Publications by authors named "Christopher A Barker"

87 Publications

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021.

J Natl Compr Canc Netw 2021 Apr 1;19(4):364-376. Epub 2021 Apr 1.

30Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.
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http://dx.doi.org/10.6004/jnccn.2021.0018DOI Listing
April 2021

Therapeutic Implications of Detecting MAPK-Activating Alterations in Cutaneous and Unknown Primary Melanomas.

Clin Cancer Res 2021 Apr 28;27(8):2226-2235. Epub 2021 Jan 28.

Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Cutaneous and unknown primary melanomas frequently harbor alterations that activate the MAPK pathway. Whether MAPK driver detection beyond BRAF V600 is clinically relevant in the checkpoint inhibitor era is unknown.

Experimental Design: Patients with melanoma were prospectively offered tumor sequencing of 341-468 genes. Oncogenic alterations in 28 RTK-RAS-MAPK pathway genes were used to construct MAPK driver groups. Time to treatment failure (TTF) was determined for patients who received first-line programmed cell death protein 1 (PD-1) monotherapy, nivolumab plus ipilimumab, or subsequent genomically matched targeted therapies. A Cox proportional hazards model was constructed for TTF using driver group and clinical variables.

Results: A total of 670 of 696 sequenced melanomas (96%) harbored an oncogenic RTK-RAS-MAPK pathway alteration; 33% had ≥1 driver. Nine driver groups varied by clinical presentation and mutational burden. TTF of PD-1 monotherapy ( = 181) varied by driver, with worse outcomes for NRAS Q61 and BRAF V600 versus NF1 or other alterations (median 4.2, 7.5, 22, and not reached; < 0.0001). Driver group remained significant, independent of tumor mutational burden and clinical features. TTF did not vary by driver for nivolumab plus ipilimumab ( = 141). Among 172 patients with BRAF V600 wild-type melanoma who progressed on checkpoint blockade, 27 were treated with genomically matched therapy, and eight (30%) derived clinical benefit lasting ≥6 months.

Conclusions: Targeted capture multigene sequencing can detect oncogenic RTK-RAS-MAPK pathway alterations in almost all cutaneous and unknown primary melanomas. TTF of PD-1 monotherapy varies by mechanism of ERK activation. Oncogenic kinase fusions can be successfully targeted in immune checkpoint inhibitor-refractory melanoma.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046739PMC
April 2021

Metastatic Cutaneous Squamous Cell Carcinoma Involving the Parotid Gland: Experience Outside of the Sun Belt.

OTO Open 2021 Jan-Mar;5(1):2473974X20984720. Epub 2021 Jan 8.

Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Objective: To characterize a subset of patients with metastatic head and neck cutaneous squamous cell carcinoma in a tertiary North American center and describe oncologic outcomes following definitive treatment.

Study Design: Retrospective chart review.

Setting: National Cancer Institute-designated Comprehensive Cancer Center.

Methods: We conducted a retrospective chart review of patients with cutaneous squamous cell carcinoma with metastases to intraparotid lymph nodes who underwent parotidectomy between 1993 and 2020. Baseline patient and tumor characteristics were assessed. Regional control, disease-specific survival, and overall survival were estimated using Kaplan-Meier method. Multivariate analysis was used to determine the relationship between adverse pathological features and survival.

Results: A total of 122 patients were included. The median age was 76, 84.4% of patients were male, and 17.2% were immunosuppressed. Regional control, disease-specific survival, and overall survival were 68.5%, 70.7%, and 59.4% at 5 years, respectively. Perineural and lymphovascular invasion were predictive of worse disease-specific survival. Extracapsular spread was observed in 90.2% of patients and was not a significant predictor of outcome.

Conclusions: We found the demographics and oncologic outcomes of our cohort in the Northeast United States to be comparable with those previously reported in Australia and the Sun Belt of the United States. We noted a high rate of extracapsular spread but did not find it to be a significant predictor of recurrence or survival. Future efforts should address the impact of extracapsular spread on prognosis and adjuvant treatment decisions.
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http://dx.doi.org/10.1177/2473974X20984720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797591PMC
January 2021

Targeting Phosphatidylserine Enhances the Anti-tumor Response to Tumor-Directed Radiation Therapy in a Preclinical Model of Melanoma.

