William M Mendenhall

• University of Florida

Objective: To evaluate the impact of postoperative radiotherapy (PORT) on oncological outcomes in node-negative early-stage oral squamous cell carcinoma (OSCC) with perineural invasion (PNI). Methods: A systematic review and meta-analysis was conducted using the PubMed, EMBASE, and Scopus databases for the period from 2000 to 2024. Studies comparin...

Background Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution. Methods This narrative literature review comprehensively discusses the...

Purpose Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT). Materials and Methods Under an institutional review boa...

Objective There is an inverse relationship between cancer cure and overall treatment time (OTT) in patients treated with surgical resection and radiotherapy (RT). Methods OTT was evaluated based on the reconstruction procedure in 420 patients with oral cavity and larynx cancers treated with surgery and RT between 1991 and 2020. Results With OTT >...

Background Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT). Procedure Using an IRB‐approved prospective outcomes registry, we evaluated patient, tumor, and tre...

Background: Prescription drug monitoring programs (PDMPs) have proliferated due to increasing opioid-related deaths. We evaluated acute opioid use changes for 64 patients treated with highly conformal radiotherapy (RT) following a state-mandated PDMP. Methods: Patients receiving proton therapy (PT) (n=40), intensity-modulated RT (IMRT) (n=14), o...

Purpose Obtaining prior authorization (PA) before treatment is becoming increasingly burdensome in oncology, especially in radiation oncology. Here, we describe the impact of a strategic novel operational PA redesign to shorten authorization time and to improve patient access to cancer care at a large United States academic proton therapy center. W...

Background: Locally recurrent prostate cancer following primary external beam radiotherapy without distant metastasis is a challenging problem, with no current consensus on the optimal management of these patients. Traditional whole-gland salvage treatments offered up to a 50% 5-year disease-free survival rate but with troubling levels of risk for...

Objective: To evaluate lymphovascular invasion as an independent predictor for overall survival in patients with oral cavity squamous cell carcinoma. Study design: Retrospective cohort study. Setting: Multi-center, population-based facilities reporting to the National Cancer Database registry. Methods: The database was accessed to collect da...

Purpose To discuss the role of proton beam therapy (PBT) in the treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Materials and Methods A review of the pertinent literature. Results Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT). The exten...

Background: Recent literature shows that tumor volume (TV) in T3 laryngeal squamous cell carcinoma (LSCC) is associated with response to radiation therapy. The aim of this study was to evaluate the effect of TV on survival outcomes in patients undergoing total laryngectomy (TL). Methods: One hundred and seventeen patients with LSCC undergoing TL...

Proton therapy (PT) is a form of highly conformal external-beam radiotherapy used to mitigate acute and late effects following radiotherapy. Indications for treatment include both benign and malignant skull-base and central nervous system pathologies. Studies have demonstrated that PT shows promising results in minimizing neurocognitive decline and...

Background: To evaluate disease control, toxicities, and variables associated with clinical outcomes for patients with head and neck squamous cell carcinoma and clinical N3 disease (HNSCC N3) treated with definitive chemoradiation therapy. Methods: We performed a retrospective review of patients with HNSCC N3 treated at two high-volume academic...

Objective: To identify best treatment practices by examining outcomes of anal margin cancer patients treated with radiotherapy. Methods: Relevant literature was compared with 38 patients at our institution treated 1979 to 2019 with curative radiotherapy. Median age was 51. Four patients had T1, 22 had T2, and 12 had T3 disease based on the Ameri...

Purpose Benign intracranial meningioma is one of the most common primary brain neoplasms. Proton therapy has been increasingly utilized for nonoperative management of this neoplasm, yet few long-term outcomes studies exist. Methods The medical records of a total of 59 patients with 64 lesions were reviewed under a prospective outcomes tracking pro...

Radiotherapy is the primary treatment modality for nasopharyngeal carcinoma (NPC). Successful curative treatment requires optimal radiotherapy planning and precise beam delivery that maximizes locoregional control while minimizing treatment-related side effects. In this article, we highlight considerations in target delineation, radiation dose, and...

