title: A volumetric analysis of GTVDand CTVHRas defined by the GEC ESTRO recommendations in FIGO stage IIB and IIIB cervical cancer patients treated with IGABT in a prospective multicentric trial (EMBRACE).
abstract: To quantify the gross tumor volume at diagnosis (GTVD) and high-risk clinical target volume (CTVHR) at brachytherapy (BT) and describe subgroups of patients with different patterns of response to chemoradiotherapy (CRT) in patients with FIGO stage IIB and IIIB cervical cancer treated with image-guided adaptive brachytherapy (IGABT). Additionally, to evaluate the feasibility of IGABT achieving adequate target coverage in these groups.
  
  
  
  Patients with FIGO stage IIB and IIIB cervical cancer enrolled in the EMBRACE study were analyzed. T2-weighted MRI scans were obtained at diagnosis and at BT. GTVDand CTVHRwere defined as per the GEC ESTRO recommendations. Patients were classified taking into account that initial tumor volume and response to CRT represented by the volume of residual disease (CTVHR) and extent of residual parametrial disease are all major factors determining local dose delivery by BT, local control, and overall disease outcome. These factors were quantified applying the following criteria: (1) volume of the GTVDrelative to the median volume of the GTVD; (2) the ratio (R) of CTVHRto GTVDfor each patient; (3) the extent of residual parametrial disease at the time of BT. Accordingly, patients were classified into six groups (G1-G6): stage IB1-like tumors (G1), tumors with good response and any size (G2), small tumors with moderate response (G3), large tumors with moderate response (G4), tumors with poor response (G5) and those with progressive disease (G6). Tumor and treatment characteristics were then compared among the first five groups (only 3 patients were allocated to G6).
  
  
  
  A total of 481 patients were evaluated. The number of patients in the 6 groups were 55, 78, 123, 147, 75 and 3, respectively. The mean (SD) GTVDwas 43.6 (32.8)cm3and the mean (SD) CTVHRwas 31.6 (16.1)cm3. The mean GTVDand CTVHRwere 12.6cm3and 23.7cm3in G1 (R>1.1), 47.5cm3and 25.3cm3in G2 (R<0.9), 23.9 cm3and 29.9cm3in G3 (R 0.9-1.1), 73.4cm3and 38.5cm3in G4 (R 0.9-1.1), 79.4cm3and 59.5cm3in G5 (R>1.1), respectively. Parametrial disease extent at BT was as follows: no involvement in G1 and G2, proximal at most in G3 and G4, distal or to the pelvic wall in G5, progressive in G6. The use of interstitial needles was progressively higher among the groups (mean 0, 0, 2, 3, 6 in G1-5, P<0.001). The mean GTVBTD100in G1-5 was 103.1Gy, 91.8Gy, 93.5Gy, 88.3Gy and 87.1Gy. The mean CTVHRD90in G1-5 was 95.1Gy, 92.1Gy, 92.6Gy, 87.6Gy and 88.4Gy.
  
  
  
  In patients with FIGO stage IIB and IIIB disease, intra-FIGO stage heterogeneity and overlap between the two stages exist with respect to tumor volume, treatment response and extent of parametrial disease at BT. Taking into account GTVD, parametrial disease at BT and the ratio of CTVHR/GTVD, five major groups exist. These enable prediction of GTVBTand CTVHRdose coverage through BT. IGABT, as performed in EMBRACE, accommodates to a considerable degree for the different variants of tumor regression in these groups through adaptation of the treatment technique including the use of needles. However, major variations remain at present with regard to dose to GTVBTand to CTVHR, which are most pronounced in G4 and G5. This new classification will be validated in future in regard to clinical outcome in EMBRACE.
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Austria; King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Electronic address: NJastaniyah@kfshrc.edu.sa.
authors.forename: Noha
authors.initials: N
authors.lastname: Jastaniyah
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Austria; Kobe University Graduate School of Medicine, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Aarhus University Hospital, Denmark.
authors.forename: Kari
authors.initials: K
authors.lastname: Tanderup
authors.affiliation: Aarhus University Hospital, Denmark.
authors.forename: Jacob Christian
authors.initials: JC
authors.lastname: Lindegaard
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Alina
authors.initials: A
authors.lastname: Sturdza
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Kirisits
authors.affiliation: Institute of Oncology Ljubljana, Slovenia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Šegedin
authors.affiliation: Tata Memorial Hospital, Mumbai, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Mahantshetty
authors.affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Rai
authors.affiliation: University Medical Center Utrecht, The Netherlands.
authors.forename: Ina-Maria
authors.initials: IM
authors.lastname: Jürgenliemk-Schulz
authors.affiliation: Institut Gustave Roussy, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Haie-Meder
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Susovan
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Pötter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D002584:Cervix Uteri / Q000000981:diagnostic imaging / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D015642:Radiology, Interventional / Q000379:methods*; D016896:Treatment Outcome; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000532:radiotherapy*; D055815:Young Adult
keywords: Adaptive brachytherapy; Cervix uteri cancer; Response groups; Target volumes