Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Micronutrients

All Drugs and Chemicals

Cobalt

Protontherapy : 4 sessions of 13 Gy, total dosis 52 Gy

Protontherapy : 8 sessions of 6.5 Gy, total dosis 52 Gy

Proton-therapy consists in four consecutive sessions. The experimental arm consists in eight sessions. Irradiation is administered over two weeks, delivering a total dose of 60 Cobalt Gris Equivalent (CGE is the physical Gray dose multiplied by a biological factor of relative efficiency of 1.1 for protons compared to photons).

Protontherapy

Juliette THARIAT, md

Ocular melanomas have been treated for a long time by enucleation, with an unfavorable major impact on the patient's quality of life, social life, self-image, how they feel about others and about living with this disability. As a matter of fact, classical radiation therapy by photons is not accurate enough to deliver a sufficiently high dose to eradicate a melanoma without causing irreversible ocular brain complications since these tumors are " relatively radio resistant ". The possibility of delivering high doses due to the precision of protons ("Bragg peak") has allowed to overcome this limitation. The conservative uveal melanoma treatment has become a standard after the Collaborative Ocular Melanoma Study (COMS) indicating an equivalent rate of metastases and a non-impaired survival rate with a conservative treatment when compared to immediate enucleation. The quality of life benefits due to a conservative treatment has been demonstrated. Protontherapy dose has been defined in an empirical manner, it is probably excessive even if it applies to radio-resistant tumors. In France, radiotherapy by protons for choroidal melanomas delivers a dose of 60 Gy cobalt equivalent (that is 52 measured Gy, or " Physical dose") in 4 fractions and 4 days.

Referential treatment of ocular melanomas (other than conjunctiva) indicates proton-therapy for T1, T2, T3 \< 40% of ocular volume, and T4 only if extra scleral extension ≤ 2mm. However, there is an enucleation indication for T3 \> 40% of ocular volume and T4.

Our purpose is to override this relative contraindication, choroidal melanoma volume ≥ 40% of ocular volume. As a matter of fact, the investigators observe an increasing demand from ophthalmologists and patients for not performing primary enucleation. Also, during the last five years treatment of complications have improved and a less " hard " hypo fractionation (6.5 Gy per fraction) has equivalent local control results as for " hard " fractionation (13 Gy per fraction).

A more fractioned proton-therapy treatment, with doses per fraction of 6.5 Gy rather than 13 Gy, can limit the rate and the severity of complications degrading the quality of life by complications (pain, diminished visual acuity) and treatments (intra-ocular injections...).

In this study, patients will receive a total dose of 52 Gy in four 13 Gy sessions for the standard arm and in eight 6.5 Gy sessions for the experimental arm.

The investigators expect an identical local control rate within 2 year's time with a decrease in rate and severity of severe complications due to adapted fractionation (eight sessions with lower doses instead of four fractions with very high doses as it is usually recommended in the guidelines for small to medium melanomas).

Study with 2 differents dosages of proton therapy

Study Assessing Two Models of Hypofractionated Protontherapy on Large Choroidal Melanomas

Phase II Trial, Randomized, Under Single-blind Conditions, Assessing Two Models of Modified Hypofractionated Proton-therapy on Patients With Large Choroidal Melanomas

Centre Antoine Lacassagne

Musculoskeletal Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Nose Neoplasms

Skull Neoplasms

Bone Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Bone Diseases

Nose Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Antineoplastic Agents

Cisplatin

Arm A

Radiation therapy: 66 to 70 Gy in fractions of 2 Gy, 1 fraction/day, 5 fractions per week.

Radiation therapy will be conducted by conformational intensity modulation radiotherapy (IMRT) or protontherapy. Irradiation by 3D conformational radiotherapy can be discussed on a case by case with the Intergroup Coordinator GORTEC.

Arm B Concomitant systemic treatment with cisplatin + radiotherapy

According to standard protocol of concomitant cisplatin 100 mg/m2 IV on day 1 - J22 - 43 (3 maximum cycles).

