- Email: [email protected]
The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin cancer
JGO-00618; No. of pages: 4; 4C: Journal of Geriatric Oncology xxx (2018) xxx–xxx
Contents lists available at ScienceDirect
Journal of Geriatric Oncology
Letter to the Editor
The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin cancer Lancellotta Valentina a,⁎, Kovács Gyoergy b, Tagliaferri Luca c, Perrucci Elisabetta d, Rembielak Agata e, Stingeni Luca f, Tramontana Marta f, Hansel Katharina f, Colloca Giuseppe g, Saldi Simonetta h, Valentini Vincenzo i, Aristei Cynthia a a
Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia and Perugia General Hospital, Perugia, Italy Interdisciplinary Brachytherapy Unit, University of Lübeck/UKSH, Lübeck, Germany Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia - Gemelli ART (Advanced Radiation Therapy), Interventional Oncology Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy d Radiation Oncology Division, Perugia General Hospital, Perugia, Italy e Clinical Oncologist, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom f Section of Clinical, Allergological and Venereological Dermatology Department of Medicine, University of Perugia, Perugia, Italy g Polo Scienze Oncologiche ed Ematologiche, Fondazione Policlinico Universitario Agostino Gemelli, GIOGER (Gruppo Italiano di Oncologia Geriatrica), Università Cattolica del Sacro Cuore, Rome, Italy h Radiation Oncology Section, University of Perugia and Perugia General Hospital, Perugia, Italy i Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Gemelli ART (Advanced Radiation Therapy) Interventional Oncology Center, Università Cattolica del Sacro Cuore, Rome, Italy b c
a r t i c l e
i n f o
Article history: Received 3 July 2018 Received in revised form 5 September 2018 Accepted 26 September 2018 Available online xxxx Keywords: Older Interventional radiotherapy Brachytherapy Local control Toxicity Personalized medicine Innovative biotechnologies
a b s t r a c t Objective: Non-melanoma skin cancer (NMSC) has been rapidly increasing in incidence over the past 30 years. Mainstays of treatment remain surgery and radiotherapy, particularly in older and/or frail patients (≥75 years old) that often require a personalized treatment strategy using innovative biotechnologies. High-dose-rate interventional radiotherapy (HDR-IRT) seems to be an excellent option for NMSC. Material and Methods: Nineteen aged patients with advanced, biopsy proven NMSC were treated with exclusively HDR-IRT. A personalized double-layer mould of thermoplastic mask material was applied to the skin surface. Plastic tubes were fixed on the mould in appropriate geometry over the target area. Planning computed tomography (CT) images were acquired with 2.5 mm slice thickness and transmitted to the planning system. Treatment intention was to deliver ≥95% of the prescribed dose to the Planning Target Volume (PTV), accepting 90% as satisfactory. Toxicities were assessed using the Common Terminology Criteria for Adverse Events scale (CTCAE) v. 4.0. Results: Median age was 86 years. Acute toxicity: Grade 2 erythema appeared in all 19 patients. Towards the end of each treatment schedule, epidermolysis developed which was resolved within 6 weeks of completing HDR-IRT. Late toxicity: Grade 1 skin atrophy, pigmentation changes and alopecia in field were observed in all patients. At last follow-up, all patients were disease free. Conclusions: Personalized HDR-IRT appears to be safe and effective for frail older patients and a valid alternative to supportive care for those with contraindication to surgery. Future investigations using also large database analysis seem to be advisory. © 2018 Elsevier Ltd. All rights reserved.
Introduction Non-melanoma skin cancer (NMSC), the most common skin malignancy in the older patients, has been rapidly increasing in incidence over the past 30 years. Therapeutic options like cryotherapy, laser ⁎ Corresponding author. E-mail address: [email protected] (V. Lancellotta).
therapy, topical treatment and photodynamic therapy are usually reserved for early stage, low risk and superficial NMSC; while surgery and radiotherapy remain mainstay treatments. Excision is known to be associated with b5% local recurrences rates [1] while limited data are available on the effectiveness of radiotherapy in NMSC as there are no reports of randomized controlled trials using advanced radiotherapy techniques, systematic reviews, and/or metanalyses [2,3].
