Christopher Houser

MRI-Guided High–Dose-Rate Intracavitary Brachytherapy for Treatment of Cervical Cancer: The University of Pittsburgh Experience

PURPOSE Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. METHODS AND MATERIALS Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated high-dose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD2) with planned HRCTV doses of 75 to 85 Gy. RESULTS From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and cancer-specific survival rates were 91.6%, 81.8%, and 87.6%, respectively. Predictors of local failure included adenocarcinoma histology (P<.01) and clinical response at 3 months (P<.01). Among the adenocarcinoma subset, receiving HRCTV D90 EQD2 ≥84 Gy was associated with improved local control (2-year local control rate 100% vs 54.5%, P=.03). Grade 3 or greater gastrointestinal or genitourinary late toxicity occurred at a 2-year actuarial rate of 0.9%. CONCLUSIONS This study constitutes one of the largest reported series of MRI-guided brachytherapy in North America, demonstrating excellent local control with acceptable morbidity. Dose escalation may be warranted when feasible for adenocarcinomas to offset the risk of local failure.

Three-dimensional High Dose Rate Intracavitary Image-guided Brachytherapy for the Treatment of Cervical Cancer Using a Hybrid Magnetic Resonance Imaging/Computed Tomography Approach: Feasibility and Early Results

AIMS To evaluate the feasibility and outcome of image-guided brachytherapy (IGBT) for treating cervical cancer using magnetic resonance imaging (MRI)-based planning for the first fraction followed by computed tomography (CT)-based planning for subsequent fractions. MATERIALS AND METHODS Forty-four patients with cervical cancer were treated with three-dimensional high dose rate IGBT. The brachytherapy dose was 5.0-6.0 Gy × five fractions. All but five patients received concurrent weekly cisplatinum at 40 mg/m(2). All patients received external beam radiotherapy (EBRT) with a median dose of 45Gy over 25 fractions. Total doses for the high-risk clinical target volume (HRCTV) and organs at risk, including the rectum, bladder and sigmoid, from EBRT and brachytherapy were summated and normalised to a biologically equivalent dose of 2Gy per fraction (EQD(2)). At 3 months after therapy, any early response was assessed with positron emission tomography (PET)/CT imaging. RESULTS The mean D(90) for the HRCTV was 83.3 (3.0) Gy. The mean 2 cm (3) dose to the bladder, rectum and sigmoid colon organs was 79.7 (5.1), 57.5 (4.4) and 66.8 (5.7) Gy, respectively. All but one (2.3%) patient had a complete response. Follow-up PET/CT was carried out in 41 (93.0%) patients, of whom 38 (92.5%) had a complete response. Of the 38 patients with a complete response on PET/CT, two had local recurrences at 6 and 8 months, respectively. Actuarial 2 year local control, disease-specific and overall survival rates were 88, 85 and 86%, respectively. CONCLUSION This is the first report of three-dimensional high dose rate IGBT for the treatment of cervical cancer using a hybrid MRI/CT approach. Early results have shown the feasibility of this approach with excellent local control. Additional studies are needed to assess long-term outcomes of local control and associated morbidities.

Dosimetric Analysis of 3D Image-Guided HDR Brachytherapy Planning for the Treatment of Cervical Cancer: Is Point A-Based Dose Prescription Still Valid in Image-Guided Brachytherapy?