Radiation therapy: 66 to 70 Gy in fractions of 2 Gy, 1 fraction/day, 5 fractions per week.

Radiation therapy will be conducted by conformational intensity modulation radiotherapy (IMRT) or protontherapy. Irradiation by 3D conformational radiotherapy can be discussed on a case by case with the Intergroup Coordinator GORTEC

66 à 70 Gy per fractions of 2 Gy, 1 fraction/day, 5 fractions/week

radiotherapy

François Régis FERRAND, MD

Juliette THARIAT, Prof

Nicolas MEERT, MD

A phase III, multicenter, randomized, open-label, french study comparing:

* Arm A : Radiotherapy alone (66 to 70 Gy; 5 fractions/week; 1fraction/day; 2 Gy/fraction) (IMRT or protontherapy)
* Arm B: Radiotherapy (66 to 70 Gy; 5 fractions/week; 1fraction/day; 2 Gy/fraction; IMRT or protontherapy) + concomitant cisplatin 100 mg/m2 IV on day 1 - J22 - 43 (3 cycles)

Carcinomas of the sinuses and the salivary glands are rare. They are heterogeneous in terms of anatomical sites and histology subtypes. For this reason and in the absence of prospective study, their treatment is still largely extrapolated from data of frequent carcinomas of the upper digestive tract. These tumors are most often diagnosed lately. Their treatment is based on a multimodal management of care, with a central place for the surgery and radiotherapy (Proof level Grade C). Despite the advances in surgical techniques, and the addition of radiation therapy, the 5-year overall survival probability does not exceed 65% mainly due to a loco regional development.

In this context, a chemotherapy administered concomitantly to radiotherapy, could increase the efficacy of the locoregional treatment by a radiosensibilization process and regardless of the histology. This point is regularly discussed in multidisciplinary concertation meeting, including bi-monthly national REFCOR meeting (network of French Expertise on rare Cancers of the head and neck). At present, the lack of data brings even to discuss the addition of cisplatin to exclusive irradiation of unresectable or not operable tumors.

No randomized study has been published in this context. The first comparative prospective study addressing the addition of weekly cisplatin to the adjuvant irradiation of salivary, is a phase II randomized study (Radiation Therapy Oncology Group - RTOG 1008) currently enrolling patients in the United States of America.

The Sponsor propose to conduct a phase III randomized study evaluating the impact of the addition of cisplatin to a treatment by radiotherapy in adjuvant setting (≥ 65 Gy) in case of a high risk of recurrence: case of radioresistant histologies (e.g. cystic fibrosis adenoids carcinomas), or case of unfavourable histo-prognostic criteria (incomplete resection, presence of emboli, etc.) in this population.

Chemo-radiotherapy Versus Radiotherapy in the Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy)

A Phase III Randomized Study of Chemo-radiotherapy Versus Radiotherapy Alone in the Adjuvant Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy)

Compare quality of life (QLQC30 overall score) between arms

Compare progression-free survival between the 2 treatment arms: radiation therapy alone versus radiochimiotherapy in adjuvant patients treatment operated.

Compare the 2 arms of treatment in operated patients in terms of overall survival

National Cancer Institute, France

Groupe Oncologie Radiotherapie Tete et Cou

Symptoms and General Pathology

Hypoxia

Chordoma

Fluoroazomycin arabinoside

Radiopharmaceuticals

In residual chordoma tumors after surgery, Investigators propose a protontherapy guided by conventional imaging (CT/MRI) and a boost guided by FAZA PET/CT, in order to target the hypoxic zones and to increase the dose in an adequate manner, which could result in improving long-term local control and reducing complications.

The operative approach and operating time will be performed according to neurosurgical practices (for head and neck) or surgical orthopaedic team (for sacrum) depending on the location, the extension and the relationship of the lesion to critical structures.

The surgery can be macroscopically complete or incomplete.

