Evidence-Based Consensus Recommendations for the Evolving Treatment of Patients with High-Risk and Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma is the second most common skin cancer in the United States. Currently, there is no standardized management approach for patients with cutaneous squamous cell carcinoma who develop metastatic or locally advanced disease and are not candidates for curative surgery or curative radiation. To address this issue, the Expert Cutaneous Squamous Cell Carcinoma Leadership program convened an expert steering committee to develop evidence-based consensus recommendations on the basis of a large, structured literature review. Consensus was achieved through modified Delphi methodology. The steering committee included five dermatologists, three medical oncologists, two head and neck surgeons, one radiation oncologist, and a patient advocacy group representative. The steering committee aligned on the following clinical topics: diagnosis and identification of patients considered not candidates for surgery; staging systems and risk stratification in cutaneous squamous cell carcinoma; the role of radiation therapy, surgery, and systemic therapy in the management of advanced disease, with a focus on immunotherapy; referral patterns; survivorship care; and inclusion of the patient's perspective. Consensus was achieved on 34 recommendations addressing 12 key clinical questions. The Expert Cutaneous Squamous Cell Carcinoma Leadership steering committee's evidence-based consensus recommendations may provide healthcare professionals with practically oriented guidance to help optimize outcomes for patients with advanced cutaneous squamous cell carcinoma.

Factors predictive of 90-day mortality after surgical resection for oral cavity cancer: Development of a recursive partitioning analysis for risk stratification.

BACKGROUND: Factors that influence postoperative mortality (POM) have been identified, but a predictive model to guide clinicians treating oral cavity cancer (OCC) has not been well established. METHODS: Patients with OCC undergoing upfront surgical resection were included. Primary outcome was 90-day POM (90dPOM). RESULTS: 33 845 were identified using the National Cancer Database. Rate of 90dPOM was 3.2%. Predictors of higher 90dPOM include older age, higher comorbidity scores, nonprivate insurance, lower income, treatment in an academic facility, higher T- and N-classification, radical excision, and presence of positive margins. On RPA, two high-risk (90dPOM > 10%) patient subsets were identified: patients ≥80 years of age with T3-4 disease and patients <80 years, with any comorbidity and T3-4, N2-3 disease. CONCLUSIONS: We identified a subset of patients in this cohort who are at high risk for 90dPOM. These patients may warrant additional perioperative and postoperative monitoring in addition to better preoperative assessment and screening.

Pathologic complete response with radiation and vismodegib in a patient with advanced basal cell carcinoma: A case report.

In locally advanced basal cell carcinoma (BCC) patients who are not surgical candidates and where radiation therapy (RT) alone would offer lower control rates, the combination of vismodegib and RT delivered concurrently may potentially improve outcomes compared to single modality treatment. The current study presents a case of very advanced, multifocal BCC who received concurrent vismodegib and RT. The patient initially came in with four large primary areas of disease including the left preauriculum, right shoulder, chest wall and right lateral ankle. All sites achieved a clinical complete response, with a pathologic complete response at the right shoulder. The ankle lesion did not require RT and continues to have a clinical complete response. The findings from our case report support several other cases with similar efficacy when vismodegib and RT are combined.

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma.

Aim: To estimate the comparative efficacy of cemiplimab, a programmed cell death protein 1 inhibitor, versus EGFR inhibitors, pembrolizumab and platinum-based chemotherapy in terms of overall survival (OS) and progression-free survival. Patients & methods: We performed an indirect treatment comparison of cemiplimab and other available systemic therapies for patients with advanced cutaneous squamous cell carcinoma. Results: Cemiplimab was associated with benefits in OS (hazard ratios range: 0.07-0.52) and progression-free survival (hazard ratios range: 0.30-0.67) versus EGFR inhibitors and pembrolizumab (data from KEYNOTE-629). Cemiplimab was more efficacious versus platinum-based chemotherapy in terms of OS. Conclusion: Cemiplimab may offer improvements in survival for advanced cutaneous squamous cell carcinoma patients compared with existing systemic therapies.

