Publications by authors named "Robert L Foote"

140 Publications

Survival outcomes in locally advanced cutaneous squamous cell carcinoma presenting with clinical perineural invasion alone.

Head Neck 2021 Feb 28. Epub 2021 Feb 28.

Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Background: Cutaneous squamous cell carcinomas (CSCC) involving the head and neck are common, but initial presentation or recurrence limited to the cranial nerves is rare.

Methods: We conducted a retrospective study of 21 patients with clinical perineural invasion (PNI) from CSCC and no measurable disease by RECIST 1.1. Patients treated with radiotherapy or chemoradiotherapy were included.

Results: The median time from symptom onset until diagnosis was 13.0 months (2.6-83.1). All patients received radiotherapy. Fourteen received concurrent systemic therapy. The median follow-up time was 30.5 months (1.1-106.0). Ten patients recurred, with the majority being locoregional. The 2-year overall survival rate was 85%. The median progression-free survival (PFS) was 21.5 months with an estimated 2-year PFS of 44.5% (95%CI: 22.3-66.8).

Conclusions: CSCCs with clinical PNI alone are difficult to diagnose and can have a long interval between appearance of symptoms and diagnosis. They can successfully be treated with chemoradiotherapy. However, many patients still suffer from locoregional recurrences.
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http://dx.doi.org/10.1002/hed.26661DOI Listing
February 2021

Risk groups of laryngeal cancer treated with chemoradiation according to nomogram scores - A pooled analysis of RTOG 0129 and 0522.

Oral Oncol 2021 Feb 25;116:105241. Epub 2021 Feb 25.

Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, United States.

Objectives: To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC).

Material And Methods: Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively.

Results: The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome.

Conclusions: We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105241DOI Listing
February 2021

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

Int J Radiat Oncol Biol Phys 2020 Dec 23. Epub 2020 Dec 23.

Division of Radiation Oncology, University of Tennessee, Knoxville, Tennessee. Electronic address:

Purpose: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273.

Methods And Materials: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods.

Results: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03).

Conclusions: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.021DOI Listing
December 2020

Estimating the Number of Patients Eligible for Carbon Ion Radiotherapy in the United States.

Int J Part Ther 2020 5;7(2):31-41. Epub 2020 Nov 5.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA.

Purpose: Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality with potential advantages over conventional photon-based therapy, including exhibiting a Bragg peak and greater relative biological effectiveness, leading to a higher degree of cell kill. Currently, 13 centers are treating with CIRT, although there are no centers in the United States. We aimed to estimate the number of patients eligible for a CIRT center in the United States.

Materials And Methods: Using the National Cancer Database, we analyzed the incidence of cancers frequently treated with CIRT internationally (glioblastoma, hepatocellular carcinoma, cholangiocarcinoma, locally advanced pancreatic cancer, non-small cell lung cancer, localized prostate cancer, soft tissue sarcomas, and specific head and neck cancers) diagnosed in the United States in 2015. The percentage and number of patients likely benefiting from CIRT was estimated with inclusion criteria from clinical trials and retrospective studies, and that ratio was applied to 2019 cancer statistics. An adaption correction rate was applied to estimate the potential number of patients treated with CIRT. Given the high dependency on prostate and lung cancers and the uncertain adoption of CIRT in those diseases, the data were then reanalyzed excluding those diagnoses.

Results: Of the 1 127 455 new cases of cancer diagnosed in the United States in 2015, there were 213 073 patients (18.9%) eligible for treatment with CIRT based on inclusion criteria. When applying this rate and the adaption correction rate to the 2019 incidence data, an estimated 89 946 patients (42.2% of those fitting inclusion criteria) are eligible for CIRT. Excluding prostate and lung cancers, there were an estimated 8922 patients (10% of those eligible for CIRT) eligible for CIRT. The number of patients eligible for CIRT is estimated to increase by 25% to 27.7% by 2025.

Conclusion: Our analysis suggests a need for CIRT in the United States in 2019, with the number of patients possibly eligible to receive CIRT expected to increase during the coming 5 to 10 years.
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http://dx.doi.org/10.14338/IJPT-19-00079.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707324PMC
November 2020

The Importance of Verification CT-QA Scans in Patients Treated with IMPT for Head and Neck Cancers.

Int J Part Ther 2020 3;7(1):41-53. Epub 2020 Aug 3.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Purpose: To understand how verification computed tomography-quality assurance (CT-QA) scans influenced clinical decision-making to replan patients with head and neck cancer and identify predictors for replanning to guide intensity-modulated proton therapy (IMPT) clinical practice.

Patients And Methods: We performed a quality-improvement study by prospectively collecting data on 160 consecutive patients with head and neck cancer treated using spot-scanning IMPT who underwent weekly verification CT-QA scans. Kaplan-Meier estimates were used to determine the cumulative probability of a replan by week. Predictors for replanning were determined with univariate (UVA) and multivariate (MVA) Cox model hazard ratios (HRs). Logistic regression was used to determine odds ratios (ORs).  < .05 was considered statistically significant.

