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Cariti, C.; Merli, M.; Avallone, G.; Rubatto, M.; Marra, E.; Fava, P.; Caliendo, V.; Picciotto, F.; Gualdi, G.; Stanganelli, I.; et al. Melanoma Management during the COVID-19 Pandemic Emergency. Encyclopedia. Available online: https://encyclopedia.pub/entry/47334 (accessed on 09 August 2024).
Cariti C, Merli M, Avallone G, Rubatto M, Marra E, Fava P, et al. Melanoma Management during the COVID-19 Pandemic Emergency. Encyclopedia. Available at: https://encyclopedia.pub/entry/47334. Accessed August 09, 2024.
Cariti, Caterina, Martina Merli, Gianluca Avallone, Marco Rubatto, Elena Marra, Paolo Fava, Virginia Caliendo, Franco Picciotto, Giulio Gualdi, Ignazio Stanganelli, et al. "Melanoma Management during the COVID-19 Pandemic Emergency" Encyclopedia, https://encyclopedia.pub/entry/47334 (accessed August 09, 2024).
Cariti, C., Merli, M., Avallone, G., Rubatto, M., Marra, E., Fava, P., Caliendo, V., Picciotto, F., Gualdi, G., Stanganelli, I., Fierro, M.T., Ribero, S., & Quaglino, P. (2023, July 27). Melanoma Management during the COVID-19 Pandemic Emergency. In Encyclopedia. https://encyclopedia.pub/entry/47334
Cariti, Caterina, et al. "Melanoma Management during the COVID-19 Pandemic Emergency." Encyclopedia. Web. 27 July, 2023.
Melanoma Management during the COVID-19 Pandemic Emergency
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This entry is adapted from the peer-reviewed paper 10.3390/cancers13236071

The COVID-19 pandemic has influenced the modus operandi of all fields of medicine, significantly impacting patients with oncological diseases and multiple comorbidities. Thus, the establishment of melanoma management during the emergency has become a major area of interest. In addition to original articles, case reports and specific guidelines for the period have been developed.

melanoma COVID-19 management

1. Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has increased the workload of the health system in the last two years, which has also presented a global challenge for dermatologists. Several elective clinical and surgical activities have been postponed to reduce the risk of nosocomial infections in patients and healthcare workers. This does not concern oncological patients, whose medical care has been guaranteed. However, cancer screening programs have clearly been interrupted by the onset of COVID-19 [1].
An early diagnosis is essential for the survival of patients with a melanoma [2]. The position statement issued by the European Academy of Dermatology and Venereology (EADV) affirmed that an in-person physical examination is obligatory for an accurate diagnosis of suspicious new cutaneous lesions, and that dermoscopy remains the gold standard for melanoma diagnosis. Although there have been no reports of COVID-19 transmission via dermatoscopes, the device must be carefully disinfected between patients and adequate personal protective equipment must be worn by physicians and patients [3]. In this context, the reduced level of access to medical care is a problem for dermatologists, due to the potential decrease in diagnoses of thin melanomas and delays in the presentation of patients with thick tumors. A survey conducted by the International Dermoscopy Society (IDS) showed that its members had experienced a 75% reduction in daily work activity since the beginning of pandemic, and remarkably, the number of melanomas diagnosed in these months was practically zero for more than half of them (56.78%) [4]. In addition to the devastating consequences for patients, delays in the treatment of melanomas can have a profound impact on the economic burden of this disease, because advanced melanomas have higher healthcare costs than earlier-stage melanomas [5].