The association between facility volume and overall survival in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is an uncommon malignancy often requiring multidisciplinary management. The purpose of this study was to determine whether high-volume facilities have improved outcomes in patients with Merkel cell carcinoma relative to lower-volume facilities. METHODS: A total of 5304 patients from the National Cancer Database with stage I-III Merkel cell carcinoma undergoing surgery were analyzed. High-volume facilities were the top 1% by case volume. Multivariable Cox regression and propensity score-matching were performed to account for imbalances between groups. RESULTS: Treatment at high-volume facilities (hazard ratio: 0.74; 95% confidence interval: 0.65-0.84, P < .001) was independently associated with improved overall survival (OS) in multivariable analyses. In propensity score-matched cohorts, 5-year OS was 62.3% at high-volume facilities vs 56.8% at lower-volume facilities (P < .001). Median OS was 111 months at high-volume facilities vs 79 months at lower-volume facilities. CONCLUSION: Treatment at high-volume facilities is associated with improved OS in Merkel cell carcinoma. Given the impracticality of referring all elderly patients with Merkel cell carcinoma to a small number of facilities, methods to mitigate this disparity should be explored.

CASE (CemiplimAb-rwlc Survivorship and Epidemiology) study in advanced cutaneous squamous cell carcinoma.

In 2018, cemiplimab-rwlc became the first systemic treatment approved by the US FDA for patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In 2019, conditional approvals were granted by Health Canada and the European Commission for the same indications. Limited data exist pertaining to the clinical characteristics, disease progression and survivorship of patients with advanced CSCC in real-world clinical practice. CemiplimAb-rwlc Survivorship and Epidemiology (CASE) is a prospective Phase IV, noninterventional, survivorship and epidemiology study that will enroll patients with advanced CSCC who have recently initiated or who plan to receive cemiplimab in a real-world setting. Trial registration number: NCT03836105.

Treatment patterns of malignant melanoma in the United States from 2011 to 2016: a retrospective cohort study.

Background: Since 2011, the approval of several new agents has improved treatment options for malignant melanoma. We describe treatment patterns for malignant melanoma in the United States from the MarketScan database from 2011 to 2016.Methods: Treatments used for patients aged >18 years diagnosed with malignant melanoma after January 1, 2011 and enrolled in the Truven MarketScan database were analyzed. Patient data were collected for the 12-month period from the date of the first melanoma diagnosis to either death, the pre-specified study end date (August 31, 2016), or date of termination of health insurance. Treatment patterns from 2011-2013 and 2014-2016 were analyzed according to agent, year of drug administration, and line of therapy.Results: From 2011 to 2016, use of cytokines (63.8; 13.3%) and chemotherapy (19.6; 12.9%) decreased, and use of checkpoint inhibitors increased (2.0; 49.9%). Checkpoint inhibitor use also increased across all lines of therapy from 2011-2013 and 2014-2016. Use of BRAF/MEK inhibitors remained relatively stable from 2011 to 2016 (6.5-12.5%); however, the use of vemurafenib monotherapy decreased (6.5; 0.8%), and treatment with combination regimens increased (0; 10.9%) from 2011-2016. BRAF/MEK inhibitor use only increased in the first line setting from 2011-2013 (9.7%) to 2014-2016 (11.2%).Conclusion: With the approval of immune checkpoint inhibitors, BRAF/MEK inhibitors, and targeted therapies, the therapeutic landscape for the treatment of metastatic melanoma has shifted dramatically away from cytokines and chemotherapy. Treatment patterns will likely continue to evolve as scientific advances are made.

Treatment patterns of melanoma by BRAF mutation status in the USA from 2011 to 2017: a retrospective cohort study.

AIM: To describe treatment changes from 2011 to 2017 and demographic/clinical characteristics of patients with advanced melanoma who received systemic therapy by BRAF status. PATIENTS & METHODS: Treatment patterns were evaluated in adults from the Oncology Services Comprehensive Electronic Records database who received antimelanoma systemic therapy. RESULTS: Checkpoint inhibitors were prevailingly prescribed (66%); usage increased from 2011 (21%) to 2017 (84%). BRAF/MEK inhibitors were the second most common (21%); usage increased from 2011 (6%) to 2012 (18%) and stabilized until 2017 (22%). BRAF/MEK inhibitors (65%) and checkpoint inhibitors (57%) were predominantly used for BRAFMut melanoma. CONCLUSION: Overall, checkpoint inhibitors have supplanted other therapies for advanced melanoma. Treatment shifts have occurred for BRAFMut melanoma, notably increased use of checkpoint inhibitors and BRAF/MEK combinations compared with monotherapies.

Indirect Treatment Comparison of Nivolumab Versus Observation or Ipilimumab as Adjuvant Therapy in Resected Melanoma Using Pooled Clinical Trial Data.