Surgery

Radiotherapy will be done with the Cyclotron, for a total dose of 78 Gray Relative Biological Effective (Gy RBE) - 70 Gy RBE to the tumor bed and macroscopic volume and 8 Gy RBE to the the hypoxic component volume, delivered in 39 fractions spread over 67 days.

FAZA PET/CT, in order to target the hypoxic zones

18F FAZA

Hamid MAMMAR, MD

Improved local control of chordoma initially treated with surgery or not, thanks to adjuvant radiotherapy oriented by conventional imaging Computed Tomography /Magnetic Resonance Imaging (CT / MRI) and guided by the \[18Fluor\] (\[18F\]) Fluoroazomycin Arabinofuranoside (FAZA) Positron Emission Tomography / Computed Tomography (PET / CT) to target the radioresistant hypoxic cells.

Due to the close contacts of the lesion with the neurovascular structures, in the case of skull base chordoma and mobile spine, surgery is often incomplete. On the contrary, surgery of the sacral region (for which the block excision is often possible) brings a better therapeutic outcome. Radiotherapy with high-dose supplement improves the outcomes for all these lesions.

Intratumoral hypoxia is a primary factor of radioresistance, it's known since long by radiation oncologists. \[18F\]FAZA gives an image of the hypoxic volume target. Investigators propose to increase the radioactive dose in the hypoxic volume target but in order to succeed, radiation oncologists have to precisely identify this hypoxic volume. Radiation oncologists would increase of 10% the radioactive dose that will allow us to improve local control at 3 years of 15% without any additional side effect.

Improvement of Local Control in Skull Base, Spine and Sacral Chordomas Treated by Surgery and Protontherapy Targeting Hypoxic Cells Revealed by [18F]FAZA) PET/CT Tracers

Investigators will share de-identified data sets with interested researchers, educators or clinicians. Materials generated under the project will be disseminated in accordance with Institut Curie policies.

Institut Curie

Craniopharyngioma

Adamantinoma

Ameloblastoma

59,5 Gy (1,7 Gy daily, 5 fractions per week).

Prospective, open labelled, phase II, monocenter trial to combine partial surgery resection and protontherapy to management paediatric craniopharyngioma.

This study is phase II prospective, open labelled, phase ii, monocenter. The main objective is to evaluate the fractionated high precision radiotherapy with a dose of 59,5 Gy (1,7 Gy daily, 5 fractions per week).

Management of Pediatric Craniopharyngioma by a Combination of Partial Surgical Resection, and Protontherapy (Craniopharyngioma)

Phase II Study on the Management of Pediatric Craniopharyngioma by a Combination of Partial Surgical Resection, and Protontherapy

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Chondrosarcoma

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Soft Tissue Sarcoma

* 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.
* 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 and spinal cord) according to the guidelines published and available in the literature.

The therapeutic schemes that will be proposed to patients based on clinical criteria such as tumor size and relationship of the tumor with adjacent critical organs are:

* For chordomas: 37.5 Gy in 5 consecutive sessions of 7.5 Gy per fraction.
* For chondrosarcomas: 35 Gy in 5 consecutive sessions of 7 Gy per fraction.

5-fraction hipofractionated protontheray

Morena Sallabanda, MD PhD

Juan Antonio Vera, PhD

Alejandro Mazal, PhD

Raul Matute, MD

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

  1. - Toxicity according to CTCAE-v5 criteria
  2. - Local control determined by Magnetic Resonance with Gadolinium.
* Secondary Objectives

  1. To evaluate the quality of life of the patients, 3 months after the end of the treatment, using a specific questionnaire.
  2. 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.

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.

Conventional normofractionated radiation therapy administered adjuvantly after resection has historically been used with median doses of 60 to 66.6 Gy to 2 Gy per fraction, offering 5-year local control rates ranging from 23% to 50%. Technological advances in the field of image-guided intensity-modulated radiotherapy have led to an improvement in the precision of treatments, allowing the dose for chordomas to be scaled up to 76 Gy (the biological equivalent dose (BED) taking into account the α/ β of 2.45Gy is 138 Gy) and for chondrosarcomas up to 70 Gy (BED of 127 Gy), achieving and improvement in 5-year local control rates of 65% and 88%, respectively for each diagnostic entity.