The purpose of this study was to analyze the dosimetric outcome of 3D image-guided high-dose-rate (HDR) brachytherapy planning for cervical cancer treatment and compare dose coverage of high-risk clinical target volume (HRCTV) to traditional Point A dose. Thirty-two patients with stage IA2-IIIB cervical cancer were treated using computed tomography/magnetic resonance imaging-based image-guided HDR brachytherapy (IGBT). Brachytherapy dose prescription was 5.0-6.0 Gy per fraction for a total 5 fractions. The HRCTV and organs at risk (OARs) were delineated following the GYN GEC/ESTRO guidelines. Total doses for HRCTV, OARs, Point A, and Point T from external beam radiotherapy and brachytherapy were summated and normalized to a biologically equivalent dose of 2 Gy per fraction (EQD2). The total planned D90 for HRCTV was 80-85 Gy, whereas the dose to 2 mL of bladder, rectum, and sigmoid was limited to 85 Gy, 75 Gy, and 75 Gy, respectively. The mean D90 and its standard deviation for HRCTV was 83.2 ± 4.3 Gy. This is significantly higher (p < 0.0001) than the mean value of the dose to Point A (78.6 ± 4.4 Gy). The dose levels of the OARs were within acceptable limits for most patients. The mean dose to 2 mL of bladder was 78.0 ± 6.2 Gy, whereas the mean dose to rectum and sigmoid were 57.2 ± 4.4 Gy and 66.9 ± 6.1 Gy, respectively. Image-based 3D brachytherapy provides adequate dose coverage to HRCTV, with acceptable dose to OARs in most patients. Dose to Point A was found to be significantly lower than the D90 for HRCTV calculated using the image-based technique. Paradigm shift from 2D point dose dosimetry to IGBT in HDR cervical cancer treatment needs advanced concept of evaluation in dosimetry with clinical outcome data about whether this approach improves local control and/or decreases toxicities.

Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification

PURPOSE Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control. MATERIALS AND METHODS Forty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4. RESULTS At a median follow-up of 18 months (range: 3-78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%. CONCLUSIONS Salvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.

Dosimetric comparison of multichannel with one single-channel vaginal cylinder for vaginal cancer treatments with high-dose-rate brachytherapy

PURPOSE To compare the three-dimensional (3D) image (CT/MR)-based planning with a multichannel vaginal cylinder (MVC) to a single-channel vaginal cylinder (SVC) for the treatment of vaginal cancer. METHODS AND MATERIALS A total of 20 consecutive patients were treated with 3D CT/MR image-based high-dose-rate (HDR) brachytherapy using an MVC. All patients received external beam radiation therapy before HDR brachytherapy. A brachytherapy dose of 20-25Gy of more than five fractions was delivered to clinical target volume (CTV). Retrospectively, treatment plans for all patients were generated using the central channel only to mimic an SVC applicator. The SVC plans were optimized to match CTV coverage with MVC plans. Dose homogeneity index as well as bladder, rectum, sigmoid, and urethral doses were compared. RESULTS The mean D90 for CTV was 74.2Gy (range: 48.8-84.1Gy). The mean (±standard deviation) of dose homogeneity index for MVC vs. SVC was 0.49 (±0.19) and 0.52 (±0.23), respectively (p=0.09). Mean bladder 0.1, 1, and 2cc doses for MVC vs. SVC were 69 vs. 71.2Gy (p=0.35), 61.4 vs. 63.8Gy (p=0.1), and 59.5 vs. 60.9Gy (p=0.31), respectively. Similarly, mean rectum 0.1, 1, and 2cc doses for MVC vs. SVC were 67.2 vs. 75.4Gy (p=0.005), 60.0 vs. 65.6Gy (p=0.008), and 57.3 vs. 62.0Gy (p=0.015), respectively, and mean sigmoid doses were 56.3 vs. 60.5Gy (p=0.10), 50.9 vs. 53.1Gy (p=0.09), and 49.1 vs. 50.7Gy (p=0.10), respectively. CONCLUSION The 3D CT-/MR-based plan with MVC may provide better dose distribution in the management of certain clinical situations of vaginal cancer requiring intracavitary brachytherapy, especially in minimizing potential late rectal complications.