Cell Rep 2021 Jan;34(2):108620

Swim Across America and Ludwig Collaborative Laboratory, Immunology Program, Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Phosphatidylserine (PS) is exposed on the surface of apoptotic cells and is known to promote immunosuppressive signals in the tumor microenvironment (TME). Antibodies that block PS interaction with its receptors have been shown to repolarize the TME into a proinflammatory state. Radiation therapy (RT) is an effective focal treatment of isolated solid tumors but is less effective at controlling metastatic cancers. We found that tumor-directed RT caused an increase in expression of PS on the surface of viable immune infiltrates in mouse B16 melanoma. We hypothesize that PS expression on immune cells may provide negative feedback to immune cells in the TME. Treatment with an antibody that targets PS (mch1N11) enhanced the anti-tumor efficacy of tumor-directed RT and improved overall survival. This combination led to an increase in proinflammatory tumor-associated macrophages. The addition of anti-PD-1 to RT and mch1N11 led to even greater anti-tumor efficacy and overall survival. We found increased PS expression on several immune subsets in the blood of patients with metastatic melanoma after receiving tumor-directed RT. These findings highlight the potential of combining PS targeting with RT and PD-1 pathway blockade to improve outcomes in patients with advanced-stage cancers.
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http://dx.doi.org/10.1016/j.celrep.2020.108620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100747PMC
January 2021

In vivo imaging characterization of basal cell carcinoma and cutaneous response to high-dose ionizing radiation therapy: A prospective study of reflectance confocal microscopy, dermoscopy, and ultrasonography.

J Am Acad Dermatol 2021 Jun 20;84(6):1575-1584. Epub 2020 Aug 20.

Brachytherapy Service, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Background: Radiation therapy (RT) is a treatment option for select skin cancers. The histologic effects of RT on normal skin or skin cancers are not well characterized. Dermoscopy, high-frequency ultrasonography (HFUS), and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that may help characterize RT response.

Objectives: To describe changes in the tumor and surrounding skin of patients with basal cell carcinoma (BCC) treated with RT.

Methods: The study was conducted between 2014 and 2018. Patients with biopsy-proven BCCs were treated with 42 Gy in 6 fractions using a commercially available brachytherapy device. Dermoscopy, HFUS, and RCM were performed before treatment and at 6 weeks, 3 months, and 12 months after RT.

Results: A total of 137 imaging assessments (RCM + dermoscopy + HFUS) were performed in 12 patients. BCC-specific features were present in 81.8%, 91%, and 17% of patients imaged with dermoscopy, RCM, and HFUS at baseline, respectively, before treatment. After treatment, the resolution of these features was noted in 33.4%, 91.7%, and 100% of patients imaged with the respective modalities. No recurrences were seen after a mean of 31.7 months of follow-up.

Limitations: Small sample size and no histopathologic correlation.

Conclusion: Dermoscopy and HFUS were not as reliable as RCM at characterizing BCC RT response.
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http://dx.doi.org/10.1016/j.jaad.2020.07.130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892640PMC
June 2021

Primary tumor volume as a predictor of distant metastases and survival in patients with sinonasal mucosal melanoma.

Head Neck 2020 11 1;42(11):3316-3325. Epub 2020 Aug 1.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with high mortality. Identifying patients at risk of distant metastasis assists with management and prognostication. We aimed to define the relationship between volume, survival, and risk of distant metastases.

Methods: A retrospective review of all patients with SNMM treated at a single institution over a 21-year period was conducted. Tumor volume was calculated using cross-sectional imaging and survival analysis was performed.

Results: Sixty-one patients were included. Tumor volume was predictive of local progression-free survival (P = .03), distant metastases-free survival (DMFS) (P = .002), and overall survival (OS) (P = .02). It was a better predictor than AJCC stage and T-classification. Tumor volume equal to or greater than 5 cm was associated with a significantly worse DMFS and OS (P = .02 and .009, respectively).

Conclusion: Calculation of tumor volume assists in quantifying the risk of distant metastases and death in SNMM.
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http://dx.doi.org/10.1002/hed.26380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722123PMC
November 2020

Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy.

J Natl Cancer Inst 2021 Mar;113(3):266-273

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure.

Methods: We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided.

Results: Among 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors.

Conclusions: We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT.
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http://dx.doi.org/10.1093/jnci/djaa095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936050PMC
March 2021

Quality of Life Concerns in Patients with Uveal Melanoma after Initial Diagnosis.

Ocul Oncol Pathol 2020 May 27;6(3):184-195. Epub 2019 Sep 27.

Department of Surgery, Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Patients with uveal melanoma (UM) are known to have quality of life (QOL) issues after treatment, but QOL concerns after initial diagnosis are ill-defined.

