Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Actas Dermosifiliogr. 2020;111(8):629---638 REVIEW Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model夽 A. Tejera-Vaquerizo,a,∗ J. Cañueto,b A. Toll,c J. Santos-Juanes,d A. Jaka,e C. Ferrandiz,f O. Sanmartín,g S. Ribero,h D. Moreno-Ramírez,i F. Almazán,j M.J. Fuente,e S. Podlipnik,c E. Nagoreg a Servicio de Dermatología, Instituto Dermatológico GlobalDerm, Palma del Río Córdoba, Spain b Servicio de Dermatología, Hospital Universitario de Salamanca, Salamanca, Spain c Servicio de Dermatología, Hospital Clìnic de Barcelona, Barcelona, Spain d Servicio de Dermatología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain e Servicio de Dermatología, Hospital Germans Trial i Pujol, Badalona, Barcelona, Spain f Servicio de Dermatología, Hospital de la Vall d’Hebron, Barcelona, Spain g Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain h Departamento de Dermatología, Hospital Universitario de Turín, Turín, Italy i Unidad de Melanoma, Servicio de Dermatología Médico-Quirúrgica, Hospital Universitario Virgen Macarena, Sevilla, Spain j Unidad de Gestión Clínica de Dermatología, Hospital Universitario San Cecilio, Granada, Spain Received 28 April 2020; accepted 5 May 2020 Available online 20 September 2020 KEYWORDS Abstract Melanoma; Background and objectives: Spain is in a situation of indefinite lockdown due to the ongoing Prognosis; coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is Early diagnosis; delays in medical and surgical procedures for common diseases. The aim of this study was to Cutaneous squamous model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma; cell carcinoma (SCC) and melanoma. COVID-19 virus Material and methods: Multicenter, retrospective, observational cohort study. We constructed disease; an exponential growth model for both SCC and melanoma to estimate tumor growth between Lockdown patient-reported onset and surgical excision at different time points. Results: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter > 4 cm or thickness > 6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of 夽 Please cite this article as: Tejera-Vaquerizo A, Cañueto J, Toll A, Santos-Juanes J, Jaka A, Ferrandiz C, et al. Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: modelo basado en un crecimiento exponencial. Actas Dermosifiliogr. 2020;155:629---638. ∗ Corresponding author. E-mail address: antoniotejera@aedv.es (A. Tejera-Vaquerizo). 1578-2190/© 2020 Published by Elsevier España, S.L.U. on behalf of AEDV. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 630 A. Tejera-Vaquerizo et al. delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (> 6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. Conclusions: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays. © 2020 Published by Elsevier España, S.L.U. on behalf of AEDV. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). PALABRAS CLAVE Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido Melanoma; al confinamiento por COVID-19: modelo basado en un crecimiento exponencial Pronóstico; Resumen Diagnóstico precoz; Antecedentes y objetivos: La pandemia del coronavirus COVID-19 ha provocado un confi- Carcinoma de células namiento indefinido. Una posible consecuencia de esta situación es un retraso en los Escamosas cutáneo; procedimientos asistenciales de las patologías comunes. El objetivo de este estudio es esti- COVID-19; mar el hipotético impacto en la supervivencia que tendría el aumento del tamaño tanto para Confinamiento los carcinomas de células escamosas (CCE) como de los melanomas. Material y método: Estudio observacional retrospectivo de cohortes multicéntrico. Se desar- rolló un modelo de crecimiento exponencial para cada tumor basado en el tiempo de evolución que refiere el paciente. Resultados: Se incluyeron un total de 200 