https://doi.org/10.1016/j.jgo.2018.09.009 1879-4068/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009
2
Letter to the Editor
In NMSC radiotherapy is delivered as superficial or orthovoltage x-rays, electron beams, megavoltage photons, or interventional radiotherapy (IRT) which is also known as brachytherapy. High-dose-rate (HDR) IRT, is usually delivered in a hypofractionated schedule and it is associated with high radiation dose conformity within the target volume, rapid dose fall-off in adjacent organs at risk, relatively short treatment time [4], excellent cosmetic and good functional outcomes [2,5]. These advantages are of particular importance in older and/or frail patients, who may be less compliant with prolonged treatments that require daily attendance and complex set-ups. This paper describes a personalized treatment strategy using individual HDR-IRT as treatment for NMSC in nineteen representative older and/or frail patients whose performance status and comorbidities precluded their candidature for any other treatment option. Materials and Methods From April 2014 to January 2018, nineteen consecutive older patients (≥75 years old) with NMSC (seven basal cell carcinoma (BSC), nine squamous cell carcinoma (SCC) underwent exclusive/adjuvant contact personalized HDR-IRT. In three other patients although biopsy was not performed due to poor performance status and high risk of bleeding, we proceeded with IRT on the basis of the clinical diagnosis and following discussions at the interdisciplinary meeting and with the patient. Eleven out of nineteen patients had received previous treatment (external beam radiotherapy (EBRT) in one, surgery in four, and topical chemotherapy in six) without clinical complete remission. The patients presented with lesions on their faces (nine), nose (three), ear (two) and arms (five). Table 1 reports demographic and clinical details of the cohort. To obtain the Planning Target Volume (PTV), the Gross Tumor Volume (GTV) was expanded by 5 mm for well-defined BCC lesions and 7–10 mm for poorly defined, large, infiltrative, morphoeic and/or sclerotic BCC. For SCC, at least 10 mm was added. If the lesion was b20 mm 10–15 mm were added. For lesions N20 mm 15–20 mm were calculated [4]. A personalized double-layer mould of thermoplastic mask material was applied on each patient's skin. At least 3 mm separated the skin from the plastic tubes which were fixed in appropriate geometry over the target area with an interspacing distance of about 1.2 cm. The PTV was marked on the mould surface by radiopaque material for lesion visualization on the computerized tomography (CT) scan. Planning CT images were acquired with 2.5 mm slice thickness and transmitted to the treatment planning system (TPS) Oncentra (Oncentra® Brachy Treatment Planning - Elekta, Sweden). Two treatment schedules were used: 36 Gray (Gy) with 4Gy/fractions twice a day for recurrent or de novo disease. The same dose fractionation was used for patients with recurrent disease and de-novo patients because the intention to treat was radical, not palliative, in all patients. For adjuvant radiotherapy or cancers in some sites like lesion close to the eye, 57.5Gy was administered in 2.5Gy/daily fractions. Treatment intention was to deliver ≥95% of the prescribed dose to the PTV, accepting 90% as satisfactory [4]. Treatment endpoints included local control, acute skin toxicity and late skin toxicity. Toxicities were assessed using the Common Terminology Criteria for Adverse Events scale (CTCAE) v. 4.0. Follow-up included a clinical check-up one month after treatment and then every three months for first two years, every six months for next two years and then annually. This study was approved by the Institutional Review Board of Department of Radiation Oncology, Perugia. Results The median age of the patients was 86 years (range 75–96). Male to female ratio was 11:8 and the SCC to BCC ratio was 9:7. The median maximum diameter and thickness of lesions were 3 mm (range
Table 1 Demographic data and treatment intent. Parameter
Number (%) or median
Median age
86 (75–96)
Gender Male Female
11 (57.9%) 8 (42.1%)
Location Face Nose Ear Upper and lower extremity
9 (47,4%) 3 (15.8%) 2 (10.5%) 5 (26.3)
Comorbidities 0–2 3 and +
3 (15.8%) 16 (84.2%)
Histology BCC SCC Unknown Median tumor thickness Median tumor size
7 (36.8%) 9 (47.4%) 3 (15.8%) 0.5 cm (0.2-1 cm) 3 cm (1-20 cm)
Intent Definitive Adjuvant
12 (63.2%) 7 (36.8%)
Abbreviations: BCC: basal cell carcinoma; SCC: squamous cell carcinoma.
