Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

Primary thyroid squamous cell carcinoma presenting as a left-sided neck lump.

The elderly patient presenting with a neck lump often raises concerns regarding a malignancy. Thyroid gland malignancies are well recognised and subtype characteristics thoroughly researched, whereas rarer types of thyroid carcinoma are reported infrequently and often behave more aggressively. An 83-year-old woman was referred from the general practitioner (GP) to otolaryngology due to a 7-month history of an unexplained enlarging left-sided neck swelling. A fine-needle aspiration revealed cytology consistent with squamous cell carcinoma (SCC). Staging imaging failed to reveal evidence of a primary foci elsewhere. The definitive diagnosis was that of a primary thyroid SCC: a rare entity with limited citations in the literature. Surgical resection has been found to comprise the optimal treatment for this disease. Recognition of the possibility of primary thyroid SCC in elderly patients presenting with a neck lump, with prompt referral to a head and neck specialist permits a timely progression to potentially curative surgical management, a more promising prognosis and reduced mortality rates.

A study of the effects of delayed patient presentation on cutaneous SCC progression.

BACKGROUND: A cohort study of patients, who underwent cutaneous squamous cell carcinoma (SCC) excision, was undertaken to evaluate the effects of the COVID-19 pandemic on treatment times and histopathological features. METHODS: We identified all patients who had SCCs excised in October 2020 (pandemic group); the control group included all patients who underwent excision of SCCs during October 2019 (pre-pandemic group). Collected data included SCC subtype, thickness, size, clearance margins, referral details, patient comorbidities and operative data. RESULTS: There were 140 patients (174 SCCs; pre-pandemic group=74; pandemic group=100) identified for study inclusion. Both groups were well matched for age, sex, previous history of cancer, cutaneous SCC and histological subtype. There was a delay in median patient presentation time to the GP in the pandemic versus pre-pandemic group (106 days vs. 56 days, p <0.001); this led to a longer overall time to surgery (167 days vs. 110.5 days, p < 0.001). Pandemic group SCCs had larger median Breslow depths (4 mm vs. 3 mm, p = 0.01), a greater proportion of Clark's level 4 and 5 lesions (76.9% vs. 61.1%, p = 0.03), and a higher rate of high (20-40 mm) and very high (>40 mm) risk SCCs as defined by British Association of Dermatology diameter criteria (56.1% vs. 39.2%, p = 0.03), versus the pre-pandemic group. CONCLUSIONS: There was a 57-day median SCC treatment delay, and an associated development of higher risk SCCs by the time of surgery. Despite the challenges of a pandemic, patients should seek early consultation for suspicious skin changes, and healthcare systems should maintain skin cancer treatment pathways.

Influence of COVID-19 confinement on the size of malignant skin tumours surgically removed at a Spanish hospital.

The COVID-19 pandemic required people to confine themselves to their homes where possible, and disrupted normal hospital activities. We examine whether this lockdown generated changes in the size of the tumours. We compared the dimensions of the surgically removed malignant skin tumours from the first 150 patients treated after the confinement ended in Spain (22 May 2020) with those of the last 150 patients to receive such treatment before the confinement began (13 March 2020). Data on tumour surface area were collected from pathology reports. Overall, no significant difference was seen in the tumour sizes. However, among men, the tumours removed after confinement were significantly larger (P < 0.05). Controversy exists over how the reduction in the number of tumours diagnosed during lockdowns might have influenced the characteristics of tumours. In this study, no overall difference was seen in the size of the tumours removed, although those removed from men after confinement were larger.

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.

Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival.

OBJECTIVE: The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC. SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC. METHODS: Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of "early" versus "delayed" surgery (surgery received 0-30 vs 90-120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses. RESULTS: In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004). CONCLUSIONS: The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.

Thoracic surgery during the coronavirus disease 2019 (COVID-19) pandemic in Madrid, Spain: single-centre report.

OBJECTIVES: We reviewed the incidence of coronavirus disease 2019 cases and the postoperative outcomes of patients who had thoracic surgery during the beginning and at the highest point of transmission in our community. METHODS: We retrospectively reviewed patients who had undergone elective thoracic surgery from 12 February 2020 to 30 April 2020 and were symptomatic or tested positive for severe acute respiratory syndrome coronavirus 2 infection within 14 days after surgery, with a focus on their complications and potential deaths. RESULTS: Out of 101 surgical procedures, including 57 primary oncological resections, 6 lung transplants and 18 emergency procedures, only 5 cases of coronavirus disease 2019 were identified, 3 in the immediate postoperative period and 2 as outpatients. All 5 patients had cancer; the median age was 64 years. The main virus-related symptom was fever (80%), and the median onset of coronavirus disease 2019 was 3 days. Although 80% of the patients who had positive test results for severe acute respiratory syndrome coronavirus 2 required in-hospital care, none of them were considered severe or critical and none died. CONCLUSIONS: These results indicate that, in properly selected cases, with short preoperative in-hospital stays, strict isolation and infection control protocols, managed by a dedicated multidisciplinary team, a surgical procedure could be performed with a relatively low risk for the patient.