Objectives: We studied the QOL concerns of patients with UM after initial diagnosis to identify factors associated with QOL.

Method: Between September 2011 and May 2016, UM planning to undergo radiotherapy completed the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ)-C30, as well as the Ophthalmic Oncology module, QLQ-OPT30. Demographic, ophthalmic, and tumor related characteristics were recorded. The primary outcome was the QOL score and fraction of patients reporting any or severe symptoms. A multiple stepwise regression model investigated the association of demographic, ophthalmic, and tumor characteristics with QOL.

Results: QOL concerns were assessed in 201 subjects. The majority (51/60) of QOL items had a high response rate (≥90%), and internal consistency on scales (median Cronbach α = 0.85) with the most common severe QOL concern being worry about disease recurrence (41%). The most common ophthalmic symptoms reported were vision impairment (81%) and ocular irritation (66%). Multivariable regression modeling demonstrated several significant associations.

Conclusions: Severe worry about UM recurrence, ocular irritation, and vision impairment was reported by many patients. Clinicians should be aware of these concerns and implement management strategies.
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http://dx.doi.org/10.1159/000502549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250345PMC
May 2020

Management of primary skin cancer during a pandemic: Multidisciplinary recommendations.

Cancer 2020 09 1;126(17):3900-3906. Epub 2020 Jun 1.

Division of Dermatologic Surgery, Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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.
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http://dx.doi.org/10.1002/cncr.32969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301000PMC
September 2020

Improved survival in women versus men with merkel cell carcinoma.

J Am Acad Dermatol 2021 Feb 15;84(2):321-329. Epub 2020 May 15.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies.

Objective: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC).

Methods: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality.

Results: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients.

Limitations: Potential selection bias from a retrospective data set.

Conclusion: In MCC, women have improved survival compared with men, driven by MCC-related mortality.
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http://dx.doi.org/10.1016/j.jaad.2020.02.034DOI Listing
February 2021

The American Brachytherapy society consensus statement for skin brachytherapy.

Brachytherapy 2020 Jul - Aug;19(4):415-426. Epub 2020 May 11.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.

Purpose: Keratinocyte carcinoma (KC, previously nonmelanoma skin cancer) represents the most common cancer worldwide. While surgical treatment is commonly utilized, various radiation therapy techniques are available including external beam and brachytherapy. As such, the American Brachytherapy Society has created an updated consensus statement regarding the use of brachytherapy in the treatment of KCs.

Methods: Physicians and physicists with expertise in skin cancer and brachytherapy created a consensus statement for appropriate patient selection, data, dosimetry, and utilization of skin brachytherapy and techniques based on a literature search and clinical experience.

Results: Guidelines for patient selection, evaluation, and dose/fractionation schedules to optimize outcomes for patients with KC undergoing brachytherapy are presented. Studies of electronic brachytherapy are emerging, although limited long-term data or comparative data are available. Radionuclide-based brachytherapy represents an appropriate option for patients with small KCs with multiple techniques available.

Conclusions: Skin brachytherapy represents a standard of care option for appropriately selected patients with KC. Radionuclide-based brachytherapy represents a well-established technique; however, the current recommendation is that electronic brachytherapy be used for KC on prospective clinical trial or registry because of a paucity of mature data.
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http://dx.doi.org/10.1016/j.brachy.2020.04.004DOI Listing
April 2021

A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma.

Clin Cancer Res 2020 07 23;26(13):3193-3201. Epub 2020 Mar 23.

Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab.

Patients And Methods: We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis that would benefit from palliative RT and one metastasis that would not be irradiated. Nivolumab 1 mg/kg + ipilimumab 3 mg/kg and extracranial RT with a dose of 30 Gy in 10 fractions was administered in Cohort A, and then 27 Gy in 3 fractions was administered in Cohort B. The primary outcome was safety.

Results: Twenty patients were treated (10 in each cohort). The rates of treatment-related grade 3-4 adverse events in Cohort A and B were 40% and 30%, respectively. There were no grade ≥3 adverse events attributed to RT. Patients responded to treatment outside of the irradiated volume (Cohort A 5/10; Cohort B 1/9). No evaluable patients had progression of irradiated metastases. Immunologic changes were seen in the peripheral blood with increases in T-cell receptor diversity in some responding patients.

Conclusions: RT with nivolumab and ipilimumab was safe compared with historical data of nivolumab and ipilimumab alone. Immunologic effects were observed in the peripheral blood. Randomized studies are ongoing to assess whether RT increases the efficacy of nivolumab and ipilimumab.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959513PMC
July 2020

Quantitation of Urinary Acylcarnitines by DMS-MS/MS Uncovers the Effects of Total Body Irradiation in Cancer Patients.

