Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay.

PURPOSE This study investigated sequential changes in tumor blood supply using magnetic resonance (MR) perfusion imaging and assessed their significance in the prediction of outcome of patients with advanced cervical cancer. The purpose of this project was to devise a simple, noninvasive method to predict early signs of treatment failure in advanced cervical cancer treated with conventional radiation therapy. METHODS AND MATERIALS Sixty-eight MR perfusion studies were performed prospectively in 17 patients with squamous carcinomas (14) and adenocarcinomas (3) of the cervix, Stages bulky IB (1), IIB (5), IIIA (1), IIIB (8), and IVA (1), and recurrent (1). Four sequential studies were obtained in each patient: immediately before radiation therapy (pretherapy), after a dose of 20-22 Gy/ approximately 2 weeks (early therapy), after a dose of 40-45 Gy/ approximately 4-5 weeks (midtherapy), and 4-6 weeks after completion of therapy (follow-up). Perfusion imaging of the tumor was obtained at 3-s intervals in the sagittal plane. A bolus of 0.1 mmol/kg of MR contrast material (gadoteridol) was injected intravenously 30 s after beginning image acquisition at a rate of 9 ml/s using a power injector. Time/signal-intensity curves to reflect the onset, slope, and relative signal intensity (rSI) of contrast enhancement in the tumor region were generated. Median follow-up was 8 months (range 3-18 months). RESULTS Tumors with a higher tissue perfusion (rSI > or = 2.8) in the pretherapy and early therapy (20-22 Gy) studies had a lower incidence of local recurrence than those with a rSI of < 2.8, but this was not statistically significant (13% vs. 67%; p = 0.05). An increase in tumor perfusion early during therapy (20-22 Gy), particularly to an rSI of > or = 2.8, was the strongest predictor of local recurrence (0% vs. 78%; p = 0.002). However, pelvic examination during early therapy (20-22 Gy) commonly showed no appreciable tumor regression. The slope of the time/signal-intensity curve obtained before and during radiation therapy also correlated with local recurrence. Follow-up perfusion studies did not provide information to predict recurrence. CONCLUSION These preliminary results suggest that two simple MR perfusion studies before and early in therapy can offer important information on treatment outcome within the first 2 weeks of radiation therapy before response is evident by clinical examination. High tumor perfusion before therapy and increasing or persistent high perfusion early during the course of therapy appear to be favorable signs. High perfusion suggests a high blood and oxygen supply to the tumor. The increase in tumor perfusion seen in some patients early during radiation therapy suggests improved oxygenation of previously hypoxic cells following early cell kill. Radiation therapy is more effective in eradicating these tumors, resulting in improved local control. Our technique may be helpful in identifying early-while more aggressive therapy can still be implemented-those patients who respond poorly to conventional radiation therapy.

[1]  C. Koch,et al.  Binding of 3H-misonidazole to solid human tumors as a measure of tumor hypoxia. , 1986, International journal of radiation oncology, biology, physics.

[2]  W T Yuh,et al.  Cervical cancer: application of MR imaging in radiation therapy. , 1993, Radiology.

[3]  Terry Jones,et al.  POSITRON EMISSION TOMOGRAPHY FOR IN-VIVO MEASUREMENT OF REGIONAL BLOOD FLOW, OXYGEN UTILISATION, AND BLOOD VOLUME IN PATIENTS WITH BREAST CARCINOMA , 1984, The Lancet.

[4]  C Vrousos,et al.  Radiotherapy alone in carcinoma of the intact uterine cervix according to G. H. Fletcher guidelines: a French cooperative study of 1383 cases. , 1988, International journal of radiation oncology, biology, physics.

[5]  M. Anderson,et al.  Staging of carcinoma of the uterine cervix: MRI-surgical correlation. , 1989, Clinical radiology.

[6]  J. van Nagell,et al.  The staging of cervical cancer: inevitable discrepancies between clinical staging and pathologic findinges. , 1971, American journal of obstetrics and gynecology.

[7]  H. Hricak,et al.  Cancer of the uterus: the value of MRI pre- and post-irradiation. , 1991, International journal of radiation oncology, biology, physics.

[8]  N Fujita,et al.  Neuromas and meningiomas: evaluation of early enhancement with dynamic MR imaging. , 1992, AJNR. American journal of neuroradiology.

