Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney
Radiation Oncologist

Judith Martland
Senior Physicist
Northern Sydney Cancer Centre,Royal North Shore Hospital, Sydney

Florence Ko
Brachytherapy Radiographer
Northern Sydney Cancer Centre,Royal North Shore Hospital, Sydney

Lesley Guo
Northern Sydney Cancer Centre,Royal North Shore Hospital, Sydney

Marita Morgia
Radiation Oncologist
Northern Sydney Cancer Centre,Royal North Shore Hospital, Sydney

Background & Purpose: To present the 6-year patterns of failure, overall survival, and detailed late toxicity outcomes of women treated with GEC-ESTRO defined adaptive MR-image guided brachytherapy (MR-IGBT) for predominantly locally advanced lymph node positive cervix cancer following intensity-modulated radio-chemotherapy.

Methods: From July 2010 to end-June 2016, 41 consecutive women with biopsy proven cervix cancer (median age 51 yrs; 25-77) were referred after FDG-PET/CT, pelvic MRI, and joint EUA staging for curative-intent EBRT and synchronous weekly platinum chemotherapy followed by MR-IGBT. 36/41 patients had FIGO Stage II (n=18) or III/IV (18) disease. All treatment was completed within 50 days. Thereafter patients were followed with 3-6 monthly clinic visits, pelvic examinations, cervical cytology and HR-HPV analysis. FDG-PET/CT were done at 3 months, 12 months, and 24 months post MR-IGBT, or as otherwise indicated.

Results: Twenty-five (61%) had positive pelvic (21) or para-aortic lymph nodes (4). Extended-field IMRT was used in 66% of cases (27). Median overall relapse-free survival (RFS) and OS was 44% and 69% respectively, at 65 months. Median GTV@diagnosis was 32.5cc (1.4-354cc ) and was reduced by 81% to 6.3cc after initial radio-chemotherapy. Further significant adaptive changes in GTV, HR-CTV and IR_CTV were noted during MR-IGBT but were not related either local or non-local relapse, or survival metrics. Local relapse was observed in only 3 patients (7%). FIGO stage was a poor predictor of RFS, DFS and OS. Any positive LN (pelvic or para-aortic) was significantly related to RFS (p=0.0007) but not OS (p=0.081) except when para-aortic LN were positive (p<0.0001). Prospective evaluation of late GI, GU, and reproductive system toxicities were recorded using NCI-CTCAE. The probability of Grade 2 or worse GI and GU toxicity-free survival was 87.5% and 90.2% at 6-years. G2 or greater reproductive system toxicities, mainly vaginal shortening and stenosis, occurred in over a third of women despite prophylactic post treatment vaginal dilation.

Conclusions: Initial complex radio-chemotherapy followed by MR-IGBT is a safe strategy for patients with advanced cervical cancer. Local disease control within the central pelvis and metastatic LN sites occurred in nearly all patients with minimal morbidity. FIGO staging (2008) alone however does not recognize positive LN status as detrimental variable reducing the OS impacts of better pelvic cancer control.

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