J Am Soc Mass Spectrom 2020 Mar 28;31(3):498-507. Epub 2020 Jan 28.

Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.

Acylcarnitines have been identified in human and animal metabolomic-profiling studies as urinary markers of radiation exposure, a result which is consistent with their cytoprotective effects and roles in energy metabolism. In the present work, a rapid method for quantitation of the more abundant acylcarnitines in human urine is developed using a valuable set of samples from cancer patients who received total body irradiation (TBI) at Memorial Sloan Kettering Cancer Center. The method uses solid-phase extraction (SPE) processing followed by differential mobility spectrometry (DMS with ethyl acetate modifier) tandem mass spectrometry (ESI-DMS-MS/MS) with deuterated internal standards. The analyzed human urine samples were collected from 38 individual patients at three time points over 24 h during and after the course of radiation treatment, a design allowing each patient to act as their own control and creatinine normalization. Creatinine-normalized concentrations for nine urinary acylcarnitine (acyl-CN) species are reported. Six acyl-CN species were reduced at the 6 h point. Acetylcarnitine (C2:0-CN) and valerylcarnitine (C5:0-CN) showed recovery at 24 h, but none of the other acyl-CN species showed recovery at that point. Levels of three acyl-CN species were not significantly altered by radiation. This rapid quantitative method for clinical samples covers the short- and medium-chain acylcarnitines and has the flexibility to be expanded to cover additional radiation-linked metabolites. The human data presented here indicates the utility of the current approach as a rapid, quantitative technique with potential applications by the medical community, by space research laboratories concerned with radiation exposure, and by disaster response groups.
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http://dx.doi.org/10.1021/jasms.9b00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489307PMC
March 2020

Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin: Executive Summary of an American Society for Radiation Oncology Clinical Practice Guideline.

Pract Radiat Oncol 2020 Jan - Feb;10(1):8-20. Epub 2019 Dec 9.

Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.

Purpose: This guideline reviews the evidence for the use of definitive and postoperative radiation therapy (RT) in patients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC).

Methods: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on indications for RT in the definitive and postoperative setting for BCC and cSCC, as well as dose-fractionation schemes, target volumes, basic aspects of treatment planning, choice of radiation modality, and the role of systemic therapy in combination with radiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.

Results: The guideline recommends definitive RT as primary treatment for patients with BCC and cSCC who are not surgical candidates while conditionally recommending RT with an emphasis on shared decision-making in those situations in which adequate resection can lead to a less than satisfactory cosmetic or functional outcome. In the postoperative setting, a number of indications for RT after an adequate resection are provided while distinguishing the strength of the recommendations between BCC and cSCC. One key question is dedicated to defining indications for regional nodal irradiation. The task force suggests a range of appropriate dose-fractionation schemes for treatment of primary and nodal volumes in definitive and postoperative scenarios. The guideline also recommends against the use of carboplatin concurrently with adjuvant RT and conditionally recommends the use of systemic therapies for unresectable primaries where treatment may need escalation.

Conclusions: Defining the role of RT in the management of BCC and cSCC has been hindered by a lack of high-quality evidence. This document synthesizes available evidence to define practice guidelines for the most common clinical situations. We encourage practitioners to enroll patients in prospective trials and to approach care in a multidisciplinary fashion whenever possible.
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http://dx.doi.org/10.1016/j.prro.2019.10.014DOI Listing
June 2020

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Lancet Oncol 2019 12;20(12):e699-e714

Department of Dermatology, University of Minnesota, Minneapolis, MN, USA.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.
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http://dx.doi.org/10.1016/S1470-2045(19)30673-4DOI Listing
December 2019

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer.

Cancer 2020 02 20;126(4):850-860. Epub 2019 Nov 20.

Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

Background: The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression.

Methods: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival.

Results: The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported.

Conclusions: The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed.
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http://dx.doi.org/10.1002/cncr.32599DOI Listing
February 2020

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.

Ophthalmology 2020 02 24;127(2):240-248. Epub 2019 Sep 24.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.

Purpose: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored.

Design: Multicenter, retrospective cohort study.

Participants: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous.

Methods: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye.

Main Outcome Measures: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes.

Results: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception.

Conclusions: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.
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http://dx.doi.org/10.1016/j.ophtha.2019.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003537PMC
February 2020

First-in-Humans Imaging with Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting.

