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Neoadjuvant sequential chemoradiotherapy versus radiotherapy alone for treatment of high-risk extremity soft tissue sarcoma: a single-institution experience

View Article: PubMed Central - PubMed

ABSTRACT

Aim of the study: Patients with large and high-grade extremity soft-tissue sarcoma are at significant risk for distant metastasis and sarcoma-related death. There is no randomized trial comparing chemoradiotherapy to radiotherapy in the neoadjuvant setting for high risk extremity soft-tissue sarcoma. The aim of this study is to evaluate the outcomes of patients treated with two different modalities (neoadjuvant sequential chemoradiotherapy vs. radiotherapy alone) in a single center.

Material and methods: Data of 67 patients were analyzed retrospectively. Thirty-four patients received neoadjuvant sequential chemoradiotherapy (2–3 cycles of doxorubicin (75 mg/m2) and ifosfamide (6 g/m2) followed by radiotherapy of 28 Grays (Gy) administered as 8 fractions of 35 Gy) and 33 patients received radiotherapy alone. R0 resection rates and 3-year survival estimates were evaluated.

Results: Median follow-up time was 37 months. The estimated 3-year overall and disease-free survival rates for the whole patient group were 79% (95% CI: 67.0–86.4) and 57.9% (95% CI: 46.3–69.0), respectively. The most common side effects were nausea and leucopenia. Three-year overall, disease-free, local recurrence-free and distant recurrence-free survival rates did not differ significantly. All patients except one underwent wide excision or compartmental resection. R0 resection rate for the whole patient group was 92.5% (n = 62). Sites of progression were similar across both treatment arms.

Conclusions: Preoperative hypofractionated radiotherapy alone or sequentially with chemotherapy result in high rates of limb salvage and acceptable toxicity. Our study results did not show a statistically significant treatment effect regarding survival and patterns of failure.

No MeSH data available.


Comparison of Kaplan-Meier survival curves for disease-free survival according to neoadjuvant treatment modalities
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f0002: Comparison of Kaplan-Meier survival curves for disease-free survival according to neoadjuvant treatment modalities

Mentions: At a median follow-up time of 37 months (interquartile range: 11–66 months) 39 patients (58.2%) were alive without any disease failure. A total of 16 deaths have been recorded so far. The estimated three-year OS and DFS rate for the whole patient group was 79% (95% CI: 67.0–86.4) and 57.9% (95% CI: 46.3–69.0), respectively. Three-year OS rates for neoadjuvant sequential CRT and RT arms were 74.1% and 90.0%, respectively (p = 0.44). Three-year DFS, LRFS, and DRFS rates also did not differ significantly for each treatment arm (for sequential CRT and RT; 50.5% vs. 65.7%, p = 0.33; 77.1% vs. 76.3%, p = 0.86; 70.1% vs. 86.1%, p = 0.12, respectively) (Figs. 1, 2). There were no statistically significant predictors of OS and DFS. Low event rates and the small size of the groups precluded comparison of outcomes. Although not statistically significant there was a tendency for better OS and DFS for female, elderly, and smaller primary tumour (≤ 10 cm) group (Table 3). Three-year DRFS and LRFS rates for the whole group were estimated as 77.7% (95% CI: 70.0–91.0) and 74.2% (95% CI: 63.4–86.1). Sites of progression did not show statistically significant differences with respect to the neoadjuvant treatment modality received (Table 4). In total, 25 patients (37.3%) had disease progression: 11 (16.4%) patients had isolated distant metastasis; 10 (14.9%) had locoregional failure; and four had failure at both local and distant sites. The most common site of metastasis was lung (n = 13). One patient with malignant schwannoma had disease progression in both lungs and bone. Upon progression, 13 patients had undergone surgery; metastasectomy was performed for four patients. Excluding amputations (n = 3) local recurrences were managed with limb-preserving surgery and RT for six cases. Five patients who had not received neoadjuvant CTX were administered chemotherapy consisting of doxorubicin and ifosfamide after surgery for disease progression. Six patients who had undergone surgery for progressive disease were alive at the time of analysis. Median OS for those who were operated for disease progression (metastasectomy and/or surgery for local recurrence) was 46.1 months (95% CI: 19.5–72.8).