2. Melanoma Surgery and Disease-Free Patient Follow-Up during the Pandemic

According to the European Society for Medical Oncology (ESMO) [6] and National Comprehensive Cancer Network (NCCN) guidelines [7], the position statement of the EADV Melanoma Task Force affirmed that the excision of a suspicious lesion should be performed as soon as possible to remove everything that is clinically visible [3]. In addition, the NCCN suggests that performing a broad-shave biopsy for larger suspected melanomas in situ and lentigo maligna, preventing the need to perform a subsequent radicalization. Wide excision should be postponed for up to 3 months for melanomas in situ and invasive melanomas for which a previous biopsy has showed clear histopathological margins or a peripheral transection of the in situ component [7]. It has been noted that delaying the surgical excision of melanoma by one month or longer increases the proportion of large or thick tumors, resulting in a lower chance of overall survival. In this regard, Tejera-Vaquerizo and Nagore built a model based on melanoma rate of growth (ROG), i.e., the rate of increase in Breslow thickness (millimeters per month) from the time a subject first observes a suspicious lesion to its excision. This predictive model was used to understand how diagnostic delays may impact the prognosis of melanomas [8].
When possible, wide excision and sentinel lymph node biopsy (SLNB—for melanoma thicker than 0.8 mm) should be performed at the same time. Otherwise, SLNB may be delayed by up to 3 months [7], as it has been demonstrated that such an interval of time does not have a negative effect on disease-free and overall survival [9]. Regarding therapeutic lymph node dissection, the EADV’s position statement indicated that it should be limited to patients with clinically evident regional lymph node metastases [3]. Conversely, NCCN guidelines affirm that lymphadenectomy should also be delayed in cases of clinically evaluable lymph adenopathy when a systemic neoadjuvant treatment is possible. In such a case, surgery should be performed 8–9 weeks after starting neoadjuvant treatment. This is not applicable when the affected lymph node is adjacent to vital organs and/or there is a contraindication to systemic therapy or a previous neoadjuvant treatment failure [7]. Finally, the guidelines agree that high surgical priority should be given to all invasive primary melanomas, resectable stage III melanomas, and oligo-metastatic disease [3].
Regarding disease-free patients, and according to the EADV’s position statement, the clinical and radiological follow-up in stage 0-I-IIA melanoma can be postponed for up to 3 months in asymptomatic patients [3]. Moreover, no clear evidence of an increase in survival in stages IB and IIA has been reported in ultrasound-based follow-ups [10]. High-risk patients should continue to have physical and imaging examinations, particularly during the first 3 years after surgery on the primary tumor [3]. On the other hand, NCCN guidelines suggest a possible deferral of up to 6 months even for stages IIB/IIC. During this delayed time, self-examination once a month is highly recommended [7].

3. Advanced Melanoma Management and Immunotherapy in the COVID-19 Era

For adjuvant therapy and treatment of unresectable stage III or IV melanomas, the indication of EADV is the same in a non-emergency setting; the treatment of melanomas with approved drugs must be started within 12 weeks of surgery. Considering these patients at higher risk for a severe course of COVID-19 infection, antibodies against Programmed Cell Death Protein 1 (PD1) should be administered using the longest approved treatment schedule to decrease hospital admissions: pembrolizumab 400 mg every 6 weeks and nivolumab 480 mg every 4 weeks [3]. Given its favorable safety profile, a monotherapy with anti-PD1 should be preferred in the majority of patients requiring immunotherapy [11]. The addition of ipilimumab, an antibody targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), significantly increases the risk of immune-related adverse events (iRAEs) from 15%–20% to 50%–60% compared to anti-PD1 monotherapy; this often leads to the need for immunosuppressive therapies and hospitalization, which in turn potentially increases the rate of COVID-19 transmission and severe disease [12]. Among the complications caused by immune checkpoint inhibitors (ICIs), immunotherapy-related pneumonitis and COVID-19 pneumonia have overlapping clinical and radiological features, leading to significant challenges in differential diagnosis [13]. Accordingly, the combination of nivolumab and ipilimumab is recommended only in subsets of patients with specific clinical features, including symptomatic and asymptomatic cerebral metastases, elevated LDH levels, bulky disease, PD-L1 negativity, and mucosal and acral melanoma [3][14]. The CheckMate 511 regimen—that is, ipilimumab 1 mg/kg plus nivolumab 3 mg/kg—is the preferred course of treatment due to a significantly lower incidence of treatment-related grade 3–5 AEs [15].
In patients undergoing BRAF and MEK inhibitor treatments, hyperpyrexia must be considered primarily as an adverse event rather than an indicator of COVID-19 infection. For this reason, encorafenib combined with binimetinib is preferred when available compared to other regimens due to its lower fever incidence [16]. In cases of fever associated with grade 2 or higher dyspnea, diarrhea, or neurological symptoms that do not resolve after therapy discontinuation, patients should be tested for a SARS-CoV-2 infection [3].
Concerning intracranial metastases, in cases of neurological deterioration or surgery, such as palliative care following treatment delays, stereotactic radiosurgery should be considered [14].
According to NCCN guidelines, in patients progressing beyond standard immune checkpoint blockade and targeted therapy, hospice care should be considered, because chemotherapy only provides a limited benefit. Oral temozolomide is the preferred option for palliative care cases [17].
As indicated by the EADV’s recommendations, all patients undergoing surgery, radiotherapy, chemotherapy, or immunotherapy must be tested for COVID-19 infection, despite studies in real-world settings showing a high safety profile in these patients. Additionally, to date, no clear evidence suggests that ICIs increase the risk of a SARS-CoV-2 infection [3]. Whether the administration of anti-PD1 drugs, by stimulating the immune system, could directly contribute to a more severe course of COVID-19, compared to that observed in patients not receiving immunotherapy, is currently an open question. The potential interplay between COVID-19 infection and treatment with immune-checkpoint inhibitors of patients with a melanoma is still unknown. Nevertheless, preliminary evidence and case reports suggest that anti-PD1 therapy does not worsen the course of COVID-19, allowing patients with cancer to continue their treatment [18]. In this Italian multicenter study by Pala et al., out of 169 patients with unresectable stage III or IV melanomas treated with immunotherapy, 104 continued without modifications, and among 15 patients showing symptoms compatible with COVID-19, only one tested positive on the nasopharyngeal swab [19].

