Chemotherapy For Soft Tissue Sarcomas Research Articles

Chemotherapy for Soft Tissue Sarcoma: Development of New Standard Treatments and Clinical Trials in Japan

Abstract Recently, pembrolizumab has been approved for microsatellite instability-high cancers, and genome profiling panel has also been approved for advanced refractory cancers including soft tissue sarcomas (STS) in Japan. However, efficacy and cost-benefit balance of these new strategies for STS should be confirmed by the future clinical trials. For localized STS, efficacy of perioperative chemotherapy has remained controversial. Meta-analysis of randomized controlled trials (RCT) comparing chemotherapy with surgery showed significant survival benefit of the chemotherapy for localized STS. Subsequently, recent RCT have compared chemotherapy regimens with each other especially in neoadjuvant setting, not with surgery. The Italian Sarcoma Group study ISG-STS1001 demonstrated significantly better survival by neoadjuvant epirubicin plus ifosfamide than histology-tailored regimens for high-risk STS. The 10-year follow-up of our trial, JCOG0304, also showed good stable results of neoadjuvant chemotherapy using adriamycin and ifosfamide (AI) for high-risk STS. These observations suggest that neoadjuvant AI could be recommended for localized high-risk STS. Besides high efficacy of AI, significant toxicities of the regimen should also be noted. We are now conducting a randomized phase II/III study, JCOG1306, to confirm the non-inferiority of neoadjuvant gemcitabine plus docetaxel (GD) to AI for high-risk STS. For advanced STS, adriamycin-based chemotherapy remains standard first-line treatment since phase III study of olaratumab resulted in negative. On the other hand, the standard second-line regimen for advanced STS has not been established yet. There are several options including GD, pazopanib, trabectedin and eribulin, however, no evidence has been shown which regimen is the best as second-line therapy. To establish the standard therapy of second-line treatment for advanced STS, we are currently conducting randomized phase II study comparing pazopanib, trabectedin and eribulin.

Benefit of intensified perioperative chemotherapy within high-risk CINSARC patients with resectable soft tissue sarcomas (CIRSARC).

TPS11078 Background: We have recently identified a gene expression signature so called “CINSARC” which is related with chromosomal instability and highly predictive of metastasis-free and overall survival in soft-tissue sarcoma (STS) patients. The prognostic relevance of this signature has been validated recently in an independent set of sarcomas from the Cancer Genome Atlas (TCGA) consortium. Despite optimal locoregional treatment, patients with high-risk CINSARC have a very poor outcome.However, the main issues with peri-operative chemotherapy in STS patients are the identification of patients who are more likely to benefit from this approach and the characterization of the best chemotherapy regimen. Indeed, in all clinical trials investigating peri-operative chemotherapy in STS, patients were included on the basis of classical histological criteria (grade, tumor size, deep location). The CINSARC is more discriminant than grade to evaluate the prognosis of STS patients (35% of grade 3 are low-risk CINSARC and 40% of grade are high-risk CINSARC). We hypothesize than: (1) 6 cycles of anthracyclines-ifosfamide is associated with improved outcome in comparison to 3 cycles of chemotherapy (ISG-STS 10-01) in patients with high-risk CINSARC STS; (2) Chemotherapy-free strategy is not associated with detrimental outcome in low-risk CINSARC STS. Methods: This is a multicenter phase III trial (sponsor: Institut Bergonié) which aims to evaluate the efficacy (intent-to-treat analysis) of 6 cycles of neoadjuvant doxorubicin + ifosfamide based chemotherapy+ surgery +/-radiotherapy (Arm B) in comparison with 3 cycles of neoadjuvant doxorubicin + ifosfamide based chemotherapy + surgery +/- radiotherapy (Arm A) in terms of 3-year progression-free survival (PFS) in high-risk CINSARC patients with resectable STS. Patients with low-risk CINSARC signature will be treated at investigator discretion. 334 patients will have to be recruited over 36 months in 10 centers of the French Sarcoma Group. This is the first study assessing the impact of peri-operative chemotherapy in STS based on a prognostic molecular signature. The study is open for accrual at time of submission. Clinical trial information: NCT03805022.