pacientes con CCEs localizados en la cabeza y el cuello y 1000 pacientes con melanoma cutáneo. Se calculó una curva de crecimiento exponencial para cada tumor y se estimó el tamaño del tumor tras 1, 2 y 3 mes tras el diagnóstico. En la muestra, los CCE mayores de 4 cm o >6 mm de grosor (definidos como T3) pasaron de 83 (41.5%) en el grupo de estudio real a una estimación de 58,5%, 70,5% y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado. Se estimó una disminución de la supervivencia específica de enfermedad (SEE) de un 6,2%, 8,2% y 5,2% a los 2, 5 y 10 años, respectivamente, tras tres meses de retraso. Para los melanomas, los melanomas ultragruesos (>6 mm) pasaron del 6,9% en el grupo de estudio al 21,9%, 30,2% y 30,2% tras 1, 2 y 3 meses de demora. La SEE a los 5 y 10 años del grupo de estudio descendió un 14,4% en ambos tiempos. Conclusiones: En ausencia de un adecuado diagnóstico y tratamiento de los pacientes con CCE y melanoma en la actual situación de confinamiento en España, podemos llegar a asistir a un considerable aumento de los casos de CCE y melanomas gruesos y de gran tamaño. Se deben fomentar los esfuerzos para promocionar la autoexploración y facilitar el acceso a los dermatólogos para no aumentar la demora de estos pacientes. © 2020 Publicado por Elsevier España, S.L.U. en nombre de AEDV. Este es un artı́culo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction and tumor size and/or thickness in SCC and melanoma, 2 of the most lethal skin cancers.8 The coronavirus disease 19 (COVID-19) pandemic, which started in Wuhan, China several months ago,1 has led to a large-scale lockdown in many countries across the world, Material and Methods including Spain. Uncertainty regarding the duration of the lockdown measures led us to consider how potential diagnos- Theoretical Framework and Case Studies tic and treatment delays due to the interruption of certain health procedures and services might affect the prognosis The assumption on which this study is based is that tumors of patients with skin cancer. Diagnostic delays are known to grow exponentially (Fig. 1).9 Although it could be argued be associated with larger tumor size in this setting.2 Tumor that tumor growth follows a Gompertz, sigmoid-like, curve, size at diagnosis also appears to be influenced by time to we assumed that the models would be superimposable for diagnosis and growth rate for both squamous cell carcinoma relatively small tumors.10 (SCC)3---5 and melanoma.6,7 The exponential function that links the dependent vari- The aim of this study was to estimate the extent to which able y (tumor size) to the independent variable x (time) is surgical delays of 1, 2, and 3 months might affect survival expressed as follows: Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model 631 We analyzed 200 SCCs and 1000 melanomas randomly selected from 2 databases. The primary outcome measure was change in estimated Exponential tumor size and/or thickness at 1, 2, and 3 months. The tumor growth results were categorized by size and thickness. SCCs were classified using a similar system to the SCC staging system Moment patient Tumor size of the American Joint Committee on Cancer (AJCC)11 : T1 notices the lesion (diameter ≤ 2 cm), T2 (diameter 2−4 cm), and T3 (diameter > 4 cm or thickness > 6 mm). Melanomas were grouped into Start of tumor growth 6 Breslow thickness categories, similar to those proposed Excision +1 mo +2 mo +3 mo by the AJCC: < 0.8 mm, 0.8−1 mm, > 1−2 mm, > 2−4 mm, Figure 1 Theoretical exponential growth model for skin > 4−6 mm, and > 6 mm. The last 2 categories of thick tumors tumors. are not part of the AJCC staging system but were included as ultrathick melanomas were recently reported to have prognostic significance.12 We also performed a stratified analysis by sex and age y = a · ebx (1) (≤ 80 vs. > 80 