10-200 mm) and 5 mm (range 2-10 mm) respectively. The most frequent treatment sites were the face (47%), lower and upper extremity (26%), nose (16%) and ear (11%). Seven (36.8%) patients were treated with a total dose of 36Gy at 4Gy/fraction twice a day, while twelve (63.2%) received 57.5Gy with daily one 2.5Gy fraction. All patients completed the treatments as prescribed. HDR-IRT resulted in excellent target coverage with the mean V90%, V95%, V100% and V150% of 98,29%, 93,4%, 75,4 and 0% respectively. The observed treatment related toxicity started with erythema. All patients developed G2 epidermolysis, which disappeared over time. In all patients late toxicity included only pigmentation changes (central hypopigmentation with peripheral hyperpigmentation) and alopecia in the field (Fig. 1). Complete remission was achieved in all patients who received radical treatment. No relapse occurred after adjuvant HDR-IRT. Acute treatment related toxicity manifested with erythema in all patients. All patients developed G2 epidermolysis, which disappeared over time. Late toxicity included pigmentation changes (central hypopigmentation with peripheral hyperpigmentation) in all patients and alopecia in the field (Fig. 1). At the median follow-up of six months (range 4–38) all patients were disease free. Discussion The lifetime risk of developing skin cancer is estimated at one in five. Since recent reports stated that health care management faced steeply increasing treatment costs [6], there is a need for effective and economic treatments, given the increasing incidence of skin cancers and longer life expectancy of the general population. Although several challenges are associated with the management of aged patients, specific treatment guidelines are lacking for skin cancer [7]. Even though surgery is the gold standard, offering excellent local disease control, postoperative complications could be high in the older patients [5]. The results of a literature review and our present experience, suggested HDR-IRT, as an excellent example of personalized medicine, might become treatment of choice in older and/or frail skin cancer patients. Innovative biotechnology reduced patient discomfort and improved compliance as well as providing satisfactory oncological
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009
Letter to the Editor
3
Fig. 1. Example of skin lesions before (panel A) and after (panel B) high-dose rate interventional radiotherapy.
outcomes. HDR-IRT might be a better choice than surgery or three dimensional conformal radiotherapy (3D-CRT) when treating large and/ or curved surfaces as well as peri-orificial tumors. In cases of unclear margins IRT alone, which provided good local control as well as cosmetic and functional results [2,5,8], might provide better cosmetic results than surgery combined with adjuvant radiotherapy [1]. Since HDR-IRT is cheaper and associated with shorter waiting-times than EBRT, it is commonly used to achieve better cosmetic results than surgery in head and neck regions (ear, nose, lips, etc.) in young populations. Although several studies evaluated the efficacy and feasibility of HDR-IRT in NMSC using the personalized surface mould technique [2,8], only a few reports included data on feasibility and outcomes in older and/or frail patients, particularly when they had already undergone surgery, EBRT and/or topical treatments. In such patients treatment options for recurrent disease are often very limited, or restricted to best supportive care. HDR-IRT may become treatment of choice for older patients with poor performance status and/or severe co-morbidities, requiring, for example, anticoagulant agents, which make anaesthesia and surgery risk procedures. It might ideally be performed as primary radiation treatment due to its relatively short total treatment time in patients with dementia, mental disease and anxiety. IRT avoids the difficulties associated with age-related loss of mobility and patient positioning due to its limited, tolerable immobilisation and no requirement for complex set-up procedures, It also has the potential to overcome inter-fraction reproducibility, set-up errors and gating techniques to compensate for moving targets and poor patient compliance. In the present small cohort of nineteen patients, eleven of whom were in relapse, all patients obtained clinical complete remission after HDR-IRT. This very encouraging outcome suggests that personalized HDR-IRT may be a valid alternative to palliative treatments. HDR-IRT was associated with acceptable acute and late toxicity rates as erythema and epidermolysis were the most frequent adverse events but resolved within 6 weeks of ending treatment. One limitation of the present study was our relatively small cohort, which precluded analysing the impact of previous treatments on toxicity and/or