Purpose/Objective(s) The aim of this study was to evaluate patient outcomes and practice patterns among patients treated for non-melanomatous skin cancers of the head and neck with microscopic or clinical perineural invasion (PNI) using radiotherapy (RT) at a single institution. Materials/Methods To determine severe (grade 3+) toxicity and clinica...

Purpose/Objective(s) Owing to the dramatic rise in opiate-related deaths, the use of online prescription drug monitoring programs (PDMPs) concurrent with new laws restricting opiate administration has become commonplace across the U.S. Some oncologists, however, have expressed concerns that they may unintentionally limit treatment access to at-risk...

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing malignancy that originates in the deep layers of the skin. It can be locally aggressive but metastasizes very rarely. DFSP is low grade. If a higher-grade fibrosarcomatous component is present, it should be treated as a soft-tissue sarcoma. Initial misdiagnosis is common, and inexperien...

Introduction Anaplastic thyroid cancer (ATC) is one of the most lethal diseases known to humans with a median survival of 5 months. The American Thyroid Association (ATA) recently published guidelines for the treatment of this dreadful thyroid malignancy. Areas covered This review presents the current therapeutic landscape of this challenging dise...

Background: We report outcomes among patients with T2 and select T3 glottic squamous cell carcinoma (SCC) treated with radiotherapy. Methods: We reviewed T2 and T3 (only paraglottic space invasion) N0 M0 glottic SCC patients treated with curative-intent hypofractionated larynx radiotherapy, with or without concurrent systemic therapy. Results:...

Background: Dose escalation for skull-based malignancies often presents risks to critical adjacent neural structures, including the brainstem. We report the incidence of brainstem toxicity following fractionated high-dose conformal proton therapy and associated dosimetric parameters. Material and methods: We performed a single-institution review...

Benign peripheral non-cranial nerve sheath tumors are rare lesions, including both schwannomas and neurofibromas. These tumors arise from Schwann cells, and may originate from any peripheral, cranial, or autonomic nerve. Most of them are localized and sporadic but multifocal systemic forms can occur. Cervical sympathetic chain, brachial plexus, cer...

Simple Summary Proton therapy is a promising type of radiation therapy used to destroy tumor cells. It has the potential to further improve the outcomes for patients with head and neck cancer since it allows to minimize the radiation dose to vital structures around the tumor, leading to less toxicity. This paper describes the current experience wor...

Objectives To evaluate the difference in overall survival (OS) in patients with retromolar trigone squamous cell carcinoma (RMT SCC) treated with surgery alone versus surgery plus postoperative radiotherapy (PORT) versus surgery plus postoperative chemoradiotherapy (POCRT). Materials and Methods Retrospective cohort study of patients from 1,500 US...

Purpose/Objective(s) The probability of cure after hypofractionated larynx radiotherapy (RT) decreases among patients with T2 glottic cancers with impaired cord mobility. The role of concurrent chemotherapy in this setting is unclear. We report outcomes of patients with T2 (and T3 based on paraglottic space invasion alone) N0 glottic squamous cell...

We evaluated outcomes in 131 patients with cutaneous melanoma (median follow-up, 3.6 years) considered at high risk of recurrence after surgery alone treated with surgery and postoperative radiotherapy. Eligible patients had one or more of the following: recurrence after surgery, positive lymph nodes, extracapsular extension, incomplete regional no...

Background To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. Material and methods We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patien...

Disparate clinical outcomes for pharyngeal squamous cell carcinoma (PSCC) of the oropharynx (OPSCC) and hypopharynx (HPSCC) have been observed in Black compared with White patients. Higher tobacco and alcohol use has been associated with decreased survival in Black patients with PSCC. Higher human papilloma virus (HPV) infection rates, associated w...