years for SCC and ≤ 70 vs. > 70 years for where a and b are both adjustable. It follows that at the melanoma).12 beginning of tumor growth (x = 0) a is the initial size of To analyze the impact of surgical delays on survival, we the tumor, such thaty = a · e0 , and b is the coefficient that estimated disease-specific survival (DSS) for patients with determines its growth. The higher this second coefficient, SCC and melanoma overall and stratified by sex and age the faster the tumor will grow. using survival curves from the Squamata database for SCCs To estimate the exponential growth of a tumor, it is nec- (n = 434) (Figs. 1---5 of the supplementary material) and the essary to know y (size) and x (time) at 2 moments in time. melanoma database of the Instituto Valenciano de Oncología In brief, y 1 is the size of the tumor when it is first noticed (n = 1637) (Figs. 6---10 of the supplementary material). The by the patient and/or a relative, y2 is the size of the tumor resulting survival rates (overall and by sex and age) were at the time of surgery, x1 is the time when the tumor is first then used to estimate survival for patients with SCC and noticed, and x2 is the time of surgery. Asy1 (the size of the melanoma after a potential surgical delay of 1, 2, and 3 tumor when it is first noticed) is unknown, it was estimated months. The Kaplan-Meier method was used to estimate for both SCCs and melanomas. overall and sex- and age-stratified DSS for the SCCs and To estimatey1 for SCCs, we used data from a series of 6 melanomas analyzed. cases that provided details of tumor size at 2 points in time The study was approved by the ethics committee of Hos- (Fig. 2) (Appendix B Table 1 of the supplementary material). pital Universitario Reina Sofía Córdoba (reference 3958, file With this information, we calculated the exponential growth no. 280). function for each of the 6 tumors (Fig. 3), where a was the diameter of the tumor at y1 (when it was first noticed by the Results patient and/or a relative). The mean of the 6 measurements (a = 8.75 mm) was used as coefficient a to estimate the expo- nential growth of the SCCs in our sample. The same method Squamous Cell Carcinoma was applied to estimate SCC thickness, which was known for 4 of the 6 tumors. Tumor thickness at diagnosis (y1 ) was Of the 200 SCCS with a known time from onset to surgery assumed to be proportional to the diameter calculated for analyzed, 52% had a diameter of < 2 cm (T1). Just 13 (6.5%) the same time point. The resulting thickness was 1.2 mm, had a diameter of 2−4 cm (T2) and 83 (41.5 %) had a diam- which was used as coefficient a to calculate the exponential eter of > 4 cm or a thickness of > 6 mm (T3) (Table 1). The function for each of the SCCs in the study sample. proportion of T3 tumors increased by 58.5% for a hypothet- We were unable to perform similar measurements for ical surgical delay of 1 month, by 70.5% for a delay of 2 melanomas, as we did not have details of mean Breslow months, and by 72% for a delay of 3 months. thickness at 2 different time points. We therefore estab- Estimated DSS for the overall group was 86.1% at 2 years, lished a thickness of 0.2 mm for coefficient a based on the 80.2% at 5 years, and 70.8% at 10 years. Survival rates assumption that this would be the minimum vertical growth decreased progressively over time to 79.9% for a delay of needed for the tumor to be noticed by the patient; x2 was 1 month, 72% for a delay of 2 months, and 65.6% for a delay defined as the time from when the patient noticed the tumor of 3 months. to the time of surgery. In the sex-stratified analysis, female sex was associated Once we had estimated initial tumor size, we obtained with worse 5-year DSS (75.2% vs. 83.3%) and 10-year DSS coefficient b of the exponential function as follows: (65.3% vs. 77.6%). Again, survival