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Fig 1. Overall survival and progression-free survival of AJCC stage 4 squamous cell carcinoma. Kaplan-Meier curves with associated 95% confidence intervals for overall survival (A) and progression-free survival (B) are shown with vertical ticks denoting censored data. The number of patients at risk at each major time point is provided below the plots.
Funding sources: This study was supported in part by the Stanford Center for Clinical Informatics (UL1 RR025744 from NIH/NCRR) for the development of REDCap, and the NCI Cancer Center Support Grant 5P30CA124435 and Stanford NIH/NCRR CTSA Award Number UL1 RR025744 for the development of the Stanford Cancer Center Research Database. Conflicts of interest: Dr Chang has been a clinical investigator for studies sponsored by Infinity, Genentech, and Novartis. Mr Zhu declares no conflicts of interest. Correspondence to: Anne Lynn Su Chang, MD, Assistant Professor of Dermatology, Department of Dermatology, Stanford University School of Medicine, 450 Broadway St, Redwood City, CA 94063 E-mail: [email protected]
REFERENCES 1. Weinstock MA. Nonmelanoma skin cancer mortality in the United States, 1969 through 1988. Arch Dermatol. 1993;129: 1286-1290. 2. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68:957-966. 3. AJCC Cancer Staging Handbook. 7th ed. Chicago, IL: American Joint Committee on Cancer; 2010. 4. Brunner M, Veness MJ, Ch’ng S, Elliott M, Clark JR. Distant metastases from cutaneous squamous cell carcinomaeanalysis of AJCC stage IV. Head Neck. 2013;35:72-75.
http://dx.doi.org/10.1016/j.jaad.2015.03.028
Facial basal cell carcinomas treated with hypo-fractionated radiotherapy: A retrospective analysis in 117 elderly patients To the Editor: Radiotherapy (RT) is an option for facial basal cell carcinomas. The optimum dose and fraction remain to be clearly defined, but the numerous treatment fractions required by the most common radiotherapy regimens1 may render RT impractical in frail patients unfit for daily irradiation. After successfully submitting a small number of patients to palliative treatment with once-weekly administrations (5 Gy per week up to 25-30 Gy), we extended this schedule to a larger population of frail patients. From February 2007 to May 2010, frail elderly outpatients with basal cell carcinoma (BCC) (Table I) were treated with the once-weekly schedule and then evaluated for inclusion in this retrospective review. Frailty characteristics were evaluated using the Katz functionality index2 (Table I) and the Charlson age-factored comorbidity index.3 All patients (n ¼ 117) had a Katz functionality index less than 6 and 98 of 117 had a Charlson age-factored comorbidity index greater than 5 with lesions requiring a complex reconstruction (Fig 1). The remaining 19 patients refused surgery. Patients with T3/T4 lesions (3 patients) or receiving re-irradiations (4 patients) were excluded because they usually underwent various palliative regimens tailored to their specific conditions. Fully informed, written consent was required. The response was assessed by means of physical examination (documented by standardized digital photography) at 4 and 8 weeks after final radiation treatment.
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Table I. Patient characteristics, baseline tumor characteristics, and results in 117 lymph nodenegative patients ( frail* and unfit for daily irradiation) with 141 histologically proven basal cell carcinomas Median age ( years) Gender: female/male T1 tumors (clinically evaluated)y T2 tumors (clinically evaluated)y Median primary tumor size (mm) Tumor sitez Nose Nasogenian furrow Eyelid-periorbital area Ear Cheek Forehead-temples Mean radiation dose/time Acute skin toxicity Complete responses 3-year RFSx rate 5-year RFSx rate Follow-up, median duration
82 44 35 106 23
(75-103) (37.6%)/73 (62.4%) (24.8%) (75.2%) (9-84)
45 (31.9%) 24 (17%) 28 (19.8%) 8 (5.7%) 11 (7.8%) 25 (17.8%) 26 Gy/5.2weeks G1/G2 36/117 (30.7%) 139/141 (98.6%) BCCs 115/117 (98.3%) patients 96.4% 94.5% 61 months (range 42-85 months)
*Frailty was evaluated using the Katz Index of Independence in Activities of Daily Living exploring 6 domains (each with a score of 1): bathing, dressing, toileting, transferring, continence, feeding. Patients with a score of 6 are independent, whereas those scoring 0 are highly dependent. y Imaging was rarely available due to the patients’ frail conditions. z Scalp lesions were preferably treated with electron beams in order to decrease the exit dose to the brain, whereas periorbital tumors that needed eye shielding were treated with orthovoltage beams due to a lower penetration depth of kV beams through eye shields. x Relapse-free survival.
