3D Conformal Brachytherapy for Inoperable Endometrial Carcinoma: Discrepancies between CTV EQD2 Values and Local Control

PurposeDefinitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer, however prescribed doses to the target volume appear to be relatively low. Despite this, series have shown good local control and outcomes. With the advent of MRI, delineation of the gross tumor volume (GTV) allows for closer dosimetric evaluation. We present our experience with definitive radiotherapy for inoperable endometrial carcinoma and highlight dosimetric findings regarding the delivered dose to the tumor volume.Materials and MethodsPatients with medically inoperable, clinical stage I endometrial adenocarcinoma were treated with definitive radiotherapy, either with brachytherapy alone or in combination with external beam radiotherapy. A retrospective analysis was carried out for patients who received HDR brachytherapy with a tandem and cylinder technique using either CT- or MRI-based planning for each fraction. Those with MRI-based plans had their GTV contoured for evaluation, however the prescribed dose was still delivered to the clinical target volume (CTV), defined as the entire uterus, cervix and upper 1-2 cm of the vagina. Doses were calculated and normalized to the equivalent 2 Gy dose (EQD2).ResultsThirty-eight patients were treated from 2007-2013, of which 20 (53%) received brachytherapy alone with a median dose of 37.5 Gy (35 - 45 Gy) in 5-6 fractions. For those treated with combined therapy, the median EBRT and brachytherapy doses were 45 Gy (45 - 46.8 Gy) and 25 Gy (20.8 - 27.5 Gy) in 4-5 fractions, totaling to a median cumulative dose of 70 Gy. All patients had clinical stage 1 disease based on examination and imaging: 22 with grade 1, 15 with grade 2, and 1 with grade 3 disease. With a median followup of 12 months (3 - 58.6 months), the 2-year actuarial local control and overall survival were 91% and 81%, respectively. Nearly all patients (95%) had cessation of vaginal bleeding. No grade 2 or greater late toxicity was observed. For brachytherapy alone, the median bladder, sigmoid and rectum EQD2 values were 48.5, 42.0, and 23.6 Gy. For combined therapy, the median bladder, sigmoid and rectum EQD2 values were 71.4, 65.9 and 59.4 Gy. The median GTV and CTV volumes were 6.2 cc (1.9 - 22.1 cc) and 84.1 cc (43.7 - 159.0 cc). Median CTV EQD2 for brachytherapy alone and combined therapy patients were 49 Gy (34.5 - 57.2 Gy) and 71.4 Gy (64.3 - 82.3 Gy). On the other hand, the median GTV EQD2, when available based on MRI, was 151.3 Gy (71.7 - 295.6 Gy).Conclusions3D conformal brachytherapy is feasible for medically inoperable early-stage endometrial cancers with excellent early results. This data suggests that for patients with early stage disease based on MRI and treated with brachytherapy alone, the entire uterus does not need full prescription dose coverage since the tumor is usually confined to the endometrium or inner myometrium, which receives 1.5-2 times the dose prescribed to the uterine serosal point. This finding likely accounts for the high tumor control. As in cervical cancer brachytherapy, guidelines for 3D image-based planning for endometrial cancer are needed to define different target volumes based on risk with differential dosing to these volumes. PurposeDefinitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer, however prescribed doses to the target volume appear to be relatively low. Despite this, series have shown good local control and outcomes. With the advent of MRI, delineation of the gross tumor volume (GTV) allows for closer dosimetric evaluation. We present our experience with definitive radiotherapy for inoperable endometrial carcinoma and highlight dosimetric findings regarding the delivered dose to the tumor volume. Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer, however prescribed doses to the target volume appear to be relatively low. Despite this, series have shown good local control and outcomes. With the advent of MRI, delineation of the gross tumor volume (GTV) allows for closer dosimetric evaluation. We present our experience with definitive radiotherapy for inoperable endometrial carcinoma and highlight dosimetric findings regarding the delivered dose to the tumor volume. Materials and MethodsPatients with medically inoperable, clinical stage I endometrial adenocarcinoma were treated with definitive radiotherapy, either with brachytherapy alone or in combination with external beam radiotherapy. A retrospective analysis was carried out for patients who received HDR brachytherapy with a tandem and cylinder technique using either CT- or MRI-based planning for each fraction. Those with MRI-based plans had their GTV contoured for evaluation, however the prescribed dose was still delivered to the clinical