Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma.

BACKGROUND: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. METHODS: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). DISCUSSION: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02442375 .

Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study.

BACKGROUND: Compared to static beam Intensity-Modulated Radiation Therapy (IMRT), the main advantage of Volumetric Modulated Arc Therapy (VMAT) is a shortened delivery time, which leads to improved patient comfort and possibly smaller intra-fraction movements. This study aims at a treatment planner-independent comparison of radiotherapy treatment planning of IMRT and VMAT for head-and-neck cancer performed by several institutes and based on the same CT- and contouring data. METHODS: Five institutes generated IMRT and VMAT plans for five oropharyngeal cancer patients using either Pinnacle3 or Oncentra Masterplan to be delivered on Elekta linear accelerators. RESULTS: Comparison of VMAT and IMRT plans within the same patient and institute showed significantly better sparing for almost all OARs with VMAT. The average mean dose to the parotid glands and oral cavity was reduced from 27.2 Gy and 39.4 Gy for IMRT to 25.0 Gy and 36.7 Gy for VMAT, respectively. The dose conformity at 95% of the prescribed dose for PTVboost and PTVtotal was 1.45 and 1.62 for IMRT and 1.37 and 1.50 for VMAT, respectively. The average effective delivery time was reduced from 13:15 min for IMRT to 5:54 min for VMAT. CONCLUSIONS: Independently of institution-specific optimization strategies, the quality of the VMAT plans including double arcs was superior to step-and-shoot IMRT plans including 5-9 beam ports, while the effective treatment delivery time was shortened by ~50% with VMAT.

Optimal normal tissue sparing in craniospinal axis irradiation using IMRT with daily intrafractionally modulated junction(s).

PURPOSE: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs). METHODS AND MATERIALS: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose-volume parameters for target volumes and OARs were compared for the two techniques. RESULTS: The maximum dose with IMRT was <107% in all patients. V<95 and V>107 were <1 cm3 for IMRT compared with 3-9 cm3 for the craniospinal and 26-43 cm3 for the spinal-spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V75 for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V75 for the heart and thyroid was 42% and 32% vs. 0% with IMRT. CONCLUSION: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues.