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Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Objective Standard techniques for primary dural repair following lateral skull base surgery are both technically challenging and time consuming without the potential for primary dural repair. Inadequate closure may result in postoperative cerebrospinal fluid (CSF) leak infectious sequalae. Traditional methods of dural repair rely on secondary obliteration of the CSF fistula. We hypothesized that the use of nonpenetrating titanium microclips may serve as a useful adjunct in primary dural repair or the establishment of an immobile repair layer following lateral skull base surgery. Methods Here, we report a novel technique for primary dural repair using nonpenetrating titanium microclips as an adjunct to standard techniques in a series of six patients with lateral skull base pathologies. Results A total of six consecutive lateral skull base tumor patients with titanium microclip dural reconstruction were included in our case series. Lateral skull base pathologies represented in this group included two jugular foramen schwannomas, one vestibular schwannoma, one petroclival meningioma, one glomus jugulare paraganglioma, and one jugular foramen chordoid meningioma. Conclusion To our knowledge, this is the first report on the use of microclips in repairing dural defects following lateral skull base surgery. Surgical outcomes for this small case series suggest that dural repair of the later skull base with nonpenetrating titanium microclips is a useful adjunct in dural repair following lateral skull base surgery.

Anterior cervical discectomy and fusion (ACDF) is the most common surgical procedure utilized for degenerative diseases of the cervical spine. The authors present the case of a 64-year-old man who underwent an ACDF for degenerative changes causing cervical stenosis with myelopathy. The patient’s symptoms consisted of pain and weakness of the bilateral upper extremities that slowly progressed over 1.5 years. During the procedure, the superior horn of the thyroid cartilage impeded proper retraction, preventing adequate visualization due to its prominent size. At this point, otorhinolaryngology was consulted, which allowed for safe resection of this portion of the thyroid cartilage while preserving nearby critical structures. With the frequent usage of this surgical approach for various etiologies, the importance of proper recognition and consultation is paramount. Encountering prominent thyroid cartilage resulting in surgical obstruction has not been described in the literature and this report represents a paradigm for the proper course of action.

Background Cancer cachexia affects up to over 50% of advanced head and neck cancer (HNC) patients. To date, the potential utility of anabolic steroids in perioperative cachectic HNC patients has not been determined. Methods Retrospective review of pre- and post-oxandrolone administration prealbumin levels in 18 perioperative HNC patients between October 2007 and October 2014 at a tertiary academic medical center. Results The median pretreatment prealbumin was 88.5 mg/L. The median post-treatment prealbumin was 227 mg/L. The median interval improvement of the prealbumin level was 131.5 mg/L. The median differences between the pretreatment and post-treatment prealbumin levels were found to be statistically significant (P

OBJECTIVES To evaluate the diagnostic performance of ultrasound (US)-guided fine-needle aspiration with optional core needle biopsy of head and neck lymph nodes and masses, with attention to differences between biopsy of treated squamous cell carcinoma (SCC) and biopsy of other lesions. METHODS Institutional Review Board approval was obtained, and the need for consent was waived for this retrospective study. All 861 US-guided biopsies of head and neck lymph nodes and masses performed between March 1, 2012, and May 16, 2016, were reviewed. RESULTS Of the 861 biopsies, 53 targeted SCC with residual masses after treatment. The biopsy procedures yielded benign or malignant pathologic results in 71.7% (38 of 53) of treated SCC and 90.7% (733 of 808) of all other lesions (P