10-year follow-up results of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-grade soft tissue sarcomas (STS) in the extremities: Japan Clinical Oncology Group study JCOG0304.

e22533 Background: STS are rare malignant tumors and relatively resistant against chemotherapy. We have previously reported 3-year follow-up on the efficacy results of perioperative chemotherapy with DXR and IFM for STS in the extremities (JCOG0304) in ASCO 2011 (abstract ID:#10078). In the present report, we analyzed 10-year follow-up results of JCOG0304. Methods: Patients with operable, FNCLCC grade 2/3 STS (T2bN0M0, AJCC 6th edition) in the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy consisted of DXR 60 mg/m2plus IFM 10 g/m2in 3-week interval. Primary endpoint was progression-free survival (PFS). Prognostic factors were evaluated by log-rank test. Results: A total of 72 patients were enrolled between March 2004 and September 2008, and 70 patients were eligible. Median follow-up period was 10.0 years for all eligible cases. The local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. Ten-year progression-free survival (PFS) was 65.7% (95% CI, 53.4%-75.5%) with no PFS event within last 5-year of follow-up. Ten-year overall survival (OS) was 78.1% (95% CI, 66.3%-86.2%). Subgroup analysis demonstrated no significant difference in PFS and OS regarding age, sex, histological grade, and histology. Secondary malignancy occurred in 6 patients. Conclusions: Only a few long-term results of clinical trials of perioperative chemotherapy for STS have been reported. Our results demonstrated that the 10-year outcome of JCOG0304 for the patients with operable, high-grade STS in the extremities was stable and remained favorable. Clinical trial information: C000000096.

Effect of chemotherapy on cancer stem cells and tumor-associated macrophages in a prospective study of preoperative chemotherapy in soft tissue sarcoma

BackgroundCancer stem cells (CSC) may respond to chemotherapy differently from other tumor cells.MethodsThis study examined the expression of the putative cancer stem cell markers ALDH1, CD44, and CD133; the angiogenesis marker CD31; and the macrophage marker CD68 in soft tissue sarcomas (STS) before and after 4 cycles of chemotherapy with doxorubicin and ifosfamide in 31 patients with high-grade soft tissue sarcoma in a prospective clinical trial.ResultsNone of the markers clearly identified CSCs in STS samples. Macrophages represented a prominent component in viable tumor areas in pre-treatment STS biopsies, ranging from < 5 to > 50%. Furthermore, macrophages expressed CD44 and ALDH1. Macrophage density correlated with baseline maximum standardized uptake value (SUVmax) on fluoro-deoxyglucose positron emission tomography (PET) imaging. Pre-chemotherapy CD68 staining correlated positively with the baseline SUVmax, and negatively with the percent of viable tumor cells in post-chemotherapy resection samples. In particular, cases with more CD68-positive cells at biopsy had fewer viable tumor cells at resection, suggesting a better response to chemotherapy.ConclusionsIn conclusion, ALDH1, CD44, and CD133 are not likely to be useful markers of CSCs in STS. However, our observation of infiltrating macrophages in STS specimens indicates that these immune cells may contribute significantly to STS biology and response to chemotherapy, and could provide a potential target of therapy. Future studies should investigate macrophage contribution to STS pathophysiology by cytokine signaling.

Call for improved design and reporting in soft tissue sarcoma studies: A systematic review and meta-analysis of chemotherapy and survival outcomes in resectable STS.

New evidence and systemic therapies demand an updated analysis of chemotherapy for soft tissue sarcoma. We completed a meta-analysis of chemotherapy in localized STS, assessing OS, PFS, and local and distant recurrence (local recurrence-free survival [LRFS] and distant recurrence-free survival [DRFS]). Ten studies, totaling 3157 patients, were included. A pooled analysis for 5-year OS, progression-free survival, LRFS, and DRFS showed no benefit of chemotherapy over locoregional therapy alone for all-comers or site-specific STS. We make recommendations to improve outcome reporting and quality indices.

The impact of chemotherapy on survival of patients with extremity and trunk wall soft tissue sarcoma: revisiting the results of the EORTC-STBSG 62931 randomised trial

