Spinal Palliation in Irradiation for Neoplastic Analgesia and Life Quality

Official title

Étude de Non infériorité Sur l'Impact de la Diminution Des Volumes d'Irradiations vertébraux en Cas d'Irradiation Palliative Rachidienne métastatique Osseuse Sur l'efficacité Antalgique

Overview

The goal of this clinical trial is to assess the impact of reducing the volume of palliative metastatic bone irradiation on analgesic effectiveness at day 30 and to evaluate the efficiency of telemonitoring in identifying patients who could benefit from Patient-Reported Outcomes (PROs) and require care. These objectives will be addressed in a multicenter, randomized, prospective study with two arms: A standard arm with spinal irradiation without sparing the adjacent vertebrae. An experimental arm with spinal irradiation sparing the adjacent vertebrae. The results will determine whether reducing the irradiated volume can maintain effective pain relief while minimizing side effects.

Detailed description

Palliative analgesic radiotherapy (RT) is used to relieve pain in patients with bone metastases. This technique involves irradiating the vertebrae above and below the ones responsible for the pain. Traditional two-dimensional radiotherapy (2D-RT) was characterized by a physical penumbra that could extend up to 50% of a vertebra's height, leading to underdosing of the target volume and, consequently, reduced analgesic effectiveness.

However, computed tomography (CT) scans or CT-based imaging have replaced these practices, allowing for high precision in delineating target volumes. Despite advancements in irradiation techniques, the physical penumbra is now negligible with modern machines, reducing the need for large margins and thereby limiting side effects associated with the irradiation of healthy tissues.

These factors have led us to conduct a clinical trial to assess the impact of reducing the volume of palliative metastatic bone irradiation on analgesic effectiveness at day 30 (D30) and to evaluate the efficiency of telemonitoring in identifying patients who could benefit from Patient-PROs and require care.

These objectives will be pursued in a multicenter, randomized, prospective study with two arms:

A standard arm, with spinal irradiation without sparing the adjacent vertebrae. An experimental arm, with spinal irradiation sparing the adjacent vertebrae. The results will determine whether reducing the irradiated volume can maintain effective pain relief while minimizing side effects. This could lead to changes in current palliative radiotherapy practices, reduce toxicity risks, and improve patients' quality of life.

Interventions

• Radiation Sparing irradiation
  For "Sparing irradiation" arm the Clinical Target Volume (CTV) = Growth Tumor Volume (GTV) + entire vertebra opposite.
• Radiation Conventional spinal irradiation
  For "conventional spinal irradiation" arm, Clinical Target Volume (CTV ) = Growth Tumor Volume (GTV) + entire vertebra opposite + 1 vertebra above and below.

Primary outcome measures

• Impact of Reducing the Volume of Palliative Bone Metastatic Irradiation on Analgesic Efficacy [Time frame: From enrollment to the end of treatment at day 30 after the first irradiation.]

Secondary outcome measures (11)

• Tolerance of Reducing the Volume of Palliative Bone Metastatic Irradiation [Time frame: From enrollment to the 30 days after the first irradiation session]
• Impact of a remote monitoring tool on quality of life [Time frame: From enrollment to the 30 days after the first irradiation session]
• Evaluation of Quality of life Bone Metastases Module [Time frame: From enrollment to the 30 days after the first irradiation session]
• Level of adherence [Time frame: From enrollment to 45 days after the first irradiation]
• Use of a remote monitoring tool [Time frame: From enrollment to 45 days after the first irradiation]
• Patient satisfaction [Time frame: From enrollment to 30 months after the first irradiation]
• Medical care patient satisfaction [Time frame: From enrollment to 30 months after the first irradiation.]
• Rate of analgesic re-irradiation [Time frame: From enrollment to 30 days after the first irradiation session and after 12 months]
• Correlation between dosimetric constraints for organs at risk (OARs) and the associated grade 0, 1, 2, and 3 acute toxicities [Time frame: From enrollment to 12 months after the first irradiation session.]
• Construction of a Prognostic Score [Time frame: From enrollment to 12 months after the first irradiation session.]
• Overall survival [Time frame: From enrollment to 12 months after the first irradiation session.]