INTRODUCTION: Nivolumab has been approved in patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting. A pivotal trial compared nivolumab with ipilimumab; however, no head-to-head trial exists comparing nivolumab to observation, a common comparator in the adjuvant setting. Here, we compared the efficacy and cost-effectiveness of nivolumab with observation or ipilimumab as adjuvant therapies in resected stage IIIB/C melanoma. METHODS: Patient data were pooled from the EORTC 18071 and CheckMate 238 trials using propensity score weighting and adjusting for cross-trial differences. Number needed to treat (NNT) and costs per recurrence-free life-month (RFLM) at 12, 16, 18, and 24 months (as data allowed) were estimated. Costs included drug acquisition, administration costs, and direct medical costs. Sensitivity analyses including patients with stage IIIB/C and resected stage IV melanoma were conducted. RESULTS: A total of 1287 patients (278 nivolumab, 365 observation, and 644 ipilimumab) with resected stage IIIB/C melanoma were pooled. NNTs to achieve one additional recurrence-free survivor with nivolumab versus observation were 3.93 at 12 months and 3.42 at 24 months; NNTs for nivolumab versus ipilimumab were 7.97 at 12 months and 6.43 at 24 months. Mean drug costs per RFLM were lower for nivolumab at 12, 18, and 24 months, respectively (nivolumab: $13,447, $9462, and $7370; ipilimumab: $52,734, $40,484, and $33,875). Mean medical costs per RFLM were the lowest for nivolumab versus observation or ipilimumab at 12 months ($449 versus $674 or $1531) and 16 months ($383 versus $808 or $1316). The sensitivity analysis results were consistent with the base case. CONCLUSION: For resected melanoma, adjuvant nivolumab is both clinically effective and cost-effective compared with observation or ipilimumab. Adjuvant nivolumab was associated with a lower drug cost per RFLM compared with ipilimumab, and a lower medical cost compared with observation. Future analyses incorporating long-term follow-up data may help increase understanding of the economic impact of nivolumab in the adjuvant setting. FUNDING: Bristol-Myers Squibb Company.

Surveillance imaging for metastasis in high-risk melanoma: importance in individualized patient care and survivorship.

Most patients newly diagnosed with melanoma have early-stage disease considered of good prognosis. However, with a risk of recurrence, appropriate follow-up may include surveillance imaging for early relapse detection. Previously, surveillance imaging to detect recurrences was considered unjustified, given the lack of effective treatments. Now, systemic therapies have improved, and patients with low tumor burden may derive benefit from surveillance imaging. Despite this, controversy exists regarding the role of surveillance imaging in early-stage melanoma survivorship, in part reflected by the lack of consensus on specific imaging protocols and broad guidelines. This review discusses published evidence on surveillance imaging to detect metastasis in high-risk melanoma, the need for early recurrence detection and implications for value-based clinical decision-making, survivorship care and multidisciplinary patient management.

The Effect of Time to Postoperative Radiation Therapy on Survival in Resected Merkel Cell Carcinoma.

OBJECTIVES: Delays from surgery to adjuvant radiation therapy (aRT) are associated with poorer prognosis in multiple neoplasms. Presently, no data exist for Merkel cell carcinoma (MCC). The authors sought to assess the time interval from surgery to aRT and effect on outcomes in MCC. MATERIALS AND METHODS: The National Cancer Database was queried for histologically confirmed nonmetastatic MCC status post resection and aRT diagnosed between 2004 and 2015 who received aRT within 24 weeks of surgery. Kaplan-Meier analysis assessed univariate overall survival (OS); multivariable Cox proportional hazards modeling assessed multivariate OS; χ and logistic regression assessed differences in baseline characteristics and predictors of delayed aRT. RESULTS: Of 5952 patients meeting criteria, 13% commenced aRT within 4 weeks, 48% between 4 and 7 weeks, 23% between 8 and 11 weeks, 11% between 12 and 15 weeks, and 6% between 16 and 24 weeks. There were no differences in OS on the basis of the surgery-aRT interval (P=0.99). Predictors of worse OS on the multivariate analysis included advanced age, greater comorbidities, male sex, lower regional income, earlier year of diagnosis, more advanced tumor and nodal staging, positive margins, head and neck location, and treatment at community facilities (P<0.05 for all). Factors predictive of delayed aRT were identified. Subset analyses on these factors, such as receipt of chemotherapy or positive lymph nodes, did not demonstrate that the timing of aRT affected survival (P≥0.37). CONCLUSION: This study of a contemporary national database revealed that delays from resection to aRT were not associated with survival in MCC, somewhat discordant from other malignancies such as squamous cell carcinoma.