BACKGROUND Merkel cell carcinoma (MCC) is a rare, highly aggressive malignancy which lacks high-level evidence-based treatment guidelines. METHODS To determine outcomes of MCC patients and assess the role of radiation in treatment, we performed a retrospective chart review of patients treated for MCC between 2006 and 2016 at a single high-volume academic medical center. The primary outcome was overall survival (OS) for the entire population and for those populations receiving specific therapies. RESULTS Forty-two patients were evaluable. OS for all patients was not reached since most remain alive at time of analysis. OS for the American Joint Committee on Cancer (AJCC) stage I was not reached. OS for stages II, III, and IV was 37.3 months (6.8, -), 49.5 months (14.2, 49.5), and 14.5 months (10.8, -), respectively. OS could not be reached in the high radiotherapy (RT) dose group (biologically equivalent dose [BED] ≥ 60) and was 49.5 months (10.8, -) in the low-dose group (BED < 60). For surgical margin status, OS was 14.9158 months (6.8008, -) for positive margins and 37.3 months (10.8, -) for negative margins. CONCLUSIONS No conclusive findings for OS were identified; however, trends for improved OS were associated with lower AJCC staging, negative surgical margins, and high RT doses.

The coronavirus disease‐2019 (COVID‐19) pandemic has rapidly spread across the world, placing unprecedented strain on the health care system. Health care resources including hospital beds, ICUs, as well as personal protective equipment are becoming increasingly rationed and scare commodities. In this environment, the laryngectomee (patient having previously undergone a total laryngectomy) continues to represent a unique patient with unique needs. Given their surgically altered airway, they pose a challenge to manage for the otolaryngologist within the current COVID‐19 pandemic. In this brief report, we present special considerations and best practice recommendations in the management of total laryngectomy patients. We also discuss recommendations for laryngectomy patients and minimizing community exposures.

Background: The prevention of cancer and the development of more effective strategies to detect cancer precursor lesions and early-stage cancers remain critical goals. It has been estimated that 50% - 60% of cancers could be prevented if known strategies were optimally used. Cancer risk is not uniform, but varies based on age, genetic susceptibility, exposures, existence of preneoplastic conditions across the population. The DNA is constantly damaged by exogenous and endogenous sources. DNA repair mechanisms maintain the integrity of the genome. DNA damage has emerged as a major culprit in tumorigenesis and progression. There are numerous strategies with inherent advantages and disadvantages that may be used for the evaluation of DNA damage and repair. We have developed a novel and highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify DNA damage in p53, the most frequently mutated gene in human cancer. Here, we have extended this assay to HPRT (hypoxanthine-guanine phosphoribosyltransferase), the gene most frequently analyzed in DNA damage studies. Aim: (1) To quantify the amount of DNA damage in HPRT in peripheral blood cells of never-smokers, smokers, and secondhand smokers. (2) To determine whether cancer patients have higher levels of DNA damage in HPRT than non-cancer patients. Methods: The assay, PADDA was used on a high-throughput setting to quantify DNA damage (q-PADDA) on the HPRT gene. DNA was extracted and damage was quantified by q-PADDA in peripheral blood cells collected from non-cancer patients [never-smokers (n=28), tobacco smokers (n=25), secondhand smokers (n=18)], and cancer patients (n=66). Pairwise comparisons in DNA damage among the diverse groups were performed using the Tukey's adjustment in a one-way ANOVA model. Linear regression models were also used to test difference in DNA damage between cancer and non-cancer groups. Results: Never-smokers, tobacco smokers, and secondhand smokers had similar age distribution. In non-cancer patients, the amount of DNA damage in the HPRT gene in smokers was significantly higher than in non-smokers (p=0.01). Secondhand smokers also showed higher levels of DNA damage than never-smokers but this difference did not reach significance. Among cancer patients (n=64), smokers (n=29) showed significantly higher levels of DNA damage (p=0.03) than non-smokers (n=16). Conclusion: Our preliminary data document PADDA's ability to quantify DNA damage on HPRT gene. Damage was significantly higher in smokers than never-smokers, both in cancer and non-cancer patients. Application of this assay to a larger population sample has a major potential to establish biomarkers of susceptibility to tobacco-induced cancer, which can guide preventive and diagnostic strategies. Funding: This work was supported by the NIH, NCI (1R33 CA202898-01, LQ). Dr. Queimado holds a Presbyterian Health Foundation Endowed Chair in Otorhinolaryngology. Citation Format: Mayilvanan Chinnaiyan, Daniel Brobst, Balaji Sadhasivam, Vengatesh Ganapathy, Sarah E. Johnston, Daniel Zhao, Greg A. Krempl, Lurdes Queimado. DNA damage on HPRT as a biomarker of susceptibility to tobacco-induced cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2075.

