Patterns of failure after use of (18)F-FDG PET/CT in integration of extended-field chemo-IMRT and 3D-brachytherapy plannings for advanced cervical cancers with extensive lymph node metastases

BACKGROUND: The study is to evaluate the patterns of failure, toxicities and long-term outcomes of aggressive treatment using (18)F-FDG PET/CT-guided chemoradiation plannings for advanced cervical cancer with extensive nodal extent that has been regarded as a systemic disease. METHODS: We retrospectively reviewed 72 consecutive patients with (18)F-FDG PET/CT-detected widespread pelvic, para-aortic and/or supraclavicular lymph nodes treated with curative-intent PET-guided cisplatin-based extended-field dose-escalating intensity-modulated radiotherapy (IMRT) and adaptive high-dose-rate intracavitary 3D-brachytherapy between 2002 and 2010. The failure sites were specifically localized by comparing recurrences on fusion of post-therapy recurrent (18)F-FDG PET/CT scans to the initial PET-guided radiation plannings for IMRT and brachytherapy. RESULTS: The median follow-up time for the 72 patients was 66 months (range, 3–142 months). The 5-year disease-free survival rate calculated by the Kaplan-Meier method for the patients with extensive N1 disease with the uppermost PET-positive pelvic-only nodes (26 patients), and the patients with M1 disease with the uppermost PET-positive para-aortic (31 patients) or supraclavicular (15 patients) nodes was 78.5 %, and 41.8–50 %, respectively (N1 vs. M1, p = 0.0465). Eight (11.1 %), 18 (25.0 %), and 3 (4.2 %) of the patients developed in-field recurrence, out-of-field and/or distant metastasis, and combined failure, respectively. The 6 (8.3 %) local failures around the uterine cervix were all at the junction between IMRT and brachytherapy in the parametrium. The rate of late grade 3/4 bladder and bowel toxicities was 4.2 and 9.7 %, respectively. When compared to conventional pelvic chemoradiation/2D-brachytherapy during 1990–2001, the adoption of (18)F-FDG PET-guided extended-field dose-escalating chemoradiation plannings in IMRT and 3D-brachytherapy after 2002 appeared to provide higher disease-free and overall survival rates with acceptable toxicities in advanced cervical cancer patients. CONCLUSIONS: For AJCC stage M1 cervical cancer with supraclavicular lymph node metastases, curability can be achieved in the era of PET and chemo-IMRT. However, the main pattern of failure is still out-of-field and/or distant metastasis. In addition to improving systemic treatment, how to optimize and integrate the junctional doses between IMRT and 3D-brachytherapy in PET-guided plannings to further decrease local recurrence warrants investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2226-0) contains supplementary material, which is available to authorized users.