Eligibility criteria

Inclusion criteria

• Patient with bone pain related to at least 1 or more bone metastases of spinal location, contiguous or not, cervical (excluding C1), thoracic, lumbar or sacral up to and including S2; a patient can be included even if he or she is irradiated concomitantly or not for analgesic purposes on another non-spinal bone metastatic site. Bone lesions are objective on an imaging examination less than 3 months old: CT and/or MRI and/or PET and/or bone scintigraphy;
• Patient with at least moderate pain with EN ≥ 5;
• Patient on analgesic drug treatment for at least 7 days or poor tolerance of analgesics;
• Patient irradiated for palliative analgesic purposes. Post-cementoplasty irradiation is possible; an extension to the soft tissues is not a contraindication to inclusion;
• Patient with a validated palliative bone irradiation plan: 8 Gy / 1 fr or 20 Gy / 5 fr;
• Patient with planning only in static IMRT, arc therapy or helical tomotherapy;
• Patient with a primary cancer or a haemopathy;
• Patient currently undergoing or not a specific oncological systemic treatment, left to the discretion of the investigating physician;
• Patient currently undergoing or not a treatment with bisphosphonates and denosumab, left to the discretion of the investigating physician;
• WHO ≤ 2;
• Patient with a life expectancy ≥ 3 months;
• Patient able and agreeing to follow all study procedures in accordance with the protocol;
• Patient having understood, signed and dated the consent form;
• Patient affiliated to the social security system.

Exclusion criteria

• Pediatric patient;
• Patient undergoing stereotaxic irradiation;
• Patient undergoing oligometastatic disease;
• Patient undergoing re-irradiation unless the dose is not limiting to OARs;
• Patient treated with RT2D (conventional 2-dimensional radiotherapy) or RT3D (conventional 3-dimensional radiotherapy);
• Patient with MESCC (metastatic epidural spinal cord compression) except for a Bilsky grade < 1b;
• Patient who does not have a means of responding to online questionnaires;
• Patient and their entourage who cannot read or express themselves in French;
• Visually impaired patient;
• Patient already included in another therapeutic trial with an experimental molecule;
• Persons deprived of liberty or under guardianship (including curatorship).
• Pregnant woman, likely to be pregnant, or breastfeeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 4 centers

• Centre Hospitalier Universitaire de Brest — Brest
• Centre Henri Becquerel Rouen — Rouen
• Institut de cancérologie de l'Ouest (ICO) — Saint-Herblain
• Institut de Cancérologie de Lorraine — Vandœuvre-lès-Nancy

Publications

• Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, Billings JA, Lynch TJ. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010 Aug 19;363(8):733-42. doi: 10.1056/NEJMoa1000678. PMID 20818875
• Fisher CG, DiPaola CP, Ryken TC, Bilsky MH, Shaffrey CI, Berven SH, Harrop JS, Fehlings MG, Boriani S, Chou D, Schmidt MH, Polly DW, Biagini R, Burch S, Dekutoski MB, Ganju A, Gerszten PC, Gokaslan ZL, Groff MW, Liebsch NJ, Mendel E, Okuno SH, Patel S, Rhines LD, Rose PS, Sciubba DM, Sundaresan N, Tomita K, Varga PP, Vialle LR, Vrionis FD, Yamada Y, Fourney DR. A novel classification system for sp PMID 20562730
• Basch E, Barbera L, Kerrigan CL, Velikova G. Implementation of Patient-Reported Outcomes in Routine Medical Care. Am Soc Clin Oncol Educ Book. 2018 May 23;38:122-134. doi: 10.1200/EDBK_200383. PMID 30231381
• Marino D, Baratelli C, Guida G, Turco CGC, Lacidogna G, Sperti E, Vignani F, De Luca E, Zichi C, Audisio M, Ballaminut D, Bellezza A, Chiotto P, Ciriolo G, Comite R, Codegone F, Florio S, Fusco L, Polimeno L, Pozzi D, Zilio E, Terzolo S, Di Maio M. Impact of adoption of patient-reported outcomes in clinical practice on the accuracy of symptom reporting in medical records of cancer patients. Recent PMID 33362171
• Basch E, Iasonos A, McDonough T, Barz A, Culkin A, Kris MG, Scher HI, Schrag D. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol. 2006 Nov;7(11):903-9. doi: 10.1016/S1470-2045(06)70910-X. PMID 17081915
• Di Maio M, Gallo C, Leighl NB, Piccirillo MC, Daniele G, Nuzzo F, Gridelli C, Gebbia V, Ciardiello F, De Placido S, Ceribelli A, Favaretto AG, de Matteis A, Feld R, Butts C, Bryce J, Signoriello S, Morabito A, Rocco G, Perrone F. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015 Mar 10;33 PMID 25624439
• Stromgren AS, Groenvold M, Sorensen A, Andersen L. Symptom recognition in advanced cancer. A comparison of nursing records against patient self-rating. Acta Anaesthesiol Scand. 2001 Oct;45(9):1080-5. doi: 10.1034/j.1399-6576.2001.450905.x. PMID 11683656
• Basch E. The missing voice of patients in drug-safety reporting. N Engl J Med. 2010 Mar 11;362(10):865-9. doi: 10.1056/NEJMp0911494. No abstract available. PMID 20220181

Identifiers

NCT: NCT06884332 · 2024-A02789-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