Brachytherapy For Uterine Cervical Cancer Research Articles

Effective timing of hyaluronate gel injection in image-guided adaptive brachytherapy for uterine cervical cancer: a proposal of the 'adjusted dose score'.

Hyaluronate gel injection (HGI) in the rectovaginal septum and vesicovaginal septum is effective in the setting of high-dose-rate image-guided adaptive brachytherapy (IGABT) for cervical cancer. We aimed to retrospectively investigate optimal conditions for HGI to achieve optimal dose distribution with a minimum number of HGI. We classified 50 IGABT plans of 13 patients with cervical cancer who received IGABT both with and without HGI in the rectovaginal septum and vesicovaginal septum into the following two groups: plan with (number of plans = 32) and plan without (number of plans = 18) HGI. The irradiation dose parameters of high-risk clinical target volume (CTVHR) and organs at risk per fraction were compared between these groups. We also developed the adjusted dose score (ADS), reflecting the overall irradiation dose status for four organs at risk and CTVHR in one IGABT plan and investigated its utility in determining the application of HGI. HGI reduced the maximum dose to the most exposed 2.0cm3 (D2.0 cm3) of the bladder while increasing the minimum dose covering 90% of CTVHR and the percentage of CTVHR receiving 100% of the prescription dose in one IGABT plan without causing any associated complications. An ADS of ≥2.60 was the optimum cut-off value to decide whether to perform HGI. In conclusion, HGI is a useful procedure for improving target dose distribution while reducing D2.0 cm3 in the bladder in a single IGABT plan. The ADS can serve as a useful indicator for the implementation of HGI.

MucoUp® as a spacer in brachytherapy for uterine cervical cancer: A first-in-human experience.

We first used MucoUp®, a hyaluronic acid used in endoscopic resection, as a spacer in brachytherapy. In five cervical cancer patients, MucoUp® insertion increased a 90% dose of the high-risk CTV to over 80Gy while decreasing the dose of organs at risk. No related adverse events were observed.

Hands-on seminar for image-guided adaptive brachytherapy and intracavitary/interstitial brachytherapy for uterine cervical cancer.

Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar. The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence). A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001). It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated.

Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer

ABSTRACTCombining external beam radiotherapy (EBRT) with intracavitary brachytherapy (ICBT) is important for definitive treatment of cervical cancer. In cervical cancer patients receiving radiotherapy, we evaluated treatment outcomes in relation to dose–volume histogram parameters, including the computed tomography (CT)-based high-risk clinical target volume (HR-CTV) for ICBT. Between 2010 and 2015, 89 consecutive cervical cancer patients were mostly treated with 40 Gy of EBRT in 20 fractions and 18 Gy of ICBT prescribed to point A in 3 fractions. CT scans were obtained during ICBT. The HR-CTV D90 was calculated and the total doses of ICBT and EBRT were converted to the equivalent dose in 2 Gy fractions (EQD2). When the patients were divided into four groups according to EQD2 of the HR-CTV D90, the 3-year local recurrence-free survival rates were 95.2, 78.4, 52.7 and 42.9% for patients receiving >80 , 70–80 , 60–70 and <60 Gy, respectively. There was a significant negative correlation between EQD2 of the HR-CTV D90 and the HR-CTV volume at first ICBT (r = −0.713). Local recurrence was more frequent when the HR-CTV volume was ≥22 cc and EQD2 of the HR-CTV D90 was <70 Gy. Multivariate analysis showed that EQD2 of the HR-CTV D90 and concurrent chemotherapy (≥4 cycles) were significant determinants of overall survival. HR-CTV D90 was an important prognostic indicator for local recurrence. HR-CTV D90 >70 Gy is required for the better local control, especially in patients with a larger HR-CTV (≥22 cc at initial ICBT).

Assessment of the anatomical position of point B and the relationship between point B dose and the dose delivered to pelvic lymph nodes in CT-based high-dose-rate brachytherapy for uterine cervical cancer.

PurposeTo examine the anatomical position of point B and the relationship between the dose at point B and the dose delivered to the pelvic lymph nodes in computed tomography (CT)-based brachytherapy for cervical cancer.Material and methodsForty-nine cervical cancer patients were treated at Kyushu University Hospital. For all cases, planning CT images obtained after the applicator insertion were imported to an Oncentra Brachy (Elekta AB, Stockholm, Sweden), and points A (dose prescription, 6 Gy) and points B were set according to the Manchester method. The pelvic lymph node regions (external iliac, internal iliac, and obturator) were contoured, and the anatomic positions of 98 points B in 49 patients were examined. Dose volume histogram (DVH) parameters (D100, D90, D50, D2cc, D1cc, and D0.1cc) were calculated for each lymph node region and compared with the point B dose.ResultsThe mean bilateral dose to point B was 1.70 ±0.18 Gy, and 26 (27%) of 98 points B were not located in any pelvic lymph node regions. The DVH analysis indicated a low degree of correlation overall, and all values were significantly different from point B doses (p < 0.05), except for D0.1cc of the external iliac node (p = 0.0594) and D1cc of the internal iliac node (p = 0.0711).ConclusionsWe investigated the anatomical location of point B in patients with cervical cancer who underwent brachytherapy, and the DVH analysis revealed that the point B dose was a poor surrogate for the dose delivered to the pelvic lymph nodes.

