiology of these eruptive CSCCs was unclear but was probably related to a combination of field cancerization because of her history of extensive phototherapy [narrowband ultraviolet (UV)B and psoralen UVA] and her treatment with etanercept and methotrexate for her psoriasis.1 The patient’s age, her poorly controlled psoriasis and the presence of multiple tumours below the knee and recent cellulitis in the same leg increased the likelihood of healing complications and precluded surgical treatment. The patient had a strong preference against extensive surgical procedures. Nonsurgical approaches were considered, including systemic therapy and radiotherapy (RT). Previous intolerance of acitretin for psoriasis precluded its use. A multidisciplinary approach of electron beam radiation to the central recurrent CSCC and intravenous cetuximab for the eruptive CSCCs was pursued. The patient received a total radiation dose of 66 Gy over 6 weeks delivered in 3 Gy fractions, with concomitant cetuximab (loading dose 400 mg/m2 and four subsequent weekly infusions of 250 mg/m2 each). By week 4, all lesions had resolved, and a shallow erosion remained in the area of the recurrent CSCC (Fig. 2a; arrow). The patient had complete clinical response after 6 weeks of therapy. Remarkably, the psoriatic lesions
ª 2014 British Association of Dermatologists
Eruptive CSCC and psoriasis: response to cetuximab M. Kamaria et al.
(a)
(b)
(c) Figure 1 (a) Diffuse erythema with coarse yellow scale on the right leg. A keratotic nodule 15 mm in size with central hemorrhagic
crust within a linear scar (arrow) and 10 smaller (5–10 mm) dome-shaped nodules with central keratotic crusts (arrowheads). (b) Right lateral shin with eruptive keratotic nodules (arrowheads). (c) Keratinocytes with full thickness severe cytological atypia extending from the epidermis into the dermis, consistent with invasive cutaneous squamous cell carcinomas. Hematoxylin and eosin stain, original magnifications as marked.
also completely responded within 2 weeks of starting cetuximab therapy (Fig. 2a), although they recurred within 3 months of cetuximab discontinuation and
ª 2014 British Association of Dermatologists
were treated topically (Fig. 2b). Adverse effects of the treatment included fatigue, shortness of breath, and residual erosion at the radiated site. The pulmonary
Clinical and Experimental Dermatology (2014) 39, pp604–607
605
Eruptive CSCC and psoriasis: response to cetuximab M. Kamaria et al.
Figure 2 (a) Complete clinical resolution
(a)
(b)
symptoms were deemed secondary to chronic obstructive pulmonary disease. No acneiform eruption developed while the patient was on cetuximab. The patient’s CSCCs showed continued response, with lack of recurrence for 9 months (Fig. 2b; arrowhead). At the 9-month follow-up, a new nodule was noted on her right lateral calf, outside the radiation field, and biopsy confirmed invasive CSCC. This was thought to be a de novo CSCC or a recurrent satellite lesion, and was treated with radiation (51 Gy total dose in 3 Gy fractions) with complete resolution. No other concerning growths were noted on the right leg at 13 months posttreatment, when she died from a stroke. Therapeutic options for nonresectable CSCC include local, field and systemic therapy. Identification of tumours at risk for recurrence or metastasis is important for optimizing outcomes. Although no universal guidelines for risk categorization exist, the American Joint Committee on Cancer (AJCC) considers the following factors as high risk (for noneyelid carcinoma): ≥ 2 mm Breslow thickness, Clark level ≥ 4, perineural invasion, location on ear or hair-bearing lip, and poorly differentiated or undifferentiated histological type.2 Eruptive CSCCs represent a therapeutic challenge, regardless of risk level. For high-risk nonresectable CSCC, treatment options include RT, combined chemotherapy and RT, or systemic chemotherapy. RT may be used when tumour size, location or comorbidities preclude surgery. RT has higher recurrence rates than surgical resection as
606
Clinical and Experimental Dermatology (2014) 39, pp604–607
of all of the satellite lesions at 4 weeks into the treatment course; a shallow erosion (arrow) in the area of the central recurrent squamous cell carcinoma (SCC) lesion being treated with radiotherapy. Note resolution of diffuse erythema and scaling on the shin. (b) At 3 months post-treatment, there was complete clinical response of the eruptive cutaneous SCC lesions as well as the recurrent SCC (arrowhead). Note the recurrence of the psoriatic plaques.
