Optimization of Fractionation Schedules of Heel Spur Radiotherapy Prospective Randomized Open-label Trial

Heel Spur Clinical Trial

Official title:

Optimization of Fractionation Schedules of Heel Spur Radiotherapy: Monocentric Prospective Randomized Open-label Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06104410
• Other study ID #: NU22-10-00479
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Masaryk Memorial Cancer Institute
• Contact: Tomas Kazda, MD
• Phone: +420543136902
• Email: tomas.kazda[@]mou.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

About 26 000 patients are treated per year with radiotherapy for non-malignant diseases in the Czech Republic, majority of them with heel spur syndrome which prevalence ranges from 8-10% in the general population. Heel spur represents important socioeconomic as well as health care issue. Radiotherapy by orthovoltage X-ray belongs to standard conservative treatment methods with proven antiinflammatory effect. Nevertheless, with increasing incidence of cancer, it may be assumed that availability of radiotherapy service for heel spur patients will be further limited including limitations related to potential pandemic or other emergency situation. This represents upcoming unmet clinical need, where alternative approaches with dramatically abbreviated fractionation schedules are needed in order to keep availability as well as effectivity of heel spur (and other non-malignant disorders) radiotherapy.

The aim to presented single institutional prospective randomized open-lable clinical trial is to evaluate low dose radiotherapy delivered in single fraction manner in the treatment of heel spur syndrome.

The project aims to design a randomized trial that compared fractionated and single fraction radiotherapy (non-inferiority). Patients will be randomized into 6 groups according to the total dose, total of 966 patients will be enrolled. The primary objective is to compare Calcaneodynia sum score at 3 months after radiotherapy between fractionated vs. single fraction radiotherapy.

Description:

Purpose/Objective The aim of this study is to optimize the fractionation schedules for radiotherapy in the treatment of heel spurs (HSS, plantar fasciitis) through a prospective randomized open-label trial conducted at Department of Radiation Oncology at Masaryk Memorial Cancer Institute Brno (MMCI). Low-dose external beam radiotherapy (LD-EBRT), known for its anti-inflammatory effect, offers effective pain relief for HSS patients. Currently, the standard LD-EBRT regimen consists of six fractions of 1 Gray (Gy) administered twice weekly, resulting in a total dose of 6 Gy. This study posits the hypothesis that very low total doses of orthovoltage radiotherapy, delivered in a single fraction, may provide pain relief comparable to that achieved with higher doses of fractionated radiotherapy. The primary goal of this research is to determine whether one-day irradiation (a single fraction) is non-inferior to fractionated radiotherapy over a three-month period in terms of pain relief for HSS patients. This study was supported by grant of the Ministry of Health of the Czech Republic AZV NU22-10-00479. All patients signed informed consent.

Material/Methods After completing the enrollment process and filling out the SF-36 questionnaire, as well as the Calcaneodynia score (CS) and visual analogue pain score (VAS) forms, patients (pts) meeting specific inclusion criteria (being over 40 years old, having a diagnosed painful unilateral plantar HSS for at least six months, and being suitable for HSS radiotherapy), and fulfilling the main exclusion criteria (having no prior history of radiotherapy for heel spur, no corticosteroid local application in the four weeks leading up to radiotherapy, no systemic rheumatic or collagen vascular diseases, lymphatic edema of the lower limb, or prior trauma and surgery on the ipsilateral foot), were randomized into six groups based on the total dose of radiotherapy. Patients in these groups received a total dose of 6 Gy in 4 fractions of 1.5 Gy twice weekly (arm A), a total dose of 3 Gy in 2 fractions of 1.5 Gy twice weekly (arm B), a single fraction of 0.5 Gy (arm C), a single fraction of 1.0 Gy (arm D), a single fraction of 1.5 Gy (arm E), and a single fraction of 2 Gy (arm F), respectively. The regimen in arm A (6 Gy in 4 fractions) is commonly used in MMCI and considered as the standard arm. In the event of inadequate pain relief, reirradiation was performed with a total dose of 6 Gy in 4 fractions of 1.5 Gy twice weekly after a waiting period of three months in any of the aforementioned groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 430
• Est. completion date: December 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

All patients referred to medical attention for non-malignant radiotherapy at the Department of Radiation oncology, Masaryk Memorial Cancer Institute (MMCI), will be screened for eligibility, and if all inclusion/exclusion criteria are met, they will be invited to participate in the present study.

Inclusion Criteria:

• 1) Patients aged over 40 years who have been diagnosed clinically and radiologically to be suffering from a painful unilateral plantar heel spur for at least six months,

• 2) indication to heel spur radiotherapy,

• 3) 40 years or older patient, good performance status (Karnofsky index = 70),

• 4) exclusion of other local diseases by the orthopaedic surgeon,

• 5) willingness of the patient to provide telephone or email contact to maintain follow up.

Exclusion Criteria:

• 1) Prior radiotherapy of heel spur (even if prior radiotherapy was performed on the contralateral heel spur because of possible bias given patient's expectations and experiences related to previous radiotherapy,

• 2) corticosteroid local application during last 4 weeks prior to planned radiotherapy,

• 3) rheumatic or vascular diseases, lymphatic edema of lower limb,

• 4) former trauma or surgery of ipsilateral foot,

• 5) any systemic illness (collagen vascular diseases) or unstable medical condition that might pose additional risk for performance of radiotherapy including claustrophobia or jactation,

• 6) any other factors that, in the opinion of the site investigators, would interfere with adherence to study requirements,

• 7) pregnancy or breastfeeding,

• 8) inability or unwillingness of subject to sign written informed consent.

Related Conditions & MeSH terms

• Heel Spur

Intervention

Radiation:
• Standard fractioned dose
Total dose of 6 Gy in 2 or 4 single fractions of 1.5 Gy applied twice weekly.
• Experimental single dose
Total dose of 0.5 Gy, 1Gy, 1.5 or 2Gy in 1 single fraction.

Locations

Country	Name	City	State
Czechia	Masaryk Memorial Cancer Institute	Brno

Sponsors (1)

Lead Sponsor	Collaborator
Masaryk Memorial Cancer Institute

Country where clinical trial is conducted

Czechia, 

References & Publications (16)

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Bentzen SM. Radiation therapy: intensity modulated, image guided, biologically optimized and evidence based. Radiother Oncol. 2005 Dec;77(3):227-30. doi: 10.1016/j.radonc.2005.11.001. Epub 2005 Nov 21. No abstract available. — View Citation

Buchbinder R. Clinical practice. Plantar fasciitis. N Engl J Med. 2004 May 20;350(21):2159-66. doi: 10.1056/NEJMcp032745. No abstract available. — View Citation

Crawford F, Thomson C. Interventions for treating plantar heel pain. Cochrane Database Syst Rev. 2003;(3):CD000416. doi: 10.1002/14651858.CD000416. — View Citation

DeMaio M, Paine R, Mangine RE, Drez D Jr. Plantar fasciitis. Orthopedics. 1993 Oct;16(10):1153-63. doi: 10.3928/0147-7447-19931001-13. No abstract available. — View Citation

Dufek V, Zackova H, Kotik L, Horakova I. RESULTS OF CZECH NATIONAL STUDY OF RADIATION EXPOSURE FROM RADIOTHERAPY OF NON-MALIGNANT DISEASES, IN PARTICULAR OF HEEL SPURS. Radiat Prot Dosimetry. 2019 Dec 31;186(2-3):386-390. doi: 10.1093/rpd/ncz237. — View Citation

Heyd R, Tselis N, Ackermann H, Roddiger SJ, Zamboglou N. Radiation therapy for painful heel spurs: results of a prospective randomized study. Strahlenther Onkol. 2007 Jan;183(1):3-9. doi: 10.1007/s00066-007-1589-1. — View Citation

Kern P, Keilholz L, Forster C, Seegenschmiedt MH, Sauer R, Herrmann M. In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol. 1999 Aug;75(8):995-1003. doi: 10.1080/095530099139755. — View Citation

Kern PM, Keilholz L, Forster C, Hallmann R, Herrmann M, Seegenschmiedt MH. Low-dose radiotherapy selectively reduces adhesion of peripheral blood mononuclear cells to endothelium in vitro. Radiother Oncol. 2000 Mar;54(3):273-82. doi: 10.1016/s0167-8140(00)00141-9. — View Citation

Kriz J, Seegenschmiedt HM, Bartels A, Micke O, Muecke R, Schaefer U, Haverkamp U, Eich HT. Updated strategies in the treatment of benign diseases-a patterns of care study of the german cooperative group on benign diseases. Adv Radiat Oncol. 2018 Feb 26;3(3):240-244. doi: 10.1016/j.adro.2018.02.008. eCollection 2018 Jul-Sep. — View Citation

Niewald M, Seegenschmiedt MH, Micke O, Graeber S, Muecke R, Schaefer V, Scheid C, Fleckenstein J, Licht N, Ruebe C; German Cooperative Group on Radiotherapy for Benign Diseases (GCGBD) of the German Society for Radiation Oncology (DEGRO). Randomized, multicenter trial on the effect of radiation therapy on plantar fasciitis (painful heel spur) comparing a standard dose with a very low dose: mature results after 12 months' follow-up. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e455-62. doi: 10.1016/j.ijrobp.2012.06.022. Epub 2012 Jul 25. — View Citation