Results: Of the 160 patients, 79 (49.4%) had verification CT-QA scans, which prompted a replan. The cumulative probability of a replan by week 1 was 13.7% (95% confidence interval [CI], 8.82-18.9), week 2, 25.0% (95% CI, 18.0-31.4), week 3, 33.1% (95% CI, 25.4-40.0), week 4, 45.6% (95% CI, 37.3-52.8), and week 5 and 6, 49.4% (95% CI, 41.0-56.6). Predictors for replanning were sinonasal disease site (UVA: HR, 1.82,  = .04; MVA: HR, 3.64,  = .03), advanced stage disease (UVA: HR, 4.68,  < .01; MVA: HR, 3.10,  < .05), dose > 60 Gy equivalent (GyE; relative biologic effectiveness, 1.1) (UVA: HR, 1.99,  < .01; MVA: HR, 2.20,  < .01), primary disease (UVA: HR, 2.00 versus recurrent,  = .01; MVA: HR, 2.46,  = .01), concurrent chemotherapy (UVA: HR, 2.05,  < .01; MVA: not statistically significant [NS]), definitive intent treatment (UVA: HR, 1.70 versus adjuvant,  < .02; MVA: NS), bilateral neck treatment (UVA: HR, 2.07,  = .03; MVA: NS), and greater number of beams (5 beam UVA: HR, 5.55 versus 1 or 2 beams,  < .02; MVA: NS). Maximal weight change from baseline was associated with higher odds of a replan (≥3 kg: OR, 1.97,  = .04; ≥ 5 kg: OR, 2.13,  = .02).

Conclusions: Weekly verification CT-QA scans frequently influenced clinical decision-making to replan. Additional studies that evaluate the practice of monitoring IMPT-treated patients with weekly CT-QA scans and whether that improves clinical outcomes are warranted.
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http://dx.doi.org/10.14338/IJPT-20-00006.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574830PMC
August 2020

Human papillomavirus oropharynx carcinoma: Aggressive de-escalation of adjuvant therapy.

Head Neck 2021 Jan 23;43(1):229-237. Epub 2020 Sep 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Background: Aggressive dose de-escalated adjuvant radiation therapy (RT) in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC).

Methods: Patients with HPV(+)OPSCC on a phase II clinical trial of primary surgery and neck dissection followed by dose de-escalated RT (N = 79) were compared with a cohort of patients who received standard adjuvant therapy (N = 115). Local recurrence-free, regional recurrence-free, distant metastases-free survival, and progression-free survival (PFS) were assessed.

Results: Of 194 patients, 23 experienced progression at a median of 1.1 years following surgery (interquartile range [IQR] 0.7-2.0; range 0.3-5.4); 10 patients in the de-escalated cohort and 13 patients in the standard cohort. The 3-year PFS rate for the de-escalated cohort was 87%, and in the standard cohort was 90% (hazard ratio [HR] 1.18, 95% confidence interval (CI) [0.50-2.75]).

Conclusion: Patients with HPV(+)OPSCC who undergo surgical resection and neck dissection and meet criteria for adjuvant therapy can undergo aggressive dose de-escalation of RT without increasing risk of progression locally, regionally or at distant sites.
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http://dx.doi.org/10.1002/hed.26477DOI Listing
January 2021

T cell fraction impacts oncologic outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma.

Oral Oncol 2020 12 23;111:104894. Epub 2020 Jul 23.

Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Background: We investigated T cell clonality (TCC) and T cell fraction (TCF) in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls].

Methods: This nested case-control study included patients undergoing intent-to-cure surgery ± adjuvant therapy from 6/1/2007-10/3/2016. Patients experiencing local/regional/distant disease (progressors), and a consecutive sample of non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and number of metastatic lymph nodes. We performed imunosequencing of the CDR3 regions of human TCRβ chains.

Results: 34 progressors and 65 non-progressors were included. There was no statistically significant difference in baseline TCF (range: 0.039-1.084) and TCC (range: 0.007-0.240) (p > 0.05). Female sex was associated with higher TCF (p = 0.03), while extranodal extension (ENE) was associated with lower TCF (p = 0.01). There was a positive correlation between tumor size and clonality (R = 0.34, p < 0.01). The strongest predictor of progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66-0.96, p = 0.02). The strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 0.47-1.00, p < 0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score (p < 0.05). Similarly, the strongest predictors of overall survival (OS) were TCF (HR 0.62, 95%CI 0.43-0.91, p = 0.01) and ACE-27 score (p = 0.03). On multivariable modeling, TCF ≥ 0.4 was independently associated with PFS (HR 0.34, 95%CI 0.14-0.85, p = 0.02) while an ACE-27 score of ≥ 2 independently predicted CSS (HR 3.85, 95%CI 1.07-13.85, p = 0.04) and OS (HR 3.51, 95%CI 1.10-11.20, p = 0.03).

Conclusions: In patients with HPV(+)OPSCC, TCF was higher in female patients and those without ENE, suggesting differential immune responses. Lower TCF was significantly and independently associated with disease progression. Better ACE-27 scores appear to predict improved oncologic control.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104894DOI Listing
December 2020

Catheter-free ablation of infarct scar through proton beam therapy: Tissue effects in a porcine model.

