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Personalized cancer vaccination in head and neck cancer.

ABSTRACT: Cancer is characterized by an accumulation of somatic mutations that represent a source of neoantigens for targeting by antigen-specific T cells. Head and neck squamous cell carcinoma (HNSCC) has a relatively high mutation burden across all cancer types, and cellular immunity to neoantigens likely plays a key role in HNSCC clinical outcomes. Immune checkpoint inhibitors (CPIs) have brought new treatment options and hopes to patients with recurrent and/or metastatic HNSCC. However, many patients do not benefit from CPI therapies, highlighting the need for novel immunotherapy or combinatorial strategies. One such approach is personalized cancer vaccination targeting tumor-associated antigens and tumor-specific antigens, either as single agents or in combination with other therapies. Recent advances in next-generation genomic sequencing technologies and computational algorithms have enabled efficient identification of somatic mutation-derived neoantigens and are anticipated to facilitate the development of cancer vaccine strategies. Here, we review cancer vaccine approaches against HNSCC, including fundamental mechanisms of a cancer vaccine, considerations for selecting appropriate antigens, and combination therapies.

SUBMITTER: Shibata H

PROVIDER: S-EPMC7935792 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Personalized cancer vaccination in head and neck cancer.

Shibata Hirofumi H Zhou Liye L Xu Na N Egloff Ann Marie AM Uppaluri Ravindra R

Cancer science 20210127 3

Cancer is characterized by an accumulation of somatic mutations that represent a source of neoantigens for targeting by antigen-specific T cells. Head and neck squamous cell carcinoma (HNSCC) has a relatively high mutation burden across all cancer types, and cellular immunity to neoantigens likely plays a key role in HNSCC clinical outcomes. Immune checkpoint inhibitors (CPIs) have brought new treatment options and hopes to patients with recurrent and/or metastatic HNSCC. However, many patients ...[more]

PMID: 33368875

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Project description:PurposeOptimal head-and-neck cancer (HNC) treatment planning requires accurate and feasible planning goals to meet dosimetric constraints and generate robust online adaptive treatment plans. A new x-ray-based adaptive radiotherapy (ART) treatment planning system (TPS) version 2.0 emulator includes novel methods to drive the planning process including the revised intelligent optimization engine algorithm (IOE2). HNC is among the most challenging and complex sites and heavily depends on planner skill and experience to successfully generate a reference plan. Therefore, we evaluate the new TPS performance via conventionally accepted planning strategies with/without artificial intelligence (AI) and knowledge-based planning (KBP).MethodsOur institution has a pre-clinical release of the Varian Ethos2.0 TPS emulator which includes several changes that may affect current planning strategies. Twenty definitive and post-operative HNC patients were retrospectively selected with a two or three-level simultaneous integrated boost (SIB) dosing scheme. Patients were replanned in the emulator using population-based, KBP-guided with/without human intervention and AI-guided planning goals. These planning strategies were compared both dosimetrically and for plan deliverability.ResultsAll strategies generally demonstrated acceptable plan quality with KBP- and AI-guided goals offering enhanced dosimetric sparing in organs-at-risk (OAR). The average contralateral parotid gland mean dose was 20.0 ± 6.1 Gy (p < 0.001) for population-based and 15.0 ± 6.1 Gy (p = n.s.) for KBP-with human intervention versus 15.1 ± 7.4 Gy for clinical plans. Target coverage, minimum dose, and plan hotspot were acceptable in all cases. KBP-enabled strategy demonstrated higher modulation and faster optimization time than both population-based and AI-guided strategies.ConclusionSimply entering population, automatic KBP-enabled or AI-generated planning goals into the new Ethos2.0 TPS produced dosimetrically compliant plans, with AI-guided goals demonstrating the most OAR sparing. Several of these approaches are easy to translate to other treatment sites and will help lower the barrier to entry for x-ray-based online-ART.

Project description:Postoperative (chemo) radiation improves tumor control and survival in high-risk patients with head and neck squamous cell carcinoma based on established risk factors. The clinical cooperation group "Personalized Radiotherapy in Head and Neck Cancer" focuses on the identification and validation of new biomarkers, which are aimed at eventually stratifying and personalizing the therapy concept. Hence, we reviewed all patients with head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, treated with postoperative (chemo) radiation from 06/2008 until 06/2015 at the Department of Radiation Oncology in the University Hospital, LMU Munich. Here we report the clinical results of the cohort, laying the foundation for further research within the framework of a clinical cooperation group.Patient data were retrospectively (until 2013) and prospectively (from 2013) collected and analyzed for outcome and treatment failures with regard to previously described and established risk factors.We identified 302 patients (median follow-up 45 months, average age 60.7 years), having received postoperative (chemo)radiation (median 64 Gy). Chemotherapy was added in 58% of cases, mostly Cisplatin/5- Fluorouracil in concordance with the ARO 96-3 study. The 3-year overall survival, local, locoregional and distant failure estimates were 70.5, 9.7, 12.2 and 13.5%, respectively. Human papillomavirus-associated oropharyngeal cancer was associated with a significant improved overall survival, locoregional, distant and overall tumor control rates in multivariate analysis. Additionally, in multivariate analysis, for local failure, resection status and perineural invasion, for locoregional and distant failure extracapsular extension and for overall survival the presence of nodal disease were significant adverse factors. Moreover, 138 patients have been treated in concordance with the ARO 96-3 protocol, corroborating the results of this study.Our cohort represents a large unselected cohort of patients with head and neck squamous cell carcinoma treated with postoperative (chemo)radiation. Tumor control rates and survival rates are consistent with the results of previously reported data.

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Personalized cancer vaccination in head and neck cancer.

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Personalized cancer vaccination in head and neck cancer.

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