Phase II Clinical Trial of Low-intervention Using Hypofractionated Protontherapy in Chordomas and Chondrosarcomas of the Skull Base
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Acute treatment tolerance
研究概览
简要总结
The project is planned as a phase II clinical trial with a low level of intervention, for the prospective evaluation of the clinical results of radical or adjuvant treatment by proton therapy in chordomas and chondrosarcomas of the skull base using hypofractionation schemes in 5 fractions, with the aim of consolidating the scientific evidence that exists with high-precision techniques with photons, increasing this evidence by adapting this treatment scheme to the proton technique.
In addition, a cross-sectional prospective evaluation of the quality parameters of the dosimetry of hypofractionated proton therapy and an evaluation of the quality of life of these patients will be carried out.
- Primary Objective
- - Toxicity according to CTCAE-v5 criteria
- - Local control determined by Magnetic Resonance with Gadolinium.
- Secondary Objectives
- To evaluate the quality of life of the patients, 3 months after the end of the treatment, using a specific questionnaire.
- To evaluate the dosimetric benefits using techniques that allow an improvement in the dose gradient, improving the coverage of the CTV (Clinical Tumor Volume) and decreasing the dose in surrounding risk organs.
详细描述
Chordomas are rare, slow-growing tumors that develop from remnants of the embryonic notochord in the clivus, sacrococcygeal region, and mobile spine. Although the frequency of distant metastases is low, these tumors are locally aggressive and have an extremely high local recurrence rate. Similarly, chondrosarcomas have a potential for slow growth with a tendency to recur locally. They usually arise at the base of the skull or spine from mesenchymal cells or from the primitive cartilaginous matrix.
Although chordomas are considered clinically more aggressive than chondrosarcomas, their tendency to settle in similar anatomical locations and the high risk of local recurrence of both diagnostic entities have conditioned a similar therapeutic approach.
Standard treatment includes surgical resection that is as radical as possible; however, complete resection is feasible in less than 50% of cases, as it can be associated with significant postoperative morbidity and mortality, since these tumors frequently invade or contact critical structures (vascular, cranial nerves or spinal roots). Therefore, adjuvant or exclusive irradiation have a fundamental role in long-term local control. Therefore, optimization of the efficacy of radiotherapy represents a critical step in the management of these patients. Given their tendency to local recurrence, chordomas require the prescription of high doses for their local control, which are associated with potentially critical adverse effects if conventional photon irradiation techniques are used.
The α/β ratio, according to the linear-quadratic model, represents a measure of the sensitivity of a tumor to variable dose-per-fraction regimens. Tumors with a low coefficient (<4 Gy) are considered more sensitive to the effects of hypofractionated treatments, which involve the administration of higher irradiation doses per session in fewer sessions.
After analyzing historical studies and institutional experiences, different publications suggest that the α/β ratio of chordomas is 2.45 Gy and it is assumed to be very similar for chondrosarcomas. Therefore, the administration of hypofractionated schedules could be associated with an increase in the sensitivity of these tumors to radiotherapy treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for 5 fractions:
- •With a baseline classification on the Karnofsky performance status scale ≥ 70%.
- •With confirmed histological diagnosis of chordoma or chondrosarcoma of the skull base.
- •Who have signed the specific informed consent of the protocol, agreeing to participate in it.
- •Completion of magnetic resonance imaging with vascular assessment ruling out pre-existing vascular pathology (stenosis or atherosclerosis), including 3D T1 black-blood sequences, pre-contrast 3D TOF, 3D T2 with fat suppression, and perfusion sequences.
- •With a maximum tumor size of 50 cc.
- •Whose relationship to organs at risk (OARs) allows compliance with the necessary dose restrictions to receive hypofractionated proton therapy in 5 fractions.
- •Patients included in the study must meet dosimetric parameters that include:
- •Tumor CTV coverage of at least D95>90%.
- •Correct compliance with the dose restrictions, at least in the nominal scenario, for critical organs (optic pathway, brain stem and spinal cord) according to the guidelines published and available in the literature:
- •Dose contnstraints for 5 fractions:
- •Optic Nerves: D0.03cc ≤ 25 GyRBE, V23.5 < 0.5cc. Chiasm:D0.03cc ≤ 25 GyRBE, V23.5 < 0.5cc. Brainstem:D0.03cc ≤ 31 GyRBE,V23 < 0.5cc. Spinal Chord: D0.03cc ≤ 30 GyRBE, V23 < 035cc. Right and left temporal lobes: D0.03 cc ≤ 35 GyRBE, V30 ≤ 5.5 cc.
- •Inclusion Criteria for 25 fractions:
- •With a baseline classification on the Karnofsky performance status scale ≥ 70%.
- •With confirmed histological diagnosis of chordoma or chondrosarcoma of the skull base.
- •Who have signed the specific informed consent of the protocol, agreeing to participate in it.