rates decreased progres-   sively over the 3 months. At the 3-month point, 5-year y2 survival was 68.5% for women and 72.6% for men (Table 2). In y1 b= (2) In the age-stratified analysis, DSS was worse in patients x2 − x1 aged >80 years at all the time points analyzed, with the With this information, we then estimated tumor size and greatest difference observed at month 3 (5-year survival of thickness for SCCs and tumor thickness for melanomas after 79% for patients aged > 80 years vs. 58.7% for those aged a hypothetical surgical delay of 1, 2, and 3 months. ≤ 80 years) (Table 3). 632 A. Tejera-Vaquerizo et al. Figure 2 Squamous cell carcinoma of the scalp that grew from 25 mm to 42 mm over 3 months. 90 Tumor growth function 80 y = 2.5105e0.4925x Time of surgery 70 60 Diagnosis of lesion Estimated tumor size 50 over coming months Tumor size, y 40 30 20 10 0 0 1 2 3 4 5 6 7 8 Time, mo (x) Figure 3 Exponential growth function for a squamous cell carcinoma in patient 1. Table 1 Tumor Size and Thickness at Diagnosis and After an Estimated Surgical Delay of 1, 2, and 3 Months Based on the Exponential Growth of 200 Squamous Cell Carcinomas of the Head and Neck from the Squamata Database. Risk Group Study Group, 1-mo Surgical 2-mo Surgical 3-mo Surgical No. (%) Delay, No. (%) Delay, No. (%) Delay, No. (%) Diameter ≤ 2 cm 104 (52) 63 (31.5) 45 (22.5) 43 (21.5) Diameter > 2−4 cm 13 (6.5) 20 (10) 14 (7) 13 (6.5) Diameter > 4 cm or thickness > 6 mm 83 (41.5) 117 (58.5) 141 (70.5) 144 (72) Estimated 2-year survival,a % 86.1 82.4 80.2 79.9 Estimated 5-year survival,a % 80.2 75.5 72.4 72 Estimated 10-year survival,a % 70.8 68.2 65.9 65.6 a Based on survival data for 434 patients from the Squamata database (Fig. 1 of the supplementary material). Cutaneous Melanoma nificantly over the 3 months analyzed, with the lowest rates observed at month 3 (71.3% for 5-year survival and 65% for Most of the tumors from the melanoma database were thin; 10-year survival) (Table 5). tumors measuring < 0.8 mm and 0.8−1 mm accounted for In the sex-stratified analysis, ultrathick melanomas 29.8% and 10.4% of all tumors, respectively. Thick and ultra- (> 6 mm) were somewhat more common in men (8% vs. 5.8% thick melanomas comprised the smallest group (9.1% for for women) both initially and at the 3 time points analyzed. melanomas with a Breslow thickness of 4−6 mm and 6.9% The increase in the proportion of these tumors was signif- for those with a Breslow thickness of > 6 mm) (Table 4). icant from 1 month onwards (27% for men vs. 16.8% for The greatest percentage increase over time was observed women) and peaked at month 3 (41.8% vs. 29%). for tumors with a thickness of > 6 mm, which accounted for Five-year DSS for the overall group was better in women 21.9% of all tumors at 1 month, 30.2% at 2 months, and 30.2% (89.2% vs 82.8%), but it decreased in both groups over the at 3 months. Five- and 10-year DSS rates for the overall group following months, reaching its lowest point at month 3 were 85.7% and 79.4% respectively, and these decreased sig- (77.5% for women vs. 70.7% for men). Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model Table 2 Tumor Size and Thickness at Diagnosis and After an Estimated Surgical Delay of 1, 2, and 3 Months Based on the Exponential Growth of 200 Squamous Cell Carcinomas of the Head and Neck from the Squamata Database: Sex-Stratified Analysis. Risk Group [0,2---3]Study [0,4---5]1-mo [0.6−7]2-mo [0.8−9]3-mo Group Surgical Delay Surgical Delay Surgical Delay Men, No. Women, Men, No. Women, Men, No. Women, Men, No. Women, (%) No. (%) (%) No. (%) (%) No. (%) (%) n (%) Diameter ≤ 2 cm 68 (54) 36 (48) 40 (32) 23 (30.7) 28 (22.4) 17 (22.7) 26 (20.8) 17 (22.7) Diameter > 2−4 cm 8 (6.4) 5 (6.7) 11 (8.8) 9 (12) 10 (8) 4 (5.3) 10 (8) 3 (4) Diameter > 4 cm or 49 (39.2) 34 (45.3) 74 (59.2) 43 (57.3) 67 (69.6) 54 (72) 89 (71.2) 55 (73.3) thickness > 6 mm Estimated 2-year 86.2 87.1 80.8 85.4 78.4 82.6 77.8 82.3 survival,a % Estimated 5-year 83.3 75.2 76.4 73.3 73.2 69 72.6 68.5 survival,a % Estimated 10-year 77.6 65.3 74 65.1 72.5 60.8 72 60.3 survival,a % a Based on survival data for 434 patients from the Squamata database (Figs. 2 and 3 of the supplementary material). 