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Heterotopic Ossification

Radiation Therapy

Radiation therapy or radiotherapy, which is the use of ionizing radiation for therapeutic ends, has been proposed as a possible adjunct treatment for HO.

Author Year; Country
Research Design
Score
Total Sample Size		 Methods Results

Honore et al. 2020; France
Case Control N=95

Population: Case Group (n=19; SCI=11, traumatic head injury=8): Mean age: 24.2 yr; Gender: males=19, females=0; Level of injury: cervical=3, thoracic=8, lumber=0; Severity of injury: complete=9, incomplete=2; Mean time since injury: 12.6 mo; Control Group (n=76; SCI=44, traumatic head injury=32): Mean Age: 25.3 yr; Gender: males=76, females=0; Level of injury: cervical=11, thoracic=30, lumber=2; Severity of injury: complete=32, incomplete=12; Mean time since injury: 18 mo.
Intervention: The case group underwent HO excision and received perioperative radiotherapy on the operated area. For the majority of case patients, the radiotherapy involved a single preoperative session (at a dose of 7.5 Gy, with 15 or 18 MV X-ray photons) carried out on the day before surgery. The control group underwent HO excision only. Each patient was paired with four control patients.
Outcome Measures: Primary Outcome Measure: recurrence of heterotopic ossification; Secondary Outcome Measures: postoperative complications (i.e., sepsis that required surgical revision).

 
  1. Symptomatic recurrence occurred in 10.5% of the case patients (n=2).
  2. Almost half of case patients (n=9) developed complications (due to postoperative sepsis) after surgical excision and radiotherapy, requiring surgical revision.
  3. Symptomatic recurrence occurred in 5.3 % of the control patients (n=4).
  4. Almost one-third of control patients (n=23) developed complications after surgical excision, and 21% (n=16) required surgical revision due to postoperative sepsis.
  5. There was no difference between the odds ratios (OR) for recurrence for each group (OR case group=0.63, OR spinal cord injury subgroup=0.45 and OR head injury subgroup=1.04).
  6. The rate of sepsis requiring surgical revision was significantly higher in the case group (p < 0.05).
Museler et al. 2017; Germany
Case Series
N=244

Population: Mean age: 46.4 yr; Gender: males=207, females=37; Severity of injury: AIS: A=220, B=8, C=12, D=4.
Interventions: Single-dose radiation therapy at the hip for HO. Mean time of treatment was 4.9 days. Treatment was administered with either 15 MV or 6 MV.
Outcome Measures: HO recurrence, side effect due to radiation.
  1. Of the 244 patients, 13 experienced recurrence of HO. All 13 patients initially experienced HO in both hips. Of the 444 initial cases of HO, there were 26 instances of recurrence.
  2. No patients experienced negative side-effects as a result of radiation treatment.
Sautter-Bihl et al. 2001; Germany
Case Series
N=52

Population: Mean age: 33 yr; Gender: males=44, females=8;
Treatment: Patients received a single dose of radiotherapy 2-10Gy through a linear accelerator at 6-8 MV photons.
Outcome Measures: Efficacy, Brooker classification, adverse effects.
  1. Prevention of HO was seen in 71% of (41 primarily treated, 9 resected) joints.
  2. Radiotherapy treatment did not result in a regression of the Brooker score in any patient.
  3. An increase in two Brooker score grades was seen in two joints (1 knee, 1 hip)
  4. No adverse effects due to therapy occurred.
  5. 16 of 32 hips treated only with radiotherapy (50%) did not show any abnormalities on follow-up.
  6. No progression of HO was noted in 30/36 subjects (83%).
  7. Re-ossification after therapy which led to a decrease in joint mobility was noted in three subjects.
Sautter-Bihl et al. 2000; Germany
Case Series
N=36

Population: Age range: 17-59 yr; Gender: males=32, females=4; Follow-up range: 4-98mo.
Treatment: 25/36 subjects received 10 Gy radiotherapy in fraction of 2-2.5 Gy, while four patients received higher doses. In phase 2 seven subjects received a single does of irradiation with 8Gy. In total, 46 joints were irradiated.
Outcome Measures: Progression of HO and complications.
  1. No statistically significant results were reported.
  2. 16 of the 32 hips treated with radiotherapy only did not show any abnormalities on follow-up.
  3. No progression of HO was noted in 30/36 subjects.
  4. Re-ossification after therapy, which led to a decrease in joint mobility was noted in three subjects.

Discussion

Sautter-Bihl et al. (2000) studied 36 patients with HO of whom 27 patients (32 joints) received radiotherapy when ossification was minimal. 11 patients (13 joints) had obvious ossifications, which had to be resected. Post-op radiotherapy was performed 24-36 hours post-operatively. Two patients received radiotherapy both before and after surgery. The mean duration of follow-up was 23.6 months. 30 of the 36 irradiated patients showed no progression of HO. In three patients, re-ossification after therapy resulted in a moderate decrease in joint mobility.

In the follow-up case series by Sautter-Bihl et al. (2001), the authors examined the effectiveness of radiotherapy administered to 52 SCI patients. Radiotherapy effectively prevented primary and secondary HO post-surgical excision in 71% of patients. However, treatment did not result in regression of HO once developed, as measured by the Brooker scale. Two joints increased in Brooker score, although neither of them developed any functional impairment. Another case series by Museler et al. (2017) used either 15 MV or 6 MV radiotherapy to target HO at the hip in 244 patients. Recurrence of HO was found to be very low (5.3%), and of those that experienced recurrence, HO was initially present in both hips.

In a case control study by Honore et al. (2020), patients with SCI and traumatic head injury underwent either excision and radiotherapy before surgery (at a dose of 7.5 Gy, with 15 or 18 MV X-ray photons; case group) or excision only (control group). The results revealed no differences between the odds ratios for HO recurrence between the case group and the control group. In addition, the case group patients were found to be significantly more likely to develop sepsis after surgical excision requiring surgical revision, compared to the control group patients. Based on these findings, the authors concluded that radiotherapy should not be combined with surgery in patients with hip HO undergoing excision.

A case study by Cramarossa et al. (2013) reported on the use of radiation therapy on a patient who had previously experienced an SCI at the C5-C6 level and had been diagnosed with dysphagia due to HO-induced osteophytes. One day after surgical intervention, which involved anterior cervical decompression and drilling of the osteophytes, the patient received a single treatment of radiation at 8 Gy. At follow-up, the patient reported that they were not experiencing any recurrence of dysphagic symptoms. The authors add that radiation should only be considered for patients at high risk of HO due to the risk of creating a radiotherapy-induced malignancy and that an expansion of the literature is required to better assist treatment decisions.

Conclusion

There is level 3 evidence (from one case control study: Honore et al. 2020) that combining radiotherapy with surgery in patients with hip HO undergoing excision may not prevent HO recurrence and may be associated with an increased risk of postoperative sepsis.

There is moderate Level 4 evidence (from three case series studies: Sautter-Bihl et al. 2000; Sautter-Bihl et al. 2001; Museler et al. 2017) that radiotherapy reduces the progression and recurrence of heterotopic ossification.

There is conflicting evidence on whether radiotherapy can reduce the progression and recurrence of heterotopic ossification.

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