functional /cosmetic results. Furthermore, the six month median follow-up time is too short for detailed analysis of radiation-related late effects. No events during follow-up precluded identifying risk factors for relapse and illustrated the need for large data-base analysis so as to construct predictive models of treatment results in NMSC [9]. Present data showed that personalized mould HDR-IRT was feasible and effective in frail older patients, emerging as a valid treatment choice for patients with contraindications to surgery or when surgery could result in disfigurement. Treatment decisions should not be based on age criteria alone as they should ensure that older patients get best quality care. Multi-disciplinary co-operation among experts in radiation therapy, dermatology, surgical oncology and geriatricians is essential for optimizing patient care and offering “personalized medicine” to the older [10]. Disclosures and Conflict of Interest Statements The authors have declared no conflict of interest. Author Contributions Conception and design: V. Lancellotta, C. Aristei, G. Kovacs, V. Valentini, L. Stingeni. Data Collection M. Tramontana, Katarina Hansel, Simonetta Saldi. Analysis and Interpretation of Data G. Colloca, A. Rembielak, E. Perrucci. Manuscript Writing V. Lancellotta, L. Tagliaferri.
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009
4
Letter to the Editor
Approval of Final Article V. Lancellotta, G. Kovacs, L. Tagliaferri, E. Perrucci, A. Rembielak, L. Stingeni, M. Tramontana, K. Hansel, G. Colloca, S. Saldi, V. Valentini, C. Aristei. All authors read and approved the final manuscript. Founding Sources The authors have declared no founding source. Conflict of Interest I wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. References [1] Chren MM, Torres JS, Stuart SE, et al. Recurrence after treatment of non-melanoma skin cancer: A prospective cohort study. Arch Dermatol 2011;147:540–6.
[2] Lancellotta V, Kovacs G, Tagliaferri L, et al. Age is not a limiting factor in interventional radiotherapy (Brachytherapy) for patients with localized cancer. Biomed Res Int 2018;217:8469. [3] Zaorsky NG, Lee CT, Zhang E, Galloway TJ. Skin cancer brachytherapy vs external beam radiation therapy (SCRiBE) meta-analysis. Radiother Oncol 2018;126:386–93. [4] Guinot JL, Rembielak A, Perez-Calatayud J, et al. GEC-ESTRO ACROP recommendations in skin brachytherapy. Radiother Oncol 2018;126:377–85. [5] Bouhassira J, Bosc R, Greta L, et al. Factors associated with postoperative complications in elderly patients with skin cancer : A retrospective study of 241 patients. J Geriatr Oncol 2016;7:10–4. [6] Guy GP, Machlin SR, Ekwueme DU, Yabroff KR. Prevalence and costs of skin cancer treatment in the U.S., 2002-2006 and 2007-2011. Am J Prev Med 2015;48:183–7. [7] Scalliet P, Van den Weingaert D, Van der Schuren E. Cancer in the Elderly Treatment and Research. Oxford: Oxford Medical Publications; 1994; 28–37. [8] Arenas M, Arguís M, Díez-Presa L, et al. Hypofractionated high-dose-rate plesiotherapy in nonmelanoma skin cancer treatment. Brachytherapy 2015;14: 859–65. [9] Tagliaferri L, Budrukkar A, Lenkowicz J, et al. ENT COBRA ONTOLOGY: the covariates classification system proposed by the Head & Neck and Skin GEC-ESTRO Working Group for interdisciplinary standardized data collection in head and neck patient cohorts treated with interventional radiotherapy (brachytherapy). J Contemp Brachytherapy 2018;10:260–6. [10] Valentini V, Maurizi F, Tagliaferri L, et al. SPIDER: Managing clinical data of cancer patients treated through a multidisciplinary approach by a palm based system. Italian J Public Health 2008;5:154–64.
