Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Treatment of actinic keratosis (AK) aims to prevent cutaneous squamous cell carcinoma (cSCC). However, whether AK can progress into invasive cSCC is a matter of debate, and little is known about the effect of treatment on preventing cSCC. Objectives: To evaluate the risk of invasive cSCC and factors that may contribute to increased risk in patients with multiple AKs. Design, Setting, and Participants: In this secondary analysis of a multicenter randomized clinical trial, 624 patients with a minimum of 5 AKs within an area of 25 to 100 cm2 on the head were recruited from the Department of Dermatology of 4 hospitals in the Netherlands. Long-term follow-up was performed from July 1, 2019, to December 31, 2020. Interventions: Patients were randomized to treatment with 5% fluorouracil, 5% imiquimod cream, methylaminolevulinate photodynamic therapy, or 0.015% ingenol mebutate gel. Main Outcomes and Measures: The primary outcome was the proportion of patients with invasive cSCC in the target area during follow-up. Secondary outcomes were the associations between risk of invasive cSCC and a priori defined potential prognostic factors, including type of treatment, severity of AK (Olsen grade), history of nonmelanoma skin cancer, and additional treatment. Results: Of the 624 patients (558 [89.4%] male; median age, 73 years [range, 48-94 years]) in the study, 26 were diagnosed with a histologically proven invasive cSCC in the target area during follow-up. The total 4-year risk of developing cSCC in a previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%), varying from 2.2% (95% CI, 0.7%-6.6%) in patients treated with fluorouracil to 5.8% (95% CI, 2.9%-11.3%) in patients treated with imiquimod. In patients with severe AK (Olsen grade III), the risk was 20.9% (95% CI, 10.8%-38.1%), and the risk was especially high (33.5%; 95% CI, 18.2%-56.3%) in patients with severe AK who needed additional treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, risk of invasive cSCC was highest in patients with Olsen grade III AK and was substantially increased in patients who received additional treatment. These patients should be closely followed up after treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02281682.

Extended Delay to Treatment for Stage III-IV Non-Small-Cell Lung Cancer and Survival: Balancing Risks During the COVID-19 Pandemic.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, patients may encounter lung cancer care delays. Here, we sought to examine the impact of extended treatment delay for stage III-IV non-small-cell lung cancer on patient survival. MATERIALS AND METHODS: Using National Lung Screening Trial (NLST) and National Cancer Data Base (NCDB) data, Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage III-IV lung adenocarcinoma and squamous cell carcinoma. In the NCDB, propensity score-matched analysis was used to compare cumulative survival in patients who received "early" versus "delayed" treatment (ie, 0-30 vs. 90-120 days following diagnosis). RESULTS: Cox regression analysis of the NLST (n = 392) and NCDB (n = 275,198) cohorts showed a decrease in hazard ratio the longer treatment was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed treatment for patients with stage IIIA, IIIB (T3-4,N2,M0), IIIC, and IV (M1B-C) adenocarcinoma and patients with IIIA, IIIB, IIIC, and IV squamous cell carcinoma (all log-rank P > .05). For patients with stage IIIB (T1-2,N3,M0) and stage IV (M1A) adenocarcinoma, delayed treatment was associated with improved survival (log-rank P = .03, P = .02). The findings were consistent in sensitivity analysis accounting for wait time bias. CONCLUSION: In this national analysis, for patients with stage III-IV adenocarcinoma and squamous cell carcinoma, an extended treatment delay by 3 to 4 months was not associated with significantly decreased overall survival compared to prompt treatment. These findings can be used to guide decision-making during the ongoing COVID-19 pandemic.

Limited impact of COVID-19-related diagnostic delay on cutaneous melanoma and squamous cell carcinoma tumour characteristics: a nationwide pathology registry analysis.

