Response to Neoadjuvant Chemotherapy Combined With Regional Hyperthermia Predicts Long-Term Survival for Adult Patients With Retroperitoneal and Visceral High-Risk Soft Tissue Sarcomas

Wendtner, Clemens-M.; Abdel-Rahman, S.; Krych, M.; Baumert, Jens; Lindner, Lars H.; Baur, Andrea; Hiddemann, Wolfgang; Issels, Rolf D.

doi:10.1200/jco.2002.07.146

Cited by 106 publications

(55 citation statements)

References 32 publications

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“…[1][2][3][4] Preoperative chemotherapy cannot be regarded as standard treatment to date; however, in 1996, available data justified the initiation of a European Organization for Research and Treatment of Cancer (EORTC) Phase III trial on neoadjuvant chemotherapy alone versus chemotherapy in conjunction with regional hyperthermia (RHT). 5,6 Today, RHT represents a standardized treatment option that usually is applied as an adjunct to radiotherapy and/or chemotherapy. In a number of Phase II and III trials, it has been shown that RHT improved local control in various locally advanced tumors.…”

Section: Resultsmentioning

confidence: 99%

“…This also has been demonstrated in patients with STS. 6,23 The impressive correspondence between !90% tumor necrosis (or even a pathologic complete response) and T 90 (or T 50 ) and the striking superiority of the hyperthermia group compared with the control group suggest a contribution of RHT to the local efficacy. Clearly, this can be clarified only by the final results from the ongoing EORTC-ESHO study.…”

Section: Discussionmentioning

confidence: 99%

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Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia

Gellermann

Hildebrandt

Issels³

et al. 2006

Cancer

128

101

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BACKGROUND The objective of this study was to evaluate noninvasive magnetic resonance (MR) thermography for the monitoring of regional hyperthermia (RHT) in patients with soft tissue sarcomas of the lower extremities and pelvis. METHODS Noninvasive MR monitoring during RHT was performed in 9 patients who had high‐risk soft tissue sarcomas of the lower extremities or pelvis during neoadjuvant chemotherapy plus RHT in the scope of the European Organization for Research and Treatment of Cancer 62961/European Society for Hyperthermic Oncology RHT‐95 study. Anatomic and temperature‐sensitive data sets were acquired every 10 minutes before and during RHT (using gradient‐echo‐sequences with variable echo times). MR temperature distributions were derived from the phase differences by using the proton‐resonance frequency shift method. A phase convolution setting phase shifts to zero in the fat tissue was performed as a drift correction. The mean MR temperatures in the tumor and muscles and the index temperatures (e.g., T90, which covers 90% of the target volume) and thermal doses were determined and compared with pathohistologic responses and direct temperature measurements if available. RESULTS Thirty of 72 MR‐thermography data sets (>40% of heat sessions) were evaluable. A significant correlation was observed between pathohistologic response (defined as a necrosis rate ≥90%) and standardized thermal parameters, such as thermal dose cumulative equivalent minutes at 43°C to 90% of the target volume (T90) (P = .050), mean T90 (P = .048), or T50 (P = .050). The correlation of 13 conventional temperature measurements performed in selected patients and sessions invasively in the tumor or noninvasively in rectum and bladder revealed an excellent correlation with MR temperatures (R2 = .96). CONCLUSIONS Noninvasive MR thermography of soft tissue sarcoma was feasible and suitable for validating the quality of heating during RHT. Cancer 2006. © 2006 American Cancer Society.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia

Gellermann

Hildebrandt

Issels³

et al. 2006

Cancer

128

101

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“…Surgical resection is difficult because of the proximity of vital structures of the retroperitoneal and adjacent vascularities. These affect local recurrence, postoperative outcomes and long-term survival rates [1,2] . A retrospective review of 143 cases of APRT in the First Affiliated Hospital of China Medical University was performed to analyze the factors influencing postoperative outcomes and optimize treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Surgical management of 143 patients with adult primary retroperitoneal tumor

Ke²,

Guo³

et al. 2007

WJG

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AIM:To analyze the surgical management of adult primary retroperitoneal tumors (APRT) and the factors influencing the outcome after operation. METHODS: RESULTS:A total of 143 cases of APRT were treated surgically. Among them, 122 (85.3%) underwent complete resection, 16 (11.2%) incomplete resection, and 3 (3%) surgical biopsies. Twenty-nine (20.2%) u n d e r w e n t t u m o r re s e c t i o n p l u s m u l t i p l e o rg a n resections. Ninety-five malignant cases were followed up for 1 mo to 5 years. The 1-year, 3-year, and 5-year survival rates of the patients subject to complete resection was 94.9%, 76.6% and 34.3% and that of patients with incomplete resection was 80.4%, 6.7%, and 0%, respectively (P < 0.001). The Cox multi-various regression analysis showed the completeness of tumor, sex and histological type were associated closely with local recurrence.