J Nucl Med 2020 04 4;61(4):512-519. Epub 2019 Oct 4.

Department of Medicine, Weill Cornell Medical College, New York, New York.

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1-2, 6-8, 24, 48, and 96-144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time-activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24-48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most Zr-IAB22M2C-positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell-rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.
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http://dx.doi.org/10.2967/jnumed.119.229781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198374PMC
April 2020

Restaging [F] fludeoxyglucose positron emission tomography/computed tomography scan in recurrent cutaneous squamous cell carcinoma: Diagnostic performance and prognostic significance.

J Am Acad Dermatol 2020 Apr 25;82(4):878-886. Epub 2019 Sep 25.

Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Background: There are no specific recommendations for [F] fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in assessing recurrent cutaneous squamous cell carcinoma (cSCC).

Objective: To evaluate FDG-PET/CT in recurrent cSCC.

Methods: FDG-PET/CT scans were retrospectively reviewed. Sites of abnormal uptake were noted and correlated with biopsy/histopathology studies, where available, and with follow-up imaging or clinical data in others. Comparison with available CT/magnetic resonance imaging was performed. The prognostic significance of PET/CT parameters was evaluated, and PET/CT-based change in management was recorded.

Results: A total of 115 FDG-PET/CT scans were analyzed in 100 consecutive patients with cSCC. Of these, 96 (84%) scans were positive for recurrence, and 25 showed distant metastases. PET/CT detected unsuspected disease sites in 39 of 115 scans (34%), locoregional disease in 14, distant metastases in 11, both locoregional disease and distant metastases in 8, additional local cutaneous disease in 5, and second malignancy in 1. Comparison of 78 PET/CT scans with available CT/magnetic resonance imaging showed 37 additional abnormalities on 23 PET/CT scans, predominantly including skin/subcutaneous lesions and nodes. PET/CT led to change in management in 28% of patients. On univariate/multivariate analysis, increased number of FDG-positive lesions and lung metastases on PET/CT was associated with increased risk of death/disease progression.

Limitations: Retrospective study.

Conclusions: FDG-PET/CT was sensitive in detecting recurrent disease in cSCC, led to change in management for 28% of patients, and proved to be of prognostic value.
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http://dx.doi.org/10.1016/j.jaad.2019.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549433PMC
April 2020

Evidence-Based Clinical Practice Guidelines for Microcystic Adnexal Carcinoma: Informed by a Systematic Review.

JAMA Dermatol 2019 Sep;155(9):1059-1068

Division of Mohs and Dermatological Surgery, Department of Dermatology and Cosmetic Dermatology, Henry Ford Hospital, Detroit, Michigan.

Importance: Microcystic adnexal carcinoma (MAC) occurs primarily in older adults of white race/ethnicity on sun-exposed skin of the head and neck. There are no formal guiding principles based on expert review of the evidence to assist clinicians in providing the highest-quality care for patients.

Objective: To develop recommendations for the care of adults with MAC.

Evidence Review: A systematic review of the literature (1990 to June 2018) was performed using MEDLINE, Embase, Web of Science, and the Cochrane Library. The keywords searched were microcystic adnexal carcinoma, sclerosing sweat gland carcinoma, sclerosing sweat duct carcinoma, syringomatous carcinoma, malignant syringoma, sweat gland carcinoma with syringomatous features, locally aggressive adnexal carcinoma, and combined adnexal tumor. A multidisciplinary expert committee critically evaluated the literature to create recommendations for clinical practice. Statistical analysis was used to estimate optimal surgical margins.

Findings: In total, 55 studies met our inclusion criteria. The mean age of 1968 patients across the studies was 61.8 years; 54.1% were women. Recommendations were generated for diagnosis, treatment, and follow-up of MAC. There are 5 key findings of the expert committee based on the available evidence: (1) A suspect skin lesion requires a deep biopsy that includes subcutis. (2) MAC confined to the skin is best treated by surgery that examines the surrounding and deep edges of the tissue removed (Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment). (3) Radiotherapy can be considered as an adjuvant for MAC at high risk for recurrence, surgically unresectable tumors, or patients who cannot have surgery for medical reasons. (4) Patients should be seen by a physician familiar with MAC every 6 to 12 months for the first 5 years after treatment. Patient education on photoprotection, periodic skin self-examination, postoperative healing, and the possible normal changes in local sensation (eg, initial hyperalgesia) should be considered. (5) There is limited evidence to guide the treatment of metastasis in MAC due to its rarity. Limitations of our findings are that the medical literature on MAC comprises only retrospective reviews and descriptions of individual patients and there are no controlled studies to guide management.

