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Postradiation Fractures after Combined Modality Treatment in Extremity Soft Tissue Sarcomas.

ABSTRACT: Soft tissue sarcoma (STS) of the extremities is typically treated with limb-sparing surgery and radiation therapy; with this treatment approach, high local control rates can be achieved. However, postradiation bone fractures, fractures occurring in the prior radiation field with minimal or no trauma, are a serious late complication that occurs in 2-22% of patients who receive surgery and radiation for STS. Multiple risk factors for sustaining a postradiation fracture exist, including high radiation dose, female sex, periosteal stripping, older age, femur location, and chemotherapy administration. The treatment of these pathological fractures can be difficult, with complications including delayed union, nonunion, and infection posing particular challenges. Here, we review the mechanisms, risk factors, and treatment challenges associated with postradiation fractures in STS patients.

SUBMITTER: Bartelstein MK

PROVIDER: S-EPMC7984930 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Postradiation Fractures after Combined Modality Treatment in Extremity Soft Tissue Sarcomas.

Bartelstein Meredith K MK Yerramilli Divya D Christ Alexander B AB Kenan Shachar S Ogura Koichi K Fujiwara Tomohiro T Fabbri Nicola N Healey John H JH

Sarcoma 20210315

Soft tissue sarcoma (STS) of the extremities is typically treated with limb-sparing surgery and radiation therapy; with this treatment approach, high local control rates can be achieved. However, postradiation bone fractures, fractures occurring in the prior radiation field with minimal or no trauma, are a serious late complication that occurs in 2-22% of patients who receive surgery and radiation for STS. Multiple risk factors for sustaining a postradiation fracture exist, including high radiat ...[more]

PMID: 33790687

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Project description:AimTo prospectively assess toxicities of curative-intent intensity-modulated conformal radiotherapy (IMRT) in patients with extremity soft tissue sarcomas (ESTS).MethodsData from 59 consecutive patients with ESTS between 2014 and 2019 were both retrospectively and prospectively analysed. Toxicity data were collected both by confidential mailed survey (39% completed) and medical charts, and graded according to CTCAE v5.0. Normal tissues dosimetric data (healthy soft tissue segment, joint and bone) were included. The healthy soft tissue segment was created by adding 5 cm on either side of the PTV on CT axial slices, the PTV and bone (and articulation if present) were then removed from the generated volume.ResultsIMRT was delivered post-operatively for nearly half of patients (n = 24, 41%), preoperatively for 18 (31%) and exclusively for 17 (28%; salvage: 13% or immediately inoperable: 15%). The median total dose delivered to the planned target volume (PTV) was 50.4 Gy (36-68 Gy) and 13 patients (22%) received a boost. With a median follow-up of 27 months (6-94 months), a total of 87 late effects were identified in 44/59 (75%) patients: 89% G1-2, and 11% G3-4. The main G1-2 toxicities were: functional limitation (36%), oedema (29%), gait disorders (20%), neurological disorders (20%) and chronic pain (32%). G3-4 toxicities were pain (n = 2), arterial stricture (n = 1) and a chronic wound requiring skin graft (n = 2). No bone fracture was observed. Quality of life was rated as good or very good in 70% patients who completed the survey. Larger (>3500 cm3) healthy soft tissue segment volume was associated with decreased late toxicities (p = 0.02). No other predictive factor of toxicity was identified. The 2-year rates of local control, overall survival and recurrence-free survival were 90%, 90% and 64%, respectively.ConclusionHealthy soft tissue segment volume influenced toxicity. Long-term prospective monitoring in a homogeneous population remains critical to assess the impact of IMRT induced chronic toxicity in ESTS patients. This should ideally lead to a validated normal tissue dose constraint (e.g.: healthy soft tissue segment volume > 3500 cm3) to recommend for practitioners to help reduce the late toxicity risk.

Project description:BackgroundExtremity soft-tissue sarcomas (STS) are commonly treated with neoadjuvant radiation therapy followed by surgical resection. However, the pathological near-complete response rate is low (9-25%). Noninvasive imaging assessment that predicts treatment response before and during treatment is desirable to optimize treatment regimens. This pilot study aimed to investigate the application of a quantitative MRI parameter, T2*, in assessing neoadjuvant radiation therapy combined with pharmacological ascorbate in extremity STS.MethodsThis prospective cohort study included seven patients diagnosed with extremity STS and scheduled to receive neoadjuvant radiation therapy combined with pharmacological ascorbate. T2* maps were obtained from each patient before treatment (baseline MRI), two weeks after initiating treatment (on-treatment MRI), and before surgery (pre-surgery MRI). The T2* values within the tumor region were transformed into z-scores with respect to the normal- appearing tissue region. The voxel-wise z-scores within the tumor region were thresholded to generate masks representing significantly high (z-score>1.96) and low z-score (z-score<-1.96) voxels. The means of the total z-scores and within each of the significantly high and low z-score mask were computed. Their correlations with percent necrosis from pathological examination were evaluated using Spearman's rank correlation coefficient r. A correlation was considered as moderate or strong when r is higher than 0.6 and 0.8, respectively. A correlation was considered as fair or weak when r is below 0.6.ResultsFor the baseline and on-treatment MRIs, the means of the significantly high z-scores of the T2* measurements showed moderate correlations with percent necrosis (r = 0.68 and 0.6; p = 0.11 and 0.24). For the pre-surgery MRI, the means of the total and significantly high z-scores showed strong correlations with percent necrosis (r = 0.8 and 0.9; p = 0.13 and 0.08). Tumor volume and baseline MRI-based percent necrosis showed fair or weak correlations (r = 0.3-0.54; p = 0.24-0.68).ConclusionT2* measurements prior to treatment, two weeks after initiating treatment, and before surgery showed moderate to strong correlations with percent necrosis. These results support the potential for using T2* mapping to predict and assess response to neoadjuvant radiation therapy combined with pharmacological ascorbate in extremity STS. Level of Evidence: IV.

