Radiation Induced Rib Fractures after Hypofractionated Stereotactic Body Radiation Therapy: The Risk Factors and Dose-Volume Relationship

Reviewer: Samuel Swisher-McClure, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 3 de noviembre del 2010

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English

Authors: K. Asai, Y. Shioyama, S. Ohga, T. Nonoshita, T. Yoshitake, K. Ohnishi, K. Terashima, K. Matsumoto, H. Hirata, H. Honda.
Affilations: Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background

  • Hypofractionated stereotactic body radiation therapy (SBRT) is an effective treatment option for early stage non-small cell lung cancer (NSCLC) and is being increasingly used as a first line treatment option for medically inoperable patients.
  • Long-term follow-up of several phase I/II studies have demonstrated excellent local control rates associated with SBRT.
    • The RTOG 0236 trial (Timmerman et al. JAMA 2010) enrolled 59 patients with medically inoperable T1N0 and T2N0 NSCLC who received SBRT (18 Gy x 3 fractions). After a median follow-up of 34.4 months, the observed local-regional control rate was 87.2% (95% CI, 71.0%-94.7%).
  • SBRT is generally well tolerated but late musculoskeletal toxicities such as chronic chest wall pain and rib fracture have been observed.
    • A retrospective analysis by Petterson et al. (Radiotherapy and Oncology, 2009) found that the risk of rib fracture could be correlated with the dose to 2 cm3 of rib and for some patients was as high as 50% following SBRT.  
  • The purpose of this study was to further clarify the incidence, the risk factors, and the dose-volume relationship of radiation induced rib fracture after SBRT

Materials/Methods

  • Between April 2003 and March 2007, 174 consecutive patients treated with SBRT for primary or metastatic lung cancer were reviewed.
  • Eligible patients were required to have at least 3 months of follow-up by CT scan and no previous overlapped radiation exposure.
  • Radiation induced rib fractures were defined as rib fractures located in the radiation field, detected by CT scan after treatment.
  • SBRT most commonly consisted of:
    • 48 Gy in delivered in 4 fractions or 60 Gy delivered in 10 fractions using 6-8 non-coplanar beams.
  • The risk factors considered in the analysis included: age, gender, GTV diameter, and chest wall - tumor distance. These factors were reviewed and each parameter was divided into two groups with differences then assessed by a log-rank test.
  • Dose-volume histogram analysis was conducted on ribs that received over 20 Gy to a maximal point dose.
  • The maximum dose and absolute volume receiving: ?10 Gy, ?20 Gy, ?30 Gy and ?40 Gy were determined for each rib as dosimetric parameters.
  • The 3- and 5- year Kaplan-Meier (KM) estimates of rib fracture were calculated.
  • The optimal cut off value for each dosimetric parameter was analyzed through the use of receiver-operating characteristic (ROC) curves.
  • The area under the curve (AUC) values were also calculated.
  • To estimate the cumulative risk of fracture, the ribs were divided into two groups according to the cutoff value and compared by log-rank test.

Results

  • There were 129 patients determined to be eligible with a total of 409 ribs that met the inclusion criteria of the study.
  • The median patient age was 75 years.
  • The median follow-up period was 19 months.
  • Among the 129 patients, 26 patients (44 ribs) experienced radiation induced rib fractures.
  • Approximately half of the cases were symptomatic
  • The KM estimates of rib fracture at 3 years and 5 years were 35.3%, and 53.7%, respectively.
  • As a risk factor, chest wall - tumor distance (?2cm vs. < 2cm) was significantly correlated with radiation induced rib fracture (p = 0.0001).
  • Among the dosimetric analyses, AUC values for the max dose, V40, V30, V20 and V10 were 0.84, 0.82, 0.79, 0.71 and 0.56, respectively.
  • The dosimetric parameters found to be associated with increased risk of rib fracture are described in the following table:

Dosimetric Parameter

5- year estimated Risk of Rib Fracture

p-value

Max dose: ? 44.9 Gy vs. < 44.9 Gy

53.5% vs. 3.0%

p < 0.0001

V40: ? 0.43cc vs. < 0.43cc

61.8% vs. 2.0%

p < 0.0001

V30: ? 1.35cc vs. < 1.35cc

54.0% vs. 2.1%

p < 0.0001

V20: ? 3.64cc vs. < 3.64cc

51.5% vs. 8.4%

p < 0.0001

V10: ? 6.01cc vs. < 6.01cc

30.2% vs. 14.6%

p= 0.002

Conclusions

  • The incidence of radiation induced rib fractures after hypofractionated SBRT is relatively high with an overall cumulative incidence of 34.1%.
  • A high dose volume is more strongly correlated with the risk of rib fracture.
  • This study identifies several dosimetric parameters that may be considered when planning SBRT and which may allow for toxicity reduction through further optimization of treatment planning technique.

Clinical Implications

  • This was a retrospective observational study that sought to identify dosimetric parameters associated with increased risk of rib fracture among lung cancer patients receiving hypofractionated SBRT.
  • The study was well designed in terms of its statistical analysis, and identified several factors associated with increased risk of rib fracture including the proximity of the tumor to the chest wall as well as specific dosimetric parameters that correlate with risk of rib fracture.
  • These dosimetric parameters may be considered during optimization of treatment planning in an effort to reduce the incidence of rib fracture in patients receiving SBRT.
  • Contouring of ribs at the time of treatment planning is labor intense and is not yet routinely being performed at many centers performing SBRT. However, given that rib fracture can have significant consequences with respect to patient quality of life; detailed assessment of rib dose should be strongly considered by centers using SBRT.
  • Potential limitations of this study include:
    • The retrospective nature of the data which creates inherent potential for bias or imbalance between patient groups.
    • The authors did not have a detailed assessment of clinical factors that might increase an individual patient's baseline risk of fracture such as decreased bone density, or long term corticosteroid use.
  • The parameters identified by this study could be considered when designing future prospective trials which would provide a more rigorous assessment of rib fracture risk after SBRT.

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