Neoadjuvant Treatment with Preoperative Radiotherapy for Extremity Soft Tissue Sarcomas: Long-Term Results from a Single Institution in Turkey (original) (raw)
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Współczesna Onkologia, 2017
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/m 2) and ifosfamide (6 g/m 2) 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.
Cancer, 2012
BACKGROUND: Patients with large, high-grade, extremity soft tissue sarcomas (STS) are at significant risk for distant recurrence and death. A regimen of preoperative chemotherapy consisting of mesna, Adriamycin (doxorubicin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT) and followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. We report the long-term follow-up data on 48 patients treated with this regimen compared to an historical matched-control patient population. METHODS: Adult patients with high-grade extremity STS 8 cm were treated with 3 cycles of preoperative chemotherapy combined with 44 Gy of RT followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy of RT was delivered postoperatively. RESULTS: Patients received the MAID/RT regimen from 1989 through 1999. After a median follow-up of 9.3 years in surviving patients in the MAID group and 13.2 years in surviving patients in the control group, the 7-year disease-specific and overall survival rates were 81% and 50% (P ¼ .004) and 79% and 45% (P ¼ .003) for the MAID and control patients, respectively. Five of 11 patients in the MAID group and 7 of 25 control patients died of sarcoma 5 years after treatment. One patient in the MAID group developed a fatal myelodysplasia at 53 months. CONCLUSIONS: For patients with high-risk, extremity STS, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery are sustained even with long-term follow-up. Cancer 2012;118:3758-65
Cancer, 2010
BACKGROUND: The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long-term (!5 years) follow-up in patients with high-grade, high-risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy. METHODS: Patients with highgrade soft tissue sarcoma !8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine). RESULTS: Sixty-four of 66 patients were analyzed. After chemotherapy and RT, 61 patients had surgery; 58 had R0 resections (5 amputations), and 3 had R1 resections. Ninety-seven percent experienced grade 3 or higher toxicity, including 3 deaths. These toxicities were short term. With a median follow-up of 7.7 years in surviving patients, the 5-year rates of locoregional failure (including amputation), and distant metastasis were 22.2% (95% confidence interval [CI], 11.8-32.6) and 28.1% (95% CI, 17.0-39.2). The most common site of metastasis was lung. Estimated 5-year rates of diseasefree survival, distant disease-free survival, and overall survival were 56.1% (95% CI, 43.9-68.3), 64.1% (95% CI, 52.3-75.8), and 71.2% (95% CI, 60.0-82.5), respectively. CONCLUSIONS: Although the toxicity was significant, it was limited in its course and for the most part resolved by 1 year. The long-term outcome was better than might be expected in such high-risk tumors. Cancer 2010;116:4613-21.
Neoadjuvant chemotherapy and radiotherapy for large extremity soft tissue sarcomas
International Journal of Radiation Oncology*Biology*Physics, 2001
Purpose: Treatment of extremity soft-tissue sarcomas yields excellent local control, but distant failure is common with large, high-grade tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment outcome. We report the mature outcome data on 48 treated patients and compare them with the data of an historical matched control patient population. Methods and Materials: Adult patients with high-grade extremity soft-tissue sarcomas >8 cm were treated with three cycles of preoperative chemotherapy combined with 44 Gy of radiotherapy followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy was delivered postoperatively. Results: All 48 patients (M0) received the MAID protocol treatment, and their outcome was superior to that of the historical control patients. The 5-year actuarial local control, freedom from distant metastasis, disease-free survival, and overall survival rate was 92% and 86% (p ؍ 0.1155), 75% and 44% (p ؍ 0.0016), 70% and 42% (p ؍ 0.0002), and 87% and 58% (p ؍ 0.0003) for the MAID and control patient groups, respectively. Acute hematologic toxicity in the MAID group included febrile neutropenia in 12 patients (25%). Wound healing complications occurred in 14 (29%) of 48 MAID patients. One MAID patient developed late fatal myelodysplasia. Conclusion: After aggressive chemoradiation and surgery, these patients showed a significant reduction in distant metastases, with a highly significant gain in disease-free and overall survival compared with a historical control group. On the basis of this experience, the Radiation Therapy Oncology Group conducted a multi-institutional trial.
