Does Complete Pathologic Response to Neoadjuvant Radiotherapy Predict Oncologic Outcome in Patients With Soft Tissue Sarcoma?

Shah, Dhvanit I.; Borys, Dariusz; Martinez, Steve R.; Li, C.; Tamurian, R.J.; Bold, Richard J.; Canter, Robert J.

doi:10.1016/j.jss.2011.11.141

Cited by 35 publications

(53 citation statements)

References 19 publications

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“…A second set (DLT-II) described toxicities in the perioperative period and was specifically so designed because surgery after preopRT without any systemic agents already results in a 35% wound complication rate [1]. The observed RT side effects and post-surgical morbidities were consistent with those reported in other studies [1,12]. we did not observe any DLT-I in the chemoradiotherapy period.…”

Section: Discussionsupporting

confidence: 85%

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A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities

et al. 2015

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Section: Discussionsupporting

confidence: 85%

“…specimens were examined for determination of percentage tumor necrosis, tumor histology and margin assessment. Near complete or complete pathological response was defined as  95% and 100% tumor necrosis, respectively [12,13]. Acta Oncol Downloaded from informahealthcare.com by Ryerson University on 08/10/15…”

Section: Pathological Responsementioning

confidence: 99%

A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities

et al. 2015

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“…In the literature, a generally accepted definition of a pathological complete remission (pCR) is represented by greater than or equal to 99–100% necrosis (or less than or equal to 1% residual visible tumor cells), whereas a near pCR can be defined as greater than or equal to 95% necrosis. Canter [42] and Shah [43] demonstrated, that a (near) pCR can be appreciated in only 8–10% of cases following RT alone to 50 Gy in 2 Gy fractions. Nevertheless, the true prognostic significance of treatment-induced pathologic necrosis in ESTS after neoadjuvant therapy has yet to be determined [44].…”

Section: Methodsmentioning

confidence: 99%

Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies

Haas

Miah

Lepéchoux

et al. 2016

Radiotherapy and Oncology

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Introduction This critical review aims to summarize published data on limb sparing surgery for extremity soft tissue sarcoma in combination with pre-operative radiotherapy (RT). Methods This review is based on peer-reviewed publications using a PubMed search on the MeSH headings “soft tissue sarcoma” AND “preoperative radiotherapy”. Titles and abstracts screened for data including “fraction size AND/OR total dose AND/OR overall treatment time”, “chemotherapy”, “targeted agents AND/OR tyrosine kinase inhibitors”, are collated. Reference lists from some articles have been studied to obtain other pertinent articles. Additional abstracts presented at international sarcoma meetings have been included as well as information on relevant clinical trials available at the ClinicalTrials.gov website. Results Data are presented for the conventional regimen of 50–50.4 Gy in 25–28 fractions in 5–6 weeks preoperative external beam RT with respect to the regimen’s local control probability compared to surgery alone, as well as acute and late toxicities. The rationale and outcome data for hypofractionated and/or reduced dose regimens are discussed. Finally, combination schedules with conventional chemotherapy and/or targeted agents are summarized. Conclusion Outside the setting of well-designed prospective clinical trials, the conventional 50 Gy in 5–6 weeks schedule should be considered as standard. However, current and future studies addressing alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may reveal regimens of equal or increased efficacy with reduced late morbidities.

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“…Specimens were examined for determination of percentage tumor necrosis as defined previously. [15, 16] Complete or near-complete pathologic response (path CR) was defined as ≥ 95% tumor necrosis. [16, 17]…”

Section: Methodsmentioning

confidence: 99%

Phase I Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients with Locally Advanced Soft Tissue Sarcoma of the Extremity

et al. 2014

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Introduction Despite effective local therapy with surgery and radiation (RT), approximately 50% of patients with high grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when anti-angiogenic targeted therapies, such as sorafenib, are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a Phase I/II trial among patients with extremity STS amenable to treatment with curative intent. Methods For the Phase I trial, eight patients with intermediate or high grade STS > 5 cm in maximal dimension or low grade STS > 8 cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 bid, cohort 2:200/400 daily) and preoperative RT (50 Gy in 25 fractions). Sorafenib was continued during entire period of RT as tolerated. Surgical resection was completed four to six weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the Phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT). Results Eight patients were enrolled in the Phase I (5 female, median age 44, 3 high grade pleomorphic, 2 myxoid/round cell liposarcoma, 3 other). Median tumor size was 16 cm (range 8–29), and all tumors were located in the lower extremity. Two of 5 patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and SVT. Radiation toxicity (grade 1 or 2 dermatitis, N=8) and post-surgical complications (3 grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (≥ 95% tumor necrosis) was observed in 3 patients (38%). Conclusion Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (NCT#00805727, ClinicalTrials.gov)

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Does Complete Pathologic Response to Neoadjuvant Radiotherapy Predict Oncologic Outcome in Patients With Soft Tissue Sarcoma?

Cited by 35 publications

References 19 publications

A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities

A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities

Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies

Phase I Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients with Locally Advanced Soft Tissue Sarcoma of the Extremity

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