High-dose-rate interstitial computed tomography–based brachytherapy for the treatment of cervical cancer: Early results

PURPOSE There is limited published data on high-dose-rate interstitial brachytherapy (HDRBT) for cervical cancer resulting in no consensus on a fractionation schedule. This study reports our experience of CT-based HDRBT for treating locally advanced cervical cancer. METHODS AND MATERIALS Forty-seven patients diagnosed with Stage IIB-IVA cervical cancer not suitable for intracavitary brachytherapy were treated with HDRBT from March 2005 to November 2010. All patients received external beam radiation therapy with a median dose of 45Gy and all had one interstitial implantation followed by 3.75-5Gy×5 fractions in a twice daily (BID) schedule. Total doses for clinical target volume and organs at risk, including rectum, bladder, and sigmoid, were summated and normalized to a biologically equivalent dose of 2Gy per fraction. At 3 months posttherapy, early response was assessed with clinical examination and positron emission tomography (PET/CT) imaging. RESULTS Median clinical target volume D(90) (dose delivered to 90% of the clinical target volume) was 76.3 (59.0-86.9) Gy and the 2cc dose to the bladder, rectum, and sigmoid colon organs were 70.2 (55.9-77.7), 65.8 (54.9-80.6), and 56.5 (45.0-71.2) Gy, respectively. Posttreatment, 12 patients had evidence of persistent disease on PET/CT. Eleven of the 35 patients who had complete response developed recurrences. Two patients developed late Radiation Therapy Oncology Group ≥3 rectal toxicities. Two-year actuarial local control, disease-free survival, overall survival, and Grade ≥3 toxicities were 61%, 43%, 59%, and 10%, respectively. CONCLUSION Our approach of a single implantation procedure followed by five fractions of HDRBT was well tolerated with early results demonstrating a moderate response and local control rate with acceptable toxicities.

Mapping of dose distribution from IMRT onto MRI-guided high dose rate brachytherapy using deformable image registration for cervical cancer treatments: preliminary study with commercially available software.

Purpose For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV). Material and methods Nine cervical cancer patients were treated to a total dose of 45 Gy in 25 fractions using intensity-modulated radiation therapy (IMRT), followed by MRI-based 3D high dose rate (HDR) brachytherapy. Retrospectively, the IMRT planning CT images were fused with the MR image for each fraction of brachytherapy using deformable image registration. The deformed IMRT dose onto MR images were converted to EQD2 and compared to the uniform dose assumption. Results For all patients, the EQD2 from the EBRT phase was significantly higher with deformable registration than with the conventional uniform dose distribution assumption. The mean EQD2 ± SD for HR-CTV D90 was 45.7 ± 0.7 Gy vs. 44.3 Gy for deformable vs. uniform dose distribution, respectively (p < 0.001). The dose to 2 cc of the bladder, rectum, and sigmoid was 46.4 ± 1.2 Gy, 46.2 ± 1.0 Gy, and 48.0 ± 2.5 Gy, respectively with deformable dose distribution, and was significantly higher than with uniform dose distribution (43.2 Gy for all OAR, p < 0.001). Conclusions This study reveals that deformed EBRT dose distribution to HR-CTV and OARs in MR images for brachytherapy is technically feasible, and achieves differences compared to a uniform dose distribution. Therefore, the assumption that EBRT contributes the same dose value may need to be carefully investigated further based on deformable image registration.

Is there any advantage to three-dimensional planning for vaginal cuff brachytherapy?

PURPOSE To evaluate whether the three-dimensional (3D) CT-based high-dose rate planning for vaginal cuff brachytherapy offers any advantage over the 2D orthogonal film-based library plans for adjuvant treatment of endometrial cancers. METHODS AND MATERIALS Eighty-four consecutive postoperative patients with endometrial cancers treated with vaginal brachytherapy as an adjuvant treatment were analyzed. Patients had CT imaging-based plans. Clinical target volume (CTV) was defined by expanding the upper 2.5cm of the cylinder by 5mm in all directions and editing to exclude any bladder and rectum. The dose prescribed was 7Gy with three fractions at 5mm depth with a goal of D(90) ≥100% for CTV. All dosimetric parameters were compared with library-based plans. RESULTS Both the 2D- and 3D-based plans allowed sufficient dosage to the CTV (D(90) for CTV ≥95%). The doses of 0.1, 1, and 2cc to rectum and bladder were significantly higher for 2D-based plans (p≤0.001 in each parameter). D(2 cc) with 2D plan for rectum and bladder was >100% (range: 103-116%) in 7 (8%) and 6 (7%) patients, respectively. In contrast, no patients had D(2 cc) >100% with 3D planning for both organs. CONCLUSION Three-dimensional CT-based planning for high-dose rate vaginal cuff brachytherapy helps to decrease dose to critical organs without compromising coverage of CTV by customizing the dosimetry according to individual patient anatomy.