Induction of the Abscopal Effect with Immunotherapy and Palliative Radiation in Metastatic Head and Neck Squamous Cell Carcinoma: A Case Report and Review of the Literature.

The induction of the abscopal effect using immunotherapy and radiation is under investigation through case reports and institutional studies. We describe a case of the abscopal effect with a combination of ipilimumab, nivolumab, and palliative radiation, in a patient with metastatic head and neck squamous cell carcinoma (mHNSCC).

Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.

Nursing Management of Advanced Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and lethal skin cancer with few known treatment options. Management of this disease is challenging, and oncology nurses must understand the medical, physical, and psychosocial burden that MCC places on the patient and family caregivers. Patients must navigate a complex medical and insurance network that often fails to support patients with rare cancers. Nurses must advocate for these patients to ensure quality comprehensive cancer care.

Effect of a multidisciplinary-assisted resident diabetes clinic on resident knowledge and patient outcomes.

BACKGROUND: Despite the rising prevalence of diabetes, there is a paucity of diabetes curricula in residency training. The multidisciplinary diabetes team approach is underused in residency education. OBJECTIVE: To assess the feasibility of an innovative multidisciplinary resident diabetes clinic (MRDC) in enhancing (1) resident diabetes knowledge via a Diabetes Awareness Questionnaire, and (2) subsequent process and patient outcomes in patients with diabetes via a Diabetes Practice Behavior Checklist. METHODS: From October 2008 to February 2010, 14 internal medicine residents managed patients with uncontrolled diabetes in a weekly half-day MRDC for 1 month (total 4-5 half-day sessions/resident), with a collaborative team of internists, diabetes educators, an endocrinologist, and a pharmacist. The curriculum included didactic sessions, required readings, and patient-specific case discussions. A 20-question Diabetes Awareness Questionnaire was administered to each resident prerotation and postrotation. Records of 47 patients with diabetes in the residents' own continuity clinics (not the MRDC) were audited 6 months before and after the MRDC for Diabetes Practice Behavior Checklist measures (glycated hemoglobin, blood pressure, low-density lipoprotein cholesterol, retinal referral, foot exam, microalbumin screen). Pre-MRDC and post-MRDC data were compared via paired t test. RESULTS: The MRDC residents exhibited a modest increase in mean (SD) scores on the Diabetes Awareness Questionnaire (before, 8.2 [2.8]; after, 10.9 [2.8]; P  =  .02) and a modest mean (SD) performance increase in overall process outcomes from the Diabetes Practice Behavior Checklist (before, 74% [18%]; after, 84% [18%]; P  =  .004). No improvements occurred in patient outcomes. CONCLUSIONS: Multidisciplinary diabetes teaching may be useful in fostering certain resident knowledge and performance measures but may not alter clinical outcomes. Further large-scale, longitudinal studies are needed to understand the effect of our curriculum on residents' diabetes knowledge and future practice behavior.

Ultrasonography in preclinical education: a pilot study.

CONTEXT: Ultrasonography is a valuable diagnostic tool in the clinical setting. Yet, medical students often have minimal familiarity with this technology. OBJECTIVE: To evaluate the ability of second-year medical students to use ultrasonography for identification of anatomic structures and pathologic conditions. DESIGN: A self-directed approach that reduced facilitator involvement, encouraging learning that mimicked the medical school's problem-based learning pathway program. METHODS: Five students were each given 10 hours of instruction in ultrasonographic techniques by three certified ultrasonographers in outpatient and hospital settings. Each student performed 40 hours of organ-specific ultrasonographic scans on another student in 2-hour sessions during 20 weeks. Images were archived for future evaluation and quality rating. Students took a 35-question posttraining examination with 10 contrived case scenarios. Questions were designed to test student knowledge in three categories: anatomic structure, technical skill, and clinical diagnosis. RESULTS: Posttraining examination results, expressed as the percent of correct answers for all five participants by category, were as follows: anatomic structure, 70%; technical skill, 70%; clinical diagnosis, 68%. Evaluations of the archived images, which were graded for proper anatomic identification and image clarity, yielded the following scores indicating "good" or "fair" quality for each anatomic region: abdominal, 80%; pelvic, 63%; cardiac, 73%. CONCLUSION: Second-year osteopathic medical students can attain a sufficient degree of proficiency in limited ultrasonographic technique.