Publications by authors named "M L Gillison"

188 Publications

Infection with Human Papilloma Virus (HPV) and risk of subsites within the oral cancer.

Cancer Epidemiol 2021 Sep 9;75:102020. Epub 2021 Sep 9.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA. Electronic address:

Background: The aim of this study was to investigate the relationship between high-risk genotypes of Human Papilloma Virus (HPV) and cancer of different subsites of the oral cavity.

Material And Methods: A pooled analysis of five studies included on the International Head and Neck Cancer Epidemiology (INHANCE) Consortium was conducted. HPV 16 and HPV 18 were considered. Adjusted odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for HPV and each oral cavity subsites were simultaneously estimated using multinomial logistic regression models.

Results: The analysis included 1157 cases and 3272 controls. This study showed a slightly higher prevalence of HPV infection among oral cancer cases than controls. In particular, an increased risk of other and not otherwise specified (NOS) sites within the oral cavity, oral tongue, palate and floor of mouth cancer was observed for overall HPV16 positivity (OR = 1.66, 95 % CI: 1.01-2.72; OR = 1.97, 95 % CI: 1.36-2.85; OR = 2.48, 95 % CI: 1.50-4.11; OR = 2.71, 95 % CI: 1.06-6.95, respectively). In particular, HPV16E7 was related to cancer of floor of mouth, oral cavity NOS and palate (OR = 2.71, 95 % CI: 1.06-6.95; OR = 3.32, 95 % CI:1.53-7.19; OR = 3.34, 95 % CI:1.38-8.06). Results were inconsistent for HPV18 due to low prevalence of infection.

Conclusion: Our study suggests that HPV16 infection may increase the risk of developing floor of mouth, gum, tongue, and palate cancers.

Clinical Relevance: Subjects with HPV infection have a higher risk of cancer from all sites of the oral cavity.
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http://dx.doi.org/10.1016/j.canep.2021.102020DOI Listing
September 2021

Proton Beam Therapy for Head and Neck Carcinoma of Unknown Primary: Toxicity and Quality of Life.

Int J Part Ther 2021 25;8(1):234-247. Epub 2021 Jun 25.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: Proton radiation therapy (PRT) may offer dosimetric and clinical benefit in the treatment of head and neck carcinoma of unknown primary (HNCUP). We sought to describe toxicity and quality of life (QOL) in patients with HNCUP treated with PRT.

Patients And Methods: Toxicity and QOL were prospectively tracked in patients with HNCUP from 2011 to 2019 after institutional review board approval. Patients received PRT to the mucosa of the nasopharynx, oropharynx, and bilateral cervical lymph nodes with sparing of the larynx and hypopharynx. Patient-reported outcomes were tracked with the MD Anderson Symptom Inventory-Head and Neck Module, the Functional Assessment of Cancer Therapy-Head and Neck, the MD Anderson Dysphagia Inventory, and the Xerostomia-Related QOL Scale. Primary study endpoints were the incidence of grade ≥ 3 (G3) toxicity and QOL patterns.

Results: Fourteen patients (median follow-up, 2 years) were evaluated. Most patients presented with human papillomavirus-positive disease (n = 12, 86%). Rates of G3 oral mucositis, xerostomia, and dermatitis were 7% (n = 1), 21% (n = 3), and 36% (n = 5), respectively. None required a gastrostomy. During PRT, QOL was reduced relative to baseline and recovered shortly after PRT. At 2 years after PRT, the local regional control, disease-free survival, and overall survival were 100% (among 7 patients at risk), 79% (among 6 patients at risk), and 90% (among 7 patients at risk), respectively.

Conclusion: Therefore, PRT for HNCUP was associated with highly favorable dosimetric and clinical outcomes, including minimal oral mucositis, xerostomia, and dysphagia. Toxicity and QOL may be superior with PRT compared with conventional radiation therapy and PRT maintains equivalent oncologic control. Further prospective studies are needed to evaluate late effects and cost-effectiveness.
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http://dx.doi.org/10.14338/IJPT-20-00034.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270080PMC
June 2021

Patient-Reported Outcomes after Intensity-Modulated Proton Therapy for Oropharynx Cancer.

Int J Part Ther 2021 25;8(1):213-222. Epub 2021 Jun 25.

The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: To report patient-reported outcomes (PROs) derived from the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) tool, in patients with oropharynx cancer (OPC) treated with intensity-modulated proton therapy (IMPT) in the context of first-course irradiation.

Materials And Methods: Patients with locally advanced OPC treated with radical IMPT between 2011 and 2018 were included in a prospective registry. FACT-HN scores were measured serially during and 24 months following IMPT. PRO changes in the FACT-HN scores over time were assessed with mixed-model analysis.