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009
Contents lists available at ScienceDirect
Journal of Geriatric Oncology
Letter to the Editor
The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin cancer Lancellotta Valentina a,⁎, Kovács Gyoergy b, Tagliaferri Luca c, Perrucci Elisabetta d, Rembielak Agata e, Stingeni Luca f, Tramontana Marta f, Hansel Katharina f, Colloca Giuseppe g, Saldi Simonetta h, Valentini Vincenzo i, Aristei Cynthia a a
Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia and Perugia General Hospital, Perugia, Italy Interdisciplinary Brachytherapy Unit, University of Lübeck/UKSH, Lübeck, Germany Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia - Gemelli ART (Advanced Radiation Therapy), Interventional Oncology Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy d Radiation Oncology Division, Perugia General Hospital, Perugia, Italy e Clinical Oncologist, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom f Section of Clinical, Allergological and Venereological Dermatology Department of Medicine, University of Perugia, Perugia, Italy g Polo Scienze Oncologiche ed Ematologiche, Fondazione Policlinico Universitario Agostino Gemelli, GIOGER (Gruppo Italiano di Oncologia Geriatrica), Università Cattolica del Sacro Cuore, Rome, Italy h Radiation Oncology Section, University of Perugia and Perugia General Hospital, Perugia, Italy i Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Gemelli ART (Advanced Radiation Therapy) Interventional Oncology Center, Università Cattolica del Sacro Cuore, Rome, Italy b c
a r t i c l e
i n f o
Article history: Received 3 July 2018 Received in revised form 5 September 2018 Accepted 26 September 2018 Available online xxxx Keywords: Older Interventional radiotherapy Brachytherapy Local control Toxicity Personalized medicine Innovative biotechnologies
a b s t r a c t Objective: Non-melanoma skin cancer (NMSC) has been rapidly increasing in incidence over the past 30 years. Mainstays of treatment remain surgery and radiotherapy, particularly in older and/or frail patients (≥75 years old) that often require a personalized treatment strategy using innovative biotechnologies. High-dose-rate interventional radiotherapy (HDR-IRT) seems to be an excellent option for NMSC. Material and Methods: Nineteen aged patients with advanced, biopsy proven NMSC were treated with exclusively HDR-IRT. A personalized double-layer mould of thermoplastic mask material was applied to the skin surface. Plastic tubes were fixed on the mould in appropriate geometry over the target area. Planning computed tomography (CT) images were acquired with 2.5 mm slice thickness and transmitted to the planning system. Treatment intention was to deliver ≥95% of the prescribed dose to the Planning Target Volume (PTV), accepting 90% as satisfactory. Toxicities were assessed using the Common Terminology Criteria for Adverse Events scale (CTCAE) v. 4.0. Results: Median age was 86 years. Acute toxicity: Grade 2 erythema appeared in all 19 patients. Towards the end of each treatment schedule, epidermolysis developed which was resolved within 6 weeks of completing HDR-IRT. Late toxicity: Grade 1 skin atrophy, pigmentation changes and alopecia in field were observed in all patients. At last follow-up, all patients were disease free. Conclusions: Personalized HDR-IRT appears to be safe and effective for frail older patients and a valid alternative to supportive care for those with contraindication to surgery. Future investigations using also large database analysis seem to be advisory. © 2018 Elsevier Ltd. All rights reserved.
Introduction Non-melanoma skin cancer (NMSC), the most common skin malignancy in the older patients, has been rapidly increasing in incidence over the past 30 years. Therapeutic options like cryotherapy, laser ⁎ Corresponding author. E-mail address: [email protected] (V. Lancellotta).
therapy, topical treatment and photodynamic therapy are usually reserved for early stage, low risk and superficial NMSC; while surgery and radiotherapy remain mainstay treatments. Excision is known to be associated with b5% local recurrences rates [1] while limited data are available on the effectiveness of radiotherapy in NMSC as there are no reports of randomized controlled trials using advanced radiotherapy techniques, systematic reviews, and/or metanalyses [2,3].
