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.

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

South Asian Journal of Cancer ◽

10.4103/2278-330x.179687 ◽

2016 ◽

Vol 05 (01) ◽

pp. 15-19 ◽

Cited By ~ 6

Author(s):

Jyoti Bajpai ◽

Deepa Susan

Keyword(s):

Adjuvant Chemotherapy ◽

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Patient Outcomes ◽

Treatment Options ◽

Specific Treatment ◽

Soft Tissue Sarcomas ◽

Metastatic Potential ◽

Diverse Group ◽

Histologic Subtypes

AbstractSoft 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.

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Indication for neoadjuvant chemotherapy in adult patients with high-risk soft-tissue sarcomas

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.9578 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 9578-9578

Author(s):

B. Kasper ◽

E. Kuehl ◽

P. Wuchter ◽

L. Bernd ◽

A. D. Ho ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Disease Progression ◽

Response Rate ◽

Objective Response ◽

Soft Tissue Sarcomas ◽

First Diagnosis

9578 Background: To determine the efficacy and safety of neoadjuvant chemotherapy for local tumour control and overall survival in patients with high-risk soft-tissue sarcomas (tumour size ≥ 5 cm, G II/III, extracompartimental and deep localisation) we have analyzed the clinical outcome in 25 patients. Methods: Patients with high-risk soft-tissue sarcomas were treated with four cycles of etoposide 125 mg/m2/day 1+4, ifosfamide 1500 mg/m2/day 1–4 and doxorubicin 50 mg/m2/day 1 (EIA regimen) followed by definitive surgery with or without postoperative radiotherapy and adjuvant chemotherapy. 21 patients received chemotherapy in a combined neoadjuvant/adjuvant clinical setting; eighteen of them completed adjuvant chemotherapy. Four patients received chemotherapy in an adjuvant setting only. Results: The objective response rate of neoadjuvant chemotherapy assessable in 21 patients was 43%. Including NED (n = 7) and partial remissions (n = 3), the radiographic response rate was 47.6% with additional 42.9% stable diseases (n = 9). Surgery was performed in two patients before completing the four neoadjuvant chemotherapy cycles because of disease progression. Median overall survival for all patients from the time of first diagnosis was 21.6+ months [range: 8 - 50] and from the start of treatment 20.5+ months [range: 8 - 49]; median progression-free survival after start of treatment was 18.6+ months [range: 1 - 49]. After completion of chemotherapy, R0-resection could be performed in 13 of 21 patients (60%). At completion of entire treatment, 21 of 25 patients (84%) had NED after R0- and R1-resection. Two patients showed no disease progression after R2-resection and are alive with disease (AWD) 21 and 18 months after start of treatment. Two patients died of disease (DOD) ten and eight months after first diagnosis due to metastases. Conclusions: The high proportion of R0-resections supports the idea of a tumour downstaging after neoadjuvant treatment. Our data support the hypothesis that neoadjuvant chemotherapy might be beneficial as an integral part in the treatment strategy of high-risk soft-tissue sarcoma patients. No significant financial relationships to disclose.

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Faculty Opinions recommendation of Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13984969.15436075 ◽

2012 ◽

Author(s):

William Tap ◽

Sandra D'Angelo

Keyword(s):

Clinical Trial ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Soft Tissue ◽

Randomized Clinical Trial ◽

Soft Tissue Sarcomas ◽

Full Dose

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Translating Molecular Profiling of Soft Tissue Sarcomas into Daily Clinical Practice

Diagnostics ◽

10.3390/diagnostics11030512 ◽

2021 ◽

Vol 11 (3) ◽

pp. 512

Author(s):

Celine Jacobs ◽

Lore Lapeire

Keyword(s):

Soft Tissue ◽

Unmet Need ◽

Soft Tissue Sarcomas ◽

Molecular Profiling ◽

Point Of View ◽

Molecular Techniques ◽

Mesenchymal Tumors ◽

The Past ◽

Cancer Types ◽

Sarcoma Treatment

Soft tissue sarcomas are a group of rare mesenchymal tumors with more than 70 subtypes described. Treatment of these subtypes in an advanced setting is mainly according to a one-size-fits-all strategy indicating a high unmet need of new and more targeted therapeutic options in order to optimize survival. The introduction of advanced molecular techniques in cancer has led to better diagnostics and identification of new therapeutic targets, leading to more personalized treatment and improved prognosis for several cancer types. In sarcoma, a likewise evolution is seen, albeit at a slower pace. This manuscript describes how in the past years advanced molecular profiling in soft tissue sarcomas was able to identify specific and often pathognomonic aberrations, deferring standard sarcoma treatment in favor of more targeted treatment from an oncologist’s point of view.

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53 Neoadjuvant chemotherapy and radiotherapy for large soft tissue sarcomas

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/s0360-3016(97)85394-1 ◽

1996 ◽

Vol 36 (1) ◽

pp. 185 ◽

Cited By ~ 1

Author(s):

Ira J. Spiro ◽

Damian Dupuis ◽

Herman Suit ◽

Henry Mankin ◽

Candace Jennings ◽

...

Keyword(s):

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Soft Tissue Sarcomas

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Molecular Determinants of Soft Tissue Sarcoma Immunity: Targets for Immune Intervention

International Journal of Molecular Sciences ◽

10.3390/ijms22147518 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7518

Author(s):

Marcella Tazzari ◽

Laura Bergamaschi ◽

Alessandro De Vita ◽

Paola Collini ◽

Marta Barisella ◽

...

Keyword(s):

Soft Tissue ◽

Malignant Tumors ◽

Soft Tissue Sarcomas ◽

Point Of View ◽

Molecular Features ◽

Molecular Determinants ◽

Genetic Landscape ◽

Current Therapies ◽

Cumulative Evidence

Soft tissue sarcomas (STSs) are a family of rare malignant tumors encompassing more than 80 histologies. Current therapies for metastatic STS, a condition that affects roughly half of patients, have limited efficacy, making innovative therapeutic strategies urgently needed. From a molecular point of view, STSs can be classified as translocation-related and those with a heavily rearranged genotype. Although only the latter display an increased mutational burden, molecular profiles suggestive of an “immune hot” tumor microenvironment are observed across STS histologies, and response to immunotherapy has been reported in both translocation-related and genetic complex STSs. These data reinforce the notion that immunity in STSs is multifaceted and influenced by both genetic and epigenetic determinants. Cumulative evidence indicates that a fine characterization of STSs at different levels is required to identify biomarkers predictive of immunotherapy response and to discover targetable pathways to switch on the immune sensitivity of “immune cold” tumors. In this review, we will summarize recent findings on the interplay between genetic landscape, molecular profiling and immunity in STSs. Immunological and molecular features will be discussed for their prognostic value in selected STS histologies. Finally, the local and systemic immunomodulatory effects of the targeted drugs imatinib and sunitinib will be discussed.

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