Heart Rhythm 2020 Dec 14;17(12):2190-2199. Epub 2020 Jul 14.

Translational Interventional Electrophysiology Laboratory, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Scar-related ventricular arrhythmias are common after myocardial infarction. Catheter ablation can improve prognosis, but the procedure is invasive and results are not always satisfactory. Noninvasive, catheter-free ablation using ionizing radiation has recently gained interest among electrophysiologists, but the tissue effects and physiological outcome have not been fully characterized.

Objective: The purpose of this study was to investigate the structural effects of cardiac scanned pencil beam proton therapy on infarct scar, the time course of imaging biomarkers, arrhythmias, and cardiac function in a porcine model.

Methods: Fourteen infarcted swine underwent proton beam treatment of the scar (40 or 30 Gy) and were followed for up to 30 weeks. Magnetic resonance imaging was performed every 4 weeks.

Results: Treated scar areas showed a significantly lower fraction of surviving myocytes at 30 weeks compared to untreated scar (30.1% ± 18.5% and 59.9% ± 10.1% in treated and untreated infarct, respectively), indicating scar homogenization. Four animals died suddenly during follow-up, all from documented monomorphic ventricular tachycardia. Cardiac function remained stable over the course of the study. Distinct imaging morphologies corresponded to certain tissue dose ranges and time points.

Conclusion: Radioablation of cardiac infarct scar leads to significant homogenization of the scar, replicating the histologic effects of radiofrequency ablation. These changes correspond to distinct imaging morphologies on delayed contrast-enhanced cardiac magnetic resonance imaging, enabling noninvasive confirmation of tissue ablation effects The present study is the first to thoroughly investigate the structural effects of cardiac proton beam therapy in infarcted myocardium.
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http://dx.doi.org/10.1016/j.hrthm.2020.07.011DOI Listing
December 2020

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2020 Jul;18(7):873-898

29National Comprehensive Cancer Network.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
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http://dx.doi.org/10.6004/jnccn.2020.0031DOI Listing
July 2020

Technical Delivery Parameters of 2000 Proton Treatment Courses.

Int J Part Ther 2020 21;6(3):27-34. Epub 2020 Feb 21.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Purpose: To summarize the technical delivery parameters of proton plans delivered at the Mayo Clinic in Rochester, Minnesota.

Materials And Methods: The database of treated patient proton plans was queried to extract field parameters such as gantry angle, patient support angle, minimum and maximum water-equivalent depth (WED) treated, number of layers, field size, patient orientation, and monitor units. The plans were analyzed in aggregate, by disease site, and by fractionation.

Results: There were 2963 proton plans for 2023 distinct treatment sites delivered between June 2015 and September 2018. The mean number of fields per plan was 2.8. The mean number of energy layers per field was 51.9. The mean monitor unit per field was 117.4. The median maximum field dimension was 12.4 cm; 95% of the fields had a maximum dimension < 28.7 cm, and the maximum field dimension was 39.8 cm. The median maximum field WED was 16.4 cm; 95% of the fields reached a maximum WED of ≤ 26.4 cm, and the maximum field WED was 32.4 cm.

Conclusion: A large variety of disease sites were treated using the maximum field size (40 cm) and WED (32.4 cm) capabilities of our half-gantry system.
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http://dx.doi.org/10.14338/IJPT-19-00066.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038916PMC
February 2020

Comparative analysis of acute toxicities and patient reported outcomes between intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) for the treatment of oropharyngeal cancer.

Radiother Oncol 2020 Jun 29;147:64-74. Epub 2020 Mar 29.

Department of Radiation Oncology, Mayo Clinic, Rochester, USA. Electronic address:

Background And Purpose: IMPT improves normal tissue sparing compared to VMAT in treating oropharyngeal cancer (OPC). Our aim was to assess if this translates into clinical benefits.

Materials And Methods: OPC patients treated with definitive or adjuvant IMPT or VMAT from 2013 to 2018 were included. All underwent prospective assessment using patient-reported-outcomes (PROs) (EORTC-QLQ-H&N35) and provider-assessed toxicities (CTCAEv4.03). End-of-treatment and pretreatment scores were compared. PEG-tube use, hospitalization, and narcotic use were retrospectively collected. Statistical analysis used the Wilcoxon Rank-Sum Test with propensity matching for PROs/provider-assessed toxicities, and t-tests for other clinical outcomes.

Results: 46 IMPT and 259 VMAT patients were included; median follow-up was 12 months (IMPT) and 30 months (VMAT). Baseline characteristics were balanced except for age (p = 0.04, IMPT were older) and smoking (p < 0.01, 10.9% IMPT >20PYs, 29.3% VMAT). IMPT was associated with lower PEG placement (OR = 0.27; 95% CI: 0.12-0.59; p = 0.001) and less hospitalization ≤60 days post-RT (OR = 0.21; 95% CI:0.07-0.6, p < 0.001), with subgroup analysis revealing strongest benefits in patients treated definitively or with concomitant chemoradiotherapy (CRT). IMPT was associated with a relative risk reduction of 22.3% for end-of-treatment narcotic use. Patients reported reduced cough and dysgeusia with IMPT (p < 0.05); patients treated definitively or with CRT also reported feeling less ill, reduced feeding tube use, and better swallow. Provider-assessed toxicities demonstrated less pain and mucositis with IMPT, but more mucosal infection.