BACKGROUND: The COVID-19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages. OBJECTIVES: To identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods. METHODS: In this population-based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands. The Breslow thickness of melanomas, invasion depth of cSCCs, and pT stage for both tumour types were compared across five time periods: (i) pre-COVID, (ii) first lockdown, (iii) between first and second lockdowns, (iv) second lockdown and (v) after second lockdown. Breslow thickness was compared using an independent t-test. pT-stage groups were compared using a χ2 -test. Outcomes were corrected for multiple testing using the false discovery rate. RESULTS: In total, 20 434 primary invasive melanomas and 68 832 cSCCs were included in this study. The mean primary melanoma Breslow thickness of the prepandemic era (period i) and the following time periods (ii-v) showed no significant difference. A small shift was found towards unfavourable pT stages during the first lockdown compared with the pre-COVID period: pT1 52·3% vs. 58·6%, pT2 18·9% vs. 17·8%, pT3 13·2% vs. 11·0%, pT4 9·1% vs. 7·3% (P = 0·001). No relevant changes were seen in subsequent periods. No significant change in pT stage distribution was observed between the pre-COVID (i) and COVID-affected periods (ii-v) for cSCCs. CONCLUSIONS: To date, the diagnostic delay caused by COVID-19 has not resulted in relatively more unfavourable primary tumour characteristics of melanoma or cSCC. Follow-up studies in the coming years are needed to identify a potential impact on staging distribution and survival in the long term.

Treatment delay and tumor size in patients with oral cancer during the first year of the COVID-19 pandemic.

BACKGROUND: We set out to investigate how the ongoing coronavirus pandemic affected the size of tumors and the duration of treatment delay in patients with surgically treated oral squamous cell carcinoma. METHODS: Patients with surgically treated oral cavity squamous cell carcinoma were assessed retrospectively and divided into two groups depending on when they had first presented at our clinic. Patients presenting from 2010 to 2019, that is, before COVID-19 onset (n = 566) were compared to patients presenting in 2020 (n = 58). RESULTS: A total of 624 patients were included. Treatment delay was significantly longer in 2020 (median = 45 days) versus 2010-2019 (median = 35 days) (p = 0.004). We observed a higher pathological T classification in 2020 (p = 0.046), whereas pathological N classification was unchanged between groups (p = 0.843). CONCLUSIONS: While extraordinary efforts continue to be made in the context of the pandemic, it is imperative that this does not lead to significant disadvantages for many people with oral cancer.

Effects of COVID-19 Lockdown on Tumour Burden of Melanoma and Cutaneous Squamous Cell Carcinoma.

The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer.

Effect of coronavirus disease 2019 on recurrences and follow up of head and neck squamous cell carcinoma.

OBJECTIVE: This prospective study aimed to evaluate possible diagnostic delays in head and neck squamous cell carcinoma recurrences due to the changed follow-up protocol during the coronavirus disease 2019 pandemic. METHODS: The follow-up appointments of head and neck squamous cell carcinoma patients treated more than one year prior to the pandemic were changed to telephone appointments in order to reduce physical visits to the hospital. All contacts, reasons for contact and recurrent cancers were recorded. RESULTS: There were 17 recurrences during a seven-month study period among 178 patients treated in the previous year (10 per cent); 14 of these recurrences occurred in patients whose treatment had ended less than one year previously and 3 occurred more than one year after treatment had ended. There was no delay in diagnoses of recurrent tumours or treatment despite reduced visits because of the coronavirus disease 2019 pandemic. CONCLUSION: According to our analyses, no delay was caused in the diagnoses of recurrent diseases. Follow up by telephone or telemedicine can be considered as part of the follow-up protocol one year after the treatment of head and neck squamous cell carcinoma when necessary.

The hidden curve behind COVID-19 outbreak: the impact of delay in treatment initiation in cancer patients and how to mitigate the additional risk of dying-the head and neck cancer model.

PURPOSE: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model. METHODS: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data. RESULTS: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation. CONCLUSIONS: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model.