Purpose/Objective(s) Pleomorphic adenoma is the most common benign salivary gland tumor. It is primarily treated with definitive surgery. Rarely, radiation therapy can be utilized for recurrent lesions and in other scenarios such as positive margins. There are relatively few studies reporting efficacy and outcomes of pleomorphic adenoma treated wit...

Purpose/Objective(s) There is controversy about the need to target the mucosa of the larynx and hypopharynx during radiotherapy (RT) for squamous cell carcinoma of unknown primary site (SCCA-UP). By 1997, the policy in our department was to target only the oropharynx and nasopharynx in patients with SCCA-UP metastatic to the level II cervical nodes...

Purpose/Objective(s) To compare patient-reported QOL/symptoms between DI IMPT(chemo) and IMRT(chemo) for HPV-OPC. Materials/Methods LCCC1612 is a multi-institutional phase II trial of DI RT(chemo) using 60 Gy/30 fx in 6 wk with weekly concurrent cisplatin, 30 mg/m2 for HPV-OPC. Eligible patients (AJCC 8 ed, T0-3, N0-2, M0, p16+, regardless of smok...

Purpose/Objective(s) To report 10-year outcomes for patients treated with proton therapy for localized prostate cancer. Materials/Methods The 10-year outcomes from a prospective outcome tracking protocol were assessed and reported for 1272 men with localized prostate cancer. Risk groups were classified per NCCN guidelines. Median proton therapy do...

Objective To compare survival outcomes between primary surgery and primary radiation therapy (RT) in patients with human papillomavirus (HPV)–negative oropharyngeal squamous cell carcinoma (OPSCC). Study Design A retrospective observational cohort study. Setting National Cancer Database. Methods A National Cancer Database review was conducted of...

Background: Breast cancer-related lymphedema (BCRL) is a source of postoperative morbidity for breast cancer survivors. Lymphatic microsurgical preventive healing approach (LYMPHA) is a technique used to prevent BCRL at the time of axillary lymph node dissection (ALND). We report the 5-year experience of a breast surgeon trained in LYMPHA and inve...

Objectives: Increasing the percentage of academic faculty who are female and/or an under-represented minority (URM) is a goal in radiation oncology. When studying diversity changes in our University Radiation Oncology Department, we found that increases in resident diversity preceded changes in faculty diversity in every major category. To illustr...

Purpose: To determine factors that influence insurance approval for definitive proton therapy (PT) for prostate cancer. Materials and Methods: Between 2014 and 2018, 1592 insured patients with localized prostate cancer were evaluated and recommended to undergo definitive PT; 547 patients (34.4%) had commercial insurance, whereas 1045 patients (65.6...

Purpose/objectives: There is controversy about the need to target the mucosa of the larynx and hypopharynx during radiotherapy (RT) for squamous cell carcinoma of an unknown primary site (SCCA-UP). By 1997, the policy in our department was to target only the oropharynx and nasopharynx in patients with SCCA-UP metastatic to the level II cervical no...

Purpose To report our experience with the delivery of passively scattered proton therapy in the management of nonmelanoma skin cancers with clinical perineural invasion. Materials and Methods We reviewed the medical records of patients who received definitive or postoperative proton therapy for nonmelanoma skin cancer with clinical perineural inva...

Purpose To evaluate the effectiveness of external-beam proton therapy (PT) on local control and survival in patients with skull-base chordoma. Materials and Methods We reviewed the medical records of patients with skull-base chordoma treated with definitive or adjuvant high-dose PT and updated their follow-up when feasible. We assessed overall sur...

Purpose To report long-term disease control, survival, and toxicity after proton therapy for sinonasal cancer. Patients and Methods We reviewed 143 cases of adults with nonmetastatic sinonasal cancers treated with primary (18%; n = 26) or adjuvant (82%; n = 117) proton therapy. The most common histologies were squamous cell carcinoma (29%; n = 42)...

Proton therapy is a promising but controversial treatment in the management of prostate cancer. Despite its dosimetric advantages when compared with photon radiation therapy, its increased cost to patients and insurers has raised questions regarding its value. Multiple prospective and retrospective studies have been published documenting the effica...

