Artificial intelligence to predict outcomes of head and neck radiotherapy.

Head and neck radiotherapy induces important toxicity, and its efficacy and tolerance vary widely across patients. Advancements in radiotherapy delivery techniques, along with the increased quality and frequency of image guidance, offer a unique opportunity to individualize radiotherapy based on imaging biomarkers, with the aim of improving radiation efficacy while reducing its toxicity. Various artificial intelligence models integrating clinical data and radiomics have shown encouraging results for toxicity and cancer control outcomes prediction in head and neck cancer radiotherapy. Clinical implementation of these models could lead to individualized risk-based therapeutic decision making, but the reliability of the current studies is limited. Understanding, validating and expanding these models to larger multi-institutional data sets and testing them in the context of clinical trials is needed to ensure safe clinical implementation. This review summarizes the current state of the art of machine learning models for prediction of head and neck cancer radiotherapy outcomes.

Long-term impact of HPV vaccination and COVID-19 pandemic on oropharyngeal cancer incidence and burden among men in the USA: A modeling study.

BACKGROUND: Oropharyngeal cancer (OPC) incidence is rising rapidly among men in the United States of America (USA). We aimed to project the impact of maintaining the current HPV vaccination uptake and achieving 80% national (Healthy People) goal on OPC incidence and burden. METHODS: We developed an open-cohort micro-simulation model of OPC natural history among contemporary and future birth cohorts of men, accounting for sexual behaviors, population growth, aging, and herd immunity. We used data from nationally representative databases, cancer registries from all 50 states, large clinical trials, and literature. We evaluated the status quo scenario (the current HPV vaccination uptake remained stable) and alternative scenarios of improvements in uptake rates in adolescents (aged 9-17 years) and young adults (aged 18-26 years) by 2025 to achieve and maintain the 80% goal. The primary outcome was to project OPC incidence and burden from 2009 to 2100. We also assessed the impact of disruption in HPV vaccine uptake during the COVID-19 pandemic. FINDINGS: OPC incidence is projected to rise until the mid-2030s, reaching the age-standardized incidence rate of 9·8 (95% uncertainty interval [UI] 9·5-10·1) per 100 000 men, with the peak annual burden of 23 850 (UI, 23 200-24 500) cases. Under the status quo scenario, HPV vaccination could prevent 124 000 (UI, 117 000-131 000) by 2060, 400 000 (UI, 384 000-416 000) by 2080, and 792 000 (UI, 763 000-821 000) by 2100 OPC cases among men. Achievement and maintenance of 80% coverage among adolescent girls only, adolescent girls and boys, and adolescents plus young adults could prevent an additional number of 100 000 (UI, 95 000-105 000), 118 000 (UI, 113 000-123 000), and 142 000 (UI, 136 000-148 000) male OPC cases by 2100. Delayed recovery of the HPV vaccine uptake during the COVID-19 pandemic could lead to 600 (UI, 580-620) to 6200 (UI, 5940-6460) additional male OPC cases by 2100, conditional on the decline in the extent of the national HPV vaccination coverage and potential delay in rebounding. INTERPRETATION: Oropharyngeal cancer burden is projected to rise among men in the USA. Nationwide efforts to achieve the HPV vaccination goal of 80% coverage should be a public health priority. Rapid recovery of the declined HPV vaccination uptake during the COVID-19 pandemic is also crucial to prevent future excess OPC burden. FUNDING: National Cancer Institute and National Institute on Minority Health and Health Disparities of the USA.

Dose-volume predictors of post-radiation primary hypothyroidism in head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We performed a systematic literature search of Medline, EMBASE and Web of Science from database inception to July 1, 2021 for articles that discuss radiation dose-volume predictors of post-radiation primary hypothyroidism in patients with HNC. Data on the incidence, clinical risk factors and radiation dose-volume parameters were extracted. A meta-analysis was performed using the random-effects model to estimate the pooled odds ratio (OR) of thyroid volume as a predictor of the risk of post-radiation hypothyroidism, adjusted for thyroid radiation dosimetry. RESULTS: Our search identified 29 observational studies involving 4,530 patients. With median follow-up durations ranging from 1.0 to 5.3 years, the average crude incidence of post-radiation primary hypothyroidism was 41.4 % (range, 10 %-57 %). Multiple radiation dose-volume parameters were associated with post-radiation primary hypothyroidism, including the thyroid mean dose (Dmean), minimum dose, V25, V30, V35, V45, V50, V30-60, VS45 and VS60. Thyroid Dmean and V50 were the most frequently proposed dosimetric predictors. The pooled adjusted OR of thyroid volume on the risk of post-radiation primary hypothyroidism was 0.89 (95 % confidence interval, 0.85-0.93; p < 0.001) per 1 cc increment. CONCLUSION: Post-radiation primary hypothyroidism is a common late complication after radiotherapy for HNC. Minimizing inadvertent exposure of the thyroid gland to radiation is crucial to prevent this late complication. Radiation dose-volume constraints individualized for thyroid volume should be considered in HNC radiotherapy planning.

The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment.

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.

Incidence of contralateral regional failure in the electively irradiated contralateral neck of patients with head and neck squamous cell carcinoma.

BACKGROUND: The vast majority of patients with head and neck squamous cell carcinoma (HNSCC) routinely undergo elective nodal irradiation (ENI) to both sides of the neck. Little is known about the extent to which bilateral ENI prevents regional failure (RF) and contralateral RF (cRF) in particular, while such knowledge is necessary to evaluate the results of more selective approaches like unilateral ENI. We investigated the rate and pattern of RF after bilateral ENI, the rate of cRF in the electively irradiated contralateral neck, and tried to identify risk factors for development of cRF. MATERIALS AND METHODS: Retrospective cohort study of a consecutive series of 605 patients with T1-4N0-3 HNSCC treated between 2008 and 2017 with primary (chemo)radiation and bilateral ENI. RESULTS: Median follow-up was 43 months (range 1.4-126). Three-year cumulative incidence of RF was 12.7%. Three-year cumulative incidences of ipsilateral RF (iRF) and cRF were 10.6% and 2.8%, respectively. All cRF occurred within the electively treated volume. Salvage treatment was possible in 65% and 59% of patients with iRF and cRF, respectively (p = 0.746). The 3-year overall survival rates after RF in patients with iRF and cRF were 27.4% and 41.2%, respectively (p = 0.713). Three-year cancer-specific survival rates were 31.6% and 48.1%, respectively (p = 0.634). In multivariate analysis, no significant predictive factors were identified for cRF after bilateral ENI. CONCLUSION: Contralateral regional failure is rare, but still occurs in 2.8% of patients treated with bilateral ENI. The possibilities for salvage treatment, the rates of overall survival and cancer-specific survival were comparable to patients with iRF.