Dataset Information

Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival.

ABSTRACT:

Background

Preoperative radiotherapy is often used to facilitate excision of soft-tissue sarcomas. We aimed define factors that affect local tumour control and patient survival.

Methods

A single institution registry study of 89 patients with non-metastatic soft-tissue sarcomas having preoperative radiotherapy between 1994 and 2014. Radiologic (presence of peritumoural oedema and volume change following radiotherapy) and histopathologic (tumour volume, grade and surgical margin) parameters were recorded. Outcomes were the events of local recurrence, amputation, metastasis and death.

Results

Local recurrence rate was low (12%) and marginal excision gave equal local control to wide excision. Pelvic localization was associated with a higher risk for amputation. The absence of peritumoural oedema on MRI defined a subgroup of tumours with more favourable oncologic outcome. Reduction of tumour volume following radiotherapy was also associated with better patient survival. Both these radiologic parameters were associated with lower tumour grade. Tumour necrosis was not significant for patient survival. The local complication rate, mainly wound healing problems and infection, was high (40%), but did not lead to any amputation.

Conclusion

Preoperative radiotherapy of high-risk soft-tissue sarcomas allows for good local control rate at the expense of local wound complications, which are however manageable. Marginal excision is sufficient for local control. Absence of peritumoural oedema on MRI, as well as tumour size reduction following radiotherapy are associated to superior patient survival and can be used ass early prognostic factors.

SUBMITTER: Tsagozis P

PROVIDER: S-EPMC6172791 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival.

Tsagozis Panagiotis P Brosjö Otte O Skorpil Mikael M

Clinical sarcoma research 20181005

<h4>Background</h4>Preoperative radiotherapy is often used to facilitate excision of soft-tissue sarcomas. We aimed define factors that affect local tumour control and patient survival.<h4>Methods</h4>A single institution registry study of 89 patients with non-metastatic soft-tissue sarcomas having preoperative radiotherapy between 1994 and 2014. Radiologic (presence of peritumoural oedema and volume change following radiotherapy) and histopathologic (tumour volume, grade and surgical margin) pa ...[more]

PMID: 30323920

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Project description:Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response.Patients with ?5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans.The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ?80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence.The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.

Project description:BackgroundThe standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients.MethodsThis single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues.FindingsBetween Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths.InterpretationModerately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited.FundingThe National Cancer Institute.

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.

Dataset Information

Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival.

Background

Methods

Results

Conclusion

Publications

Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival.

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