633 634 Table 3 Tumor Size and Thickness at Diagnosis and After an Estimated Surgical Delay of 1, 2, and 3 Months Based on the Exponential Growth of 200 Squamous Cell Carcinomas of the Head and Neck from the Squamata Database: Age-Stratified Analysis. Risk Group [0,2---3]Study [0,4---5]1-mo [0.6−7]2-mo [0.8−9]3-mo Group Surgical Delay Surgical Delay Surgical Delay ≤ 80 y, > 80 y, ≤ 80 y, > 80 y, ≤ 80 y, > 80 y, ≤ 80 y, > 80 y, No. (%) No. (%) No. (%) No. (%) No. (%) No. (%) No. (%) No. (%) Diameter ≤ 2 cm 67 (59.8) 37 (42) 39 (34.8) 24 (27.3) 25 (22.3) 20 (22.7) 24 (21.4) 19 (21.6) Diameter > 2−4 cm 3 (2.7) 10 (11.4) 14 (12.5) 6 (6.8) 12 (10.7) 2 (2.3) 10 (8.9) 3 (3.4) Diameter > 4 cm or 42 (37.5) 41 (46.6) 59 (52.7) 58 (65.9) 75 (67) 66 (75) 78 (69.6) 66 (75) thickness > 6 mm Estimated 2-year 90.9 84.9 88.8 81.6 86.5 80.4 85.9 73.5 survival,a % Estimated 5-year 85.7 72.7 83 66.5 79.8 63.7 79.0 58.7 survival,a % Estimated 10-year 74.8 67.3 74.8 62.9 72.6 60.8 71.8 55.9 survival,a % a Based on survival data for 434 patients from the Squamata database (Figs. 4 and 5 of the supplementary material). A. Tejera-Vaquerizo et al. Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model 635 Table 4 Tumor thickness at Diagnosis and After an Estimated Surgical Delay of 1, 2, and 3 Months Based on the Exponential Growth of 1000 Melanomas from the Instituto Valenciano de Oncología Melanoma Database. Risk Group Study Group, 1-mo Surgical 2-mo Surgical 3-mo Surgical No. (%) Delay, No. (%) Delay, No. (%) Delay, No. (%) < 0.8 mm 298 (29.8) 253 (25.3) 220 (22) 204 (20.4) 0.8−1.0 mm 104 (10.4) 65 (6.5) 57 (5.7) 48 (4.8) > 1.0−2.0 mm 259 (25.9) 214 (21.4) 188 (18.8) 166 (16.6) > 2.0−4.0 mm 179 (17.9) 165 (16.5) 164 (16.4) 153 (15.3) > 4.0−6.0 mm 91 (9.1) 84 (8.4) 69 (6.9) 75 (7.5) > 6.0 mm 69 (6.9) 219 (21.9) 302 (30.2) 302 (30.2) Estimated 5-year survival,a % 85.7 79.5 76.3 71.3 Estimated 10-year survival,a % 79.8 73.1 69.7 65 a Based on survival data for 1637 patients from the Instituto Valenciano de Oncología (Fig. 6 of the supplementary material). Table 5 Tumor thickness at Diagnosis and After an Estimated Surgical Delay of 1, 2, and 3 Months Based on the Exponential Growth of 1000 Melanomas from the Instituto Valenciano de Oncología Melanoma Database: Sex-Stratified Analysis. Risk Group [0,2---3]Study [0,4---5]1-mo [0.6−7]2-mo [0.8−9]3-mo Group Surgical Delay Surgical Delay Surgical Delay Men, No. Women, Men, No. Women, Men, No. Women, Men, No. Women, (%) No. (%) (%) No. (%) (%) No. (%) (%) No. (%) < 0.8 mm 122 176 106 147 93 (18.6) 127 84 (16.8) 120 (24) (24.4) (35.2) (21.2) (29.4) (25.4) 0.8−1.0 mm 39 (7.8) 65 (13) 24 (4.8) 41 (8.2) 21 (4.2) 36 (7.2) 19 (3.8) 29 (5.8) > 1.0−2.0 mm 129 130 (26) 99 (19.8) 115 (23) 91 (18.2) 97 (19.4) 77 (15.4) 89 (17.8) (25.8) > 2.0−4.0 mm 109 70 (14) 81 (16.2) 84 (16.8) 74 (14.8) 90 (18) 74 (14.8) 79 (15.8) (21.8) > 4.0−6.0 mm 61 (12.2) 30 (6) 55 (11) 29 (5.8) 42 (8.4) 27 (5.4) 37 (7.4) 38 (7.6) > 6.0 mm 40 (8) 29 (5.8) 135 (27) 84 (16.8) 179 123 209 145 (29) (35.8) (24.6) (41.8) Estimated 5-year 82.8 89.2 75.7 83.5 73 79.8 70.7 77.5 survival,a % Estimated 10-year 76.1 83.5 68.8 77.2 66 73.2 63.6 70.9 survival,a % a Based on survival data for 1637 patients from the Instituto Valenciano de Oncología (Figs. 7 and 8 of the supplementary material). In the age-stratified analysis, thick melanomas the proportion of large or thick tumors and results in worse (> 4−6 mm) were more common in patients aged > 70 