Dataset Information

Neoadjuvant image-guided helical intensity modulated radiotherapy of extremity sarcomas - a single center experience.

ABSTRACT:

Background

Advanced radiotherapy (RT) techniques allow normal tissue to be spared in patients with extremity soft tissue sarcoma (STS). This work aims to evaluate toxicity and outcome after neoadjuvant image-guided radiotherapy (IGRT) as helical intensity modulated radiotherapy (IMRT) with reduced margins based on MRI-based target definition in patients with STS.

Methods

Between 2010 to 2014, 41 patients with extremity STS were treated with IGRT delivered as helical IMRT on a tomotherapy machine. The tumor site was in the upper extremity in 6 patients (15%) and lower extremity in 35 patients (85%). Reduced margins of 2.5?cm in longitudinal direction and 1.0?cm in axial direction were used to expand the MRI-defined gross tumor volume, including peritumoral edema, to the clinical target volume. An additional margin of 5?mm was added to receive the planning target volume. The full total dose of 50?Gy in 2?Gy fractions was sucessfully applied in 40 patients. Two patients received chemotherapy instead of surgery due to systemic progression. All patients were included into a strict follow-up program and were seen interdisciplinarily by the Departments of Orthopaedic Surgery and Radiation Oncology.

Results

Thirty eight patients that received total RT total dose and subsequent resection were analyzed for outcome. After a median follow-up of 38.5?months cumulative OS, local PFS and systemic PFS at 2?years were determined at 78.2, 85.2 and 54.5%, respectively. Two of 6 local recurrences were proximal marginal misses. Negative resection margins were achieved in 84% of patients. The rate of major wound complications was comparable to previous IMRT studies with 36.8%. RT was overall tolerable with low toxicity rates.

Conclusions

IMRT-IGRT offers neoadjuvant treatment for extremity STS with reduced safety margins and thus low toxicity rates. Wound complication rates were comparable to previously reported frequencies. Two reported marginal misses suggest a word of caution for reduction of longitudinal safety margins.

SUBMITTER: Peeken JC

PROVIDER: S-EPMC6327451 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Neoadjuvant image-guided helical intensity modulated radiotherapy of extremity sarcomas - a single center experience.

Peeken Jan C JC Knie Christoph C Kessel Kerstin A KA Habermehl Daniel D Kampfer Severin S Dapper Hendrik H Devecka Michal M von Eisenhart-Rothe Rüdiger R Specht Katja K Weichert Wilko W Wörtler Klaus K Knebel Carolin C Wilkens Jan J JJ Combs Stephanie E SE

Radiation oncology (London, England) 20190109 1

<h4>Background</h4>Advanced radiotherapy (RT) techniques allow normal tissue to be spared in patients with extremity soft tissue sarcoma (STS). This work aims to evaluate toxicity and outcome after neoadjuvant image-guided radiotherapy (IGRT) as helical intensity modulated radiotherapy (IMRT) with reduced margins based on MRI-based target definition in patients with STS.<h4>Methods</h4>Between 2010 to 2014, 41 patients with extremity STS were treated with IGRT delivered as helical IMRT on a tomo ...[more]