Conclusions And Relevance: The presented clinical practice guidelines provide an outline for the diagnosis and management of MAC. Future efforts using multi-institutional registries may improve our understanding of the natural history of the disease in patients with lymph node or nerve involvement, the role of radiotherapy, and the treatment of metastatic MAC with drug therapy.
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http://dx.doi.org/10.1001/jamadermatol.2019.1251DOI Listing
September 2019

Clinical value of 18F-FDG-PET/CT in staging cutaneous squamous cell carcinoma.

Nucl Med Commun 2019 Jul;40(7):744-751

Departments of Radiology.

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy. Computed tomography (CT) and/or MRI are commonly used for staging, however, the role of fluorine-18-fluorodeoxyglucose (F-FDG)-PET is not clearly established. In this study, we evaluated F-FDG-PET/CT imaging for initial staging of cSCC.

Patients And Methods: F-FDG-PET/CT scans performed in patients with newly diagnosed cSCC were reviewed retrospectively. Images were visually assessed for lesions and F-FDG uptake [standardized uptake value (SUV)] in primary and secondary sites was measured. Suspected lesions on F-FDG-PET/CT were correlated with histopathology when available, follow-up imaging or clinical data in others.

Results: Twenty-three cSCC patients who underwent F-FDG-PET/CT at diagnosis were evaluated. Primary sites were in head/neck (n=21), chest (n=1), and foot (n=1). All patients had F-FDG-positive scans with a total of 51 F-FDG-positive lesions. All primary lesions (n=24) were F-FDG-positive (SUV: 2.3-22.8; mean 10.2), and additional 27 F-FDG-positive lesions, including 21 nodes, four cutaneous, one osseous and one lung lesion, were noted in 13 patients. Mean size of F-FDG-positive nodes was 0.9 cm (range: 0.4-2.5 cm), predominantly clinically impalpable. Pathology was available for 40/51 lesions; 31 sites positive for malignancy. SUV (mean±SD) was 9.2±6.2 for malignant and 2.7±1.2 for benign lesions. Sensitivity, positive predictive value, and accuracy of F-FDG-PET/CT scan were 100, 77.5, and 77.5%, respectively. F-FDG detected seven additional lesions in three patients, compared to CT/MRI. Overall, staging F-FDG-PET/CT detected nine prior unknown lesions in five patients that were proven metastatic disease by histopathology or follow-up; F-FDG-PET/CT modified management in 5/23 (21.7%) patients.

Conclusion: F-FDG-PET/CT has high sensitivity in the detection of cSCC lesions, including small cutaneous and nodal disease, and has a potential role in initial staging and management.
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http://dx.doi.org/10.1097/MNM.0000000000001029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518232PMC
July 2019

Chemoreduction of Orbital Recurrence of Uveal Melanoma by Intra-Arterial Melphalan.

Ocul Oncol Pathol 2019 Apr 9;5(3):186-189. Epub 2018 Oct 9.

Weill-Cornell Medical Center, New York, New York, USA.

Background/aims: The treatment of orbital melanoma poses a management challenge. This case explores the delivery of high-dose melphalan to an orbital recurrence of uveal melanoma via intra-arterial delivery of melphalan to the orbit. A 62-year-old man developed recurrent orbital disease 7 months after enucleation for a large uveal melanoma. He received 6 monthly intra-arterial infusions of melphalan to the orbit, ranging in dose from 20 to 30 mg per infusion. Following the last infusion, mild temporary erythema was noted on the forehead along the distribution of the supratrochlear artery. The orbital recurrence was reduced in size by 66% in the longest dimension as measured by magnetic resonance imaging (MRI). However, 9 months following intra-arterial melphalan, tumor regrowth was detected on MRI, and additional treatment options were pursued.

Conclusion: This case demonstrates that intra-arterial melphalan can result in nonsustained tumor regression of recurrent orbital uveal melanoma. It suggests that local delivery of high-dose melphalan may be helpful as a neoadjuvant treatment for uveal melanoma, and future studies will be useful to confirm the value of this approach in additional cases of recurrent and possibly in primary uveal melanoma.
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http://dx.doi.org/10.1159/000490061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489044PMC
April 2019

Organ preservation for patients with anterior mucosal squamous cell carcinoma of the nasal cavity: Rhinectomy-free survival in those refusing surgery.

Head Neck 2019 08 1;41(8):2741-2747. Epub 2019 Apr 1.

Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Standard treatment of squamous cell carcinoma (SCC) of the anterior nasal mucosa is surgical resection with or without postoperative radiation.

Methods: Retrospective review of patients diagnosed with SCC of the nasal cavity between January 2000 and July 2018 who refused total rhinectomy and who were treated with radiation with or without chemotherapy with curative intent.

Results: Eleven patients were identified, 73% had stage III or stage IV disease. Four patients were treated with intensity-modulated radiotherapy and seven with intensity-modulated proton radiotherapy. Concurrent chemoradiotherapy was used in nine patients (82%). With a median follow-up of 15 months (3-124 months), two patients experienced recurrence and one developed distant metastasis and died from disease. The 2-year rhinectomy-free survival rate was 88%. Two-year overall survival and recurrence-free survival were 100% and 75%, respectively.

Conclusion: A radiation-based approach for SCC of the nasal cavity mucosa is a valid option for selected patients who refuse up-front surgery.
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http://dx.doi.org/10.1002/hed.25751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709873PMC
August 2019

Tumor mutational load predicts survival after immunotherapy across multiple cancer types.

Nat Genet 2019 02 14;51(2):202-206. Epub 2019 Jan 14.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.
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http://dx.doi.org/10.1038/s41588-018-0312-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365097PMC
February 2019

Imatinib Treatment for Locally Advanced or Metastatic Dermatofibrosarcoma Protuberans: A Systematic Review.

JAMA Dermatol 2019 03;155(3):361-369

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Dermatofibrosarcoma protuberans (DFSP) has the potential for local destruction and recurrence, although it carries a low risk of metastasis. Complete surgical resection with negative margins is considered the gold standard for treatment; however, there are cases that are unresectable owing to tumor extension or size or owing to risk of cosmetic and/or functional impairment. Imatinib treatment has been used for locally advanced or metastatic DFSP.

Objective: To evaluate the usefulness of imatinib for treating DFSP.

Evidence Review: We conducted a systematic review on the PubMed and Embase databases for articles published from September 2002 through October 2017 using the key words "dermatofibrosarcoma" or "dermatofibrosarcoma protuberans" AND "therapy" AND "imatinib." References within retrieved articles were also reviewed to identify additional studies. Studies of adults with histologically proven DFSP treated with imatinib as monotherapy or as an adjuvant or neoadjuvant therapy to surgery were included. Extracted data were analyzed using descriptive statistics. PRISMA guidelines were followed. All analysis took place October through December 2017.

Findings: Nine studies met inclusion criteria; 152 patients were included. The calculated mean patient age was 49.3 years (range, 20-73 years). Calculated mean tumor diameter was 9.9 cm (range, 1.2-49.0 cm). When COL1A1-PDGFβ protein translocation (collagen, type 1, alpha 1-platelet-derived growth factor β) was reported, it was present in 90.9% of patients (111 of 122). Complete response was seen in 5.2% of patients (8 of 152), partial response in 55.2% (84 of 152), stable disease in 27.6% (42 of 152), and progression in 9.2% (14 of 152). Four of the 152 patients (2.6%) were excluded from the analysis owing to unknown or unevaluable response. There were no differences in response rate using 400-mg or 800-mg daily doses (67.5% or 27 of 40 patients for 400-mg dose vs 67.1% or 49 of 73 patients for 800-mg dose complete or partial response; P > .99). Adverse events were present in at least 73.5% of cases (78 of 106); severe adverse events were present in 15.1% of cases (20 of 132).

Conclusions And Relevance: Imatinib is a useful directed therapy in patients with DFSP who are not surgical candidates owing to disease extension or significant cosmetic or functional impairment. There seems to be no difference between 400- or 800-mg daily doses.
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http://dx.doi.org/10.1001/jamadermatol.2018.4940DOI Listing
March 2019

Hepatic abnormalities identified by staging MRI and accuracy of MRI of patients with uveal melanoma.

Br J Ophthalmol 2019 09 31;103(9):1266-1271. Epub 2018 Oct 31.

Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, USA.

Background: Metastases to the liver are often the first finding in patients with uveal melanoma with extraocular disease, but little has been published on the utility of staging MRI at initial diagnosis. We aimed to evaluate the proportion of abnormal hepatic findings on baseline MRI and accuracy of MRI in patients with newly diagnosed uveal melanoma.

