To assess the role of radiotherapy in anti-PD-1-treated melanoma patients, we studied retrospectively a cohort of 206 consecutive anti-PD-1 monotherapy-treated advanced melanoma patients (59% M1c/d, 50% ≥ 3 metastasis sites, 33% ECOG PS ≥ 1, 33% > 1st line, 32% elevated serum LDH) having widely (49%) received concurrent radiotherapy, with RECIST 1.1 evaluation of radiated and non-radiated lesions. Overall (OS) and progression-free (PFS) survivals were calculated using Kaplan–Meier. Radiotherapy was performed early (39 patients) or after 3 months (61 patients with confirmed anti-PD-1 failure). The first radiotherapy was hypofractionated extracranial radiotherapy to 1–2 targets (26 Gy-4 weekly sessions, 68 patients), intracranial radiosurgery (25 patients), or palliative. Globally, 67 (32.5% [95% CI: 26.1–38.9]) patients achieved complete response (CR), with 25 CR patients having been radiated. In patients failing anti-PD-1, PFS and OS from anti-PD-1 initiation were 16.8 [13.4–26.6] and 37.0 months [24.6–NA], respectively, in radiated patients, and 2.2 [1.5–2.6] and 4.3 months [2.6–7.1], respectively, in non-radiated patients (p < 0.001). Abscopal response was observed in 31.5% of evaluable patients who radiated late. No factors associated with response in radiated patients were found. No unusual adverse event was seen. High-dose radiotherapy may enhance CR rate above the 6–25% reported in anti-PD-1 monotherapy or ipilimumab + nivolumab combo studies in melanoma patients.
Reply to A. Ruggiero et al. to our article 'Impact of the French COVID-19 pandemic lockdown on newly diagnosed melanoma delay and severity'Dear Editor, We read with interest the response from Ruggiero et al. 1 to our article. 2 They report no significant impact of the COVID-19 pandemic in numbers nor severity of melanoma diagnosed in a third-level centre in the South of Italy, which seems contradictory with our results. Wide variations between countries have been reported. 3 France and Italy were not impacted in a homogeneous way according to affected regions. Indeed, Northern Italy was the first place in Europe to face a massive outbreak of SARS-COV-2. This might have led to more severe restrictions to access hospitals and healthcare structures, with different shifts of health care resources and different emotional impacts for patients in the North of Italy compared with the South. This is highlighted by Gualdi et al.,4 who reported a reduction in the number of melanoma in 2020 compared with previous years in Northern and Central Italy, whereas there were no differences in the South of Italy. However, they reported a significant increase in the mean Breslow index even in Southern Italy. Moreover, Scharf et al. 5 recently published a multicentre retrospective study from six European referral centres, reviewing histopathologic reports, showing a significant decrease of 25.5% in diagnosis, along with a mean invasion thickness increased by 0.3 mm (p < 0.001). We hypothesize that the longer duration of 'lockdown and post-lockdown' periods used by Ruggiero et al. 1 (1 year) as compared with our study 2 (33 weeks) has made it possible to smooth out the differences between periods. However, Scharf et al. 5 also defined a 1-year period for 'lockdown and post-lockdown'. The major difference between our results and those by Ruggiero et al. 1 is the absence of a reduction in the number of melanomas diagnosed, which probably explains the absence of impact on melanoma severity. On the contrary, the high mean Breslow index reported by Ruggiero et al. 1 has strongly surprised us (and the number of stage IV), with 4.4 mm before COVID-19 and 4.9 mm after the first wave. This is much higher than our figures (1.7 mm ± 2.1 and 2.2 mm ± 2.4, respectively), 2 and those from the literature. 4,5 This could also explain the difficulty to show a difference in severity, as patients were much more severe at diagnosis.As the authors, 1 we believe that teledermatology could be a useful tool, as it has already shown efficacy in the diagnosis and management of skin cancer. 6 Interestingly, Skayem et al. 7 assessed the effect of first versus second COVID-19 waves on skin cancer requests via teledermatology, in a centre in the greater Paris area. As in our study, the authors showed a significant decline in skin cancer diagnoses during the first wave. Finally, 1 million people (out of 13) had left the great Paris area during the first lockdown. 8 Thus, even if the level of activity is maintained (face-toface and via teledermatology), awareness cam...
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