Pathologic necrosis following neoadjuvant radiotherapy or chemoradiotherapy is prognostic of poor survival in soft tissue sarcoma

Gannon, Nicholas P.; Stemm, Matthew; King, David M.; Bedi, Meena

doi:10.1007/s00432-019-02885-4

Cited by 25 publications

(21 citation statements)

References 39 publications

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“…This could be explained by the fact that tumor necrosis varies widely between different tumors rather than being solely an indicator of NRT treatment efficacy. 8 , 14 For example, Gannon et al demonstrated that tumor necrosis in STS patients treated with neoadjuvant therapy was associated with poorer overall survival, distant metastasis‐free survival, and progression‐free survival. 15 However, in this study, necrosis was highly correlated with size and grade, two factors which are independently associated with poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft‐tissue sarcoma

et al. 2021

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Introduction: Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few studies that attempt to correlate histopathologic response to NRT with oncologic outcomes in patients with STS.Methods: Using our institutional database, we identified 58 patients who received NRT followed by surgical resection for primary intermediate or high-grade STS and 34 patients who received surgical resection without NRT but did receive adjuvant radiation therapy or did not receive any radiation therapy. We analyzed four histologic parameters of response to therapy: residual viable tumor, fibrosis/ hyalinization, necrosis, and infarction (each ratiometrically determined). Data were stratified into two binary groups. Unadjusted, 5-and 10-year overall survival, and relapsed-free survival (RFS) were calculated using the Kaplan-Meier method.Results: Analysis of pathologic characteristics showed that patients treated with NRT demonstrate significantly higher tumor infarction, higher tumor fibrosis/ hyalinization, and a lower percent viable tumor compared with patients not treated with NRT (p < 0.0001). Based on Kaplan-Meier curve analysis and multivariate cox proportional hazard model for OS and RFS, patients treated with NRT and showing >12.5% tumor fibrosis/hyalinization have significantly higher overall survival and recurrence-free survival at 5 and 10 years. Discussion and Conclusion:We have identified three histopathologic characteristics-fibrosis, hyalinization, and infarction-that may serve as predictive biomarkers of response to NRT for STS patients. Future prospective studies will be needed to confirm this association.

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Section: Discussionmentioning

confidence: 99%

Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft‐tissue sarcoma

et al. 2021

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“…However, 5 of the 10 patients who developed local recurrence had 90% necrosis on their surgical pathology. Because there have been conflicting results regarding the prognostic value of pathologic necrosis after neoadjuvant therapy, [18][19][20] additional studies are needed to evaluate other possible histologic findings, such as hyalinization or fibrosis, which may be better predictors of outcome. 21,22 The major concern and hesitation in using an aggressive neoadjuvant chemotherapy regimen is due to toxicity.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant Chemoradiation Compared With Neoadjuvant Radiation Alone in the Management of High-Grade Soft Tissue Extremity Sarcomas

Hazell

Alcorn

et al. 2020

Advances in Radiation Oncology

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Patients with large, high-grade soft tissue sarcomas are commonly treated with aggressive limb preservation regimens. This study aimed to assess cancer control outcomes of patients treated with neoadjuvant chemoradiation (CRT) compared with radiation therapy (RT) alone. Methods: We reviewed records of patients with high-grade extremity or trunk soft tissue sarcomas 5 cm who were treated with neoadjuvant radiation with or without chemotherapy. Patient and disease characteristics were compared using t test and c 2 tests. Standardized mortality ratio weighted method was used to compare overall survival (OS), local control, and disease-free (DFS) survival. Acute radiation and surgical toxicity were reported. Results: In the study, 64 patients (34 CRT and 30 RT) treated between 1997 and 2015 were analyzed. In the RT group compared with the CRT group, the patient population was older, with a median age of 65 versus 50 years (P < .001), and more likely to have cardiovascular disease (CVD; 30% vs 0%, P < .001). At a median follow-up of 41 months, after adjusting for propensity score of receiving RT, the 3-year LC was 87.3% versus 86.1%, DFS was 58.5% versus 56.6%, and OS was 75.6% versus 69.0% for the CRT and RT groups, respectively (P > .05). Acute dermatitis occurred in 18% versus 3% and surgical complications occurred in 32% versus 17% of CRT and RT patients, respectively. Conclusions: In this study, patients receiving RT alone were more likely to be older and have comorbid cardiovascular disease. When controlling for baseline differences, neoadjuvant CRT and RT provided similar rates of LC, DFS, and OS.

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“…There are many other methods to evaluate the perioperative efficacy of neoadjuvant therapy—including imaging, pathological necrosis rate, R0 assessment, etc. However, it is unclear which method most accurately predicts DFS [ 4 , 22 , 23 ]. Well-powered prospective studies are required to answer these questions.…”

Section: Discussionmentioning

confidence: 99%

Apatinib with doxorubicin and ifosfamide as neoadjuvant therapy for high-risk soft tissue sarcomas: a retrospective cohort study

et al. 2021

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Summary Background There is a need to establish an effective neoadjuvant therapy for soft tissue sarcomas (STSs). We previously showed that apatinib, administered in combination with doxorubicin-based chemotherapy, improves the efficacy of treatment. This study aimed to clarify the effectiveness and safety of apatinib combined with doxorubicin and ifosfamide (AI) neoadjuvant chemotherapy for STSs. Methods This retrospective study included patients with STS who received neoadjuvant therapy and surgery between January 2016 and January 2019. The patients were divided into two treatment groups: AI + apatinib group and AI group (doxorubicin + ifosfamide). Results The study included 74 patients (AI + apatinib: 26, AI: 48) with STS. There were significant between-group differences in objective response rates (53.85% vs. 29.17%, p = 0.047) and the average change in target lesion size from baseline (-40.46 ± 40.30 vs. -16.31 ± 34.32, p = 0.008). The R0 rate (84.62% vs. 68.75%; p = 0.170) and 2-year disease-free survival (73.08% vs. 62.50%, p = 0.343) were similar across groups. Finally, the rates of neoadjuvant therapy-related adverse effects and postoperative complications were similar in both groups (p > 0.05). Conclusion Apatinib plus doxorubicin and ifosfamide regimen is safe and effective as neoadjuvant therapy for patients with STS. However, the significantly improved preoperative ORR observed after neoadjuvant therapy did not translate into a significantly improved R0 rate and 2-year DFS. Prospective, well-powered studies are warranted to determine the long-term efficacy and optimal application of these protocols.

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Pathologic necrosis following neoadjuvant radiotherapy or chemoradiotherapy is prognostic of poor survival in soft tissue sarcoma

Cited by 25 publications

References 39 publications

Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft‐tissue sarcoma

Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft‐tissue sarcoma

Neoadjuvant Chemoradiation Compared With Neoadjuvant Radiation Alone in the Management of High-Grade Soft Tissue Extremity Sarcomas

Apatinib with doxorubicin and ifosfamide as neoadjuvant therapy for high-risk soft tissue sarcomas: a retrospective cohort study

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