( graded according to the Common Toxicity Criteria Adverse Events) nor hospitalization due to side effects occurred. At the last follow-up (March 30, 2014), no late toxicities interfering with patients’ quality of life were reported; local recurrent disease occurred in 2 of 117 (1.7%) patients. Thus, a complete tumor response was seen in 98.3% of the patients (98.6% of the tumors). The fact that results obtained with this palliative RT schedule are similar to those reported for more conventional schedules,1,4 which deliver a total higher dose (60 Gy) with more fractions (15 to 30), could lead radiation oncologists to reconsider BCC radiosensitivity and to study these low dosages as possible definitive treatments in future prospective trials. Indeed, recent retrospective trials5,6 of once-weekly RT in frail elderly patients unfit for daily irradiation showed local control rates ([90%) similar to ours and to those of a conventional schedule.1 Despite its major limits (e.g., retrospective cohort design, age-related mortality), our study showed that a low-dose hypofractionated regimen is feasible in elderly patients unfit for daily RT. Antonio Pelissero, MD,a Elvio G. Russi, MD,a Antonella Melano, MD,a Claudia Fillini, MD,a Riccardo Vigna-Taglianti, MD,a Nicola Settineri, PhD,b Francesco Lucio, MP,c Giampiero Girolomoni, MD,d and Stefano Pergolizzi, MDe Department of Radiation Oncology,a Department of Medical Physic,c A.O. S. Croce e Carle Cuneo; Department of Radiological Scienceb and Radiation Oncology Department Unit,e University of Messina, Department of Medicine, Section of Dermatology and Venereology, University of Verona,d Italy Funding sources: None.
Patients received 25 to 30 Gy in 5 to 6 weekly fractions. The higher total dosage was delivered to lesions thicker than 1.5 cm. For each patient, the beam energy (55 to 150 kV orthovoltage or 4 to 8 MeV electron beam) was chosen according to the estimated tumor depth and anatomic site (Table I). The margin between the planning target volume and clinical target volume was more than 1 cm around the clinical extension of the tumor. A customized lead mask was constructed to collimate the beam on the skin surface. The follow-up time was the time from the start of RT until the date of this analysis. Recurrence-free survival (Kaplan-Meier method) was measured from day 1 of RT to death or the date of the last follow-up. All the patients completed the treatment without interruptions. Neither grade 3 acute toxicities
Conflicts of interest: None declared. Correspondence to: Elvio G. Russi, MD, Department of Radiation Oncology, A.O. S. Croce e Carle Cuneo, Via M. Coppino 26, 12100 Cuneo, Italy E-mail: [email protected] REFERENCES 1. Avril MF, Auperin A, Margulis A, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer. 1997;76:100-106. 2. Katz S, Downs TD, Cash HR, Grotz RC. Progress in development of the index of ADL. Gerontologist. 1970;10:20-30. 3. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40: 373-383. 4. Mendenhall WM, Amdur RJ, Hinerman RW, Cognetta AB, Mendenhall NP. Radiotherapy for cutaneous squamous and
J AM ACAD DERMATOL
168 Letters
JULY 2015
Fig 1. Hypofractionated radiotherapy for facial basal cell carcinomas. Patient deemed unfit for surgery due to its significant invasiveness and the need for demanding reconstructive plastic surgery. The photos show the patient before radiotherapy (A) and at 8 weeks (B), 6 months (C) and 12 months (D) after the end of radiotherapy. basal cell carcinomas of the head and neck. Laryngoscope. 2009;119:1994-1999. 5. Kouloulias V, Papadavid E, Mosa E, et al. A new hypofractionated schedule of weekly irradiation for basal cell carcinoma of the head and neck skin area in elderly patients. Dermatol Ther. 2014;27:127-130. 6. Marriappan L, Ramasamy S, Robert F. Weekly radiotherapy for basal cell carcinoma in the frail and elderly. Br J Dermatol. 2014;171:1237-1239. http://dx.doi.org/10.1016/j.jaad.2015.03.030