Conclusion: IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT.
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http://dx.doi.org/10.1016/j.radonc.2020.03.010DOI Listing
June 2020

Risk of internal carotid artery stenosis or occlusion after single-fraction radiosurgery for benign parasellar tumors.

J Neurosurg 2019 Oct 25:1-8. Epub 2019 Oct 25.

Departments of1Neurologic Surgery.

Objective: Stereotactic radiosurgery (SRS) is an accepted treatment option for patients with benign parasellar tumors. Here, the authors' objective was to determine the risk of developing new or progressive internal carotid artery (ICA) stenosis or occlusion after single-fraction SRS for cavernous sinus meningioma (CSM) or growth hormone-secreting pituitary adenoma (GHPA).

Methods: The authors queried their prospectively maintained registry for patients treated with single-fraction SRS for CSM or GHPA in the period from 1990 to 2015. Study criteria included no prior irradiation and ≥ 12 months of post-SRS radiological follow-up. Pre-SRS grading of ICA involvement was applied according to the 1993 classification schemes of Hirsch for CSM or Knosp for GHPA.

Results: The authors conducted a retrospective review of 283 patients, 155 with CSMs and 128 with GHPAs. Ninety-three (60%) CSMs were Hirsch category 2 and 3 tumors; 97 (76%) GHPAs were Knosp grade 2-4 tumors. Median follow-up after SRS was 6.6 years (IQR 1-24.9 years). No GHPA or category 1 CSM developed ICA stenosis or occlusion. Three (5.2%) patients with category 2 CSMs had asymptomatic ICA stenosis (n = 2) or occlusion (n = 1); 1 (1.1%) category 2 CSM patient had transient ischemic symptoms. Five (14.3%) category 3 CSMs progressed to ICA occlusion (4 asymptomatic, 1 symptomatic). The median time to stenosis/occlusion was 4.8 years (IQR 1.8-7.6). Five- and 10-year risks of ICA stenosis/occlusion in category 2 and 3 CSM patients were 7.5% and 12.4%, respectively. Five- and 10-year risks of ischemic stroke from ICA stenosis/occlusion in category 2 and 3 CSM patients were both 1.2%. Multivariate analysis showed patient age (HR 0.92, 95% CI 0.86-0.98, p = 0.01), meningioma pathology (HR and 95% CI not defined, p = 0.03), and pre-SRS carotid category (HR 4.51, 95% CI 1.77-14.61, p = 0.004) to be associated with ICA stenosis/occlusion. Internal carotid artery stenosis/occlusion was not related to post-SRS tumor growth (HR and 95% CI not defined, p = 0.41).

Conclusions: New or progressive ICA stenosis/occlusion was common after SRS for CSM but was not observed after SRS for GHPA, suggesting a tumor-specific mechanism unrelated to radiation dose. Pre-SRS ICA encasement or constriction increases the risk of ICA stenosis/occlusion; however, the risk of ischemic complications is very low.
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http://dx.doi.org/10.3171/2019.8.JNS191285DOI Listing
October 2019

A Phase 2 Study of Pembrolizumab Combined with Chemoradiotherapy as Initial Treatment for Anaplastic Thyroid Cancer.

Thyroid 2019 11;29(11):1615-1622

Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.

Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival (OS) of ∼6 months. We previously reported high PD-1/PDL-1 staining in ATC, raising the possibility of the productive application of the immunotherapeutic pembrolizumab. However, having found pembrolizumab to anecdotally have limited single-agent activity in ATC, we sought to alternatively define whether pembrolizumab might synergistically combine with chemoradiotherapy as initial ATC therapy. An investigator-initiated therapeutic phase 2 trial of pembrolizumab, 200 mg intravenously (IV) every 3 weeks, combined with chemoradiotherapy (docetaxel/doxorubicin, 20 mg/m each IV weekly plus volumetric modulated arc therapy) was initiated as frontline therapy (with or without surgery) in ATC to assess efficacy and toxicities. Six-month OS was selected as the primary endpoint using a Simon's optimal design with interim analysis (targeting accrual of 25 patients; Cohort A: prior resection, Cohort B: no resection). Based on a prior patient cohort-treated similarly, but without pembrolizumab, the design was such that, if 6-month true survival is 75%, the probability of declaring the approach worthy of further pursuit would be 91%. Three patients were enrolled, two with rapidly enlarging unresectable neck masses. Early tumor responses were favorable in all three, and all three satisfactorily completed: intended radiotherapy, preceding and radiotherapy-concurrent pembrolizumab, and concurrent chemoradiotherapy. However, all three patients died <6 months following therapy initiation-one from pulmonary metastases and two from otherwise unexpected fatal pulmonary complications occurring subsequent to chemoradiotherapy completion-prompting study closure. Although initially tolerated and effective in terms of locoregional disease control, disappointing survival outcomes compared with historical controls raise uncertainty that the piloted approach merits further pursuit in ATC.
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http://dx.doi.org/10.1089/thy.2019.0086DOI Listing
November 2019

Reply to A.S. Garden.