target volume (CTV), defined as the entire uterus, cervix and upper 1-2 cm of the vagina. Doses were calculated and normalized to the equivalent 2 Gy dose (EQD2). Patients with medically inoperable, clinical stage I endometrial adenocarcinoma were treated with definitive radiotherapy, either with brachytherapy alone or in combination with external beam radiotherapy. A retrospective analysis was carried out for patients who received HDR brachytherapy with a tandem and cylinder technique using either CT- or MRI-based planning for each fraction. Those with MRI-based plans had their GTV contoured for evaluation, however the prescribed dose was still delivered to the clinical target volume (CTV), defined as the entire uterus, cervix and upper 1-2 cm of the vagina. Doses were calculated and normalized to the equivalent 2 Gy dose (EQD2). ResultsThirty-eight patients were treated from 2007-2013, of which 20 (53%) received brachytherapy alone with a median dose of 37.5 Gy (35 - 45 Gy) in 5-6 fractions. For those treated with combined therapy, the median EBRT and brachytherapy doses were 45 Gy (45 - 46.8 Gy) and 25 Gy (20.8 - 27.5 Gy) in 4-5 fractions, totaling to a median cumulative dose of 70 Gy. All patients had clinical stage 1 disease based on examination and imaging: 22 with grade 1, 15 with grade 2, and 1 with grade 3 disease. With a median followup of 12 months (3 - 58.6 months), the 2-year actuarial local control and overall survival were 91% and 81%, respectively. Nearly all patients (95%) had cessation of vaginal bleeding. No grade 2 or greater late toxicity was observed. For brachytherapy alone, the median bladder, sigmoid and rectum EQD2 values were 48.5, 42.0, and 23.6 Gy. For combined therapy, the median bladder, sigmoid and rectum EQD2 values were 71.4, 65.9 and 59.4 Gy. The median GTV and CTV volumes were 6.2 cc (1.9 - 22.1 cc) and 84.1 cc (43.7 - 159.0 cc). Median CTV EQD2 for brachytherapy alone and combined therapy patients were 49 Gy (34.5 - 57.2 Gy) and 71.4 Gy (64.3 - 82.3 Gy). On the other hand, the median GTV EQD2, when available based on MRI, was 151.3 Gy (71.7 - 295.6 Gy). Thirty-eight patients were treated from 2007-2013, of which 20 (53%) received brachytherapy alone with a median dose of 37.5 Gy (35 - 45 Gy) in 5-6 fractions. For those treated with combined therapy, the median EBRT and brachytherapy doses were 45 Gy (45 - 46.8 Gy) and 25 Gy (20.8 - 27.5 Gy) in 4-5 fractions, totaling to a median cumulative dose of 70 Gy. All patients had clinical stage 1 disease based on examination and imaging: 22 with grade 1, 15 with grade 2, and 1 with grade 3 disease. With a median followup of 12 months (3 - 58.6 months), the 2-year actuarial local control and overall survival were 91% and 81%, respectively. Nearly all patients (95%) had cessation of vaginal bleeding. No grade 2 or greater late toxicity was observed. For brachytherapy alone, the median bladder, sigmoid and rectum EQD2 values were 48.5, 42.0, and 23.6 Gy. For combined therapy, the median bladder, sigmoid and rectum EQD2 values were 71.4, 65.9 and 59.4 Gy. The median GTV and CTV volumes were 6.2 cc (1.9 - 22.1 cc) and 84.1 cc (43.7 - 159.0 cc). Median CTV EQD2 for brachytherapy alone and combined therapy patients were 49 Gy (34.5 - 57.2 Gy) and 71.4 Gy (64.3 - 82.3 Gy). On the other hand, the median GTV EQD2, when available based on MRI, was 151.3 Gy (71.7 - 295.6 Gy). Conclusions3D conformal brachytherapy is feasible for medically inoperable early-stage endometrial cancers with excellent early results. This data suggests that for patients with early stage disease based on MRI and treated with brachytherapy alone, the entire uterus does not need full prescription dose coverage since the tumor is usually confined to the endometrium or inner myometrium, which receives 1.5-2 times the dose prescribed to the uterine serosal point. This finding likely accounts for the high tumor control. As in cervical cancer brachytherapy, guidelines for 3D image-based planning for endometrial cancer are needed to define different target volumes based on risk with differential dosing to these volumes. 3D conformal brachytherapy is feasible for medically inoperable early-stage endometrial cancers with excellent early results. This data suggests that for patients with early stage disease based on MRI and treated with brachytherapy alone, the entire uterus does not need full prescription dose coverage since the tumor is usually confined to the endometrium or inner myometrium, which receives 1.5-2 times the dose prescribed to the uterine serosal point. This finding likely accounts for the high tumor control. As in cervical cancer brachytherapy, guidelines for 3D image-based planning for endometrial cancer are needed to define different target volumes based on risk with differential dosing to these volumes.