Results: Fifty-seven patients met inclusion criteria. Median age was 60 years (range, 41-84), and 91% had human papillomavirus-associated disease. In total, 28% received induction chemotherapy and 68% had concurrent chemotherapy. Compliance to FACT-HN questionnaire completion was 59%, 48%, and 42% at 6, 12, and 24 months after treatment, respectively. The mean FACT-General (G), FACT-Total, and FACT-Trial Outcome Index (TOI) score changes were statistically and clinically significant relative to baseline from week 3 of treatment up to week 2 after treatment. Nadir was reached at week 6 of treatment for all scores, with maximum scores dropping by 15%, 20%, and 39% compared to baseline for FACT-G, FACT-Total, and FACT-TOI, respectively. Subdomain scores of physical well-being, functional well-being, and head and neck additional concerns decreased from baseline during treatment and returned to baseline at week 4 after treatment.

Conclusions: IMPT was associated with a favorable PRO trajectory, characterized by an acute decline followed by rapid recovery to baseline. This study establishes the expected acute, subacute, and chronic trajectory of PROs for patients undergoing IMPT for OPC.
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http://dx.doi.org/10.14338/IJPT-20-00081.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270092PMC
June 2021

Proton Therapy for Head and Neck Cancer: A 12-Year, Single-Institution Experience.

Int J Part Ther 2021 25;8(1):108-118. Epub 2021 Jun 25.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: To characterize our experience and the disease control and toxicity of proton therapy (PT) for patients with head and neck cancer (HNC).

Patients And Methods: Clinical outcomes for patients with HNC treated with PT at our institution were prospectively collected in 2 institutional review board-approved prospective studies. Descriptive statistics were used to summarize patient characteristics and outcomes. Overall survival, local-regional control, and disease-free survival were estimated by the Kaplan-Meier method. Treatment-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events (version 4.03) scale.

Results: The cohort consisted of 573 patients treated from February 2006 to June 2018. Median patient age was 61 years. Oropharynx (33.3%; n = 191), paranasal sinus (11%; n = 63), and periorbital tissues (11%; n = 62) were the most common primary sites. Patients with T3/T4 or recurrent disease comprised 46% (n = 262) of the cohort. The intent of PT was definitive in 53% (n = 303), postoperative in 37% (n = 211), and reirradiation in 10% (n = 59). Median dose was 66 Gy (radiobiological equivalent). Regarding systemic therapy, 43% had received concurrent (n = 244), 3% induction (n = 19), and 15% (n = 86) had both. At a median follow-up of 2.4 years, 88 patients (15%) had died and 127 (22%) developed disease recurrence. The overall survival, local-regional control, and disease-free survival at 2 and 5 years were, respectively, 87% and 75%, 87% and 78%, and 74% and 63%. Maximum toxicity (acute or late) was grade 3 in 293 patients (51%), grade 2 in 234 patients (41%), and grade 1 in 31 patients (5%). There were 381 acute grade 3 and 190 late grade 3 unique toxicities across 212 (37%) and 150 (26%) patients, respectively. There were 3 late-grade 4 events across 2 patients (0.3%), 2 (0.3%) acute-grade 5, and no (0%) late-grade 5 events.

Conclusions: The overall results from this prospective study of our initial decade of experience with PT for HNC show favorable disease control and toxicity outcomes in a multidisease-site cohort and provide a reference benchmark for future comparison and study.
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http://dx.doi.org/10.14338/IJPT-20-00065.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270083PMC
June 2021

The Biological Basis for Enhanced Effects of Proton Radiation Therapy Relative to Photon Radiation Therapy for Head and Neck Squamous Cell Carcinoma.

Int J Part Ther 2021 25;8(1):3-13. Epub 2021 Jun 25.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Head and neck squamous cell carcinomas (HNSCCs) often present as local-regionally advanced disease at diagnosis, for which a current standard of care is x-ray-based radiation therapy, with or without chemotherapy. This approach provides effective local regional tumor control, but at the cost of acute and late toxicity that can worsen quality of life and contribute to mortality. For patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) in particular, for whom the prognosis is generally favorable, de-escalation of the radiation dose to surrounding normal tissues without diminishing the radiation dose to tumors is desired to mitigate radiation-related toxic effects. Proton radiation therapy (PRT) may be an excellent de-escalation strategy because of its physical properties (that eliminate unnecessary radiation to surrounding tissues) and because of its biological properties (including tumor-specific variations in relative biological effectiveness [RBE] and linear energy transfer [LET]), in combination with concurrent systemic therapy. Early clinical evidence has shown that compared with x-ray-based radiation therapy, PRT offers comparable disease control with fewer and less severe treatment-related toxicities that can worsen the quality of life for patients with HNSCC. Herein, we review aspects of the biological basis of enhanced HNSCC cell response to proton versus x-ray irradiation in terms of radiation-induced gene and protein expression, DNA damage and repair, cell death, tumor immune responses, and radiosensitization of tumors.
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http://dx.doi.org/10.14338/IJPT-20-00070.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270087PMC
June 2021
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