J Clin Oncol 2019 12 26;37(36):3559-3560. Epub 2019 Sep 26.

Daniel J. Ma, MD; Katharine A. Price, MD; and Eric J. Moore, MD, Mayo Clinic, Rochester, MN; Samir H. Patel, MD and Michael L. Hinni, MD, Mayo Clinic, Phoenix, AZ; Joaquin J. Garcia, MD; Darlene E. Graner, SLPD; Michelle Neben-Wittich, MD; Yolanda I. Garces, MD; Ashish V. Chintakuntlawar, MBBS, PhD; Daniel L. Price, MD; Kathryn M. Van Abel, MD; Jan L. Kasperbauer, MD; and Jeffrey R. Janus, MD, Mayo Clinic, Rochester, MN; Mark Waddle, MD, Mayo Clinic, Jacksonville, FL; Robert C. Miller, MD, University of Maryland School of Medicine, Baltimore, MD; and Satomi Shiraishi, PhD; Robert W. Mutter, MD; Kimberly S. Corbin, MD; Sean S. Park, MD, PhD; and Robert L. Foote, MD, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1200/JCO.19.02144DOI Listing
December 2019

N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial.

Mayo Clin Proc 2019 09 9;94(9):1814-1824. Epub 2019 Aug 9.

Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, AZ. Electronic address:

Objective: To determine whether N-acetylcysteine rinse was safe and could improve thickened secretions and dry mouth during and after radiotherapy.

Patients And Methods: We designed a prospective pilot double-blind, placebo-controlled randomized clinical trial (Alliance MC13C2). Adult patients (age ≥18 years) were enrolled if they underwent chemoradiotherapy (≥60 Gy). Patients initiated testing rinse within 3 days of starting radiotherapy. With swish-and-spit, they received 10% N-acetylcysteine (2500 mg daily) or placebo rinse solution 5 times daily during radiotherapy and 2 weeks postradiotherapy. The primary aim was to evaluate N-acetylcysteine in improvement of saliva viscosity with the Groningen Radiotherapy-Induced Xerostomia questionnaire. Secondary aims included evaluating xerostomia improvement by the same questionnaire and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-35 Questions survey and adverse-event profiles. The type I error rate was 20%.

Results: Thirty-two patients undergoing chemoradiotherapy were enrolled. Baseline characteristics were balanced for placebo (n=17) and N-acetylcysteine (n=15). N-acetylcysteine was better for improving sticky saliva (area under curve, P=.12). Scores of multiple secondary end points favored N-acetylcysteine, including sticky saliva daytime (P=.04), daytime and total xerostomia (both P=.02), pain (P=.18), and trouble with social eating (P=.15). Repeated measures models confirmed the findings. Taste was a major dissatisifer for N-acetylcysteine rinse; however, both testing rinses were safe and well tolerated overall.

Conclusion: Our pilot data showed that N-acetylcysteine rinse was safe and provided strong evidence of potential efficacy for improving thickened saliva and xerostomia by patient-reported outcome. A confirmatory phase 3 trial is required.

Trial Registration: clinicaltrials.gov Identifier: NCT02123511.
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http://dx.doi.org/10.1016/j.mayocp.2019.03.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742495PMC
September 2019

Impact of cochlear modiolus dose on hearing preservation following stereotactic radiosurgery for non-vestibular schwannoma neoplasms of the lateral skull base: a cohort study.

J Neurosurg 2019 Jul 12:1-6. Epub 2019 Jul 12.

Departments of1Neurologic Surgery.

Objective: Radiation dose to the cochlea has been proposed as a key prognostic factor in hearing preservation following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). However, understanding of the predictive value of cochlear dose on hearing outcomes following SRS for patients with non-VS tumors of the lateral skull base (LSB) is incomplete. The authors investigated rates of hearing loss following high-dose SRS in patients with LSB non-VS lesions compared with patients with VS.

Methods: Patients with LSB meningioma or jugular paraganglioma and serviceable pretreatment hearing who underwent SRS treatment during 2007-2016 and received a modiolus dose > 5 Gy were included in a retrospective cohort study, along with a similarly identified control group of consecutive patients with sporadic VS.

Results: Sixteen patients with non-VS tumors and a control group of 43 patients with VS met study criteria. Serviceable hearing, defined as American Academy of Otololaryngology-Head and Neck Surgery class A/B, was maintained in 13 non-VS versus 23 VS patients (81% vs 56%, p = 0.07). All 3 instances of hearing loss in non-VS patients were observed in cerebellopontine angle (CPA) meningiomas. Non-VS with preserved hearing had a median modiolus dose of 6.9 Gy (range 5.7-19.2 Gy), versus 7.4 Gy (range 5.4-7.6 Gy) in those patients with post-SRS hearing loss (p = 0.53). Sporadic VS patients received an overall median modiolus point-dose of 6.8 Gy (range 5.4-11.7 Gy).