https://doi.org/10.1016/j.jgo.2018.09.009 1879-4068/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009
2
Letter to the Editor
In NMSC radiotherapy is delivered as superficial or orthovoltage x-rays, electron beams, megavoltage photons, or interventional radiotherapy (IRT) which is also known as brachytherapy. High-dose-rate (HDR) IRT, is usually delivered in a hypofractionated schedule and it is associated with high radiation dose conformity within the target volume, rapid dose fall-off in adjacent organs at risk, relatively short treatment time [4], excellent cosmetic and good functional outcomes [2,5]. These advantages are of particular importance in older and/or frail patients, who may be less compliant with prolonged treatments that require daily attendance and complex set-ups. This paper describes a personalized treatment strategy using individual HDR-IRT as treatment for NMSC in nineteen representative older and/or frail patients whose performance status and comorbidities precluded their candidature for any other treatment option. Materials and Methods From April 2014 to January 2018, nineteen consecutive older patients (≥75 years old) with NMSC (seven basal cell carcinoma (BSC), nine squamous cell carcinoma (SCC) underwent exclusive/adjuvant contact personalized HDR-IRT. In three other patients although biopsy was not performed due to poor performance status and high risk of bleeding, we proceeded with IRT on the basis of the clinical diagnosis and following discussions at the interdisciplinary meeting and with the patient. Eleven out of nineteen patients had received previous treatment (external beam radiotherapy (EBRT) in one, surgery in four, and topical chemotherapy in six) without clinical complete remission. The patients presented with lesions on their faces (nine), nose (three), ear (two) and arms (five). Table 1 reports demographic and clinical details of the cohort. To obtain the Planning Target Volume (PTV), the Gross Tumor Volume (GTV) was expanded by 5 mm for well-defined BCC lesions and 7–10 mm for poorly defined, large, infiltrative, morphoeic and/or sclerotic BCC. For SCC, at least 10 mm was added. If the lesion was b20 mm 10–15 mm were added. For lesions N20 mm 15–20 mm were calculated [4]. A personalized double-layer mould of thermoplastic mask material was applied on each patient's skin. At least 3 mm separated the skin from the plastic tubes which were fixed in appropriate geometry over the target area with an interspacing distance of about 1.2 cm. The PTV was marked on the mould surface by radiopaque material for lesion visualization on the computerized tomography (CT) scan. Planning CT images were acquired with 2.5 mm slice thickness and transmitted to the treatment planning system (TPS) Oncentra (Oncentra® Brachy Treatment Planning - Elekta, Sweden). Two treatment schedules were used: 36 Gray (Gy) with 4Gy/fractions twice a day for recurrent or de novo disease. The same dose fractionation was used for patients with recurrent disease and de-novo patients because the intention to treat was radical, not palliative, in all patients. For adjuvant radiotherapy or cancers in some sites like lesion close to the eye, 57.5Gy was administered in 2.5Gy/daily fractions. Treatment intention was to deliver ≥95% of the prescribed dose to the PTV, accepting 90% as satisfactory [4]. Treatment endpoints included local control, acute skin toxicity and late skin toxicity. Toxicities were assessed using the Common Terminology Criteria for Adverse Events scale (CTCAE) v. 4.0. Follow-up included a clinical check-up one month after treatment and then every three months for first two years, every six months for next two years and then annually. This study was approved by the Institutional Review Board of Department of Radiation Oncology, Perugia. Results The median age of the patients was 86 years (range 75–96). Male to female ratio was 11:8 and the SCC to BCC ratio was 9:7. The median maximum diameter and thickness of lesions were 3 mm (range
Table 1 Demographic data and treatment intent. Parameter
Number (%) or median
Median age
86 (75–96)
Gender Male Female
11 (57.9%) 8 (42.1%)
Location Face Nose Ear Upper and lower extremity
9 (47,4%) 3 (15.8%) 2 (10.5%) 5 (26.3)
Comorbidities 0–2 3 and +
3 (15.8%) 16 (84.2%)
Histology BCC SCC Unknown Median tumor thickness Median tumor size
7 (36.8%) 9 (47.4%) 3 (15.8%) 0.5 cm (0.2-1 cm) 3 cm (1-20 cm)
Intent Definitive Adjuvant
12 (63.2%) 7 (36.8%)
Abbreviations: BCC: basal cell carcinoma; SCC: squamous cell carcinoma.