A correction to this paper has been published: https://doi.org/10.1007/s11060-021-03740-8

Cancers of the head and neck region often present with nodal involvement. There is a long‐standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guide...

Up to 85% of the patients with nasopharyngeal carcinoma present with regional nodal metastasis. Although excellent nodal control is achieved with radiotherapy, a thorough understanding of the current TNM staging criteria and pattern of nodal spread is essential to optimize target delineation and minimize unnecessary irradiation to adjacent normal t...

Purpose Postprostatectomy radiation improves disease control, but limited data exist regarding outcomes, toxicities, and patient-reported quality of life with proton therapy. Method and Materials The first 102 patients who were enrolled on an outcome tracking protocol between 2006 and 2017 and treated with double-scattered proton therapy after pro...

Electrochemotherapy (ECT) is a local ablative treatment that is based on the reversible electroporation and intracellular accumulation of hydrophilic drug molecules, which greatly increases their cytotoxicity. In mucosal head and neck cancer (HNC), experience with ECT is limited due to the poor accessibility of tumors. In order to review the experi...

Purpose Re-irradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging as prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lac...

Background & Purpose Dose escalation for skull-based chordoma and chondrosarcoma can put critical adjacent structures at risk, specifically the anterior optic pathway. We report the incidence of vision loss following high-dose conformal proton-based radiotherapy. Materials and Methods We reviewed patients with skull-base chordoma or chondrosarcoma...

The aim of this review is to analyze the latest trends in the management of non-vestibular skull base and intracranial schwannomas in order to optimize tumor control and quality of life. Non-vestibular cranial nerve schwannomas are rare lesions, representing 5–10% of cranial nerve schwannomas. Management decisions should be individualized depending...

Purpose Post-radiation therapy salvage surgeries are challenging for surgeons due to tissue fibrosis. The woody hardness classification is valuable in differentiating the degree of neck stiffness, but its clinical utility has not been evaluated. We applied it to patients undergoing salvage laryngectomies to study the impact of woody hardness on pos...

Purpose Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) treatment outcomes are re-defining management. Traditional margins, the role of extranodal extension (ENE) and adjuvant treatment intensity continue to be debated. This study aimed to determine the impact of margins, ENE and adjuvant therapy on survival fol...

Purpose To compare the planning target volume (PTV) margins needed for prostate patients who have used hydrogel spacer or rectal balloon during proton treatments. Method Total of 190 prostate patients treated with proton therapy during 2017 were selected for this study. Of these patients, 96 had hydrogel spacer injection and 94 patients had only r...

We updated the University of Florida experience treating head and neck small cell carcinoma. Eight patients received a median 67.7 Gy between 1989 and 2017. The 2-year rates of local, regional, distant, and disease control were 73%, 60%, 33%, and 13%, respectively. The 2-year overall survival rate was 38%; median survival was 1.4 years. The longest...

Objectives: Increasing diversity in radiation oncology with respect to sex, under-represented minorities (URMs), and people of color is a major objective of our profession. The purpose of this project is to plot diversity percentages in our residency program over the past 52 years and explain major causes for change when identified. Materials and...

Background Patients with metastases in the lymph nodes of the neck and no obvious primary tumor, neck cancer with unknown primary (NCUP), represent a management challenge. A majority of patients have metastatic squamous cell carcinoma (SCC), although other histologies do occur. Methods We comprehensively reviewed the literature, compared available...

Study Design Literature review. Objective To review the current role of radiotherapy (RT) in the management of oral cavity squamous cell carcinoma (SCC). Methods Review of selected literature. Results T1-T2N0 SCCs may be treated with either RT alone or surgery with a high likelihood of cure. The pendulum swung toward surgery with postoperative R...

IntroductionAs a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of radiation-induced sarcomas of the head and neck (RISHN) may be increasing. The main objective of this systematic review was to determine the existing evidence on the frequency...

