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Radiotherapy for head and neck tumours in 2012 and beyond: conformal, tailored, and adaptive?

ABSTRACT: Intensity-modulated radiation therapy (IMRT) is a conformal irradiation technique that enables steep dose gradients. In head and neck tumours this approach spares parotid-gland function without compromise to treatment efficacy. Anatomical and molecular imaging modalities may be used to tailor treatment by enabling proper selection and delineation of target volumes and organs at risk, which in turn lead to dose prescriptions that take into account the underlying tumour biology (eg, human papillomavirus status). Therefore, adaptations can be made throughout the course of radiotherapy, as required. Planned dose increases to parts of the target volumes may also be used to match the radiosensitivity of tumours (so-called dose-painting), assessed by molecular imaging. For swift implementation of tailored and adaptive IMRT, tools and procedures, such as accurate image acquisition and reconstruction, automatic segmentation of target volumes and organs at risk, non-rigid image and dose registration, and dose summation methods, need to be developed and properly validated.

SUBMITTER: Gregoire V

PROVIDER: S-EPMC6225523 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Radiotherapy for head and neck tumours in 2012 and beyond: conformal, tailored, and adaptive?

Grégoire Vincent V Jeraj Robert R Lee John Aldo JA O'Sullivan Brian B

The Lancet. Oncology 20120628 7

Intensity-modulated radiation therapy (IMRT) is a conformal irradiation technique that enables steep dose gradients. In head and neck tumours this approach spares parotid-gland function without compromise to treatment efficacy. Anatomical and molecular imaging modalities may be used to tailor treatment by enabling proper selection and delineation of target volumes and organs at risk, which in turn lead to dose prescriptions that take into account the underlying tumour biology (eg, human papillom ...[more]

PMID: 22748268

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Project description:No clear criteria have yet been established to guide decision-making for patient selection and the optimal timing of adaptive radiotherapy (ART) based on image-guided radiotherapy (IGRT). We have developed a novel protocol-the Best for Adaptive Radiotherapy (B-ART) protocol-to guide patient selection for ART. The aim of the present study is to describe this protocol, to evaluate its validity in patients with head and neck (HN) cancer, and to identify the anatomical and clinical predictors of the need for replanning. We retrospectively evaluated 82 patients with HN cancer who underwent helical tomotherapy (HT) and subsequently required replanning due to soft tissue changes upon daily MVCT. Under the proposed criteria, patients with anatomical changes >3 mm on three to four consecutive scans are candidates for ART. We compared the volumes on the initial CT scan (iCT) and the replanning CT (rCT) scan for the clinical target volumes (CTV1, referring to primary tumor or tumor bed and CTV2, metastatic lymph nodes) and for the parotid glands (PG) and body contour (B-body). The patients were stratified by primary tumor localization, clinical stage, and treatment scheme. The main reasons for replanning were: (1) a planning target volume (PTV) outside the body contour (n = 70; 85.4%), (2) PG shrinkage (n = 69; 84.1%), (3) B-body deviations (n = 69; 84.1%), and (4) setup deviations (n = 40; 48.8%). The replanning decision was made, on average, during the fourth week of treatment (n = 47; 57.3%). The mean reductions in the size of the right and left PG volumes were 6.31 cc (20.9%) and 5.98 cc (20.5%), respectively (p < 0.001). The reduction in PG volume was ≥30% in 30 patients (36.6%). The volume reduction in all of the anatomical structures was statistically significant. Four variables-advanced stage disease (T3-T4), chemoradiation, increased weight loss, and oropharyngeal localization-were significantly associated with the need for ART. The B-ART protocol provides clear criteria to eliminate random errors, and to allow for an early response to relevant changes in target volumes.

