Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas

Pennington, J.D.D.; Eilber, Fritz C.; Eilber, Frederick R.; Singh, Arun S.; Reed, Jarred P; Chmielowski, Bartosz; Eċkardt, Jeffrey J.; Bukata, Susan V.; Bernthal, Nicholas M.; Federman, Noah; Nelson, Scott D.; Dry, Sarah M.; Wang, Pin-Chieh; Luu, Michael; Selch, Michael T.; Steinberg, Michael L.; Kalbasi, Anusha; Kamrava, Mitchell

doi:10.1097/coc.0000000000000443

Cited by 42 publications

(20 citation statements)

References 55 publications

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“…This is in contradiction to the findings of Mack et al [9], who did find a significant negative impact of positive surgical margins (present in 10.7% of the patients, and marginal margins in 44%) on LRFS in univariate analysis. Negative impact of positive surgical margins on LRFS has been also observed in other studies with mostly high rate of positive margins [15,[49][50][51][52]. On the other hand, Sadoski et al [53] and Gronchi et al [42] did not find any significant impact of positive surgical margins in patients with nRT on the LR (who had positive margins [R1] in 21.2% and 9.5% of cases, respectively).…”

Section: Discussionsupporting

confidence: 53%

Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities

Rauch

Agaimy

Semrau

et al. 2021

Cancers

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Background: Neoadjuvant treatment modalities in soft tissue sarcoma (STS) of the extremities have become more popular in recent years, but because of the rarity and heterogeneity of STS, there are yet few studies on the long-term impact of neoadjuvant treatment modalities, especially in terms of neoadjuvant radiochemotherapy. Methods: The study enrolled 136 patients with primary STS of the extremities who underwent surgery with curative intent or neoadjuvant therapy, followed by surgery in a 15-year period. Neoadjuvant treatment consisted of radiotherapy (RT) with 60 Gy and in most cases simultaneous chemotherapy (CTx) with ifosfamide (1.5 g/m2/d, d1–5, q28) and doxorubicine (50 mg/m2/d, d3, q28). We investigated the clinical, (post)-operative and histopathological data and the oncological follow-up as well. The median follow-up period was 82 months (range 6–202). Results: A total of 136 patients (M:F = 73:63) with a mean age of 62 years (range; 21–93) was observed. Seventy-four patients (54.4%) received neoadjuvant therapy (NT), 62 patients (45.6%) received primary surgery (PS). When receiving NT, patients with high-risk STS had a lower risk to develop distant metastasis (p = 0.025). Age, histological type, tumor size and surgical margins (R0 vs. R1) had no influence on any survival rates. There was an association between NT and the occurrence of postoperative complications (p = 0.001). The 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), disease free survival (DFS) and overall survival (OS) rate of the whole cohort was 89.9%, 77.0%, 70.6% and 72.6%; whereas the 5-year LRFS, MFS, DFS and OS rate was 90.5%, 67.2%, 64.1% and 62.8% for the NT group and 89.5%, 88.3%. 78.4% and 83.8% for the PS group. Conclusion: Multimodal treatment strategies in patients with STS of extremities lead to excellent oncological outcomes. Patients with high-risk STS had a significantly better MFS when receiving NT than patients with low-risk STS. NT was associated with a higher probability of postoperative but well-manageable complications.

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Section: Discussionsupporting

confidence: 53%

Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities

Rauch

Agaimy

Semrau

et al. 2021

Cancers

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“…Preoperative HFRT in STS has been validated in retrospective analyses, prospective registries, and phase I-II clinical trials (5,(23)(24)(25)(26)(27)(28)(29)(30)(31). However, randomized phase III trials comparing preoperative CFRT with HFRT are lacking.…”

Section: Available Evidence and Hfrt Regimensmentioning

confidence: 99%

Coronavirus Disease (COVID-19) Outbreak: Hypofractionated Radiotherapy in Soft Tissue Sarcomas as a Valuable Option in the Environment of Limited Medical Resources and Demands for Increased Protection of Patients

Spałek

Rutkowski

2020

Front. Oncol.

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“…For patients with STS who also receive neoadjuvant chemotherapy, a condensed (hypofractionated) form of neaodjuvant RT has been used at our institution for decades. This regimen of neoadjuvant chemoradiation (the "Eilber" protocol, 28 Gy over eight fractions with ifosfamide-based chemotherapy) demonstrated an actuarial local recurrence rate of 11% and 17% at 3 and 6 years (10,11). Another Polish study utilizing 5-day neaodjuvant radiation (25 Gy over five fractions) for STS resulted in 19.1% rate of local recurrence at median follow-up of 35 months (12).…”

Section: Introductionmentioning

confidence: 99%

A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma

Kalbasi

Kamrava

Chu

et al. 2020

Clinical Cancer Research

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In a single-institution phase II study, we evaluated the safety of a 5-day dose-equivalent neoadjuvant radiotherapy (RT) regimen for high-risk primary soft tissue sarcoma.Patients and Methods: Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late-radiation toxicity. Major wound complications, local recurrences, and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization.Results: Over 2 years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline SNPs in miRNA-binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared with the preceding 2-year period, the number of patients treated with neoadjuvant RT alone at our institution increased 3-fold, with a concomitant increase in the catchment area.Conclusions: A shorter 5-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after 2-year follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization.

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Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas

Abstract: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.

Cited by 42 publications

References 55 publications

Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities

Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities

Coronavirus Disease (COVID-19) Outbreak: Hypofractionated Radiotherapy in Soft Tissue Sarcomas as a Valuable Option in the Environment of Limited Medical Resources and Demands for Increased Protection of Patients

A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma

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