Project description:BackgroundAlthough clinicians and patients with extremity bone and soft tissue (EBST) are increasingly interested in limb salvage surgery (LSS), because of the minimal damage to physical appearance and function, however, there is still a lack of large-scale population studies on whether LSS improves the prognosis of patients.PurposeThe aim of this study was to compare the survival of patients with EBST sarcomas after receiving LSS and amputation.MethodsTo conduct the population-based study, we identified 6,717 patients with a histologically diagnosed bone sarcoma and 24,378 patients with a histologically diagnosed soft tissue sarcoma from the Surveillance, Epidemiology, and End Results database. We analyzed overall survival (OS), cancer-specific survival (CSS), and non-sarcoma survival (NSS) using the Kaplan-Meier method, log-rank test or Gray test, Cox regression model, propensity score-matched analysis, and landmark analysis.ResultsLSS could improve the prognosis in patients with most EBST subtypes, except for Ewing sarcomas and MPNST. However, in the subgroup without distant metastases, limb salvage increased CSS only for patients with osteosarcoma, Ewing sarcoma, and leiomyosarcoma, as well as NSS for patients with chondrosarcoma and synovial sarcoma. Landmark analysis further demonstrated that sarcoma survivors surviving <10 years could benefit from LSS but not for long-term survivors ≥10 years. Moreover, for patients with distant metastases, LSS could improve survival of osteosarcoma patients but worsen CSS among patients with MPNST. Landmark analysis further demonstrated that LSS improved survival among osteosarcomas patients with distant metastases only within 1 year after surgery. Moreover, patients receiving LSS and those receiving amputation had a high risk of dying from different non-sarcoma diseases during the postoperative follow-up.ConclusionsThe impact of limb salvage on the prognosis of patients depends on the pathological subtype and stage of EBST sarcomas.

Project description:BackgroundNeoadjuvant radiotherapy (RT) and chemotherapy are applied to large, high-grade extremity soft tissue sarcomas to treat metastatic disease earlier and sterilize margins to perform R0 surgery. However, preoperative RT increases wound complication rates (rWC), delaying adjuvant chemotherapy or preventing it from being administered altogether. Hypofractionated neoadjuvant RT can be offered in this situation, concomitant to chemotherapy, allowing patients to receive chemotherapy as a preoperative treatment in less time with an acceptable rWC.ObjectiveThe objectives of this protocol are to maintain low rates of morbidity and mortality compared to literature data, improving survival rates and avoiding poor responders from receiving unnecessary adjuvant chemotherapy.MethodsThis noncontrolled, single-arm, phase 2 clinical trial recruited patients aged over 18 years with high-grade soft tissue sarcomas in the girdles or extremities. Three neoadjuvant chemotherapy (ifosfamide and doxorubicin) cycles were administered with 5 days of hypofractionated RT (25 Gy in 5 fractions) in the second cycle of doxorubicin only. Viable cell counts in the surgical specimen were measured, and patients in whom this value was less than 30% continued to receive an additional 3 full chemotherapy cycles as adjuvant treatment.ResultsPrimary endpoint will be disease-specific survival measured by the evaluation of local and distant recurrence after neoadjuvant treatment. The secondary endpoints will be wound complication and amputation rates and chemotherapy toxicity. We also will record the viable cell rates after the schema and correlate this with survival.ConclusionsAs seems with other solid tumors, hypofractionated RT has comparable efficacy and safety as conventional fractionation. This modality of treatment combined with chemotherapy could increase the pathological response rates and improve the outcomes of select patients.Trial registrationClinicalTrials.gov NCT02812654; https://clinicaltrials.gov/ct2/show/NCT02812654 (Archived by WebCite at http://www.webcitation.org/6qC3puBOy).

Dataset Information

Postradiation Fractures after Combined Modality Treatment in Extremity Soft Tissue Sarcomas.

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Postradiation Fractures after Combined Modality Treatment in Extremity Soft Tissue Sarcomas.

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