Objectives/Hypothesis This study compares the overall durability, phonation effort, and speech quality achieved by the Blom-Singer Dual Valve prosthesis to the same characteristics achieved by the single-valve prosthesis used in a select population of total laryngectomy patients who have demonstrated single-valve prosthesis failure within 3 months of placement. Study Design Prospective phase IV study. Methods Fourteen patients who had previously experienced early valve failure using a single-valve prosthesis had a Dual Valve placed by a speech language pathologist. A total of seventeen Dual Valves were inserted during routine clinical visits for valve replacement. Time intervals from insertion to replacement of the Dual Valve, as well as the average lifespan of patients’ three previous single valves were collected. Subjective, categorical responses to speech quality and phonation effort for the Dual Valve compared to the single valve were collected on a questionnaire upon failure of the device. Results The mean duration of the single valve was 60 days, with a median of 51 days, whereas the mean duration of the Dual Valve was 164 days, with a median duration of 84 days. Both sets of data were statistically significant, with a P value of .0131. Valve life was increased in 86% of patients, with 43% experiencing greater than 150 days improvement in valve duration when using the Dual Valve. Phonation effort was increased in 14% of patients, and speech quality was not significantly affected in any patients. Conclusions In this select population, the Dual Valve offers improved durability over the single valve without sacrificing speech quality, making it a preferred prosthesis option for patients experiencing single-valve failure in less than 3 months. Level of Evidence 4. Laryngoscope, 128:422–426, 2018

Objectives Preferential use of fine-needle aspiration (FNA) versus core needle biopsy (CNB) for distinguishing benign from malignant major salivary gland tumors is highly debated. The main disadvantage of FNA is lower sensitivity, whereas arguments against CNB include use of a larger bore needle and greater risk of complications. The aim of this study is to evaluate our experience performing ultrasound-guided (UG) FNA with selective use of CNB based on preliminary cytopathology, and to determine whether our preoperative diagnostic approach is more sensitive and specific than FNA alone—and at least as sensitive and specific as CNB alone. Study Design Retrospective review of UG needle biopsy sampling of lesions arising in or around parotid and submandibular glands. Methods Ultrasounds of 141 needle biopsies were identified. Patient/lesion/needle biopsy characteristics, preliminary cytopathology, final pathology, imaging studies, and subsequent clinical course and treatment were documented. Results Needle biopsies performed according to our protocol provided results that guided clinical decision making in 125 of 135 cases, 92.6% (95% confidence interval [CI], 86.8%–96.4%) of the time. Using 41 cases that had histologic verification, sensitivity was 100% (95% CI, 79.6%–100%), and specificity was 92.3% (95% CI, 75.9%–97.9%) for detecting malignancy. We definitively characterized 120 lesions as benign (84) or malignant (36). Conclusion Preoperative needle biopsy diagnoses allowed clinical management to progress 92.6% of the time. The protocol of FNA with selective use of CNB may potentially reduce patient exposure to risks associated with CNB without the tradeoff of lower sensitivity seen with FNA. Level of Evidence 4. Laryngoscope, 2017

Objectives IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). Methods A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm2 were used to characterize immune responders (IR). Results Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11). Conclusions The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT 02609386).

Here we present the case of a 36-year-old man who was found to have a symptomatic malignant neural sheath tumor growing from the C2 nerve root following a period of progressively worsening headaches. The patient was successfully treated with surgical resection resulting in resolution of cranial nerve deficits. Though uncommon, malignant peripheral nerve sheath tumor must be considered in the differential diagnosis of tumors involving the cervical nerve roots and carotid space.