BackgroundThis study was aimed at determining whether patients with high-risk soft tissue sarcoma (STS), as identified using the nomogram Sarculator, benefitted from adjuvant chemotherapy in the EORTC-STBSG 62931 randomised controlled trial (RCT), which failed to detect an impact for adjuvant doxorubicin plus ifosfamide (Adj) over observation (Obs). MethodsPatients with extremity and trunk wall STS in the EORTC-STBSG 62931 RCT were analysed (N = 290/351). Ten-year predicted probability of overall survival (pr-OS) was calculated using the prognostic nomogram Sarculator. Patients were grouped into three categories of predicted pr-OS: high (pr-OS>66%), intermediate (51<pr-OS≤66) and low (pr-OS≤51%). OS and disease-free survival (DFS) were calculated. ResultsNomogram pr-OS was dispersed (median 72%, interquartile range 57–83%) and had prognostic value for OS and DFS (log-rank test: P < 0.001). One hundred seventy, 68 and 52 patients had high (58.6%, 90 Obs/80 Adj), intermediate (23.5%, 34 Obs/34 Adj) and low pr-OS (17.9%, 24 Obs/28 Adj), respectively. Adjuvant chemotherapy halved the risk of recurrence (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.24–0.89) and death (HR = 0.46, 95% CI 0.23–0.94) in the low pr-OS category, while no effect was detected in intermediate and high pr-OS categories. To strengthen these findings, study participants with pr-OS<60% were combined (N = 80, 27.6%, 39 Obs/41 Adj), and a significant DFS (HR = 0.49, 95% CI 0.28–0.85) and OS (HR = 0.50, 95% CI 0.30–0.90) benefit was detected. ConclusionPatients of the EORTC-STBSG 62931 RCT with extremity and trunk wall STS and a low predicted pr-OS (high-risk patients) had better outcomes when treated with adjuvant chemotherapy. This may help reconcile the disparate results of clinical studies on adjuvant/neoadjuvant chemotherapy in STS.

1627P - Single arm prospective study evaluating the role of neoadjuvant chemotherapy in soft tissue sarcoma

Background: Surgery is the primary standard of care for localized soft tissue sarcoma (STS). In certain cases, upfront surgery may not be possible, or it may be mutilating and disfiguring. We conducted this study to evaluate the role of neoadjuvant chemotherapy in this setting. Methods: This single arm prospective study included patients of age ≥18 years with chemotherapy naïve STS of size ≥ 5 cm and which were grade II/III. These tumors were either upfront unresectable or possibly resectable with undesirable outcomes. Ewings sarcoma, osteosarcoma, rhabdomyosarcoma and other chemoresistant STS were excluded. The patients received three cycles of Ifosfamide (1.8 gm/m2 d1-d5) and epirubicin (60 mg/m2 d1-d2) followed by clinical and radiologic reassessment. The primary objective was overall response rate (ORR), and the secondary objective was to assess conversion to limb salvage surgery (LSS). Overall response was defined as complete response (CR) plus partial response (PR). Results: We included 36 patients in this study with a mean age of 36.9±14.7 years. The ratio male: female was 1.1. The most common histology in our cohort was synovial sarcoma [16 (44.4%)] followed by MPNST [5 (13.8%)]. Extremity [ 23 (63.8%)] was the most common site followed by trunk [8 (22.2%)] and head and neck [5 (13.8%)]. PR was seen in 14 (38.8%) patients, 16 (44.4%) patients had stable disease, three patients had progression and none of the patients had CR. The response could not be assessed in three patients. The ORR was 44.4%. LSS could be done for 13 (56.5%) patients with extremity STS. Ten patients with extremity STS required amputation despite neoadjuvant chemotherapy of which 6 (60%) patients did not give consent for amputation. The chemotherapy regimen was well tolerated, febrile neutropenia was seen in 12.5%. There was no treatment-related mortality. Conclusions: Neoadjuvant chemotherapy is an effective and safe option for unresectable STS or those who are resectable but require mutilating or disfiguring surgery. The acceptance of amputation as a mean of treatment of STS is low in our population. Clinical trial identification: CTRI/2017/07/008997. Legal entity responsible for the study: AIIMS. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

The Quest for Histology Driven Neoadjuvant Chemotherapy in Soft-Tissue Sarcoma: End of Road or Just the Beginning?

The Quest for Histology Driven Neoadjuvant Chemotherapy in Soft-Tissue Sarcoma: End of Road or Just the Beginning?

Controversies and consensus of neoadjuvant chemotherapy in soft-tissue sarcomas

Together with surgery and radiotherapy, systemic treatment with cytotoxic chemotherapy and molecular targeted agents is one of the main therapeutic pillars in the treatment of soft-tissue sarcomas and is the mainstay of treatment in patients with advanced or metastatic disease. Unlike other more common malignancies such as breast and colorectal cancer, the role of chemotherapy when used in the adjuvant setting in soft-tissue sarcomas is less well defined. Results from prior studies have been conflicting, in part due to the heterogeneity and rarity of the disease, and large-scale meta-analysis has been performed to address this issue. Neoadjuvant chemotherapy, defined as the use of chemotherapy before definitive treatment with surgery or radiotherapy, has distinct theoretical and practical advantages, which can potentially be beneficial to the patient. However, the currently available evidence to support its use is even more scarce. In this review article, we describe the current established data behind the use of adjuvant chemotherapy in selected patients with localised soft-tissue sarcomas and, through extrapolation of available data, discuss the potential role of it when used in the upfront setting.