Conclusions: The modiolus dose threshold of 5 Gy does not predict hearing loss in patients with non-VS tumors undergoing SRS, suggesting that dosimetric parameters derived from VS may not be applicable to this population. Differential rates of hearing loss appear to vary by pathology, with paragangliomas and petroclival meningiomas demonstrating decreased risk of hearing loss compared to CPA meningiomas that may directly compress the cochlear nerve similarly to VS.
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http://dx.doi.org/10.3171/2019.4.JNS19201DOI Listing
July 2019

More II It than Meets the Eye: Outcomes After Single-Fraction Stereotactic Radiosurgery in a Case Series of Low-Grade Arteriovenous Malformations.

Oper Neurosurg (Hagerstown) 2020 02;18(2):136-144

Department of Neurological Surgery, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.

Background: Surgical resection is typically cited as the optimal treatment of patients with Spetzler-Martin Grade I-II arteriovenous malformation (AVM).

Objective: To report our experience with single-fraction stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I-II AVM.

Methods: A prospectively maintained registry was reviewed for patients with nonsyndromic Spetzler-Martin Grade I-II AVM having SRS from 1990 to 2011. Patients with <24 mo of follow-up or prior radiotherapy/SRS were excluded, resulting in a study population of 173 patients. Actuarial analysis was performed using the Kaplan-Meier method, and Cox proportional hazards modeling was performed with excellent outcomes (obliteration without new deficits) as the dependent variable.

Results: Median post-SRS follow-up was 68 mo (range, 24-275). AVM obliteration was achieved in 132 (76%) after initial SRS. Eleven additional patients achieved obliteration after repeat SRS for an overall obliteration rate of 83%. The rate of obliteration was 60% at 4 yr and 78% at 8 yr. Post-SRS hemorrhage occurred in 7 patients (4%), resulting in 3 minor deficits (2%) and 1 death (<1%). Radiation-induced complications occurred in 5 patients (3%), resulting in minor deficits only. One hundred and thirty-seven patients (79%) had excellent outcomes at last follow-up.

Conclusion: SRS is a safe and effective treatment for patients with Spetzler-Martin Grade I-II AVM. Selection bias is likely a contributing factor to explain the superior outcomes generally noted in reported series of microsurgery for patients with low grade AVM.
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http://dx.doi.org/10.1093/ons/opz153DOI Listing
February 2020

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma.

J Clin Oncol 2019 08 4;37(22):1909-1918. Epub 2019 Jun 4.

1Mayo Clinic, Rochester, MN.

Purpose: The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL).

Patients And Methods: MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL.

Results: Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement.

Conclusion: Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.
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http://dx.doi.org/10.1200/JCO.19.00463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098832PMC
August 2019

Left ventricular function after noninvasive cardiac ablation using proton beam therapy in a porcine model.

Heart Rhythm 2019 11 18;16(11):1710-1719. Epub 2019 Apr 18.

Translational Interventional Electrophysiology Laboratory, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Noninvasive cardiac ablation of ventricular tachycardia (VT) using radiotherapy has recently gained interest among electrophysiologists. The effects of left ventricular (LV) ablative radiation treatment on global LV function and volumes are unknown.

Objective: The purpose of this study was to investigate the effects of noninvasive ablation on LV function over time.

Methods: Twenty domestic swine underwent proton beam treatment of LV sites in a dose-finding design and were followed for up to 40 weeks by cardiac magnetic resonance imaging at 4-week intervals. Doses investigated were either 40 Gy at 1 site (n = 8) or 30 Gy at 2 sites (n = 4) in the low-dose group and 40 Gy at 3 sites (n = 8) in the high-dose group.

Results: LV mean dose (13.2 ± 1.8 Gy vs 4.6 ± 1.8 Gy) and the volume receiving at least 20 Gy (V) (24.7% ± 4.8% vs 6.4% ± 3.0%) differed significantly between groups. Dose-dependent effects on left ventricular ejection fraction (LVEF) and LV end-diastolic volume became manifest about 3 months after treatment. LVEF decline was correlated to mean dose (correlation coefficient ρ = -0.69; P = .008) and V (ρ = -0.66; P = .01), as was LV dilation (ρ = 0.72; P = .005; and ρ = 0.75, P = .003 respectively).

Conclusion: Possible adverse effects on LV function, seen about 3 months after treatment, are dose dependent. Therefore, precise target definition and focused energy delivery are paramount in catheter-free ablation.
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http://dx.doi.org/10.1016/j.hrthm.2019.04.030DOI Listing
November 2019

Evaluating the Role of Adjuvant Radiotherapy in the Management of Sacral and Vertebral Chordoma: Results from a National Database.

World Neurosurg 2019 Jul 14;127:e1137-e1144. Epub 2019 Apr 14.

Department of Neurologic Surgery, Mayo Clinic Neuro-Informatics Laboratory, Mayo Clinic, Rochester, Minnesota, USA; Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

Background: Chordomas are slow-growing but locally invasive tumors. The standard of care consists of surgical resection and radiotherapy (RT) when complete resection is not possible. The reported data has reached equivocal results regarding the effect of adding RT to increase patient survival. We investigated the effect of adjuvant RT on patient survival.