Digital dermoscopy monitoring in patients with multiple nevi: How many lesions should we monitor per patient? To the Editor: Digital dermoscopy monitoring (DDM) of melanocytic lesions in patients with multiple nevi ([50 nevi) or atypical mole syndrome (AMS) have been demonstrated to increase early melanoma detection, while minimizing the unnecessary excision of benign lesions.1 Several studies have investigated different follow-up protocols to determine the best strategy for optimizing clinical outcome and patient compliance.2-5 However, data are lacking, especially in the context of the number of lesions to monitor per patient.2 We conducted an online survey among the 90 board members of the International Dermoscopy
Society to determine current behaviors in the use of DDM. The questionnaire included 9 questions regarding (1) age; (2) gender; (3) work setting; (4) percentage of skin cancer patients seen per year; (5) number of primary melanomas diagnosed per year; (6) attitude for using DDM; (7) attitude for imaging all lesions or selected lesions; (8) number of selected lesions imaged; (9) use of total body photography (TBP). Seventy-five board members (83.3%) participated in the survey. The majority (n ¼ 60, 80%) indicated that they perform DDM in patients with multiple nevi or AMS (Table I). Among these, only 8 (13.3%) reported that they image all lesions in a given patient, whereas 52 (86.7%) reported that they select skin lesions for DDM, with almost 60% reporting that they image fewer than 10 lesions per patient. Interestingly, the great majority (n ¼ 56, 74.7%) of the interviewed members declared they use TBP. Moreover, 8 of the 15 participants (53.3%) who did not use a DDM, stated that they perform TBP. To analyze factors influencing the decision to select or to monitor all lesions per patient, we used Spearman’s rho coefficient to flag significant correlations, which were subsequently quantified via logistical regression. We expected that the decision to select lesions to monitor would depend
166 Letters
JULY 2015
Fig 1. Overall survival and progression-free survival of AJCC stage 4 squamous cell carcinoma. Kaplan-Meier curves with associated 95% confidence intervals for overall survival (A) and progression-free survival (B) are shown with vertical ticks denoting censored data. The number of patients at risk at each major time point is provided below the plots.
Funding sources: This study was supported in part by the Stanford Center for Clinical Informatics (UL1 RR025744 from NIH/NCRR) for the development of REDCap, and the NCI Cancer Center Support Grant 5P30CA124435 and Stanford NIH/NCRR CTSA Award Number UL1 RR025744 for the development of the Stanford Cancer Center Research Database. Conflicts of interest: Dr Chang has been a clinical investigator for studies sponsored by Infinity, Genentech, and Novartis. Mr Zhu declares no conflicts of interest. Correspondence to: Anne Lynn Su Chang, MD, Assistant Professor of Dermatology, Department of Dermatology, Stanford University School of Medicine, 450 Broadway St, Redwood City, CA 94063 E-mail: [email protected]
REFERENCES 1. Weinstock MA. Nonmelanoma skin cancer mortality in the United States, 1969 through 1988. Arch Dermatol. 1993;129: 1286-1290. 2. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68:957-966. 3. AJCC Cancer Staging Handbook. 7th ed. Chicago, IL: American Joint Committee on Cancer; 2010. 4. Brunner M, Veness MJ, Ch’ng S, Elliott M, Clark JR. Distant metastases from cutaneous squamous cell carcinomaeanalysis of AJCC stage IV. Head Neck. 2013;35:72-75.