10-200 mm) and 5 mm (range 2-10 mm) respectively. The most frequent treatment sites were the face (47%), lower and upper extremity (26%), nose (16%) and ear (11%). Seven (36.8%) patients were treated with a total dose of 36Gy at 4Gy/fraction twice a day, while twelve (63.2%) received 57.5Gy with daily one 2.5Gy fraction. All patients completed the treatments as prescribed. HDR-IRT resulted in excellent target coverage with the mean V90%, V95%, V100% and V150% of 98,29%, 93,4%, 75,4 and 0% respectively. The observed treatment related toxicity started with erythema. All patients developed G2 epidermolysis, which disappeared over time. In all patients late toxicity included only pigmentation changes (central hypopigmentation with peripheral hyperpigmentation) and alopecia in the field (Fig. 1). Complete remission was achieved in all patients who received radical treatment. No relapse occurred after adjuvant HDR-IRT. Acute treatment related toxicity manifested with erythema in all patients. All patients developed G2 epidermolysis, which disappeared over time. Late toxicity included pigmentation changes (central hypopigmentation with peripheral hyperpigmentation) in all patients and alopecia in the field (Fig. 1). At the median follow-up of six months (range 4–38) all patients were disease free. Discussion The lifetime risk of developing skin cancer is estimated at one in five. Since recent reports stated that health care management faced steeply increasing treatment costs [6], there is a need for effective and economic treatments, given the increasing incidence of skin cancers and longer life expectancy of the general population. Although several challenges are associated with the management of aged patients, specific treatment guidelines are lacking for skin cancer [7]. Even though surgery is the gold standard, offering excellent local disease control, postoperative complications could be high in the older patients [5]. The results of a literature review and our present experience, suggested HDR-IRT, as an excellent example of personalized medicine, might become treatment of choice in older and/or frail skin cancer patients. Innovative biotechnology reduced patient discomfort and improved compliance as well as providing satisfactory oncological
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009
Letter to the Editor
3
Fig. 1. Example of skin lesions before (panel A) and after (panel B) high-dose rate interventional radiotherapy.
outcomes. HDR-IRT might be a better choice than surgery or three dimensional conformal radiotherapy (3D-CRT) when treating large and/ or curved surfaces as well as peri-orificial tumors. In cases of unclear margins IRT alone, which provided good local control as well as cosmetic and functional results [2,5,8], might provide better cosmetic results than surgery combined with adjuvant radiotherapy [1]. Since HDR-IRT is cheaper and associated with shorter waiting-times than EBRT, it is commonly used to achieve better cosmetic results than surgery in head and neck regions (ear, nose, lips, etc.) in young populations. Although several studies evaluated the efficacy and feasibility of HDR-IRT in NMSC using the personalized surface mould technique [2,8], only a few reports included data on feasibility and outcomes in older and/or frail patients, particularly when they had already undergone surgery, EBRT and/or topical treatments. In such patients treatment options for recurrent disease are often very limited, or restricted to best supportive care. HDR-IRT may become treatment of choice for older patients with poor performance status and/or severe co-morbidities, requiring, for example, anticoagulant agents, which make anaesthesia and surgery risk procedures. It might ideally be performed as primary radiation treatment due to its relatively short total treatment time in patients with dementia, mental disease and anxiety. IRT avoids the difficulties associated with age-related loss of mobility and patient positioning due to its limited, tolerable immobilisation and no requirement for complex set-up procedures, It also has the potential to overcome inter-fraction reproducibility, set-up errors and gating techniques to compensate for moving targets and poor patient compliance. In the present small cohort of nineteen patients, eleven of whom were in relapse, all patients obtained clinical complete remission after HDR-IRT. This very encouraging outcome suggests that personalized HDR-IRT may be a valid alternative to palliative treatments. HDR-IRT was associated with acceptable acute and late toxicity rates as erythema and epidermolysis were the most frequent adverse events but resolved within 6 weeks of ending treatment. One limitation of the present study was our relatively small cohort, which precluded analysing the impact of previous treatments on toxicity and/or
functional /cosmetic results. Furthermore, the six month median follow-up time is too short for detailed analysis of radiation-related late effects. No events during follow-up precluded identifying risk factors for relapse and illustrated the need for large data-base analysis so as to construct predictive models of treatment results in NMSC [9]. Present data showed that personalized mould HDR-IRT was feasible and effective in frail older patients, emerging as a valid treatment choice for patients with contraindications to surgery or when surgery could result in disfigurement. Treatment decisions should not be based on age criteria alone as they should ensure that older patients get best quality care. Multi-disciplinary co-operation among experts in radiation therapy, dermatology, surgical oncology and geriatricians is essential for optimizing patient care and offering “personalized medicine” to the older [10]. Disclosures and Conflict of Interest Statements The authors have declared no conflict of interest. Author Contributions Conception and design: V. Lancellotta, C. Aristei, G. Kovacs, V. Valentini, L. Stingeni. Data Collection M. Tramontana, Katarina Hansel, Simonetta Saldi. Analysis and Interpretation of Data G. Colloca, A. Rembielak, E. Perrucci. Manuscript Writing V. Lancellotta, L. Tagliaferri.