Ott OJ, Jeremias C, Gaipl US, Frey B, Schmidt M, Fietkau R. Radiotherapy for benign calcaneodynia: long-term results of the Erlangen Dose Optimization (EDO) trial. Strahlenther Onkol. 2014 Jul;190(7):671-5. doi: 10.1007/s00066-014-0618-0. Epub 2014 Mar 26. — View Citation

Rowe CR, Sakellarides HT, Freeman PA, Sorbie C. Fractures of the Os Calcis: A Long-Term Follow-up Study of 146 Patients. JAMA. 1963;184(12):920-923. doi:10.1001/jama.1963.03700250056007

Seegenschmiedt MH, Keilholz L, Katalinic A, Stecken A, Sauer R. Heel spur: radiation therapy for refractory pain--results with three treatment concepts. Radiology. 1996 Jul;200(1):271-6. doi: 10.1148/radiology.200.1.8657925. — View Citation

Seegenschmiedt MH, Keilholz L, Stecken A, Katalinic A, Sauer R. [Radiotherapy of plantar heel spurs: indications, technique, clinical results at different dose concepts]. Strahlenther Onkol. 1996 Jul;172(7):376-83. German. — View Citation

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* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-inferiority of single fraction radiotherapy of heel spur	Comparison of 2 arms in 3 months after radiotherapy.Follow-up examinations consist of personal examination,questionnaire survey.Calcaneodynia sum score (100=free of symptoms, 0=very intense symptoms) is calculated by evaluation of Pain symptoms (up to 30 points),Use of appliances (up to 15 points),Professional activities (up to 20 points),Daily/leisure activities (up to 15 points) and Gaint/limp (up to 20 points). Complete pain relief will be assumed if patients will be completely free of pain and regained full ability to walk and function well.Insufficient pain relief will be assumed,if the patient's subjective evaluation (VAS score) of improvement of pain will be less than 80% or if the temporal pattern of clinical response will be unsatisfactory (ie, response will be delayed >3 months or there will be need for second radiotherapy course.Skin toxicity will be evaluated according Common Terminology Criteria for Adverse Events (CTCAE) v5. VAS and SF36 are described in Outcome 4.	44 months
Secondary	Comparison of different single fraction radiotherapy prescription	Comparison of Calcaneodynia sum score at 3 months after radiotherapy between different single fraction radiotherapy prescription. Calcaneodynia sum score (100 = free of symptoms, 0 = very intense symptoms) is calculated by evaluation of Pain symptoms (up to 30 points), Use of appliances (up to 15 points), Professional activities (up to 20 points), Daily/leisure activities (up to 15 points) and Gaint/limp (up to 20 points).	44 months
Secondary	Comparison of the need for reirradiation till 1 year after radiotherapy between fractionated vs. single fraction radiotherapy	To compare the need for reirradiation till 1 year after radiotherapy between fractionated vs.; single fraction radiotherapy. To compare the need of reirradiation till 1 year after radiotherapy between different single fraction radiotherapy prescription. Evaluated simply by keeping score of patients returning for irradiation till 1 year after radiotherapy.	44 months
Secondary	Comparison of quality of life and VAS score at 1.5, 3, 6, 9 and 12 months and Calcaneodynia sum score at 1.5, 6, 9 and 12 months between fractionated vs. single fraction radiotherapy and between different single fractions radiotherapy prescription.	Visual analogue scale (VAS) score is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain." (0 = no pain, 100 = maximum imaginable pain intensity).SF-36 questionnaire score taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions and single item that provides an indication of perceived change in health. High values indicates good quality of life.	44 months
Secondary	Evaluation of individual (not sum) parts of Calcaneodynia score and individual domains of quality of life	Evaluation of individual (not sum) parts of Calcaneodynia score and individual domains of quality of life as per outcome 1,2 and 4. Calcaneodynia score form is attached in separate file in this project proposal. Sum score (100 = free of symptoms, 0 = very intense symptoms) is calculated by evaluation of Pain symptoms (up to 30 points), Use of appliances (up to 15 points), Professional activities (up to 20 points), Daily/leisure activities (up to 15 points) and Gaint/limp (up to 20 points).	44 months
Secondary	Analysis of the heel spur radiotherapy techniques in Czechia	Conducting a questionnaire survey analyzing the technique of heel spur radiotherapy at individual workplaces performing this type of treatment in Czechia. The questionnaires will be conducted by Masaryk Memorial Cancer Institute and sent to other facilities in Czechia. Results will be evaluated.	44 months