Evaluating repetitive 18F-fluoroazomycin-arabinoside (18FAZA) PET in the setting of MRI guided adaptive radiotherapy in cervical cancer

Abstract Background. The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer 18F-fluoroazomycin-arabinoside (18FAZA ). Material and methods. Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm3 (+/− 67, SD). Dynamic and static 18FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/− concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk. Results. Five patients had visually identifiable tumours on 18FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five 18FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten 18FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/−12, SD). Conclusion. PET imaging with 18FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of 18FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance.

[1]  P Vaupel,et al.  Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[2]  Christian Kirisits,et al.  Adaptive management of cervical cancer radiotherapy. , 2010, Seminars in radiation oncology.

[3]  Jens Overgaard,et al.  Tumor hypoxia is independent of hemoglobin and prognostic for loco-regional tumor control after primary radiotherapy in advanced head and neck cancer , 2004, Acta oncologica.

[4]  Christian Kirisits,et al.  Dose-volume histogram parameters and local tumor control in magnetic resonance image-guided cervical cancer brachytherapy. , 2009, International journal of radiation oncology, biology, physics.

[5]  J. Dimopoulos,et al.  The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: clinical feasibility and preliminary results. , 2006, International journal of radiation oncology, biology, physics.

[6]  H. Machulla,et al.  Fluoroazomycin arabinoside (FAZA): synthesis, 2H and 3H‐labelling and preliminary biological evaluation of a novel 2‐nitroimidazole marker of tissue hypoxia , 1999 .

[7]  John M Buatti,et al.  Method and timing of tumor volume measurement for outcome prediction in cervical cancer using magnetic resonance imaging. , 2002, International journal of radiation oncology, biology, physics.

[8]  R Pötter,et al.  Image-guided adaptive brachytherapy for cervix carcinoma. , 2008, Clinical oncology (Royal College of Radiologists (Great Britain)).

[9]  A. Fyles,et al.  Oxygenation predicts radiation response and survival in patients with cervix cancer. , 1998, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  P Vaupel,et al.  Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. , 1991, Cancer research.

[11]  D. Brizel,et al.  Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[12]  Lester J. Peters,et al.  Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[13]  J. Dimopoulos,et al.  Dose-effect relationship for local control of cervical cancer by magnetic resonance image-guided brachytherapy. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  Marianne Patt,et al.  [18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]Fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. , 2003, Nuclear medicine and biology.

[15]  K. Krohn,et al.  Radiolabelled fluoromisonidazole as an imaging agent for tumor hypoxia. , 1989, International journal of radiation oncology, biology, physics.

[16]  R. Fisher,et al.  Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  R. Pötter,et al.  Intratumoral pO2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[18]  Christian Kirisits,et al.  Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[19]  Steen Jakobsen,et al.  Can hypoxia-PET map hypoxic cell density heterogeneity accurately in an animal tumor model at a clinically obtainable image contrast? , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[20]  D. Hedley,et al.  Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  P. Vaupel,et al.  Carcinomas of the Uterine Cervix : Evaluation by Computerized O 2 Tension Measurements , 2006 .

[22]  M. Picchio,et al.  Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[23]  D. Binns,et al.  Imaging of tumor hypoxia with [124I]IAZA in comparison with [18F]FMISO and [18F]FAZA--first small animal PET results. , 2007, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[24]  K. Krohn,et al.  Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells. , 1987, Radiation research.

[25]  Jian Z. Wang,et al.  Synergistic effects of hemoglobin and tumor perfusion on tumor control and survival in cervical cancer. , 2009, International journal of radiation oncology, biology, physics.