Assessment Of Parametrial Response By Growth Pattern In Patients With Figo Stage Iib And Iiib Cervical Cancer: Analysis Of Patients From A Prospective Multicentric Trial (Embrace)

Considerable reduction in tumor volume during external beam radiation therapy (EBRT) is a prominent feature of cervical cancer treatment. Defining and quantifying residual disease at the time of brachytherapy (BT) is a prerequisite for image guided adaptive BT (IGABT). Tumor morphology subtype in cervical cancer, ranging from expansive to infiltrative, is considered to correlate with treatment response. The purpose of this study is to assess disease response along the parametrial space according to tumor morphology in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and IIIB cervical cancer at the time of IGABT using the database of a large prospective multicentric trial, an international study on magnetic resonance imaging (MRI)-guided BT in locally advanced cervical cancer (EMBRACE). Patients with FIGO stage IIB and IIIB cervical cancer registered as of November 2013 in the EMBRACE study were evaluated. Tumors were stratified according to morphologic subtype (expansive and infiltrative) on MRI at diagnosis and the characteristics of those subtypes were analyzed. Parametrial involvement at diagnosis and at BT was evaluated and the response to EBRT and chemotherapy (CRT) was classified as good, moderate, or poor. The response grade was compared between the 2 groups. Then, tumor volumes and dosimetric parameters at diagnosis and at BT were analyzed and compared. A total of 452 patients were evaluated, of which 186 had expansive growth type and 266 had infiltrative morphology. Patients with infiltrative tumors had more extensive disease as indicated by higher rate of FIGO stage IIIB disease as well as radiological evidence of extension into the distal parametrial space and to pelvic sidewall on MRI. Cervical necrosis was more common in the infiltrative group. Good response was more common in the expansive group (34% vs 24%) and poor response was more common in the infiltrative group (11% and 18%). Significant difference in response was observed between 2 groups (P = .01). Mean gross tumor volume at diagnosis (GTVD) was equal in both groups (51.7 cm3). The high-risk clinical target volume (CTVHR) was larger in infiltrative groups (37.9 cm3 vs. 33.3 cm3, P = .005). The mean CTVHR D90was higher in expansive group (92.7 Gy and 89.4 Gy, P < .001). Interstitial needles were used more in the infiltrative group (39% vs 54%, P = .002). Infiltrative tumors are more advanced at presentation and respond less favorably to CRT when compared to expansive tumors. Both are comparable in size at diagnosis. Therefore, CTVHR becomes larger and CTVHR D90 smaller in infiltrative tumors. However, more frequent use of interstitial needles allows to compensate and to achieve high doses, also in infiltrative tumors. Outcomes for Stage IIB and IIIB cervical cancer treated with IGABT according to tumor morphologic subtype need to be analyzed.