Outcomes of major head and neck reconstruction during the COVID-19 pandemic: The St. Andrew's centre experience.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has generated enormous pressure on healthcare establishments, prompting the restructuring of services to rationalise resources. Complex head and neck reconstructive surgery in this setting may carry substantial risk to patients and staff. This paper outlines the management strategy and outcomes of major head and neck oncological cases at a single regional tertiary referral centre. METHODS: A database review was undertaken of consecutive patients undergoing major head and neck surgery and reconstruction during the COVID-19 pandemic at St Andrew's Centre for Plastic Surgery & Burns, Chelmsford UK. Patient demographics, tumour and reconstruction characteristics as well as peri­operative information were determined. Patients were prospectively contacted with regard to COVID-related symptoms and investigations. RESULTS: Twenty-two patients (15 males and 7 females) with a mean age of 67 years (range: 36-92 years) were included between March 1 and June 13, 2020. Patients underwent pre-operative throat swabs at 72 h and 24 h as well as chest CT scanning as part of a robust protocol. Twelve free flaps, four loco-regional flaps, four parotidectomies and 23 cervical lymphadenectomies were performed. Two patients required a return to theatre. No post-operative deaths occurred and flap survival rate was 100%. A single patient tested positive for COVID-19 pre-operatively and no post-operative COVID-19 infections occurred. CONCLUSION: Although head and neck surgery represents a high-risk procedure to patients and healthcare professionals, our institutional experience suggests that in the presence of a robust peri­operative protocol and judicious patient selection, major head and neck surgery, including free tissue transfer reconstruction, may be performed safely.

Expression of the COVID-19 receptor ACE2 in the human conjunctiva.

SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctivas, 12 melanomas, seven squamous cell carcinomas, and seven papilloma samples, were analyzed using high-throughput RNA sequencing to assess messenger RNA (mRNA) expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median: 0.0 transcripts per million [TPM], min: 0.0 TPM, max: 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.

Severe acute respiratory syndrome coronavirus-2 in post-laryngectomy patients: case series of four patients.

OBJECTIVE: To report our experience of diagnosis, investigation and management in patients who had undergone laryngectomy secondary to previous squamous cell carcinoma, who were subsequently infected with severe acute respiratory syndrome coronavirus-2 during the coronavirus disease 2019 pandemic. CASE REPORTS: Four post-laryngectomy patients with laboratory-proven severe acute respiratory syndrome coronavirus-2 infection were admitted to our institution from 1 March to 1 May 2020. All patients displayed symptoms of coronavirus disease 2019 and underwent investigations, including swab and serum sampling, and chest X-ray where indicated. All were managed conservatively on dedicated coronavirus disease 2019 wards and were discharged without the requirement of higher level care. CONCLUSION: It is hypothesised that laryngectomy may offer a protective effect against severe or critical disease in severe acute respiratory syndrome coronavirus-2 infection. We hope sharing our experience will aid all practitioners in the management of this, often intimidating, cohort of patients.

Clinical Course of Three Postoperative Symptomatic COVID-19 Cases in Patients After Lung Lobectomy.

The novel coronavirus disease 2019 is a highly contagious viral infection caused by the severe acute respiratory syndrome coronavirus 2 virus. Its rapid spread and severe clinical presentation influence patient management in all specialties including thoracic surgery. We report 3 cases of coronavirus disease 2019 occurring in patients shortly after thoracotomy and thoracoscopy procedures, illustrating the imminent threat of severe acute respiratory syndrome coronavirus 2 infection for thoracic surgery patients.

SARS-CoV-2 detection in formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma.

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens. Here we report the detection of SARS-CoV-2 in formalin-fixed paraffin-embedded samples from surgical resection of tongue squamous cell carcinoma of a patient who developed COVID-19 postsurgery. RNA of SARS-CoV-2 strain was detected in the tumour and the normal submandibular gland samples using real-time PCR-based assay. No viral RNA was found in metastatic and reactive lymph nodes. We demonstrated that SARS-CoV-2 RNA can be detected in routine histopathological samples even before COVID-19 disease development. These findings may give important information on the possible sites of infection or virus reservoir, and highlight the necessity of proper handling and fixation before sample processing.