Methods: The National Cancer Database was queried for patients with a diagnosis of sacral and vertebral column chordoma from 2004 to 2010. The primary outcome was overall survival, which was assessed using Kaplan-Meier plots. Cox proportional hazards were performed to evaluate the effect of each treatment modality on survival after adjusting for an array of patient demographics, facility type, and tumor characteristics.

Results: The data from 282 patients with chordoma were analyzed; 209 patients (74.1%) had undergone gross total resection (GTR) alone. The median follow-up period for the GTR alone and GTR plus RT groups was 63.4 and 67.6 months, respectively. The mean survival was comparable between patients receiving GTR alone and those receiving adjuvant RT, for both sacral (7.7 and 6.9 years, respectively; P = 0.56) and vertebral chordoma (8.8 and 6.2 years, respectively; P = 0.59). Using Cox proportional hazards, we found that compared with GTR alone, GTR plus adjuvant RT did not add any significant survival benefit, for patients with either sacral chordoma (hazard ratio, 0.55; P = 0.43) or vertebral chordoma (hazard ratio, 7.29; P = 0.23).

Conclusion: Using data from a large national cancer registry, we found that the available evidence is not enough to suggest that the addition of RT offers a survival benefit for patients with sacral and spinal chordoma after GTR. Given the non-negligible complications associated with RT, the balance of benefits and risks must be considered during preoperative tailoring of the treatment decisions.
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http://dx.doi.org/10.1016/j.wneu.2019.04.070DOI Listing
July 2019

Diagnosis and Management of Anaplastic Thyroid Cancer.

Endocrinol Metab Clin North Am 2019 03;48(1):269-284

Division of Medical Oncology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. Electronic address:

Anaplastic thyroid cancer (ATC) is a devastating and usually incurable diagnosis. Clinical and pathologic diagnosis is best assessed at a tertiary center with concentrated ATC expertise. Expeditious multidisciplinary management is recommended for optimal patient outcomes. Based on multiinstitutional and population-based studies, multimodal therapy that includes chemoradiotherapy with surgery (when feasible) is the preferred initial treatment because it is associated with incrementally improved overall survival. In ATC that carries a BRAF V600E somatic mutation, combination therapy with BRAF and MEK inhibitors has shown promise but needs further study. Immunotherapeutic agents in neoadjuvant and metastatic settings are being investigated.
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http://dx.doi.org/10.1016/j.ecl.2018.10.010DOI Listing
March 2019

Utility of adjuvant chemotherapy in patients receiving surgery and adjuvant radiotherapy for primary treatment of esthesioneuroblastoma.

Head Neck 2019 05 10;41(5):1335-1341. Epub 2018 Dec 10.

Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.

Background: Past research established that surgery plus adjuvant radiotherapy (S + AR) improves overall survival (OS) in esthesioneuroblastoma (ENB). However, it is unknown if the addition of adjuvant chemotherapy (AC) further improves survival. The primary objective of this study was to compare survival among patients treated with S + AR alone to patients who underwent S + AR + AC.

Methods: Retrospective review of patient records.

Results: Thirty-eight patients met inclusion criteria for either S + AR or S + AR + AC treatment groups. The S + AR + AC group contained more patients with Kadish stage D disease, dural invasion, and positive histologic margins postsurgery. All S + AR + AC patients received platinum-based regimens, combined with etoposide in 67%. OS and recurrence-free survival did not differ between the two groups, even when restricting the analysis to patients with Kadish stages B and C disease.

Conclusion: Patients who received platinum-based AC did not exhibit improved survival compared to S + AR alone. Further investigation, preferably prospective, into the optimal use of systemic therapy in ENB is warranted.
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http://dx.doi.org/10.1002/hed.25558DOI Listing
May 2019

Treatment outcomes of squamous cell carcinoma of the oral cavity in young adults.

Oral Oncol 2018 12 22;87:43-48. Epub 2018 Oct 22.

Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, AZ, United States. Electronic address:

Objectives: The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger.

Materials And Methods: We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980-2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts.

Results: Median patient age was 35 years (range, 19-40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001).

Conclusion: Young adults with primary OC SCC may be treated with a similar treatment approach as older adults.
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http://dx.doi.org/10.1016/j.oraloncology.2018.10.014DOI Listing
December 2018

Radiation-Related Alterations of Taste Function in Patients With Head and Neck Cancer: a Systematic Review.

Curr Treat Options Oncol 2018 11 9;19(12):72. Epub 2018 Nov 9.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1840 Old Spanish Trail, Box 1150, Houston, TX, 77054, USA.

Opinion Statement: Taste sensation is vital for a healthy body as it influences our food intake, acts as a defense mechanism and elicits pleasure. Majority of the head and neck cancer (HNC) patients undergoing radiotherapy suffer from altered taste function and often complain of inability to taste their food, reduced food intake, and weakness. However, there are not many studies conducted to assess this commonly reported side effect. Furthermore, clinical research on radiotherapy-induced taste alterations has proven to be difficult, considering a lack of reliable and validated study tools for assessing objective and subjective outcomes. Developing standardized tools for assessment of taste function and conducting prospective studies in larger population of HNC is the need of the hour. Taste sensation being critically important for sustenance, we need to focus on ways to preserve it. The physical properties of proton particle enable localization of the radiation dose precisely to the tumor and minimizing the exposure of the adjacent healthy tissues. By using Intensity-Modulated Proton Therapy in HNC patients, we anticipate preserving the taste sensation by reducing the dose of radiation to the taste buds.
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http://dx.doi.org/10.1007/s11864-018-0580-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244914PMC
November 2018

Prospective Immunophenotyping of CD8 T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT.