http://dx.doi.org/10.1016/j.jaad.2015.03.028
Facial basal cell carcinomas treated with hypo-fractionated radiotherapy: A retrospective analysis in 117 elderly patients To the Editor: Radiotherapy (RT) is an option for facial basal cell carcinomas. The optimum dose and fraction remain to be clearly defined, but the numerous treatment fractions required by the most common radiotherapy regimens1 may render RT impractical in frail patients unfit for daily irradiation. After successfully submitting a small number of patients to palliative treatment with once-weekly administrations (5 Gy per week up to 25-30 Gy), we extended this schedule to a larger population of frail patients. From February 2007 to May 2010, frail elderly outpatients with basal cell carcinoma (BCC) (Table I) were treated with the once-weekly schedule and then evaluated for inclusion in this retrospective review. Frailty characteristics were evaluated using the Katz functionality index2 (Table I) and the Charlson age-factored comorbidity index.3 All patients (n ¼ 117) had a Katz functionality index less than 6 and 98 of 117 had a Charlson age-factored comorbidity index greater than 5 with lesions requiring a complex reconstruction (Fig 1). The remaining 19 patients refused surgery. Patients with T3/T4 lesions (3 patients) or receiving re-irradiations (4 patients) were excluded because they usually underwent various palliative regimens tailored to their specific conditions. Fully informed, written consent was required. The response was assessed by means of physical examination (documented by standardized digital photography) at 4 and 8 weeks after final radiation treatment.
J AM ACAD DERMATOL
Letters 167
VOLUME 73, NUMBER 1
Table I. Patient characteristics, baseline tumor characteristics, and results in 117 lymph nodenegative patients ( frail* and unfit for daily irradiation) with 141 histologically proven basal cell carcinomas Median age ( years) Gender: female/male T1 tumors (clinically evaluated)y T2 tumors (clinically evaluated)y Median primary tumor size (mm) Tumor sitez Nose Nasogenian furrow Eyelid-periorbital area Ear Cheek Forehead-temples Mean radiation dose/time Acute skin toxicity Complete responses 3-year RFSx rate 5-year RFSx rate Follow-up, median duration
82 44 35 106 23
(75-103) (37.6%)/73 (62.4%) (24.8%) (75.2%) (9-84)
45 (31.9%) 24 (17%) 28 (19.8%) 8 (5.7%) 11 (7.8%) 25 (17.8%) 26 Gy/5.2weeks G1/G2 36/117 (30.7%) 139/141 (98.6%) BCCs 115/117 (98.3%) patients 96.4% 94.5% 61 months (range 42-85 months)
*Frailty was evaluated using the Katz Index of Independence in Activities of Daily Living exploring 6 domains (each with a score of 1): bathing, dressing, toileting, transferring, continence, feeding. Patients with a score of 6 are independent, whereas those scoring 0 are highly dependent. y Imaging was rarely available due to the patients’ frail conditions. z Scalp lesions were preferably treated with electron beams in order to decrease the exit dose to the brain, whereas periorbital tumors that needed eye shielding were treated with orthovoltage beams due to a lower penetration depth of kV beams through eye shields. x Relapse-free survival.
( graded according to the Common Toxicity Criteria Adverse Events) nor hospitalization due to side effects occurred. At the last follow-up (March 30, 2014), no late toxicities interfering with patients’ quality of life were reported; local recurrent disease occurred in 2 of 117 (1.7%) patients. Thus, a complete tumor response was seen in 98.3% of the patients (98.6% of the tumors). The fact that results obtained with this palliative RT schedule are similar to those reported for more conventional schedules,1,4 which deliver a total higher dose (60 Gy) with more fractions (15 to 30), could lead radiation oncologists to reconsider BCC radiosensitivity and to study these low dosages as possible definitive treatments in future prospective trials. Indeed, recent retrospective trials5,6 of once-weekly RT in frail elderly patients unfit for daily irradiation showed local control rates ([90%) similar to ours and to those of a conventional schedule.1 Despite its major limits (e.g., retrospective cohort design, age-related mortality), our study showed that a low-dose hypofractionated regimen is feasible in elderly patients unfit for daily RT. Antonio Pelissero, MD,a Elvio G. Russi, MD,a Antonella Melano, MD,a Claudia Fillini, MD,a Riccardo Vigna-Taglianti, MD,a Nicola Settineri, PhD,b Francesco Lucio, MP,c Giampiero Girolomoni, MD,d and Stefano Pergolizzi, MDe Department of Radiation Oncology,a Department of Medical Physic,c A.O. S. Croce e Carle Cuneo; Department of Radiological Scienceb and Radiation Oncology Department Unit,e University of Messina, Department of Medicine, Section of Dermatology and Venereology, University of Verona,d Italy Funding sources: None.