Urethral dosimetry and toxicity with high-dose-rate interstitial brachytherapy for vaginal cancer

PURPOSE The tolerance and complication rates of the urethra are unknown for the interstitial high-dose-rate brachytherapy (HDR-BT) for vaginal cancer. METHODS AND MATERIALS Patients with vaginal cancer near/involving the urethra who were treated with HDR-BT between 2008 and 2011 were included. Patients received mean external beam dose of 48.0Gy followed by mean HDR-BT dose of 4.5Gy/fraction for five fractions. With CT-based planning, the urethra was contoured from the bladder neck to the meatus. Doses were converted to the biologically equivalent dose in 2Gy/fraction (EQD2). RESULTS A total of 16 patients were included, and the EQD2D90 was 74.9Gy. The urethral volume was 1.31cm(3), and the EQD2 to 0.1 and 1cm(3) were 76.2 and 48.9Gy, respectively. Two of the 6 patients with urethral involvement developed urethral necrosis. The D90 for these 2 patients was 76.8Gy, and the urethral doses to 0.1 and 1cm(3) were 95.1 and 45.8, respectively. Those who developed severe urethral toxicity had a trend to urethral EQD2 (95.1Gy vs. 73.4Gy, p=0.1) and significantly higher dose per fraction of HDR-BT to 0.1cm(3) of the urethra (5.7Gy vs. 3.7Gy, p=0.02) when compared with those who did not develop severe urethral toxicity. CONCLUSIONS This study is among the first to assess urethral dosimetry for patients treated with HDR-BT for vaginal cancer. Patients who received five fractions of higher than 5Gy/fraction to 0.1cm(3) of urethra (estimated EQD2 of 85Gy) are at increased risk of severe urethral toxicity.

Image-based multichannel vaginal cylinder brachytherapy for vaginal cancer.

PURPOSE To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR) brachytherapy using an intracavitary multichannel vaginal cylinder for the definitive treatment of vaginal cancers. METHODS AND MATERIALS A total of 41 patients with vaginal cancer (24% primary vaginal and 76% recurrence from other gynecologic primaries) treated with definitive radiotherapy ± chemotherapy including image-based HDR brachytherapy with a multichannel vaginal cylinder were included in the study. Image-based brachytherapy was completed using either CT- (41%) or MR-based planning (59%) with each fraction. The high-risk clinical target volume was defined based on the pre- and postexternal beam radiotherapy gross tumor volume. Doses were converted to equivalent dose of 2Gy per fraction. Endpoints examined were dose-volume parameters and early clinical outcomes. RESULTS The median high-risk clinical target volume was 24.2 cc (interquartile range [IQR], 12.6), with a median dose to 90% (D90) of 77.1 Gy (IQR, 3.4). The median dose to 2 cc (D(2 cc)) for the bladder, rectum, and sigmoid were 59.4 Gy (IQR, 5.6), 58.2 Gy (IQR, 4.1), and 52.3 Gy (IQR, 5.5), respectively. After a median followup of 16 months (range, 3-35), complete clinical response was documented in 98% of the patients. The 2-year local, regional, and distant control; and disease-free and overall survival were 93%, 100%, 81%, 78%, and 88%, respectively. The 2-year actuarial rate of late Grade 3 or higher toxicity was 4% overall with 0%, 0%, 0%, and 4% for vaginal, bladder, urethral, and gastrointestinal, respectively. CONCLUSIONS Image-based HDR brachytherapy using an intracavitary multichannel cylinder seems feasible in definitive vaginal cancer treatment. The described clinical implementation shows promising early clinical outcomes with high rates of local control and little toxicity, which should be validated with extended followup.