Int J Radiat Oncol Biol Phys 2019 01 8;103(1):229-240. Epub 2018 Sep 8.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8 T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa).

Methods And Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8 T-cell subpopulations, including tumor-reactive (T), effector memory, central memory (T), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk.

Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the T cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the T cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032).

Conclusions: An increase in the T cell subpopulation was protective against the risk of disease progression, and an increase in the T cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8 T-cell subpopulations and by enhancing their antitumor effect.
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http://dx.doi.org/10.1016/j.ijrobp.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301146PMC
January 2019

Magnitude of benefit for adjuvant radiotherapy following minimally invasive surgery in intermediate to high risk HPV-positive oropharyngeal squamous cell carcinoma.

Oral Oncol 2018 07 6;82:181-186. Epub 2018 Jun 6.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Objective: To determine the outcomes and toxicities of minimally-invasive surgery with adjuvant intensity-modulated radiotherapy +/- chemotherapy (AT) compared to definitive surgical therapy (ST) in a contemporary cohort of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).

Methods: From 2005 to 2013, a consecutive cohort of 190 HPV-positive OPSCC patients was retrospectively reviewed from multi-institutional databases maintained by the Departments of Otorhinolaryngology and Radiation Oncology. A total of 116 AT patients and 42 ST patients with intermediate or high risk pathologic features were included in the final analysis. All patients received minimally invasive surgery. Time to recurrence and time to death from the onset of surgery were evaluated. Toxicity data collected included dysphagia or xerostomia requiring feeding tube placement >6 months, or mandibular osteonecrosis requiring surgery or hyperbaric oxygen.

Results: All AT patients received IMRT to a median dose of 60 Gy. Chemotherapy delivered to 67.2% of AT patients. AT group included more high-risk patients given higher nodal classification (p = 0.005) and extracapsular extension (p = 0.0005). AT improved disease-free survival (HR 2.77, CI 1.22-6.28; p = 0.02) and local-regional control (HR 14.83, CI 3.240-67.839; p = 0.001). Disease-free survival with AT and tumor extracapsular extension was improved when compared to ST (HR of 4.34, CI 1.540-12.213; p = 0.006). Dysphagia or mandibular osteonecrosis toxicity after AT vs. ST of 19.0% vs. 2.4%.

Conclusions: AT improved local-regional control and disease-free survival but was associated with greater toxicity. The recurrence benefit was most pronounced in tumors with extracapsular extension.
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http://dx.doi.org/10.1016/j.oraloncology.2018.05.026DOI Listing
July 2018

Esthesioneuroblastoma with distant metastases: Systematic review & meta-analysis.

Head Neck 2018 10 13;40(10):2295-2303. Epub 2018 May 13.

Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.

Background: The purpose of this study was to determine the clinical outcomes and review the management strategies for metastatic esthesioneuroblastoma.

Methods: We conducted a systematic review and meta-analysis.

Results: Forty-eight studies totaling 118 patients met inclusion criteria. Chemotherapy in combination with surgery and/or radiation exhibited the best overall survival when compared to monotherapy and no treatment (P < .001). However, most patients (66%) received either monotherapy or no therapy. The number and location of metastases among the 3 treatment groups did not significantly differ (P = .85). Treatment modality remained significantly associated with overall survival on multivariable analysis (P < .001). Platinum-based chemotherapy was most commonly utilized but did not provide a survival benefit when compared with all other regimens (P = .88).

Conclusion: Distant metastases with esthesioneuroblastoma portend a poor prognosis. Chemotherapy in combination with surgery and/or radiation was associated with improved overall survival. Further research into the optimal systemic therapeutic regimen for patients with distant metastases is critical.
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http://dx.doi.org/10.1002/hed.25209DOI Listing
October 2018

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018.

J Natl Compr Canc Netw 2018 05;16(5):479-490

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.
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http://dx.doi.org/10.6004/jnccn.2018.0026DOI Listing
May 2018

Protons vs Photons for Brain and Skull Base Tumors.

Semin Radiat Oncol 2018 04;28(2):97-107

Department of Radiation Oncology, Mayo Clinic, Rochester, MN.

The physical characteristics of proton therapy result in steeper dose gradients and superior dose conformality compared to photon therapy. These properties render proton therapy ideal for skull base tumors requiring dose escalation for optimal tumor control, and may also be beneficial for brain tumors as a means of mitigating radiation-related adverse effects. This review summarizes the literature regarding the role of proton therapy compared to photon therapy in the treatment of adult brain and skull base tumors.
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http://dx.doi.org/10.1016/j.semradonc.2017.11.001DOI Listing
April 2018