Although promising, the use of high-dose photons is limited by the lower ability to protect nearby critical organs. Therefore, particle therapy (protons and carbon ions) has established its role as a standard technique, due to its potential to achieve greater conformation and better dose distribution. The main studies with proton therapy for these tumors appear to show statistically significant results in favor of increased survival when dose escalation above 70 Gy to 2 Gy per fraction (BED \>127 Gy) is compared with techniques using irradiation with intensity modulated photons (IMRT). The 5-year local control rate is above 60% for chordomas and above 80% for chondrosarcomas with moderate toxicity and preservation of critical structures. However, the limited availability of these facilities together with the administration of very long treatment schedules, often of seven weeks or more, poses a significant problem for patients and remains an obstacle to the widespread adoption of this technique as a therapeutic standard.

Due to all these limitations and the important advances in terms of precision and dose distribution, the concept of hypofractionation has gained weight within radiation oncology thanks to its potential benefits in terms of reducing the duration of treatment and costs. The first publications on the hypofractionated treatment of chordomas, mainly of the skull base, go hand in hand with photon radiosurgery systems, using dedicated equipment such as the GammaKnife or CyberKnife. In the last 15 years, single-dose or hypofractionated treatment schemes have been explored as a therapeutic alternative to escalate the dose, improve the protection of organs at risk and reduce treatment time.

Some studies have evaluated single fraction stereotactic radiosurgery (SRS) in the management of chordomas and chondrosarcomas mainly located in the skull base with results comparable to proton therapy. The most relevant studies included series of 22 to 71 patients treated with median doses of SRS ranging from 12.7-24 Gy (BED 78.5-259 Gy). Five-year local control rates ranged from 21-85%, depending on the doses prescribed (higher doses, ≥15 Gy, were associated with better relapse-free survival).

However, based on the experience of Kano et al., for single-dose treatments, irradiation of volumes \> 7 cc is associated with a significant worsening of tumor control. It is essential to emphasize that the tumor volumes that are usually treated in chordomas and chondrosarcomas, both at the base of the skull and, to a greater extent, in the spine, exceed, in most cases, 7 cc, since the entire clivus or affected vertebral bodies must be included in the majority of cases, in order to reduce the risk of marginal recurrence. For this reason, the role of single-dose radiosurgery loses weight in favor of hypofractionated stereotactic radiotherapy (HFSRT), which has theoretical advantages compared to single-dose treatment in volumes greater than 7 cc, including a lower risk of radiation-induced toxicity in nearby critical structures and the possibility of safely treating larger tumor volumes with multiple fractions (usually 5).

Several publications evaluate HFSRT for chordomas and chondrosarcomas. The number of cases included in these series ranged from 9 to 24 patients. The median follow-up was 24 to 46 months. Most patients were treated with 5 fractions with a prescription dose of 24-43 Gy (BED 52.7-194 Gy), depending on histology and therapeutic setting (radical, adjuvant, or reirradiation). The best local control results at 3 and 5 years obtained were 90 and 60% for chordomas, respectively, and 100% for chondrosarcomas. The most widely used regimen was 37.5 Gy in 5 fractions of 7.5 Gy (BED 152.3 Gy equivalent to 80 Gy at 2 Gy per fraction) for chordomas and 35 Gy in 5 fractions of 7 Gy per fraction in Chondrosarcomas (BED of 135 Gy equivalent to 74 Gy at 2 Gy per fraction). The toxicity described in most of these studies does not register worse data than those published with conventional fractionation in proton therapy, when it comes to primary treatments.