Pre- and Postoperative Chemotherapy in Localized Extremity Soft Tissue Sarcoma: A European Organization for Research and Treatment of Cancer Expert Survey.

The management of localized extremity soft tissue sarcomas (STS) is challenging and the role of pre- and postoperative chemotherapy is unclear and debated among experts. Medical oncology experts of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group were asked to participate in this survey on the use of pre- and postoperative chemotherapy in STS. Experts from 12 centers in Belgium, France, Germany, Great Britain, Italy, Switzerland, and The Netherlands agreed to participate and provided their treatment algorithm. Answers were converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies. Several criteria used for decision-making in extremity STS were identified: chemosensitivity, fitness, grading, location, and size. In addition, resectability and resection status were relevant in the pre- and postoperative setting, respectively. Preoperative chemotherapy is considered in most centers for marginally resectable tumors only. Yet, in some centers, neoadjuvant chemotherapy is used routinely and partially combined with hyperthermia. Although most centers do not recommend postoperative chemotherapy, some offer this treatment on a regular basis. Radiotherapy is an undisputed treatment modality in extremity STS. Due to lacking evidence on the utility of pre- and postoperative chemotherapy in localized extremity STS, treatment strategies vary considerably among European experts. The majority recommended neoadjuvant chemotherapy for marginally resectable grade 2-3 tumors; the majority did not recommend postoperative chemotherapy in any setting. The management of localized extremity soft tissue sarcomas (STS) is challenging and the role of pre- and postoperative chemotherapy is unclear and debated among experts. This study analyzed the decision-making process among 12 European experts on systemic therapy for STS. A wide range of recommendations among experts regarding the use of perioperative chemotherapy was discovered. Discrepancies in the use of decision criteria were also uncovered, including the definition of what constitutes high-risk cancer, which is a basis for many to recommend chemotherapy. Before any standardization is possible, a common use of decision criteria is necessary.

Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas: a personal point of view.

Dr. Gianni Bonadonna is internationally recognized as one of the foremost medical oncologists of the 20th century. He is best known for his pioneering work in the development of adjuvant chemotherapy for breast cancer, but he was also the father of sarcoma chemotherapy. The first investigator to study the new chemotherapeutic agent adriamycin in the late 1960s, he noted activity against sarcomas. This article, focusing on adjuvant chemotherapy, adriamycin, and sarcomas, memorializes his achievements and their progeny.

Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications.

Soft tissue sarcomas are a rare and multifaceted group of solid tumours. Neoadjuvant chemotherapy is increasingly used to limit loss of function after wide surgical excision with the ultimate aim of improving patient survival. Recently, advances in the identification of effective treatment strategies and improvements in patient risk stratification have been reached. A randomized trial demonstrated that neoadjuvant epirubicin and ifosfamide improves survival of patients affected by five high-risk soft tissue sarcoma histologies of trunk and extremities, including undifferentiated pleomorphic sarcoma, myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumours, and leiomyosarcoma. Selection of patients for these treatments is expected to be improved by the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system, as it tailors T-stage categories on primary tumour site and considers a prognostic nomogram for retroperitoneal sarcoma, which also includes soft tissue sarcoma histology and other patient and tumour features not directly included in the TNM staging. Within this framework, this article will present neoadjuvant treatment strategies for high-risk soft tissue sarcoma, emphasizing the most recent advances and discussing the need for further research to improve the effectiveness of neoadjuvant treatments.

Chemotherapy for soft tissue sarcoma.

Soft tissue sarcoma is a term used to describe a heterogeneous group of many rare tumors. Since the initial description of activity of doxorubicin, several additional agents have been brought to bear in the treatment of these diseases. Despite 2 recent drug approvals, doxorubicin and ifosfamide remain the most effective chemotherapy drugs available for the treatment of majority of these tumors. Optimal dosing and administration influence outcomes because of the steep dose-response curves associated with these agents. The debate endures regarding whether patients who have advanced disease should routinely receive single agents sequentially or in combination. Adjuvant therapy remains similarly controversial, although meta-analyses do support its use. Contemporary treatment of soft tissue sarcoma routinely incorporates additional lines of treatment that have become available over the last 15 years. Fixed-dose-rate gemcitabine with or without docetaxel is a standard second-line treatment. In keeping with the paradigm shift favoring subset-specific therapy, several recent approvals are linked with specific sarcoma subtypes. Eribulin has recently been approved on the basis of improved overall survival for patients with adipocytic sarcomas, and trabectedin is now approved in the United States for patients with leiomyosarcoma and liposarcoma. Within the spectrum of targeted therapies, pazopanib is approved for all nonadipocytic sarcomas, and imatinib is approved for dermatofibrosarcoma protuberans. Each of these drugs represents incremental rather than radical progress, although they constitute important and much needed treatment options for patients with these diseases. Cancer 2016;122:2952-2960. © 2016 American Cancer Society.