PMID: 30626408

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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:BACKGROUND AND PURPOSE:Radiotherapy (RT) is persistently gaining significance in the treatment of pediatric tumors. However, individual features of a growing body and multifocal stages complicate this approach. Tomotherapy offers advantages in the treatment of anatomically complex tumors with low risks of side effects. Here we report on toxicity incidence and outcome of tomotherapy with a focus on multitarget RT (mtRT). MATERIALS AND METHODS:From 2008 to 2017, 38 children diagnosed with sarcoma were treated with tomotherapy. The median age was 15 years (6-19 years). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03 and classified into symptoms during RT, acutely (0-6 months) and late (>6 months) after RT, and long-term sideeffects (>24 months). RESULTS:The main histologies were Ewing sarcoma (n?=?23 [61%]) and alveolar rhabdomyosarcoma (n?=?5 [13%]). RT was performed with a median total dose of 54?Gy (40.5-66.0?Gy) and a single dose of 2?Gy (1.80-2.27?Gy). Twenty patients (53%) received mtRT. Median follow-up was 29.7 months (95% confidence interval 15.3-48.2 months) with a 5-year survival of 55.2% (±9.5%). The 5?year survival rate of patients with mtRT (n?=?20) was 37.1?±?13.2%, while patients who received single-target RT (n?=?18) had a 5-year survival rate of 75?±?10.8%. Severe toxicities (grade 3 and 4) emerged in 14 patients (70%) with mtRT and 7 patients (39%) with single-target RT. Two non-hematological grade 4 toxicities occurred during RT: one mucositis and one radiodermatitis. After mtRT 5 patients had grade 3 toxicities acute and after single-target RT 4 patients. One patient had acute non-hematological grade 4 toxicities (gastritis, pericarditis, and pericardial effusion) after mtRT. Severe late effects of RT occurred in 2 patients after mtRT and in none of the single-target RT patients. No severe long-term side effects appeared. CONCLUSION:Our results showed acceptable levels of acute and late toxicities, considering the highly advanced diseases and multimodal treatment. Hence, tomotherapy is a feasible treatment method for young patients with anatomically complex tumors or multiple targets. Especially mtRT is a promising and innovative treatment approach for pediatric sarcomas, delivering unexpectedly high survival rates for patients with multifocal Ewing sarcomas in this study, whereby the limited number of patients should invariably be considered in the interpretation.

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).

Project description:PURPOSE:This study reported long-term outcomes of patients with cervical cancer who were treated with intensity modulated radiation therapy and 3-dimensional (3D) image-guided adapted brachytherapy (IMRT/3D-IGABT) compared with those treated with 2-dimensional (2D) external irradiation and 2D brachytherapy (2D EBRT/BT). METHODS AND MATERIALS:This study included patients with newly diagnosed cervical cancer and pretreatment fluorodeoxyglucose positron emission tomography scans who were treated with curative-intent irradiation from 1997 to 2013. The treatment policy changed from using 2D EBRT/BT to IMRT/3D-IGABT in 2005. Patterns of recurrence, cancer-specific survival (CSS), and overall survival (OS) were evaluated. Late gastrointestinal and genitourinary toxicity were scored with National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS:The median follow-up for patients alive at the time of last follow-up in the 2D EBRT/BT group (n = 300) was 15.3 years (range, 10.8-20.5 years). In the IMRT/3D-IGABT group (n = 300), it was 7 years (range, 5-12.4 years). According to the International Federation of Gynecology and Obstetrics, 33% of tumors were stage IB1 to IB2, 41% were stage IIA to IIB, and 26% were stage IIIA to IVA. The results after 5 years for patients treated with 2D EBRT/BT showed that freedom from relapse (FFR) was 57%, CSS was 62%, and OS was 57%. For the IMRT/3D-IGABT group, the 5-year results showed that FFR was 65% (P = .04), CSS was 69% (P = .01), and OS was 61% (P = .04). When stratified by lymph node status according to positron emission tomography scan results, disease control was most improved with IMRT/3D-IGABT versus 2D EBRT/BT in patients with positive pelvic lymph nodes only (P = .02). Cumulatively, 88 of 600 patients (15%) had grade ?3 late bowel/bladder toxicity. The 2D EBRT/BT group had 55 patients (18%), and the IMRT/3D-IGABT group had 33 patients (11%; P = .02). CONCLUSIONS:IMRT/3D-IGABT was associated with improved survival and decreased gastrointestinal and genitourinary toxicity in patients with cervical cancer compared with those who received 2D EBRT/BT.

Dataset Information

Neoadjuvant image-guided helical intensity modulated radiotherapy of extremity sarcomas - a single center experience.

Background

Methods

Results

Conclusions

Publications

Neoadjuvant image-guided helical intensity modulated radiotherapy of extremity sarcomas - a single center experience.

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