This growing evidence, which is described as a justification for the implementation of hypofractionated regimens, demonstrates that the standard implementation of these therapeutic modalities in patients who meet the appropriate characteristics can suppose a great advantage to improve accessibility and comfort for patients, potentially reduce acute side effects during treatment and increase therapeutic cost-efficiency.

Proton therapy, today, remains a limited resource, with only 99 facilities currently in operation worldwide in 2021, of which two new centers are in Spain, active since 2020. In addition, many patients must travel to access to this technology, so reducing the time a patient is away from home and their support network can have significant financial and psychosocial implications. Added to all this are the aforementioned radiobiological advantages of high doses per fraction, in tumors with a low α/β coefficient, such as chordomas and chondrosarcomas. That is why the implementation of hypofractionation within proton therapy has gained weight in the last 10 years, increasing the number of publications in this regard, which reflects the interest in this treatment approach.

Cao et al. presented a dosimetric study comparing different hypofractionated stereotactic treatment schemes in the treatment of intracranial tumors \> 3 cm in greatest diameter. Treatment plans with GammaKnife, Cyberknife and VMAT were generated compared with proton therapy plans with or without modulated intensity. The authors suggest that proton therapy represents a desirable alternative to advanced photon techniques for treating large, irregularly shaped volumes near critical structures, such as chordomas and chondrosarcomas.

For all these reasons, a fundamental and necessary challenge today consists of increasing the scientific evidence of hypofractionated schemes in the treatment of chordomas and chondrosarcomas, adapting them to protontherapy, to increase clinical experience and combine the benefits of high-precision hypofractionated treatments to the dosimetric advantages of protontherapy (ability to treat volumes \> 7 cc with a homogeneity index close to 1 and a decrease in the integral dose in healthy tissue).

In summary, considering the growing scientific evidence available from other studies on different therapeutic entities, we have a solid basis to reinforce hypofractionation protocols with protontherapy in the treatment of chordomas and chondrosarcomas.

The research project is based on the performance of a phase II clinical trial with a low level of intervention, which consists of the prospective evaluation of the clinical and radiological response after the administration of a treatment using radical or adjuvant hypofractionated proton therapy in 5 sessions in patients diagnosed with chordoma or chondrosarcoma of the skull base.

In addition, a cross-sectional evaluation of the quality parameters of the dosimetry of the hypofractionated proton therapy treatments administered to the patients included in the study and an evaluation of the quality of life by means of specific questionnaires, 3 months after treatment, will be carried out.

Hypofractionated Protontherapy in Chordomas and Chondrosarcomas of the Skull Base

Phase II Clinical Trial of Low-intervention Using Hypofractionated Protontherapy in Chordomas and Chondrosarcomas of the Skull Base

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.

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.

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%).

To evaluate the quality of life of the patients included in the study, for this, in a period of 3 months after the end of treatment, the patients will be summoned in person at the center to carry out the questionnaire of quality of life for cancer patients EORTC QLQ-C30.

To evaluate the quality of life of the patients included in the study, for this, in a period of 3 months after the end of treatment, the patients will be summoned in person at the center to carry out the questionnaire of quality of life for cancer patients with central nervous system tumors, EORTC QLQ-BN20.

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. For this, apertures will be used whenever necessary to reduce the dose in surrounding tissues and the pre-treatment dosimetric distributions will be verified.

Quironsalud

MD, PhD

Osteosarcoma

Sarcoma, Ewing

Neoplasms, Bone Tissue

Ewing Sarcoma

A single daily beam is used, doubling the dose delivered for this treatment incidence.