- •Not considered candidates for the 5-fraction protocol due to tumor size exceeding 50 cc and/or the presence of vascular pathology (stenosis or atherosclerosis) identified on MRI with vascular sequences.
- •Tumor relationship to organs at risk allows compliance with the dose constraints required to receive hypofractionated proton therapy delivered in 27 fractions.
- •Patients included in the study must meet dosimetric parameters that include:
- •Tumor CTV coverage of at least D95>90%.
- •Correct compliance with the dose restrictions, at least in the nominal scenario, for critical organs (optic pathway, brain stem and spinal cord) according to the guidelines published and available in the literature:
- •Dose constraints for 25 fractions:
- •Optic nerves: D0.03 cc ≤ 54.7 GyRBE. Optic chiasm: D0.03 cc ≤ 54.7 GyRBE. Brainstem: Surface: D0.03 cc ≤ 57.9 GyRBE. Core: D0.03 cc ≤ 54 GyRBE. Spinal cord: D0.03 cc ≤ 54 GyRBE. Right and left temporal lobes: V65 < 1.7 cc, V60 ≤ 5.5 cc.
- •Treatment planning with a minimum of 5 beams. In general, the use of a class solution with 6 beams will be proposed, including 2 lateral beams with gantry angles between 20° and 80°, depending on tumor location; 2 posterior oblique beams; and 2 anterior oblique beams. The latter four beams may include a couch rotation of at least 20° relative to the two lateral beams, with a minimum angular separation of at least 30° between ipsilateral oblique beams. Depending on individual patient characteristics, this class solution will be adapted to adjust specific gantry and couch angles for each field.
- •If this solution is not feasible due to patient-specific characteristics (surgical constraints, tumor location or laterality, etc.), a 5-beam solution will be evaluated, including 2 posterior oblique beams and 2 anterior oblique beams, in addition to a coronal field with the couch at 270° and a gantry angle between 40° and 90° depending on tumor location, or other configurations that increase the number of ipsilateral oblique beams with a minimum inter-beam separation of at least 30°.
- •Evaluation of Linear Energy Transfer (LET) and biological dose:
- •For each treatment plan, the LET distribution obtained from the treatment planning system (TPS) will be evaluated, with particular attention to regions where LET values exceed 5 keV/μm, aiming to minimize such values. Equivalent biological dose distributions based on recognized models in the literature may also be assessed to support decision-making regarding the suitability of a given treatment plan
排除标准
- •Patients with distant metastases.
- •Patients who have received previous irradiation in the same location.
- •Patients whose clinical or dosimetric characteristics do not meet the inclusion criteria.
- •Patients who are simultaneously participating in another study that may affect the results of this protocol.
研究组 & 干预措施
5 fractions
- Patients > 18 years old.
- With a baseline classification on the Karnofsky performance status scale ≥ 70%.
- With confirmed histological diagnosis of chordoma or chondrosarcoma of the skull base.
- With a maximum tumor size of 50 cc.
- With a magnetic resonance imaging (MRI) t ruling out pre-existing vascular pathology (stenosis or atherosclerosis).
- Whose relationship to organs at risk (OARs) allows compliance with the necessary dose restrictions to receive hypofractionated proton therapy in 5 fractions.
Patients included in the study must meet dosimetric parameters that include:
- Clinical Target Volume (CTV) coverage of at least D95>90%.
- Correct compliance with the dose restrictions, at least in the nominal scenario, for critical organs (optic pathway, brain stem, spinal cord and temporal lobes) according to the guidelines published and available in the literature.
干预措施: 5-fraction hipofractionated protontheray (Radiation)
25 fractions
- Patients > 18 years old.
- With a baseline classification on the Karnofsky performance status scale ≥ 70%.
- With confirmed histological diagnosis of chordoma or chondrosarcoma of the skull base.
- Not considered candidates for the 5-fraction protocol due to tumor size exceeding 5 cc and/or the presence of vascular pathology identified on MRI with vascular sequences.
- Tumor relationship to organs at risk allows compliance with the dose constraints required to receive hypofractionated proton therapy delivered in 27 fractions.
干预措施: 25-fraction hypofractionated proton therapy (Radiation)
结局指标
主要结局
Acute treatment tolerance
时间窗: 0 - 3 months
To evaluate acute toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) scale, of the implementation of hypofractionation schemes in the treatment with protontherapy of skull base chordomas and chondrosarcomas.
Chronic treatment tolerance
时间窗: 3 months - 10 years
To evaluate chronic toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) scale, of the implementation of hypofractionation schemes in the treatment with protontherapy of skull base chordomas and chondrosarcomas.
Local control
时间窗: 1 - 10 years
To evaluate the clinical impact in terms of local control based on the radiological findings by MRI with gadolinium (considering progression to an increase in tumor volume \> 10%).
次要结局
- Quality of life after treatment - QLQ-C30(3 months)
- Quality of life after treatmenT- QLQ-BN20(3 months)
- Dosimetric benefits(3 months)
研究者
Morena Sallabanda
MD, PhD
Quironsalud