To evaluate the diagnostic performance of ultrasound (US)-guided fine-needle aspiration with optional core needle biopsy of head and neck lymph nodes and masses, with attention to differences between biopsy of treated squamous cell carcinoma (SCC) and biopsy of other lesions.Institutional Review Board approval was obtained, and the need for consent was waived for this retrospective study. All 861 US-guided biopsies of head and neck lymph nodes and masses performed between March 1, 2012, and May 16, 2016, were reviewed.Of the 861 biopsies, 53 targeted SCC with residual masses after treatment. The biopsy procedures yielded benign or malignant pathologic results in 71.7% (38 of 53) of treated SCC and 90.7% (733 of 808) of all other lesions (P .001). A reference standard based on subsequent pathologic results or clinical and imaging follow-up was established in 68.4% of procedures. In cases with benign or malignant biopsy results and a subsequent reference standard, the sensitivity values for malignancy were 87.5% (95% confidence interval, 64.0%-96.5%) in treated SCC and 98.3% (95% confidence interval, 96.0%-99.3%) in all other cases (P = .047), and the specificity values were 63.6% (95% confidence interval, 35.4%-84.8%) in treated SCC and 99.5% (95% confidence interval, 97.3%-99.9%) in all other cases (P .001). There were no major complications related to the biopsy procedures.Excluding treated SCC, US-guided fine-needle aspiration with optional core needle biopsy of head and neck lymph nodes and masses has excellent diagnostic performance. Needle biopsy of head and neck SCC with a residual mass after therapy has a high rate of nondiagnostic samples, suboptimal sensitivity, and poor specificity.

ContextThe 15-item University of Washington Quality of Life questionnaire-Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG0537.ObjectivesThis study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales.MethodsEFA on the UW-QOL-RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability.ResultsThe 15-item EFA of the modified tool resulted in 11 items split into four factors: mucus, eating, pain, and activities. Cronbach α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ≥0.60) between consecutive time points and between total score and the Xerostomia Related Quality of Life Scale total score (ρ>0.65).ConclusionThe UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items.

Preferential use of fine-needle aspiration (FNA) versus core needle biopsy (CNB) for distinguishing benign from malignant major salivary gland tumors is highly debated. The main disadvantage of FNA is lower sensitivity, whereas arguments against CNB include use of a larger bore needle and greater risk of complications. The aim of this study is to evaluate our experience performing ultrasound-guided (UG) FNA with selective use of CNB based on preliminary cytopathology, and to determine whether our preoperative diagnostic approach is more sensitive and specific than FNA alone-and at least as sensitive and specific as CNB alone.Retrospective review of UG needle biopsy sampling of lesions arising in or around parotid and submandibular glands.Ultrasounds of 141 needle biopsies were identified. Patient/lesion/needle biopsy characteristics, preliminary cytopathology, final pathology, imaging studies, and subsequent clinical course and treatment were documented.Needle biopsies performed according to our protocol provided results that guided clinical decision making in 125 of 135 cases, 92.6% (95% confidence interval [CI], 86.8%-96.4%) of the time. Using 41 cases that had histologic verification, sensitivity was 100% (95% CI, 79.6%-100%), and specificity was 92.3% (95% CI, 75.9%-97.9%) for detecting malignancy. We definitively characterized 120 lesions as benign (84) or malignant (36).Preoperative needle biopsy diagnoses allowed clinical management to progress 92.6% of the time. The protocol of FNA with selective use of CNB may potentially reduce patient exposure to risks associated with CNB without the tradeoff of lower sensitivity seen with FNA.4. Laryngoscope, 127:2522-2527, 2017.

The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS).A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization.There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm.Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

When managing a patient with nasopharyngeal carcinoma there are a number of clinical and imaging factors a clinician will use to make the appropriate staging evaluation and treatment recommendations. In this chapter a sample case of a patient with a poorly differentiated non-keratinizing carcinoma of the lateral wall of the nasopharynx with palpable lymphadenopathy, clinically staged T2N1M0, is used to assist the reader in formulating decisions about the best methods for assessing skull base involvement, the role of PET imaging, the role of viruses in tumorigenesis, and pertinent decisions regarding the treatment of the primary tumor in both untreated and recurrent disease. The unique decisions pertaining to managing the neck nodes and the role of adjuvant chemotherapy are reviewed as well.