Neoadjuvant sequential chemoradiotherapy versus radiotherapy alone for treatment of high-risk extremity soft tissue sarcoma: a single-institution experience
Comparison of Kaplan-Meier survival curves for disease-free survival according to neoadjuvant treatment modalities
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385480&req=5

f0002: Comparison of Kaplan-Meier survival curves for disease-free survival according to neoadjuvant treatment modalities
Mentions: At a median follow-up time of 37 months (interquartile range: 11–66 months) 39 patients (58.2%) were alive without any disease failure. A total of 16 deaths have been recorded so far. The estimated three-year OS and DFS rate for the whole patient group was 79% (95% CI: 67.0–86.4) and 57.9% (95% CI: 46.3–69.0), respectively. Three-year OS rates for neoadjuvant sequential CRT and RT arms were 74.1% and 90.0%, respectively (p = 0.44). Three-year DFS, LRFS, and DRFS rates also did not differ significantly for each treatment arm (for sequential CRT and RT; 50.5% vs. 65.7%, p = 0.33; 77.1% vs. 76.3%, p = 0.86; 70.1% vs. 86.1%, p = 0.12, respectively) (Figs. 1, 2). There were no statistically significant predictors of OS and DFS. Low event rates and the small size of the groups precluded comparison of outcomes. Although not statistically significant there was a tendency for better OS and DFS for female, elderly, and smaller primary tumour (≤ 10 cm) group (Table 3). Three-year DRFS and LRFS rates for the whole group were estimated as 77.7% (95% CI: 70.0–91.0) and 74.2% (95% CI: 63.4–86.1). Sites of progression did not show statistically significant differences with respect to the neoadjuvant treatment modality received (Table 4). In total, 25 patients (37.3%) had disease progression: 11 (16.4%) patients had isolated distant metastasis; 10 (14.9%) had locoregional failure; and four had failure at both local and distant sites. The most common site of metastasis was lung (n = 13). One patient with malignant schwannoma had disease progression in both lungs and bone. Upon progression, 13 patients had undergone surgery; metastasectomy was performed for four patients. Excluding amputations (n = 3) local recurrences were managed with limb-preserving surgery and RT for six cases. Five patients who had not received neoadjuvant CTX were administered chemotherapy consisting of doxorubicin and ifosfamide after surgery for disease progression. Six patients who had undergone surgery for progressive disease were alive at the time of analysis. Median OS for those who were operated for disease progression (metastasectomy and/or surgery for local recurrence) was 46.1 months (95% CI: 19.5–72.8).

View Article: PubMed Central - PubMed

ABSTRACT

Aim of the study: Patients with large and high-grade extremity soft-tissue sarcoma are at significant risk for distant metastasis and sarcoma-related death. There is no randomized trial comparing chemoradiotherapy to radiotherapy in the neoadjuvant setting for high risk extremity soft-tissue sarcoma. The aim of this study is to evaluate the outcomes of patients treated with two different modalities (neoadjuvant sequential chemoradiotherapy vs. radiotherapy alone) in a single center.

Material and methods: Data of 67 patients were analyzed retrospectively. Thirty-four patients received neoadjuvant sequential chemoradiotherapy (2–3 cycles of doxorubicin (75 mg/m2) and ifosfamide (6 g/m2) followed by radiotherapy of 28 Grays (Gy) administered as 8 fractions of 35 Gy) and 33 patients received radiotherapy alone. R0 resection rates and 3-year survival estimates were evaluated.

Results: Median follow-up time was 37 months. The estimated 3-year overall and disease-free survival rates for the whole patient group were 79% (95% CI: 67.0–86.4) and 57.9% (95% CI: 46.3–69.0), respectively. The most common side effects were nausea and leucopenia. Three-year overall, disease-free, local recurrence-free and distant recurrence-free survival rates did not differ significantly. All patients except one underwent wide excision or compartmental resection. R0 resection rate for the whole patient group was 92.5% (n = 62). Sites of progression were similar across both treatment arms.

Conclusions: Preoperative hypofractionated radiotherapy alone or sequentially with chemotherapy result in high rates of limb salvage and acceptable toxicity. Our study results did not show a statistically significant treatment effect regarding survival and patterns of failure.

No MeSH data available.