First-line treatment in advanced or metastatic disease: one size fits all or adapted to specific histiotypes?

This article evaluates the supporting evidence for adapting choice of first-line chemotherapy to specific histological subtypes in advanced or metastatic soft tissue sarcoma (STS). The evidence for the current standard of care for first-line chemotherapy in STS is reviewed. This is followed by an overview of the evidence for use of specific chemotherapy drugs in a number of specific STS histological subtypes. The more recent literature on newer drugs being used in the first-line setting in STS is then reviewed, and finally an assessment is made as to whether it is possible at this time to tailor first-line chemotherapy to histiotype. The review shows that at present there is insufficient evidence to support the concept of adapting choice of first-line chemotherapy in advanced or metastatic STS to specific histiotypes.

Effect of chemotherapy in patients with early stage synovial sarcoma on disease-free survival or overall survival.

e22550Background: The benefit of adjuvant chemotherapy for soft tissue sarcoma is controversial. Methods: We retrosectivly analyzed the database of Northern California Kaiser Permanente from 1981 t...

Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies.

Soft tissue sarcomas (STSs) are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations.

Adjuvant chemotherapy for soft tissue sarcomas: a 10-year mono-institutional experience.

PurposeThe role of adjuvant chemotherapy (ACT) for soft tissue sarcomas (STS) is not standard practice. We investigated effectiveness and tolerability of ACT in patients (pts) with operated high-risk STS in clinical practice.MethodsMedical records of pts with localized STS referred to Istituto Oncologico Veneto, Padova, from January 1, 2003 to July 07, 2012 were reviewed. Data were collected for pts with high-risk STS (size ≥5 cm, high grade and stage III). For those who received ACT, regimens used, drug doses, number of cycles, toxicity, and reasons for dose reduction or treatment interruption were recorded. Disease-free survival (DFS) and overall survival (OS) were calculated with the Kaplan–Meier method.ResultsOut of 96 eligible pts, median age 62 years, 36 received ACT after loco-regional treatment. Median DFS was 29.6 months (95 % CI 13.2–46.0) in pts receiving ACT and 7.8 months (95 % CI 3.9–11.7) in untreated pts (p < 0.0001); median OS was 67.0 months (95 % CI 25.4–108.6) in treated and 33.7 months (95 % CI 23.3–44.2) in untreated pts (p = 0.005). Among pts receiving ACT, a significant difference in DFS was observed between pts with limb/girdle disease (median DFS 82.4 months; 95 % CI 0.0–184.7) and pts with other primary sites (median DFS 18.3 months; 95 % CI 8.0–28.5) (p = 0.052). Grade ≥3 toxicities occurred in 20 pts (20.8 %), leading to dose reductions, delays, and treatment discontinuation in five cases. There was no treatment-related death.ConclusionOur data confirm benefit of ACT with regard to DFS and OS in pts with high-risk STS, greatest for limb/girdle STS.

Adjuvant chemotherapy for soft tissue sarcoma.

Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence.

First line palliative chemotherapy in elderly patients with advanced soft tissue sarcoma.

BackgroundThe efficacy and toxicity of first line palliative chemotherapy for soft tissue sarcomas (STS) in the elderly is poorly described.MethodsPatients over the age of 65 years receiving first line chemotherapy for advanced non-GIST STS January 1998 - January 2012 at the Royal Marsden Hospital were identified. Data regarding survival and predictive factors were collected retrospectively.Results120 patients (52 females) with a median age of 72 (range 65–83) were treated. The most common histological subtypes were undifferentiated sarcoma (30%), leiomyosarcoma (27%), angiosarcoma (14%). 42% of patients had high grade tumours. 70% of patients had metastatic disease at presentation; lung metastasis being the most common disease site (72%). 80% received single agent chemotherapy, mostly with doxorubicin (60%). The median number of cycles was 2 (IQR 3). A partial response was reported in 20% of patients with disease stabilisation in a further 20%. 38% of patients were hospitalised for chemotherapy related toxicity. The median overall survival (OS) was 6.5 months (95% CI 4.7-8.3). Anaemia, lymphopenia, hypoalbuminemia, sarcoma subtype and co-morbidities were predictive for overall survival.ConclusionThe overall survival for elderly patients with STS is poor but several predictive factors have been identified. Hospital admissions for chemotherapy related toxicity are common.

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials

The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor. A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms. Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.