Elsevier

Bone

Volume 94, January 2017, Pages 84-89
Bone

Full Length Article
Early dose-dependent cortical thinning of the femoral neck in anal cancer patients treated with pelvic radiation therapy

https://doi.org/10.1016/j.bone.2016.10.021Get rights and content

Highlights

  • The proximal femur absorbs a large radiation dose in anal cancer patients treated with radiation therapy (RT).

  • Rapid, dose-dependent cortical thinning and BMD loss was observed in the inferior femoral neck (FN) of anal cancer patients.

  • FN volume receiving ≥ 40 Gy (V40Gy) was a significant predictor of clinically significant focal cortical bone thinning.

Abstract

Background and purpose

Anal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT).

Materials and methods

RT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (≤ 4 months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed.

Results

Twenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p < 0.05). FN volume receiving ≥ 40 Gy (V40Gy) was a significant predictor of focal cortical thinning ≥ 30% (p = 0.03). A significant decrease in FN trBMD was observed (− 6.4% [range − 34.4 to 3.3%]; p = 0.01).

Conclusion

Significant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning.

Introduction

Definitive chemo-radiation therapy (CRT) has become the standard of care for treating localized squamous cell carcinoma (SCC) of the anal canal [1]. Bone toxicity is a major concern after pelvic radiation therapy (RT) [2], [3], [4]. Incidence of femoral and pelvic insufficiency fracture is significantly higher in patients that receive pelvic RT [5], [6], [7], [8]. Female anal cancer patients over the age of 65 treated with pelvic RT have a three-fold increase in pelvic and femoral fractures within the first five years following treatment based on Surveillance, Epidemiology, and End Results (SEER) cancer registry data [8]. Importantly, these fractures are associated with direct exposure of bone to ionizing radiation [8], [9]. Femoral fractures tend to be located within the subcapsular femoral neck (FN) and intertrochanteric region [10], [11].

Treating fractures in irradiated bone is complicated due to associated morbidity and mortality. The rate of non-union is high in RT-induced fractures [12], [13]. Even with effective intervention, chronic pelvic and back pain and impaired mobility are common after fracture [14]. These complications are detrimental to quality of life [14]. Pelvic fractures, especially FN fractures, are particularly morbid in geriatric patients. Mortality rates are twice as high within five years following fracture due to associated complications [15].

Significant toxicity after CRT for anal cancer has motivated the use of more conformal RT techniques, such as intensity-modulated radiotherapy (IMRT). IMRT conforms to a given target volume, allowing for sparing of higher RT doses to surrounding structures [16]. This technique reduces dose to organs at risk (OARs), but may increase the integral dose deposited to the surrounding tissue by each beamlet [17].

Anal cancer has a high propensity to spread to pelvic lymph nodes [2]. Involved inguinal nodes, which abut the FN, are usually treated in anal cancer. Nodal irradiation exposes the hip to a relatively high RT dose, even with highly conformal techniques [16], [17]. Major Radiation Therapy Oncology Group (RTOG) prospective trials have included dose constraints for the femoral head in anal cancer patients; however constraints for the FN, a region biomechanically at risk for fracture, have not been employed [2].

The etiology of radiation-induced fracture is unclear, however, it appears fracture likely results from bone damage and deterioration [10–12, 18]. Cortical thickness (Ct.Th) is a major feature of bone strength, and thinning may reflect microstructural deterioration [10], [18]. We have previously identified acute cortical bone thinning at sites within the ribcage that receive ≥ 10 Gy during thoracic stereotactic body radiation therapy (SBRT) for primary and metastatic lung lesions [19]. In this study, we examine early post-treatment changes in Ct.Th and trabecular bone mineral density (trBMD) of the proximal femur in anal cancer patients treated with IMRT and assess the dose-volume relationships between RT and focal cortical thinning within the FN.

Section snippets

Data collection

Pelvic computed tomography (CT) scans and RT plans of 23 patients treated for anal cancer with CRT from 2012 to 2014 at our institution were retrospectively reviewed as part of an Institutional Review Board-approved study. Patients were treated with dynamic multi-leaf collimator IMRT using 6–9 coplanar or non-coplanar, non-uniform beams. Doses, fractionation schemes, and treatment volumes were based on the guidelines used in the RTOG 0529 protocol [2]. Mesorectal, inguinal, internal and

Results

Between November 2012 and December 2014, 23 patients were treated with CRT for localized squamous cell carcinoma (SCC) of the anal canal at our institution. Of these 23, one patient was excluded due to a leg amputation prior to treatment. Patients were treated to a median total dose of 55 Gy (range 53.4–58.1 Gy) to the gross tumor volume (GTV), with pelvis and inguinal lymph nodes receiving a median dose of 50 Gy (45–58 Gy) in 1.8 Gy daily fractions (Table 1). The planned treatment volume (PTV) was

Discussion

Pelvic and femoral fractures are a substantial source of morbidity and mortality in patients treated with pelvic RT [5], [6], [8], [9], [21], [22], [23]. In 2005, Baxter et al. conducted a retrospective cohort study using SEER cancer registry data and identified a significant increase in the incidence of pelvic and hip fracture in older women (≥ 65 years) who were treated for rectal, anal, or cervical cancer between 1989 through 1999 [8]. Interestingly, the increase in fracture risk was

Conclusion

In this study, we applied novel CT image processing techniques to measure early post-RT changes in FN Ct.Th and trBMD of anal cancer patients receiving CRT using IMRT. Early (< 4 months) focal Ct.Th and trBMD loss was observed in the FN. The FN V40Gy was the most significant predictor for focal FN cortical thinning. These early structural changes may contribute to post-RT fracture in these patients.

Conflict of interest

None.

Funding

This research received no specific grant from any funding agency.

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