Methods: This is a single-centre, retrospective, institutional review board-approved study of 145 consecutive patients diagnosed with uveal melanoma, at Memorial Sloan Kettering Cancer Center between 2004 and 2016, who had staging MRI within 1 month of diagnosis. Scans were classified as normal or abnormal, and further distinguished as abnormal non-metastatic, uncharacterisable lesions and suspicious for metastasis. Where available, follow-up MRI (at ~1 year) or biopsies were reviewed.

Results: MRI in 145 patients revealed 62% (90) with abnormal hepatic findings; out of these 87% (78) had non-metastatic benign findings, 6.7% (6) had unclassifiable lesions and 6.7% (6) were suspicious for metastasis (6). Abnormal non-metastatic findings included 72 focal (36 solitary and 36 multiple) and 12 diffuse lesions. Lesions suspicious for metastases were found in 6 of 145 patients (4%), despite normal liver function tests. Of these, five had confirmed liver metastases and one patient had a stable, presumed non-metastatic lesion on follow-up. In this study, the sensitivity and specificity of staging MRI for all findings were 83.3% (95% CI 35.9 to 99.6) and 99.0% (95% CI 94.3 to 99.9), respectively.

Conclusion: Staging MRI of patients with newly diagnosed uveal melanoma accurately identified early metastases. Furthermore, imaging revealed hepatic abnormalities in the majority of patients, although as expected few of these represented metastatic disease.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312612DOI Listing
September 2019

Tumor Board Conferences for Multidisciplinary Skin Cancer Management: A Survey of US Cancer Centers.

J Natl Compr Canc Netw 2018 10;16(10):1209-1215

Tumor board conferences (TBCs) are used by oncologic specialists to review patient cases, exchange knowledge, and discuss options for cancer management. These multidisciplinary meetings are often a cornerstone of treatment at leading cancer centers and are required for accreditation by certain groups, such as the American College of Surgeons' Commission on Cancer. Little is known regarding skin cancer TBCs. The objective of this study was to characterize the structure, function, and impact of existing skin cancer TBCs in the United States. A cross-sectional online survey was administered to physician leaders of skin cancer TBCs at NCI-designated Comprehensive and Clinical Cancer Centers. Of the 59 centers successfully contacted, 14 (24%) reported not having a conference where skin cancer cases were discussed, and 45 (76%) identified 53 physician leaders. A total of 38 physicians (72%) completed the survey. Half of the meeting leaders were medical and/or surgical oncologists, and dermatologists led one-third of meetings. TBCs had a moderate to significant impact on patient care according to 97% of respondents. All respondents indicated that the meetings enhanced communication among physicians and provided an opportunity for involved specialists and professionals to discuss cases. The most frequently cited barrier to organizing TBCs was determining a common available date and time for attendees (62%). The most common suggestion for improvement was to increase attendance, specialists, and/or motivation. Results showed overall consistency in meeting structure but variability in function, which may be a reflection of institutional resources and investment in the conference. Future directions include defining metrics to evaluate changes in diagnosis or management plan after tumor board discussion, attendance, clinical trial enrollment, and cost analysis. Results of this survey may aid other institutions striving to develop and refine skin cancer TBCs.
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http://dx.doi.org/10.6004/jnccn.2018.7044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446238PMC
October 2018

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.

Adv Radiat Oncol 2018 Jul-Sep;3(3):391-398. Epub 2018 May 9.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: The objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors.

Methods And Materials: Patient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n = 79). Receiving both treatments within 1 month was considered concurrent (n = 35; 44%), and any treatment up to 6 months apart was considered sequential (n = 44; 56%). The primary endpoint of this study was the rate of Grade ≥2 AEs from combination therapy (immunotherapy and RT), specifically those that are relevant to thoracic RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue. Further univariate analysis was performed to compare AE rates with clinical and therapy-related variables.

Results: A total of 79 patients were identified, with lung cancer (n = 45) and melanoma (n = 15) being the most common primary histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1 antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti-PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9 months (range, 2.4-55.6 months). Grade ≥2 AEs included pneumonitis (n = 5; 6%), esophagitis (n = 6; 8%), and dermatitis (n = 8; 10%). No statistically significant correlation was found between these AEs when comparing concurrent versus sequential treatment. The only significant variable was a correlation of immunotherapy drug category with Grade ≥2 esophagitis ( = .04).

Conclusions: Overall, Grade ≥2 AE rates of thoracic RT and immunotherapy appeared as expected and acceptable. The lack of significant differences in AE rates with concurrent versus sequential treatment suggests that even concurrent immunotherapy and thoracic RT may be safe.
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http://dx.doi.org/10.1016/j.adro.2018.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128092PMC
May 2018