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009
4
Letter to the Editor
Approval of Final Article V. Lancellotta, G. Kovacs, L. Tagliaferri, E. Perrucci, A. Rembielak, L. Stingeni, M. Tramontana, K. Hansel, G. Colloca, S. Saldi, V. Valentini, C. Aristei. All authors read and approved the final manuscript. Founding Sources The authors have declared no founding source. Conflict of Interest I wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. References [1] Chren MM, Torres JS, Stuart SE, et al. Recurrence after treatment of non-melanoma skin cancer: A prospective cohort study. Arch Dermatol 2011;147:540–6.
[2] Lancellotta V, Kovacs G, Tagliaferri L, et al. Age is not a limiting factor in interventional radiotherapy (Brachytherapy) for patients with localized cancer. Biomed Res Int 2018;217:8469. [3] Zaorsky NG, Lee CT, Zhang E, Galloway TJ. Skin cancer brachytherapy vs external beam radiation therapy (SCRiBE) meta-analysis. Radiother Oncol 2018;126:386–93. [4] Guinot JL, Rembielak A, Perez-Calatayud J, et al. GEC-ESTRO ACROP recommendations in skin brachytherapy. Radiother Oncol 2018;126:377–85. [5] Bouhassira J, Bosc R, Greta L, et al. Factors associated with postoperative complications in elderly patients with skin cancer : A retrospective study of 241 patients. J Geriatr Oncol 2016;7:10–4. [6] Guy GP, Machlin SR, Ekwueme DU, Yabroff KR. Prevalence and costs of skin cancer treatment in the U.S., 2002-2006 and 2007-2011. Am J Prev Med 2015;48:183–7. [7] Scalliet P, Van den Weingaert D, Van der Schuren E. Cancer in the Elderly Treatment and Research. Oxford: Oxford Medical Publications; 1994; 28–37. [8] Arenas M, Arguís M, Díez-Presa L, et al. Hypofractionated high-dose-rate plesiotherapy in nonmelanoma skin cancer treatment. Brachytherapy 2015;14: 859–65. [9] Tagliaferri L, Budrukkar A, Lenkowicz J, et al. ENT COBRA ONTOLOGY: the covariates classification system proposed by the Head & Neck and Skin GEC-ESTRO Working Group for interdisciplinary standardized data collection in head and neck patient cohorts treated with interventional radiotherapy (brachytherapy). J Contemp Brachytherapy 2018;10:260–6. [10] Valentini V, Maurizi F, Tagliaferri L, et al. SPIDER: Managing clinical data of cancer patients treated through a multidisciplinary approach by a palm based system. Italian J Public Health 2008;5:154–64.
Please cite this article as: Lancellotta V, et al, The role of personalized Interventional Radiotherapy (brachytherapy) in the management of older patients with non-melanoma skin ca, J Geriatr Oncol (2018), https://doi.org/10.1016/j.jgo.2018.09.009