Brewer, Jerry D.

AbstractBackgroundComprehensive treatment recommendations for Merkel cell carcinoma are complex. We aimed to systematically review the published data on recurrence and mortality rates associated with various treatment approaches for Merkel cell carcinoma.MethodsSearch of MEDLINE, Embase, Web of Science, and Scopus from inception to August 2015. Studies were included that reported comparative survival and recurrence data for two or more treatment modalities. Two reviewers independently reviewed and abstracted recurrence and mortality rates. Event rates for individual treatment arms in each study were pooled and meta‐analyzed across studies using a random‐effects model.ResultsFifty‐two retrospective studies met inclusion criteria, revealing a total of 1,804 patients with primary Merkel cell carcinoma with data available for analyses. The recurrence rate was higher for surgery alone (55.0%) versus a combination of surgery and radiotherapy (39.0%) (odds ratio, 2.089; 95% CI, 1.374–3.177; P < 0.001). Combination therapy including surgery, radiotherapy, and chemotherapy had a higher mortality rate (44.6%) than did combined surgery and radiotherapy (23.2%) (odds ratio, 2.688; 95% CI, 1.196–6.037; P = 0.02).ConclusionsThe treatment of Merkel cell carcinoma with surgery plus adjuvant radiotherapy may produce lower recurrence rates.

AbstractBackgroundEpidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.MethodsWe examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsHigher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02–1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08–1.38, Ptrend = 1.36 × 10–5), which was driven by shared genetic susceptibility at the 6p25.3 locus.ConclusionThese findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.

BACKGROUND Perioperative anxiety can negatively impact patient satisfaction and can complicate outpatient dermatologic procedures. OBJECTIVE Evaluate adverse events associated with oral midazolam as a perioperative anxiolytic during dermatologic surgery and assess whether an enhanced monitoring approach is associated with an increased detection rate. MATERIALS AND METHODS Five hundred cases (250 before and after change in monitoring) where patients were administered oral midazolam between July 2015 and May 2017 were retrospectively reviewed. The number of procedures, type of procedures, dose in milligrams, number of doses, major and minor adverse events, and vital signs were recorded. RESULTS The difference in number of treatment sites, types of procedures, and total dose administered was not significant. There were minor but significant differences in the mean change in blood pressure, heart rate, respiratory rate, and Richmond Agitation and Sedation Scale score before and after the procedure but not oxygen saturation. These vital sign changes were not clinically significant. There were zero major adverse events in both groups. There were 2 patients who became transiently hypoxic. CONCLUSION Oral midazolam administration was not associated with major adverse events including in the more intensively monitored group. This supports its use as an anxiolytic for outpatient dermatologic procedures.

Abstract Ultrasound-guided percutaneous ethanol ablation procedures for locoregional recurrences in papillary thyroid carcinoma (PTC) can be repeatedly performed over years. Skin metastases (SM) from PTC generally portend a lethal prognosis. Our patient case report demonstrates the innovative use in low-risk PTC (LRPTC) of treatment modalities designed to prevent neck re-explorations and capable of eliminating both locoregional recurrences and SM. In 2004, a 48-year-old man presented with neck nodal metastases due to PTC. He underwent a near-total thyroidectomy and nodal dissection, confirming an 8-mm PTC involving 2 ipsilateral node metastases. Postoperatively, he received 2 doses of radioactive iodine (RAI) for remnant uptake (cumulative dose 338 mCi); posttherapy scanning was unrevealing. In 2007, he underwent right neck dissection for further node metastases. In 2008, a guided biopsy confirmed a level IV node metastasis. He was referred to our institution for ethanol ablation. Two node metastases were ablated and subsequently disappeared. During 2010-2016, he developed an additional 6 node metastases, which were treated with ethanol ablation; all disappeared on high-resolution sonography. FDG-PET-CT scans in 2009 and 2016 were negative for distant spread. In 2016, a SM in his right neck was removed by dermatologic surgery. In 2017-2018, 2 further SM were excised with negative margins, one after Mohs surgery. He has now been disease-free for 20 months. In conclusion, despite 3 neck surgeries and 2 RAI therapies, our patient repeatedly developed both locoregional recurrences and SM. All 11 disease foci were eliminated with minimally invasive procedures which should more often be considered as effective treatment options in LRPTC.

During the coronavirus disease 2019 (COVID‐19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID‐19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID‐19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID‐19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early‐stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID‐19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1‐month to 2‐month delay is unlikely to worsen disease‐specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.

9073 Background: An accumulating body of evidence suggests that the outcome of early-stage melanoma is influenced by endocrine and menopausal status. However, it remains controversial as to whether the superior female melanoma-specific survival (MSS) is restricted to early stage disease or if it also pertains to patients with metastatic melanoma (MM). Methods: We analyzed data from the 13 registries that participate in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. We identified all cases of primary invasive melanoma diagnosed between 1992 and 2009; none of the patients had a prior history of another cancer. MSS was compared between males and females, stratified by stage of disease. Age groups were defined as 18-45y, 46-54y, 55-64y, 65+y as a proxy of female menopausal status. Results: The study population included 87,165primary invasive melanoma cases (unstaged n=2834). MSS was significantly poorer for males compared to females for localized (n=72,456) and regional (n=8,945) disease for all age groups (Hazard ratio (HR) ranging from 1.21 to 2.09, all p<0.001). MSS was not significantly different between males and females for patients with distant disease at diagnosis (n= 2930; HR 0.99, 0.92, 1.11, 1.07 for each age group) and remained non-significant after adjusting for Breslow thickness, histologic subtype, anatomic site, and age group (adjusted HR 1.04 males vs. females; 95% CI 0.95-1.14; p=0.41). Conclusions: While our results were consistent with earlier reports that women have higher MSS rates compared to men for early (stage I-III) melanoma, the intriguing finding of this study was that the female survival advantage does not vary with age or menopausal status as compared to men, which is contrary to previously published reports. Furthermore, we found that the difference in survival was no longer significant for patients with MM, suggesting that sex may influence local and regional, but not distant cancer progression.

6571 Background: Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the natural history of these cancers once they occur. Methods: All patients with breast (n=583,838), colon (n=412,932), prostate (n=632,922), lung (n=489,290), kidney (n=95,902), pancreas (n=82,121) and ovarian (n=61,958) cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1990 to 2007 were identified. Overall survival (OS; death due to any cause) and cancer-specific survival (death due to cancer site of interest) were examined, comparing patients with or without pre-existing CLL. Age- and sex-adjusted hazard ratios (HRs) were calculated. Results: OS for patients with pre-existing CLL was inferior for patients with breast (HR=1.61; p<0.001), colon (HR=1.65; p<0.001), kidney (HR=1.41; p<0.001), prostate (HR=1.75; p<0.001), and lung (HR=1.22; p<0.001) cancer after adjusting for age and sex. After excluding CLL-related deaths, OS remained shorter among patients with breast (p<0.001), colon (p<0.001), kidney (p=0.03), prostate (p<0.001), and lung (p<0.001) cancer. Cancer-specific survival was inferior for patients with breast (HR=1.29; p=0.03), colon (HR=1.75; p<0.001), and lung cancer (HR=1.17; p<0.001) who had pre-existing CLL after adjusting for age and sex. Conclusions: Several common cancers, including breast, colon, and lung, have inferior overall and cancer-specific survival when there is coexistent CLL. [Table: see text]