Project description:PurposeA planning strategy was developed and the utility of online-adaptation with the Ethos CBCT-guided ring-gantry adaptive radiotherapy (ART) system was evaluated using retrospective data from Head-and-neck (H&N) patients that required clinical offline adaptation during treatment.MethodsClinical data were used to re-plan 20 H&N patients (10 sequential boost (SEQ) with separate base and boost plans plus 10 simultaneous integrated boost (SIB)). An optimal approach, robust to online adaptation, for Ethos-initial plans using clinical goal prioritization was developed. Anatomically-derived isodose-shaping helper structures, air-density override, goals for controlling hotspot location(s), and plan normalization were investigated. Online adaptation was simulated using clinical offline adaptive simulation-CTs to represent an on-treatment CBCT. Dosimetric comparisons were based on institutional guidelines for Clinical-initial versus Ethos-initial plans and Ethos-scheduled versus Ethos-adapted plans. Timing for five components of the online adaptive workflow was analyzed.ResultsThe Ethos H&N planning approach generated Ethos-initial SEQ plans with clinically comparable PTV coverage (average PTVHigh V100% = 98.3%, Dmin,0.03cc = 97.9% and D0.03cc = 105.5%) and OAR sparing. However, Ethos-initial SIB plans were clinically inferior (average PTVHigh V100% = 96.4%, Dmin,0.03cc = 93.7%, D0.03cc = 110.6%). Fixed-field IMRT was superior to VMAT for 93.3% of plans. Online adaptation succeeded in achieving conformal coverage to the new anatomy in both SEQ and SIB plans that was even superior to that achieved in the initial plans (which was due to the changes in anatomy that simplified the optimization). The average adaptive workflow duration for SIB, SEQ base and SEQ boost was 30:14, 22.56, and 14:03 (min: sec), respectively.ConclusionsWith an optimal planning approach, Ethos efficiently auto-generated dosimetrically comparable and clinically acceptable initial SEQ plans for H&N patients. Initial SIB plans were inferior and clinically unacceptable, but adapted SIB plans became clinically acceptable. Online adapted plans optimized dose to new anatomy and maintained target coverage/homogeneity with improved OAR sparing in a time-efficient manner.

Project description:The success of immune checkpoint receptor blockade has brought exciting promises for the treatment of head and neck squamous cell carcinoma (HNSCC). While patients who respond to checkpoint inhibitors tend to develop a durable response, <15% of patients with HNSCC respond to immune checkpoint inhibitors, underscoring the critical need to alleviate cancer resistance to immunotherapy. Major advances have been made to elucidate the intrinsic and adaptive resistance mechanisms to immunotherapy. Central genomic events in HNSCC have been found to possess previously unknown roles in suppressing immune sensing. Such inhibitory function affects both the innate and adaptive arms of tumor-specific immunity. While checkpoint blockade effectively reinvigorates adaptive T-cell responses, additional targeting of the oncogenic inhibitors of innate immune sensing likely informs a novel and potent strategy for immune priming. This review discusses the recent advances on the identification of key HNSCC oncogenes that impair antitumor immunity and emerging immune-priming approaches that sensitize poorly immunogenic HNSCCs to checkpoint blockade. These approaches include but are not limited to cancer vaccine systems utilizing novel type I interferon agonists as immune adjuvants, radiation, DNA damage-inducing agents, and metabolic reprogramming. The goal of these multipronged approaches is to expand tumor-specific effector T-cells, break checkpoint receptor-mediated tolerance, and metabolically support sustained T-cell activation. The translation of therapeutics that reverses oncogenic inhibition of immune sensing requires thorough characterization of the HNSCC regulators of innate immune sensors, development of additional immunocompetent HNSCC mouse models, as well as engineering of more robust immune adjuvant delivery systems. Built on the success of checkpoint blockade, validation of novel immune-priming approaches holds key promises to expand the pool of responders to immunotherapy.

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Radiotherapy for head and neck tumours in 2012 and beyond: conformal, tailored, and adaptive?

Publications

Radiotherapy for head and neck tumours in 2012 and beyond: conformal, tailored, and adaptive?

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