References

  1. Alkatout, I.; Biebl, M.; Momenimovahed, Z.; Giovannucci, E.; Hadavandsiri, F.; Salehiniya, H.; Allahqoli, L. Has COVID-19 Affected Cancer Screening Programs? A Systematic Review. Front. Oncol. 2021, 11, 675038.
  2. Villani, A.; Fabbrocini, G.; Costa, C.; Scalvenzi, M. Melanoma Screening Days during the Coronavirus Disease 2019 (COVID-19) Pandemic: Strategies to Adopt. Dermatol. Ther. (Heidelb.) 2020, 10, 525–527.
  3. Arenbergerova, M.; Lallas, A.; Nagore, E.; Rudnicka, L.; Forsea, A.M.; Pasek, M.; Meier, F.; Peris, K.; Olah, J.; Posch, C. Position Statement of the EADV Melanoma Task Force on Recommendations for the Management of Cutaneous Melanoma Patients during COVID-19. J. Eur. Acad. Dermatol. Venereol. 2021, 35, e427–e428.
  4. Conforti, C.; Lallas, A.; Argenziano, G.; Dianzani, C.; di Meo, N.; Giuffrida, R.; Kittler, H.; Malvehy, J.; Marghoob, A.A.; Soyer, H.P.; et al. Impact of the COVID-19 Pandemic on Dermatology Practice Worldwide: Results of a Survey Promoted by the International Dermoscopy Society (IDS). Dermatol. Pract. Concept. 2021, 11, e2021153.
  5. Gomolin, T.; Cline, A.; Handler, M.Z. The Danger of Neglecting Melanoma during the COVID-19 Pandemic. J. Dermatol. Treat. 2020, 31, 444–445.
  6. ESMO ESMO Management and Treatment Adapted Recommendations in the COVID-19 Era: Melanoma. Available online: https://www.esmo.org/guidelines/cancer-patient-management-during-the-covid-19-pandemic/melanoma-in-the-covid-19-era (accessed on 4 October 2021).
  7. NCCN Short-Term Recommendations for Cutaneous Melanoma Management during COVID-19 Pandemic. Available online: https://www.nccn.org/covid-19/pdf/Melanoma.pdf (accessed on 6 May 2020).
  8. Tejera-Vaquerizo, A.; Nagore, E. Estimated Effect of COVID-19 Lockdown on Melanoma Thickness and Prognosis: A Rate of Growth Model. J. Eur. Acad. Dermatol. Venereol. 2020, 34, e351–e353.
  9. Mandalà, M.; Galli, F.; Patuzzo, R.; Maurichi, A.; Mocellin, S.; Rossi, C.R.; Rulli, E.; Montesco, M.; Quaglino, P.; Caliendo, V.; et al. Timing of Sentinel Node Biopsy Independently Predicts Disease-Free and Overall Survival in Clinical Stage I-II Melanoma Patients: A Multicentre Study of the Italian Melanoma Intergroup (IMI). Eur. J. Cancer 2020, 137, 30–39.
  10. Ribero, S.; Podlipnik, S.; Osella-Abate, S.; Sportoletti-Baduel, E.; Manubens, E.; Barreiro, A.; Caliendo, V.; Chavez-Bourgeois, M.; Carrera, C.; Cassoni, P.; et al. Ultrasound-Based Follow-up Does Not Increase Survival in Early-Stage Melanoma Patients: A Comparative Cohort Study. Eur. J. Cancer 2017, 85, 59–66.
