Hyperthermic Pelvic Perfusion With Tumor Necrosis Factor-α for Locally Advanced Cancers

Bonvalot, Sylvie; Baère, Thierry De; Mendiboure, Jean; Paci, Angélo; Farace, Françoise; Drouard-Troalen, L.; Bonnet, Laure; Hakimé, Antoine; Bonniaud, G.; Raynard, Bruno; Israël, Philippe; Cesne, Axel Le; Eggermont, Alexander M.M.; Laplanche, Agnès; Muret, Jane

doi:10.1097/sla.0b013e318242ebe7

Cited by 22 publications

(17 citation statements)

References 30 publications

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“…Vaginal reconstruction should be proposed to young patients when possible. The option of isolated perfusion of the pelvis could represent an alternative to mutilating surgical procedures or could be used to control unresectable patients but this technique still needs further evaluation [39]. Given all these consequences, in palliative indications and in case of endometrial cancer recurrences which can not be treated with radiotherapy, best supportive care should be put in balance with pelvic exenteration.…”

Section: Resultsmentioning

confidence: 99%

Long term outcome and quality of life after pelvic exenteration for recurrent endometrial and cervical cancers

Ngô¹,

Abboud²,

Fourchotte³

et al. 2013

OJOG

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Introduction: Pelvic exenteration can cure recurrent gynecological malignancies. However, treatment morbidity is over 50% in radiated pelves. We evaluated the outcome, the morbidity and the quality of life after exenteration. Methods: Patients who underwent an exenteration for recurrent cervical or endometrial cancer in our institution between 1999 and 2011 were retrieved. Survival rates were calculated according to Kaplan-Meier method and compared using the logrank test. The EORTC QLQ-C30 and QLQ-CX24 questionnaires were sent to patients alive in January 2012. Results: We identified 25 patients: 17 (68%) had cervical cancer and 8 (32%) endometrial cancer. 92% of them had received radiotherapy previously. All patients had a central pelvic recurrence, within a median time of 30 months [4 - 384] from initial treatment. Early complications requiring a re-laparotomy occurred in 9 patients (36%). Late complications included 2 (8%) fistulas, 2 (8%) occlusion and 1 (4%)

ureteral stenosis. Complete resection was obtained in 92% of patients. Disease Free and Overall survival rates were better in cervical rather than in endometrial cancer (median DFS in months 17 [2 - 145] vs 9.5 [3 - 21], p = 0.064, median OS in months 20 [2 - 145] vs 13 [4 - 42], p = 0.019). 69% of patients answered the quality of life questionnaires. Mean global quality of life score was 45 on a scale of 0 - 100, none of the patients had a sexual activity. Conclusions: Morbidity of exenteration remains high and quality of life is altered. Endometrial cancer is associated with a poorer prognosis. In those patients, exenteration should be put in balance with best supportive care.

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Section: Resultsmentioning

confidence: 99%

Long term outcome and quality of life after pelvic exenteration for recurrent endometrial and cervical cancers

Ngô¹,

Abboud²,

Fourchotte³

et al. 2013

OJOG

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“…Local hyperthermia in combination with chemotherapy and/or radiotherapy for treatment of rectal cancer warrants further study . Bonvalot et al . achieved 30% complete response rate using hyperthermic perfusion of tumour necrosis factor α in patients with unresectable pelvic tumours.…”

Section: Discussionmentioning

confidence: 99%

“…Local hyperthermia in combination with chemotherapy and/or radiotherapy for treatment of rectal cancer warrants further study [42]. Bonvalot et al [43] achieved 30% complete response rate using hyperthermic perfusion of tumour necrosis factor a in patients with unresectable pelvic tumours. A combination of local hyperthermia and metronidazole allows a high tumour drug concentration (150 mg/g) to be achieved, which is necessary for its radiosensitizing effect [22,44].…”

Section: Discussionmentioning

confidence: 99%

Phase II study of concomitant chemoradiotherapy with local hyperthermia and metronidazole for locally advanced fixed rectal cancer