Rare Tumors, 2013
The aim of the present study is to assess the disease profile, outcome and prognostic factors in patients treated with surgery combined with radiotherapy (RT), with or without chemotherapy (CXT), for soft-tissue sarcoma (STS) in a multidisciplinary setting. One hundred and sixty-four patients with STS treated between 1980 and 2010 at the Centre Hospitalier Universitaire Vaudois were enrolled in this retrospective study. Seventy-six percent of patients underwent postoperative RT with (24%), or without (52%) CXT, 15% preoperative RT with (5%), or without (10%) CXT, surgery alone (7%), or RT alone (2%) with or without CXT. The median follow-up was 60 months (range 6-292). Local failure was observed in 18%, and distant failure in 21% of the patients. Overall survival (OS), diseasefree survival (DFS), local control (LC) and distant metastases-free survival (DMFS) were 88%, 68%, 83%, and 79% at 5 years, and 80%, 56%, 76%, and 69% at 10 years, respectively. In univariate analyses, favorable prognostic factors for OS, DFS, and DMFS were tumor size 6 cm or less, World Health Organization (WHO)/Zubrod score 0, and stage 2 or less. Age and superficial tumors were favorable only for OS and DMFS respectively. STS involving the extremities had a better outcome regarding DFS and LC. Histological grade 2 or less was favorable for DFS, DMFS, and LC. Radical surgery was associated with better LC and DMFS. RT dose more than 60 Gy was favorable for OS, DFS, and LC. In multivariate analyses, independent factors were age for OS; tumor size for OS, DFS and DMFS; WHO/Zubrod score for OS, DFS and LC; hemoglobin level for DFS; site for DFS and LC; tumor depth for DMFS; histological grade for DFS and LC; surgical procedure for LC and DMFS; and RT dose for OS.
Biomedical Journal of Scientific & Technical Research
Background: It is unknown if the radiologic response after neoadjuvant radiation (RT) in patients with soft tissue sarcoma correlates with the histologic response or disease outcomes. The purpose of this study is to evaluate radiographic and histologic responses in patients who received neoadjuvant RT, and to evaluate the relation between these short-term surrogates. Patients and Methods: We sought to review consecutive patients with primary localized STS, who were treated with preoperative RT, between 2016 and 2018 at a single institution. All patients were required to have initiated RT with the intention to be followed by curative surgical resection. Data on demographics and disease characteristics were retrospectively collected, the tumor volume (cc) was calculated before and after RT, pathology specimens were reviewed for percent of necrosis and status of surgical margins. Results: Twenty-three patients with primary localized STS were treated with preoperative radiotherapy followed by surgery. There were 11 extremity (48%), 7 retroperitoneal (30%) and 5 thoracic (22%) tumors. The tumor volume decreased after neoadjuvant RT in 10 cases (43%) to a maximum of 50% (range,-5 to-50%), while in eight patients (35%) the tumor grew in size to a maximum of 40% (range, +10 to +40%). The tumor volume was stable in five patients (22%). Complete resection (R0) was achieved in 18 cases (79%), microscopically involved margins (R1) were observed in 4 (17%), and gross residual (R2) in one patient (4%). The median tumor necrosis was 40%. Five patients (22%) demonstrated complete or near-complete pathologic response (≥ 95% necrosis). Pearson correlation coefficient test revealed no correlation between radiologic and histologic responses (-0.07). Major wound complication after surgery was observed in four patients (17%). Conclusion: Radiologic response after neo-adjuvant RT was a poor predictor of pathologic response. Complete and near complete histologic responses seem to be associated with favorable clinical outcomes. Larger studies are needed to test these surrogates in a prospective fashion.
BMC Cancer, 2011
Background: The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Method: Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m 2 iv days 1 and 4, ifosfamide 1500 mg/m 2 iv days 1 -4, doxorubicin 50 mg/m 2 day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Result: Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. Conclusion: The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account. Trial registration
International Journal of Radiation Oncology*Biology*Physics, 2011
Purpose: To assess the impact of radiotherapy (RT) sequencing with surgery on overall survival (OS), causespecific survival (CSS), local failure, and distant failure in soft-tissue sarcoma (STS). Methods and Materials: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC Medical Systems (Sunnyvale, CA). Patients with STS of all major anatomic sites who received definitive surgery and either preoperative (preop) or postoperative (postop) RT were included. Patients were also required to have known stage and grade. Prognostic factors for survival were identified using multivariate techniques. Survival was calculated using the Kaplan-Meier method, and compared for statistical significance (p < 0.05) using the log-rank test. Results: A total of 821 patients met inclusion criteria. The median follow-up time was 63 months. Age, stage, histology, gender, tumor size, and RT sequence were independent predictors for OS (p < 0.05). Preop RT was associated with significantly improved OS and CSS compared with postop RT (hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.56-0.91, p < 0.01, and HR = 0.64, 95% CI 0.46-0.88, p < 0.01, respectively). The 5-year CSS was 79% and 74%, in favor of preop RT (log-rank, p < 0.05). Preop RT was also significantly associated with a reduced risk for local and distant relapse compared with postop RT. Conclusion: Preoperative RT is associated with a reduced cancer-specific mortality compared with postoperative RT in STS. The results of this study may serve as motivation to conduct future prospective studies with larger patient numbers. Ó