  11. Rogiers, A.; Pires da Silva, I.; Tentori, C.; Tondini, C.A.; Grimes, J.M.; Trager, M.H.; Nahm, S.; Zubiri, L.; Manos, M.; Bowling, P.; et al. Clinical Impact of COVID-19 on Patients with Cancer Treated with Immune Checkpoint Inhibition. J. Immunother. Cancer 2021, 9, e001931.
  12. Patrinely, J.R.; Johnson, D.B. Pandemic Medicine: The Management of Advanced Melanoma during COVID-19. Melanoma Manag. 2020, 7, MMT45.
  13. Abid, M.B. Overlap of Immunotherapy-Related Pneumonitis and COVID-19 Pneumonia: Diagnostic and Vaccine Considerations. J. Immunother. Cancer 2021, 9, e002307.
  14. Nahm, S.H.; Rembielak, A.; Peach, H.; Lorigan, P.C. Consensus Guidelines for the Management of Melanoma during the COVID-19 Pandemic: Surgery, Systemic Anti-Cancer Therapy, Radiotherapy and Follow-Up. Clin. Oncol. (R. Coll. Radiol.) 2021, 33, e54–e57.
  15. Lebbé, C.; Meyer, N.; Mortier, L.; Marquez-Rodas, I.; Robert, C.; Rutkowski, P.; Menzies, A.M.; Eigentler, T.; Ascierto, P.A.; Smylie, M.; et al. Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial. J. Clin. Oncol. 2019, 37, 867–875.
  16. Meirson, T.; Asher, N.; Bomze, D.; Markel, G. Safety of BRAF+MEK Inhibitor Combinations: Severe Adverse Event Evaluation. Cancers 2020, 12, 1650.
  17. Swetter, S.M.; Thompson, J.A.; Albertini, M.R.; Barker, C.A.; Baumgartner, J.; Boland, G.; Chmielowski, B.; DiMaio, D.; Durham, A.; Fields, R.C.; et al. NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021: Featured Updates to the NCCN Guidelines. J. Natl. Compr. Cancer Netw. 2021, 19, 364–376.
  18. Maio, M.; Lahn, M.; di Giacomo, A.M.; Covre, A.; Calabrò, L.; Ibrahim, R.; Fox, B. A Vision of Immuno-Oncology: The Siena Think Tank of the Italian Network for Tumor Biotherapy (NIBIT) Foundation. J. Exp. Clin. Cancer Res. 2021, 40, 240.
  19. Pala, L.; Conforti, F.; Saponara, M.; de Pas, T.; Giugliano, F.; Omodeo Salè, E.; Jemos, C.; Rubatto, M.; Agostini, A.; Quaglino, P.; et al. Data of Italian Cancer Centers from Two Regions with High Incidence of SARS CoV-2 Infection Provide Evidence for the Successful Management of Patients with Locally Advanced and Metastatic Melanoma Treated with Immunotherapy in the Era of COVID-19. Semin. Oncol. 2020, 47, 302–304.
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Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Caterina Cariti
,
Martina Merli
,
Gianluca Avallone
,
Marco Rubatto
,
Elena Marra
,
Paolo Fava
,
Virginia Caliendo
,
Franco Picciotto
,
Giulio Gualdi
,
Ignazio Stanganelli
,
Maria Teresa Fierro
,
Simone Ribero
,
Pietro Quaglino
View Times: 163
Revisions: 3 times (View History)
Update Date: 27 Jul 2023
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