monotherapy, but is an excellent adjuvant to surgical excision or chemotherapy. However, RT cannot be used at previously irradiated sites because of the risk of tissue necrosis. Various chemotherapy agents for high-risk tumours have been reported, including cytotoxic agents (cisplatin, 5-fluorouracil, capecitabine, bleomycin and doxyrubicin), 13-cis-retinoic acid and interferon, and epidermal growth factor receptor (EGFR)-blocking agents. Clinical efficacy data is limited by small study populations and lack of randomization. The choice of agent is conditional upon comorbidities, toxicities and side-effect profiles.3 Utility in eruptive CSCCs has not been reported. Cetuximab is a monoclonal antibody that competitively inhibits EGFR. It is approved for head and neck SCC (HNSCC) and colorectal cancer. A phase II trial4 in patients (n = 36) with unresectable CSCC demonstrated disease control in 69% of patients at 6 weeks. Several case reports have also shown efficacy for refractory or unresectable CSCC.5,6 Evidence from patients with HNSCC demonstrates synergy between cetuximab and RT in improving locoregional control and survival, without increasing RT-associated toxicity.7 Cetuximab has a favourable side effect profile, with folliculitis as the most common adverse effect. These studies, combined with our case, suggest that cetuximab is a viable option for eruptive CSCCs, especially in elderly patients. We chose a combination approach of RT for the higher-risk recurrent lesion, and cetuximab to treat the
ª 2014 British Association of Dermatologists
Eruptive CSCC and psoriasis: response to cetuximab M. Kamaria et al.
surrounding CSCCs and provide a radiosensitizing effect. Concerns about poor healing and extensive tissue necrosis precluded irradiation of the entire leg. No cases of eruptive CSCCs treated with radiation and cetuximab have been reported previously, to our knowledge. Remarkably, complete response of both the eruptive CSCCs and psoriasis were observed. Previous case reports demonstrated similar dual response to cetuximab in psoriasis and colon carcinoma.8,9 Dual efficacy in epithelial tumours and psoriasis probably relates to increased cell proliferation and EGFR activity, which is downregulated by cetuximab. This case highlights a role for cetuximab in the treatment of eruptive CSCCs, as an adjunct to RT in high-risk SCC, and as a potential therapy for psoriasis. Our patient had an excellent response to treatment of multiple CSCCs, with only one recurrent lesion posttreatment and complete clearance of psoriasis within 3 months after therapy. Further studies are needed to better elucidate the therapeutic role of cetuximab in CSCCs and psoriasis.
Learning points ● Around 20–30% of NMSCs are CSCCs. ● Limited data exist, and there are no standard
guidelines on optimal treatment for nonresectable tumours, particularly eruptive CSCCs. ● Treatment may involve RT, chemotherapy, or combination chemotherapy and RT, and outcomes are highly variable. ● Cetuximab is a viable and efficacious option in nonresectable and multiply eruptive CSCCs, particularly in elderly patients. ● Cetuximab synergizes with RT to improve locoregional control and survival, without increasing RT-associated toxicity. ● EGFR inhibitors may have a potential therapeutic role in psoriasis.
ª 2014 British Association of Dermatologists
References 1 Bangash SJ, Green WH, Dolson DJ et al. Eruptive postoperative squamous cell carcinomas exhibiting a pathergy-like reaction around surgical wound sites. J Am Acad Dermatol 2009; 61: 892–7. 2 Edge S, Byrd DR, Compton CC et al. AJCC Cancer Staging Manual, 7th edn. New York: Springer, 2010. 3 Cranmer LD, Engelhardg C, Morgan SS. Treatment of unresectable and metastatic cutaneous squamous cell carcinoma. Oncologist 2010; 15: 1320–8. 4 Maubec E, Petrow P, Scheer-Senyarich I et al. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol 2011: 29: 3419–26. 5 Kalapurakal SJ, Malone J, Robbins KT et al. Cetuximab in refractory skin cancer treatment. J Cancer 2012; 3: 357–61. 6 Goppner D, Nekwasil S, Franke I et al. Successful combination therapy of a locally advanced squamous cell carcinoma of the skin with cetuximab and c-radiation. J Dtsch Dermatol Ges 2010; 8: 826–8. 7 Bernier J, Schneider D. Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squmaous cell carcinoma of the head and neck? Eur J Can 2007; 43: 35–45. 8 Neyns B, Meert V, Vandenbroucke F. Cetuximab treatment in a patient with metastatic colorectal cancer and psoriasis. Curr Oncol 2008; 15: 196–7. 9 Trivin F, Boucher E, Raoul J. Complete sustained regression of extensive psoriasis with cetuximab combination chemotherapy. Acta Oncol 2004; 43: 592–3.
Clinical and Experimental Dermatology (2014) 39, pp604–607
607