Patients received 25 to 30 Gy in 5 to 6 weekly fractions. The higher total dosage was delivered to lesions thicker than 1.5 cm. For each patient, the beam energy (55 to 150 kV orthovoltage or 4 to 8 MeV electron beam) was chosen according to the estimated tumor depth and anatomic site (Table I). The margin between the planning target volume and clinical target volume was more than 1 cm around the clinical extension of the tumor. A customized lead mask was constructed to collimate the beam on the skin surface. The follow-up time was the time from the start of RT until the date of this analysis. Recurrence-free survival (Kaplan-Meier method) was measured from day 1 of RT to death or the date of the last follow-up. All the patients completed the treatment without interruptions. Neither grade 3 acute toxicities
Conflicts of interest: None declared. Correspondence to: Elvio G. Russi, MD, Department of Radiation Oncology, A.O. S. Croce e Carle Cuneo, Via M. Coppino 26, 12100 Cuneo, Italy E-mail: [email protected] REFERENCES 1. Avril MF, Auperin A, Margulis A, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer. 1997;76:100-106. 2. Katz S, Downs TD, Cash HR, Grotz RC. Progress in development of the index of ADL. Gerontologist. 1970;10:20-30. 3. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40: 373-383. 4. Mendenhall WM, Amdur RJ, Hinerman RW, Cognetta AB, Mendenhall NP. Radiotherapy for cutaneous squamous and
J AM ACAD DERMATOL
168 Letters
JULY 2015
Fig 1. Hypofractionated radiotherapy for facial basal cell carcinomas. Patient deemed unfit for surgery due to its significant invasiveness and the need for demanding reconstructive plastic surgery. The photos show the patient before radiotherapy (A) and at 8 weeks (B), 6 months (C) and 12 months (D) after the end of radiotherapy. basal cell carcinomas of the head and neck. Laryngoscope. 2009;119:1994-1999. 5. Kouloulias V, Papadavid E, Mosa E, et al. A new hypofractionated schedule of weekly irradiation for basal cell carcinoma of the head and neck skin area in elderly patients. Dermatol Ther. 2014;27:127-130. 6. Marriappan L, Ramasamy S, Robert F. Weekly radiotherapy for basal cell carcinoma in the frail and elderly. Br J Dermatol. 2014;171:1237-1239. http://dx.doi.org/10.1016/j.jaad.2015.03.030
Digital dermoscopy monitoring in patients with multiple nevi: How many lesions should we monitor per patient? To the Editor: Digital dermoscopy monitoring (DDM) of melanocytic lesions in patients with multiple nevi ([50 nevi) or atypical mole syndrome (AMS) have been demonstrated to increase early melanoma detection, while minimizing the unnecessary excision of benign lesions.1 Several studies have investigated different follow-up protocols to determine the best strategy for optimizing clinical outcome and patient compliance.2-5 However, data are lacking, especially in the context of the number of lesions to monitor per patient.2 We conducted an online survey among the 90 board members of the International Dermoscopy
Society to determine current behaviors in the use of DDM. The questionnaire included 9 questions regarding (1) age; (2) gender; (3) work setting; (4) percentage of skin cancer patients seen per year; (5) number of primary melanomas diagnosed per year; (6) attitude for using DDM; (7) attitude for imaging all lesions or selected lesions; (8) number of selected lesions imaged; (9) use of total body photography (TBP). Seventy-five board members (83.3%) participated in the survey. The majority (n ¼ 60, 80%) indicated that they perform DDM in patients with multiple nevi or AMS (Table I). Among these, only 8 (13.3%) reported that they image all lesions in a given patient, whereas 52 (86.7%) reported that they select skin lesions for DDM, with almost 60% reporting that they image fewer than 10 lesions per patient. Interestingly, the great majority (n ¼ 56, 74.7%) of the interviewed members declared they use TBP. Moreover, 8 of the 15 participants (53.3%) who did not use a DDM, stated that they perform TBP. To analyze factors influencing the decision to select or to monitor all lesions per patient, we used Spearman’s rho coefficient to flag significant correlations, which were subsequently quantified via logistical regression. We expected that the decision to select lesions to monitor would depend