Introduction: IRX-2 is a primary-cell-derived immune-restorative biologic consisting of a well-defined set of human cytokines that act on multiple immune system cell types to overcome tumor-mediated immunosuppression. The IRX-2 biologic stimulates T cells and natural killer cells and turns immature or defective dendritic cells into mature antigen-presenting cells. The IRX-2 biologic is provided as part of the IRX-2 regimen, which contains cyclophosphamide, indomethacin, and zinc to support an anticancer immune response. In a phase 2a clinical trial in 27 patients with therapy-naïve head and neck squamous cell carcinoma (HNSCC), treatment with the IRX-2 regimen was well tolerated and associated with immunologically mediated antitumor effects. The new multicenter randomized IRX-2 Neoadjuvant Therapy in Head and Neck SCC to Provide Immune Response Enhancement (INSPIRE) trial (NCT02609386) is designed to evaluate the safety and effectiveness of combined neoadjuvant and adjuvant therapy with the IRX-2 regimen in patients with oral cavity HNSCC, a disease known to have a disordered immune function. Study Design: Patients enrolled in INSPIRE must be at least 18 years of age; have previously untreated Stage II, III, or IVa SCC of the oral cavity that is surgically resectable with curative intent; and have a Karnofsky Performance status ≥70%. Up to 200 patients will be randomized 2:1 to either the IRX-2 biologic regimen arm or the IRX-2 regimen control arm (the IRX regimen minus the IRX-2 biologic). The neoadjuvant stage of INSPIRE begins 21 days before resection, when patients in both treatment arms will receive the IRX-2 regimen each day until resection. This regimen consists of the immunomodulatory chemotherapeutic agent cyclophosphamide, provided as a low-dose intravenous infusion, as well as two oral drugs, a zinc-containing multivitamin and indomethacin, a nonselective COX-1/COX-2 inhibitor. During this period, patients in the IRX-2 biologic regimen arm will also receive 10 days of the IRX-2 biologic subcutaneously injected into their bilateral sternocleidomastoid insertion regions. After resection, patients receive standard adjuvant radiation or chemoradiation therapy followed by adjuvant IRX-2 booster regimens at 3, 6, 9, and 12 months. During each 10-day booster period, patients in the IRX-2 biologic regimen arm also receive, for 5 consecutive days, the IRX-2 biologic subcutaneously injected into their bilateral deltoid regions. Study Endpoints: INSPIRE is now enrolling patients at 12 selected institutions in the United States. The primary endpoint of INSPIRE is event-free survival (EFS). Secondary endpoints include overall survival (OS) and safety as assessed by the incidence and severity of adverse events. Exploratory endpoints include changes in tumor size and histologic differences between pre- and post-treatment specimens in lymphocytic infiltration, assessed by both cell-surface marker expression (Perkin Elmer multiplex IHC) and immune cell gene signatures (NanoString). Conclusion: With enrollment of up to 200 patients, the randomized INSPIRE trial provides the opportunity to assess the ability of the IRX-2 regimen to improve EFS and OS by inhibiting tumor-mediated immunosuppression. Analysis of the exploratory endpoints will generate data to better describe the mechanism of action of the IRX-2 regimen and provide insight into the differences between inflammatory and non-inflammatory responses to SCCs of the oral cavity. Citation Format: Gregory T. Wolf, Mihir Patel, Audrey Erman, Jason G. Newman, Greg Krempl, Jorge Nieva, R. Bryan Bell, Michael Kaplan, Dennis Kraus, Jeffrey Moyer, Aru Panwar, Joseph Valentino. The INSPIRE trial: A randomized trial of neoadjuvant and adjuvant therapy with the IRX-2 regimen in patients with newly diagnosed stage II, III, or IVa squamous cell carcinoma of the oral cavity [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 31.