survival. years (16.8% vs 7.2% in patients aged ≤ 70 years), while People in Spain and many other countries around the ultrathick melanomas were present to a similar degree in world have been confined to their homes for several weeks both age categories (5.8% vs. 5%). A significant increase now due to the COVID-19 pandemic. Significant time and in the proportion of ultrathick tumors was observed for resources are being invested to learn more about this dis- each of the 3 time points analyzed, and was particularly ease and about how to manage it both now and in the high in both age groups at month 3 (52% for patients future. There is little discussion, however, about how the aged > 70 years vs. 31.3% for those aged ≤ 70 years) vast diversion of healthcare resources towards the COVID- (Table 6). 19 outbreak might affect other diseases, such as cancer. In Patients in the over-70 category experienced the greatest recent weeks, numerous governments have ruled that doc- change in survival rates from baseline to month 3 (86.3% tors should not deal with deferrable medical procedures. to 75.6% for 5-year survival and 75.7% to 61.9% for 10-year Cancer surgery, however, cannot be deferred and should survival). continue during the pandemic. Nonetheless, there are signs that the provision of care to patients with severe illness is declining at an alarming rate. One oral medicine unit in Italy, for example, reported that it had diagnosed practi- Discussion cally no cases of oral squamous cell carcinoma during the lockdown period,13 while an Austrian study reported a sig- The main finding of this study is that delaying the surgical nificant decline in hospital admissions for acute coronary excision of SCC or melanoma by 1 month or longer increases syndrome in the first days of lockdown, which could result 636 Table 6 Tumor thickness at Diagnosis and After an Estimated Surgical Delay of 1, 2, and 3 Months Based on the Exponential Growth of 1000 Melanomas from the Instituto Valenciano de Oncología Melanoma Database: Age-Stratified Analysis. Risk Group [0,2---3]Study [0,4---5]1-mo [0.6−7]2-mo [0.8−9]3-mo Group Surgical Delay Surgical Delay Surgical Delay ≤ 70 y, > 70 y, ≤ 70 y, > 70 y, ≤ 70 y, > 70 y, ≤ 70 y, > 70 y, No. (%) No. (%) No. (%) No. (%) No. (%) No. (%) No. (%) No. (%) < 0.8 mm 265 (33) 33 (16.8) 222 31 (15.8) 193 (24) 27 (13.8) 179 25 (12.8) (27.6) (22.3) 0 8−1.0 mm 93 (11.6) 11 (5.6) 59 (7.3) 6 (3.1) 49 (6.1) 8 (4.1) 41 (5.1) 7 (3.6) > 1.0−2.0 mm 218 41 (20.9) 185 (23) 29 (14.8) 166 22 (11.2) 146 20 (10.2) (27.1) (20.6) (18.2) > 2.0−4.0 mm 130 49 (25) 132 33 (16.8) 133 31 (15.8) 126 27 (13.8) (16.2) (16.4) (16.5) (15.7) > 4.0−6.0 mm 58 (7.2) 33 (16.8) 57 (7.1) 27 (13.8) 53 (6.6) 16 (8.2) 60 (7.5) 15 (7.7) > 6.0 mm 40 (5) 29 (5.8) 149 70 (35.7) 210 92 (46.9) 252 102 (52) (18.5) (26.1) (31.3) Estimated 5-year 88.4 86.3 81.7 81.7 78.2 78.2 75.7 75.7 survival,a % Estimated 10-year 83.5 75.6 77.1 68.3 73.9 64.5 71.6 61.9 survival,a % a Based on survival data for 1637 patients from the Instituto Valenciano de Oncología (Figs. 9 and 10 of the supplementary material). A. Tejera-Vaquerizo et al. Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model 637 in an increase in infarct-related morbidity and mortality in Funding the coming weeks.14 Similar concerns have been reported for prostate cancer.15 This study was partially funded by a grant from the Fun- In the case of skin cancer, many patients feel confident dación Piel Sana (Healthy Skin Foundation) of the Spanish that they can postpone seeking care for what is actually Academy of Dermatology and Venereology (AEDV). The a malignant lesion,2 and in the current scenario, in many research work of J.C. is partially funded by Instituto de Salud cases this behavior may be compounded by fear of becoming Carlos III (project PI18/00587), which is confunded