Barsukov¹,

Gordeev²,

Ткачев³

et al. 2013

Colorectal Disease

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Aim Locally advanced fixed T4 rectal cancer has a poor prognosis and no standard treatment strategy. The aim of this study was to investigate the safety and efficacy of neoadjuvant chemoradiotherapy using hypofractionated radiotherapy combined with local hyperthermia, capecitabine, oxaliplatin and metronidazole.Method Radiotherapy was given to a total dose of 40 Gy in 10 fractions. Capecitabine 650 mg/m 2 twice a day was given on days 1À22 and intravenous oxaliplatin 50 mg/m 2 was administered on days 3, 10 and 17. Local hyperthermia, 41À45°C for 60 min, was performed on days 8, 10, 15 and 17. Metronidazole 10 g/m 2 was administered per rectum on days 8 and 15. Surgery was carried out within 6À8 weeks after neoadjuvant treatment. The primary end-point was R0 resection rate. Secondary end-points included 2-year disease-free survival, 2-year overall survival, local recurrence rate, grade IIIÀIV tumour regression (Dworak) and treatment toxicity.Results From July 2006 to February 2011, 64 previously untreated patients were enrolled. R0 resection was carried out in 59 (92.2%). Five (7.8%) remained inoperable. Seven (10.9%) patients had grade IV and 30 (46.9%) had grade III regression. The main grade III toxic events included diarrhoea (15.6%, n = 10), vomiting (3.1%, n = 2), proctitis (3.1%, n = 2) and skin reaction (1.6%, n = 1). Only one (1.6%) patient had grade IV diarrhoea and vomiting. The median follow-up was 24.9 months. Two-year overall survival was 91% and 2-year disease-free survival was 83%.Conclusion Hyperthermia combined with chemotherapy to produce radiosensitization for locally advanced fixed primary rectal cancer is followed by a high R0 resection rate, with toxicity comparable with standard regimens.Keywords Fixed rectal cancer, chemoradiotherapy, hyperthermia, metronidazoleWhat does this paper add to the literature?The results of a phase II trial testing a new chemoradiotherapy regime with local hyperthermia for locally advanced fixed T4 rectal cancer treatment are presented. They show considerable improvement in the R0 resection rate for patients considered unresectable or borderline at presentation.

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“…Furthermore, 60% of patients in progression after first-line intensive systemic chemotherapy do not respond to second-line systemic therapy (Bruera et al 2014). Currently, only Japanese guidelines for the treatment of colorectal cancer include locoregional therapy as a third-line therapy for these patients (Watanabe et al 2018), and this is only offered in a few specialists centers (Bonvalot et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Precision oncotherapy based on liquid biopsies in multidisciplinary treatment of unresectable recurrent rectal cancer: a retrospective cohort study

Guadagni

Fiorentini

Simone

et al. 2019

J Cancer Res Clin Oncol

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Background Third line innovative systemic treatments and loco-regional chemotherapy by hypoxic pelvic perfusion (HPP) have both been proposed for the treatment of unresectable not responsive recurrent rectal cancer (URRC). In the present study, we have compared the safety and efficacy of HPP/target therapy, using drug regimens selected by liquid biopsy precision oncotherapy, to third-line systemic therapy based on tissue specimens precision oncotherapy. Methods HPP/target therapy regimens were selected based on precision oncotherapy, including assays for chemosensitivity and viability, and qRT-PCR for tumor-related gene expression. In the control group, systemic third-line and further lines of therapy were defined according to clinical and biological parameters. Results From 2007 to 2019, 62 URRC patients were enrolled, comprised of 43 patients in the HPP/target-therapy group and 19 patients in the systemic therapy control group. No HPP related complications were reported and the most common adverse events were skin and bone marrow toxicity. In the HPP/target-therapy group, the ORR was 41.8% whereas in the systemic therapy control group was 15.8%. DCR of the HPP/target-therapy group was significantly improved over the systemic therapy group (P = 0.001), associated with a PFS of 8 vs 4 months (P = 0.009), and OS of 20 vs 8 months (P = 0.046). Conclusions The present data indicate that in URCC patients, the integration of HPP/target-therapy and precision oncotherapy based upon liquid biopsy is as effective and efficacious as third-line treatment in local disease control and, therefore, deserves to be further assessed and compared to conventional systemic treatments in future prospective randomized trials.

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Hyperthermic Pelvic Perfusion With Tumor Necrosis Factor-α for Locally Advanced Cancers

Abstract: Isolated pelvic perfusion with TNF-α compares favorably with historical data, as it was observed in limb perfusion and could provide a chance to translate its successful combination with chemotherapy into treatment of locally advanced pelvic cancers.

Cited by 22 publications

References 30 publications

Long term outcome and quality of life after pelvic exenteration for recurrent endometrial and cervical cancers

Long term outcome and quality of life after pelvic exenteration for recurrent endometrial and cervical cancers

Phase II study of concomitant chemoradiotherapy with local hyperthermia and metronidazole for locally advanced fixed rectal cancer

Precision oncotherapy based on liquid biopsies in multidisciplinary treatment of unresectable recurrent rectal cancer: a retrospective cohort study

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