[9]  T. Silveira,et al.  A randomized trial of chemotherapy followed by pelvic radiation therapy in stage IIIB carcinoma of the cervix. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  J W Belliveau,et al.  Ultrafast imaging of brain tumors , 1993, Topics in magnetic resonance imaging : TMRI.

[11]  B. I. Choi,et al.  Uterine cervical carcinoma: comparison of CT and MR findings. , 1990, Radiology.

[12]  K. Yamamoto,et al.  Vascularity of meningiomas and neuromas: assessment with dynamic susceptibility-contrast MR imaging. , 1994, AJR. American journal of roentgenology.

[13]  E F Halpern,et al.  Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. , 1994, Radiology.

[14]  E. Hall,et al.  Radiobiology for the radiologist , 1973 .

[15]  P. Vaupel,et al.  Tumor tissue oxygenation as evaluated by computerized-pO2-histography. , 1990, International journal of radiation oncology, biology, physics.

[16]  W. Hoskins,et al.  Staging of cervical cancer. , 1975, Clinical obstetrics and gynecology.

[17]  G. Hanks,et al.  A reappraisal of the international federation of gynecology and obstetrics staging system for cervical cancer. A study of patterns of care , 1992, Cancer.

[18]  L Axel,et al.  Tumor recurrence versus fibrosis in the female pelvis: differentiation with MR imaging at 1.5 T. , 1988, Radiology.

[19]  R. Mortel,et al.  Pelvic exenteration: A morbidity and mortality analysis of a seven‐year experience , 1989, Gynecologic oncology.

[20]  L. Brady,et al.  Treatment of recurrent carcinoma of the cervix. , 1978, International journal of radiation oncology, biology, physics.

[21]  F. Bova,et al.  Prognostic and treatment factors affecting pelvic control of stage ib and iia‐b carcinoma of the intact uterine cervix treated with radiation therapy alone , 1984, Cancer.

[22]  H. Hricak,et al.  Invasive cervical carcinoma: comparison of MR imaging and surgical findings. , 1988, Radiology.

[23]  H. Hricak,et al.  Cervical Carcinoma: Computed Tomography and Magnetic Resonance Imaging for Preoperative Staging , 1995, Obstetrics and gynecology.

[24]  C. Hudson,et al.  Synchronous 5-fluorouracil, mitomycin-C and radiation therapy in the treatment of locally advanced carcinoma of the cervix. , 1988, International journal of radiation oncology, biology, physics.

[25]  C. Haie-meder,et al.  Oxygen tension measurements in human tumors: The institut gustave-roussy experience , 1993 .

[26]  F. Ebner,et al.  Magnetic resonance imaging in cervical cancer: a basis for objective classification. , 1989, Gynecologic oncology.

[27]  P Kolstad,et al.  Intercapillary distance, oxygen tension and local recurrence in cervix cancer. , 1968, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[28]  S. Lindenauer,et al.  Pelvic exenteration, University of Michigan: 100 patients at 5 years , 1989, Obstetrics and gynecology.

[29]  S. Hewitt,et al.  Concomitant radiation therapy and chemotherapy in the treatment of advanced squamous carcinoma of the lower female genital tract. , 1989, Gynecologic oncology.

[30]  L. Balducci,et al.  Chemotherapy for advanced or recurrent gynecologic cancer , 1987, Cancer.

[31]  R. Gatenby,et al.  Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. , 1988, International journal of radiation oncology, biology, physics.

[32]  B. Clark,et al.  Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix. , 1993, International Journal of Radiation Oncology, Biology, Physics.

[33]  A J Dembo,et al.  Definitive evidence for hypoxic cells influencing cure in cancer therapy. , 1978, The British journal of cancer. Supplement.

[34]  P. Grigsby,et al.  Outcome of recurrent cervical carcinoma following definitive irradiation. , 1989, Gynecologic oncology.

[35]  U. Klose,et al.  Dynamic contrast enhancement of intracranial tumors with snapshot-FLASH MR imaging. , 1993, AJNR. American journal of neuroradiology.

[36]  M E Moseley,et al.  Echo-planar perfusion-sensitive MR imaging of acute cerebral ischemia. , 1993, Radiology.