Introduction: Our purpose is to review the role radiotherapy (RT) in the treatment of glottic squamous cell carcinoma (SCC). Methods: A concise review of the pertinent literature. Results: RT cure rates are Tis- T1N0, 90% to 95%; T2N0, 70% to 80%; low-volume T3-T4a, 65% to 70%. Concomitant cisplatin is given for T3-T4a SCCs. Severe complicatio...

Background The aim of the study was to update our experience treating patients with glottic carcinoma in situ (CIS) with curative radiotherapy (RT). Methods Fifty patients received continuous‐course RT using once‐daily fractionation. Twenty‐eight (56%) had recurrent or persistent CIS after resection. Median total dose was 63.0 Gy; median dose per...

Objective: Definitive radiotherapy (RT) with or without surgery is the standard of care for solitary plasmacytoma. Here, we report clinical outcomes for this rare malignant neoplasm. Patients and methods: We retrospectively reviewed the medical records of adults with solitary plasmacytoma treated with definitive RT between 1963 and 2015 at a sin...

There is no standardized format for presenting and discussing the results of a radiotherapy dosimetry comparison study. The purpose of this report is to describe a format that we have found useful in evaluating plans in our department and in reviewing studies from other groups.

Objective: Surgery followed by postoperative radiation therapy (RT) is the standard of care for soft tissue sarcomas (STS) of the head and neck that are high grade or have close or positive margins. Methods: The authors retrospectively reviewed adult patients with head and neck STS treated with RT at a single institution between 1981 and 2017. A...

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,...

Background Recent historical management of oropharyngeal squamous cell carcinoma typically includes radiotherapy with/without chemotherapy. Novel surgical techniques such as robotic surgery have made primary surgery more frequent; however, postoperative radiotherapy may be recommended. We aimed to assess adherence to guidelines for postoperative th...

The 2019 novel coronavirus disease (COVID‐19) is a highly contagious zoonosis produced by SARS‐CoV‐2 that is spread human‐to‐human by respiratory secretions. It was declared by the WHO as a public health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an...

Background Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the...

Objective: To determine the rate and risk factors for osteoradionecrosis (ORN) in osseous free flaps after postoperative radiation therapy (PORT). To describe the treatment of free flap ORN. Methods: Seventy-four patients undergoing osseous free flap reconstruction were analyzed. Thirty-eight completed PORT. Patients were followed for ≥6 months....

PURPOSE Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. METHOD...

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemoth...

Non-melanomatous skin cancer (NMSC) is the most common malignancy worldwide. Perineural invasion (PNI) is an uncommon (<5%), high-risk feature observed with NMSC more commonly seen in those with squamous cell carcinoma. One-third of these patients will have clinical PNI, which refers to tumor cell invasion extensive enough to cause clinically detec...

PIK3CA is the most frequently mutated gene in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-asso...

We evaluated treatment outcomes following definitive or adjuvant high-dose, image-guided proton therapy in 91 patients with skull-base chordoma enrolled on a prospective outcomes tracking protocol and treated between February 2007 and February 2018. The median age was 53 years (range, 22–78 years). Patients received passively scattered 3-dimensiona...

Background: Larynx preservation with chemoradiotherapy (CRT) is used frequently in the treatment of locally advanced hypopharyngeal/laryngeal squamous cell carcinoma (LSCC). Multiple large retrospective analyses have shown that CRT is associated with worse overall survival (OS) compared to total laryngectomy (TL) in patients with T4a disease. Burg...

Background: To report our institution's experience treating soft palate squamous cell carcinoma with radiotherapy alone or combined with adjuvant chemotherapy and/or neck dissection for residual disease. Methods: We analyzed 159 patients treated curatively between 1963 and 2016. Median follow-up was 4 years. Results: The 5-year local control r...

Purpose To determine factors that influence insurance approval for breast cancer patients for whom adjuvant proton therapy (PT) is recommended. Patients and Methods We sought to identify factors associated with PT approval among 131 insured patients seen in consultation between 2014 and 2018 and recommended adjuvant PT. Insurance status included:...