by the infected or infecting their family if they do seek care. European Regional Development Fund. The COVID-19 pandemic has brought unprecedented times. While a patient with primary skin cancer should be offered surgery without delay as the first line of action, Acknowledgments in light of the current shortages of equipment, healthcare personnel, and ICU beds,16 other options such as radiation We would like to thank Inmaculada Morales Villagrás and therapy or intralesional methotrexate (for SCCs) could be Mónica Moya Pareja for their mathematical advice and contemplated in certain cases, such as slow-growing SCCs Miguel Ángel Descalzo-Gallego for his statistical advice. or thin tumors.17 Our study has some limitations. First, our findings are based on a mathematical estimation of a growth curve built Appendix A. Supplementary data using data from a small number of patients and assuming a scenario in which the entire population is affected by sur- Supplementary material related to this article can be found, gical delays. This may, however, not actually be the case, in the online version, at doi: https://doi.org/10.1016/ as some patients have undergone surgery during lockdown j.ad.2020.05.001. or continued to see a doctor or use teledermatology ser- vices. Second, the impact on melanoma thickness may be References overestimated, as many tumors are thicker than the esti- mated thickness of 0.2 mm when they are first noticed by 1. Phelan AL, Katz R, Gostin LO. The novel coronavirus a patient. Third, we did not use the same stages as those originating in Wuhan, China. JAMA. 2020;323:709, proposed by the AJCC, as we were unable to determine http://dx.doi.org/10.1001/jama.2020.1097. which patients would develop ulceration, or, in the case of 2. Renzi C, Mastroeni S, Passarelli F, Mannooranparampil TJ, SCC, which patients would experience progression to per- Caggiati A, Potenza C, et al. Factors associated with large cuta- ineural or bone invasion. Finally, the survival curves used to neous squamous cell carcinomas. J Am Acad Dermatol. 2010, estimate survival were not adjusted for other variables. http://dx.doi.org/10.1016/j.jaad.2009.09.044. Our study also has strengths. Although our sample was 3. Martorell-Calatayud A, Sanmartín Jimenez O, Cruz Mojarrieta small, the distribution of melanoma thicknesses is almost J, Guillén Barona C. Cutaneous squamous cell carcinoma: defin- ing the high-risk variant. Actas Dermosifiliogr. 2013;104:367---79, identical to that in the Spanish Melanoma Registry.18 The http://dx.doi.org/10.1016/j.adengl.2011.12.012. proportion of thicker tumors in our sample of SCCs is higher 4. Cañueto J, Martín-Vallejo J, Cardeñoso-Álvarez E, Fernández- than that documented in large series19 (probably because López E, Pérez-Losada J, Román-Curto C. Rapid growth we included tumors with bone involvement or other poor rate is associated with poor prognosis in cutaneous prognostic factors), and this would have resulted in worse squamous cell carcinoma. Clin Exp Dermatol. 2018, survival curves. http://dx.doi.org/10.1111/ced.13570. 5. Kricker A, Armstrong B, Hansen V, Watson A, Singh-Khaira G, Lecathelinais C, et al. Basal cell carcinoma and squa- mous cell carcinoma growth rates and determinants of size Conclusions in community patients. J Am Acad Dermatol. 2014;70:456---64, http://dx.doi.org/10.1016/j.jaad.2013.11.009. We have shown that a failure to prioritize diagnosis and 6. Martorell-Calatayud A, Nagore E, Botella-Estrada R, treatment of SCC and melanoma in the current lockdown Scherer D, Requena C, Serra-Guillén C, et al. Defining situation in Spain could lead to a considerable increase in fast-growing melanomas: reappraisal of epidemiological, more advanced tumors and healthcare costs.9 clinical, and histological features. 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