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“…In another retrospective analysis for retroperitoneal and visceral STS recruited to both studies, the RHT-91 and RHT-95 protocols demonstrated that the initial response to chemotherapy combined with RHT was predictive of long-term survival. 13 Most recently, under the auspices of the EORTC and the European Society of Hyperthermic Oncology (ESHO), we were able to complete a randomised intergroup phase III trial (EORTC 62961/ESHO RHT-95) of multimodal treatment in patients with primary (S1 group) and recurrent (S2 group) disease or after inadequate surgery (S3 group: resections with HR-STS to extremity and non-extremity received neoadjuvant systemic chemotherapy (four cycles of the EIA regimen) and were randomised to one of two arms -chemotherapy alone or combined with RHT -followed by definitive surgery and radiotherapy. Thereafter, in addition, four cycles of the EIA regimen were administered with or without RHT, according to the initial randomisation (see Figure 2).…”

Section: Regional Hyperthermia Combined With Chemotherapymentioning

confidence: 99%

Regional Hyperthermia as Targeted Therapy in the Management of High-risk Soft-tissue Sarcoma

Issels¹

2007

European Oncology &Amp; Haematology

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For high-risk soft-tissue sarcomas (HR-STS) in adults, new treatment strategies are needed to improve outcome with regard to local control and overall survival. Systemic chemotherapy has been integrated either after (adjuvant) or before (neoadjuvant) optimal local treatment by surgery and radiotherapy in HR-STS. This short article summarises the results of this combination with regional hyperthermia (RHT) as a targeted treatment strategy.The optimal treatment for HR-STS in adults remains a challenge for the multidisciplinary approach in modern oncology. Patients with large primary or recurrent STS (>5cm in diameter, grade 2-3) remain at increased risk of distant metastases and tumour-related mortality. Nearly all deaths are due to metastatic disease (e.g. lung, liver). The tendency for early haematogenous spread of STS may explain why distant metastases still occur in these patients despite optimal local treatment. Also, the invasiveness or anatomical location of locally advanced tumours often prevents resection with adequate margins, and the toxicity of radiotherapy limits the use of potentially therapeutic doses with a negative impact on local control. Innovative Treatment StrategyWith regard to prognostic factors, it can be concluded that for each A programme of aggressive chemotherapy interdigitated with radiotherapy for patients with large, high-grade extremity sarcomas used as neoadjuvant chemotherapy mesna-doxorubicin-ifosfamidedacarbazine (MAID) with split-course radiotherapy followed by resection and post-operative adjuvant MAID chemotherapy. 4 On the basis of these data, the Radiation Therapy Oncology Group (RTOG) initiated a phase II trial to evaluate the efficacy and toxicity of a modified MAID regimen in similar patients in a multi-institutional setting. Efficacy results showed three-year rates for disease-free and overall survival of 56.5, 64.5 and 75.1%, respectively, but 83% of patients experienced grade 4 toxicities and another 5% fatal grade 5 toxicities. 5 The only randomised trial of neoadjuvant chemotherapy for patients with resectable, high-risk sarcoma was performed by the European Organisation for Research and Treatment of Cancer (EORTC), but this trial was stopped because of low recruitment. Neoadjuvant treatment showed an objective response rate of 29%, but after a median follow-up of

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Response to Neoadjuvant Chemotherapy Combined With Regional Hyperthermia Predicts Long-Term Survival for Adult Patients With Retroperitoneal and Visceral High-Risk Soft Tissue Sarcomas

Abstract: Response to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.

Cited by 106 publications

References 32 publications

Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia

Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia

Surgical management of 143 patients with adult primary retroperitoneal tumor

Regional Hyperthermia as Targeted Therapy in the Management of High-risk Soft-tissue Sarcoma

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