Proteus ONE one daily beam

two daily beams are used, in accordance with the initial treatment plan and the patient's standard of care

Proteus ONE two daily beam

Clement DEVIC, PhD

BONDIAU Pierre Yves

Thanks to the intrinsic qualities of the proton beam, proton therapy will reduce adverse effects of irradiation. The Proteus®One is the latest generation of proton therapy equipment, enabling the Centre Antoine Lacassagne to expand its range of treatments by carrying out new proton therapy treatments. It has an innovative compact isocentric rotating head (Gantry) that allows the radiation beam to be directed at different angles around the patient. In some cases, two beams are used to treat tumours, and by convention, both beams are delivered during the same session. However, it is necessary to position the patient before each beam, which is time-consuming because 2 beams have to be positioned very precisely each day. The aim of this study is therefore to assess the toxicity of proton therapy delivered by a single daily beam compared with proton therapy delivered by two daily beams, which is the conventional technique.

Analysis of the Toxicity and Efficacy of Daily 1 vs 2 Beam Proton Therapy

Analysis of the Toxicity and Efficacy of Daily 1 vs 2 Beam Proton Therapy : Analysis of the Toxicity and Efficacy of Daily 1 vs 2 Beam Proton Therapy

Assessment of the incidence of grade ≥2 medical device-related toxicities assessed according to CTCAE version 5.0 in each of the two treatment arms.

Efficacy will be assessed in terms of relapse rate

Efficacy will be assessed in terms of local control by MRI assessment

Efficacy will be assessed in terms of overall survival

Quality of life will be assessed using the EORTC QLQ-C30 scale (Appendix 2), version 3 at the inclusion assessment, at the end-of-treatment visit and at each assessment visit for five years. Version 3.0 of the QLQ-C30 has four-point scales for the items 1 to 28 namely : 1 : "Not a tall", 2 : "A little", 3 : "Quite a bit" and 4 : "Very much." Higher score mean worse outcome. Item 29 and 30 has seven-point scales from 1 : " very bad " to 7 "Excellent". Lower score mean worse outcome.

Time savings will be assessed by measuring the time taken for door-to-door proton therapy treatment sessions.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Assessing Two Models of Hypofractionated Protontherapy on Large Choroidal Melanomas	NCT02602756	Melanoma	Protontherapy	18 Years -	Centre Antoine Lacassagne
Chemo-radiotherapy Versus Radiotherapy in the Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy)	NCT02998385	HNSCC	Cisplatin radiotherapy	18 Years -	Groupe Oncologie Radiotherapie Tete et Cou
Improvement of Local Control in Skull Base, Spine and Sacral Chordomas Treated by Surgery and Protontherapy Targeting Hypoxic Cells Revealed by [18F]FAZA) PET/CT Tracers	NCT02802969	Skull Base Chor... Vertebral Chord...	Surgery Protontherapy 18F FAZA	18 Years -	Institut Curie
Management of Pediatric Craniopharyngioma by a Combination of Partial Surgical Resection, and Protontherapy (Craniopharyngioma)	NCT02842723	Craniopharyngio...	Protontherapy	3 Years - 16 Years	Institut Curie
Hypofractionated Protontherapy in Chordomas and Chondrosarcomas of the Skull Base	NCT05861245	Chordoma Chondrosarcoma	5-fraction hipo...	18 Years -	Quironsalud
Analysis of the Toxicity and Efficacy of Daily 1 vs 2 Beam Proton Therapy	NCT06029218	Chordoma Chondrosarcoma Ewing Sarcoma Osteosarcoma	Proteus ONE one... Proteus ONE two...	18 Years -	Centre Antoine Lacassagne
Improvement of Local Control in Skull Base, Spine and Sacral Chordomas Treated by Surgery and Protontherapy Targeting Hypoxic Cells Revealed by [18F]FAZA) PET/CT Tracers	NCT02802969	Skull Base Chor... Vertebral Chord...	Surgery Protontherapy 18F FAZA	18 Years -	Institut Curie
Improvement of Local Control in Skull Base, Spine and Sacral Chordomas Treated by Surgery and Protontherapy Targeting Hypoxic Cells Revealed by [18F]FAZA) PET/CT Tracers	NCT02802969	Skull Base Chor... Vertebral Chord...	Surgery Protontherapy 18F FAZA	18 Years -	Institut Curie

Spots Global Cancer Trial Database for protontherapy