Complications of combined radiotherapy and isolated limb perfusion with tumor necrosis factor alpha ± interferon gamma and melphalan in patients with irresectable soft tissue tumors

Vrouenraets, B. C.; Keus, Ronald B.; Nieweg, Omgo E.; Kroon, Bin B. R.

doi:10.1002/(sici)1096-9098(199706)65:2<88::aid-jso4>3.0.co;2-j

Cited by 25 publications

(18 citation statements)

References 26 publications

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“…Little is known about the combined effects of ILP and EBRT. Vrouenraets et al22 described one brachial arterial occlusion, but this was only 4 months after treatment. Olieman et al16 described the occurrence of necrosis after ILP but did not find any increased tumor-related morbidity after ILP followed by EBRT.…”

Section: Discussionmentioning

confidence: 98%

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

et al. 2007

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Background: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-a) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated.Methods: Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up.Results: Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17-159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50-1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median, 10.95; range, 8.0-32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011).Conclusions: ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity.

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Section: Discussionmentioning

confidence: 98%

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

et al. 2007

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“…Hoven-Gonderie et al28 reported that two-thirds of all patients experienced serious late toxic problems after combined treatment for STS. Major problems with wound healing and continuous wound infections (8–14%) are described in literature 29,30. Vascular damage (4–14%) is a common long-term complication of RTx 6,30,31.…”

Section: Discussionmentioning

confidence: 99%

“…Major problems with wound healing and continuous wound infections (8–14%) are described in literature 29,30. Vascular damage (4–14%) is a common long-term complication of RTx 6,30,31. Kalman et al32 described four cases of long-term vascular side-effects in the axillary artery after mastectomy with adjuvant RTx, 10–27 years after treatment.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients?

et al. 2010

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BackgroundStandard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity.MethodsIn our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation.ResultsSurgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2–182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up.ConclusionsIn patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit.

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“…Therefore, radiation therapy after delayed surgical resection following ILP has been proposed to improved local control, as retrospective studies have demonstrated a significantly lower local recurrence rate for patients receiving adjuvant radiotherapy [148,149]. Although some reports have focused on the morbidity of this combined approach [150][151][152], the only study available comparing a series of 34 consecutive patients who were either additionally treated with radiotherapy after ILP or not found no differences in treatment-related toxicity between the two groups at a median follow-up of 34 months [148].…”

Section: Ilp With Tnf and Doxorubicinmentioning

confidence: 99%

Isolierte Extremitätenperfusion mit TNFα und Zytostatika: eine Revolution in der Behandlung lokal fortgeschrittener Weichgewebssarkome der Extremitäten

et al. 2009

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Zusammenfassung. Grundlagen: Lokal fortgeschrittene Weichgewebssarkome der Extremitäten stellen mit dem Ziel der lokalen Tumorkontrolle und dem gleichzeitigen Funktionserhalt eine stetige operative Herausforderung dar. Die isolierte hypertherme Extremitätenperfusion mit TNF und Melphalan ist als neoadjuvante Therapieoption eingeführt worden, um Amputationen zu vermeiden, ohne die Prognose zu verschlechtern.Methodik: Literaturrecherche über die PubMed Datenbank mittels Entrez, kombiniert mit den Erfahrungen der Autoren.Ergebnisse: Anhand mehrerer Studien wurde belegt, dass durch die ILP ein Extremitätenerhalt in bis zu 80 % der Fälle bei tolerablen lokalen und systemischen Komplikationen zu realisieren ist. Die Lokalrezidivrate liegt zwischen 10-20 %.Schlussfolgerungen: Die isolierte Extremitätenperfu-sion mit TNF und Melphalan hat die Behandlung von lokal fortgeschrittenen Weichgewebssarkomen der Extremitäten durch eine deutliche Reduktion der Amputationsraten revolutioniert. Weitere Fortschritte können nach Einführung neuer Substanzen erwartet werden.

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Complications of combined radiotherapy and isolated limb perfusion with tumor necrosis factor alpha ± interferon gamma and melphalan in patients with irresectable soft tissue tumors

Cited by 25 publications

References 26 publications

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients?

Isolierte Extremitätenperfusion mit TNFα und Zytostatika: eine Revolution in der Behandlung lokal fortgeschrittener Weichgewebssarkome der Extremitäten

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