Evaluation of clinical efficacy and safety of single-channel intracavitary applicator for uterine cervical cancer: early results of a prospective randomized phase II clinical trial

Objective To evaluate whether the self-designed single-channel intracavitary applicator yields equivalent clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the high-dose-rate (HDR) brachytherapy for uterine cervical cancer. Methods From December 2011 to April 2017, patients initially diagnosed with cervical cancer were randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. Whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (BED at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m2 once weekly during EBRT.Clinical efficacy and safety were evaluated after the treatment. Results In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. The short-term clinical efficacy and acute toxicity did not significantly differ between two groups. The response rate was 94.0% in the Fletcher group, and 94.7% in the patent single-channel group. In the Fletcher applicator group, 76(50.7%) patients developed ≥ grade 3 hematologic toxicity and 61(40.9%) in the patent group (P=0.195). Conclusions The self-designed patent single-channel intracavitary applicator yields equivalent clinical efficacy and safety (acute toxicity) to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer. Clincal Trial Registration Chinese Clinical Trial Registry (ChiCTR-TRC-12002321). Key words: Uterine cervical neoplasm/brachytherapy; Clinical trial

Efficacy of in-room Computed Tomography-based Brachytherapy for Uterine Cervical Cancer

Since April 2014, three-dimensional image guided brachytherapy (IGBT) based on computed tomography (CT) for uterine cervical cancer has been conducted in our institution. Between April 2014 and April 2016, brachytherapy room, which was used for the insertion of applicators and the treatment of high dose rate brachytherapy, and CT room had been separated (separate-room CT: SRCT). In April 2016, CT system was installed in the brachytherapy room (in-room CT: IRCT). It enabled to complete all treatment procedure on the same couch. To investigate the improvement of IRCT-based IGBT from SRCT, we evaluated the parameters of dose-volume histogram (DVH) according to the recommendations of GEC-ESTRO Gynecological Working Group and the total treatment time in each IGBT session in patients with uterine cervical cancer.

In-room computed tomography-based brachytherapy for uterine cervical cancer: results of a 5-year retrospective study.

Herein, we investigate the long-term clinical outcomes for cervical cancer patients treated with in-room computed tomography–based brachytherapy. Eighty patients with Stage IB1–IVA cervical cancer, who had undergone treatment with combined 3D high-dose rate brachytherapy and conformal radiotherapy between October 2008 and May 2011, were retrospectively analyzed. External beam radiotherapy (50 Gy) with central shielding after 20–40 Gy was performed for each patient. Cisplatin-based chemotherapy was administered concurrently to advanced-stage patients aged ≤75 years. Brachytherapy was delivered in four fractions of 6 Gy per week. In-room computed tomography imaging with applicator insertion was performed for treatment planning. Information from physical examinations at diagnosis, and brachytherapy and magnetic resonance imaging at diagnosis and just before the first brachytherapy session, were referred to for contouring of the high-risk clinical target volume. The median follow-up duration was 60 months. The 5-year local control, pelvic progression-free survival and overall survival rates were 94%, 90% and 86%, respectively. No significant differences in 5-year local control rates were observed between Stage I, Stage II and Stage III–IVA patients. Conversely, a significant difference in the 5-year overall survival rate was observed between Stage II and III–IVA patients (97% vs 72%; P = 0.006). One patient developed Grade 3 late bladder toxicity. No other Grade 3 or higher late toxicities were reported in the rectum or bladder. In conclusion, excellent local control rates were achieved with minimal late toxicities in the rectum or bladder, irrespective of clinical stage.

Investigation of whether in-room CT-based adaptive intracavitary brachytherapy for uterine cervical cancer is robust against interfractional location variations of organs and/or applicators.

This study investigates whether in-room computed tomography (CT)-based adaptive treatment planning (ATP) is robust against interfractional location variations, namely, interfractional organ motions and/or applicator displacements, in 3D intracavitary brachytherapy (ICBT) for uterine cervical cancer. In ATP, the radiation treatment plans, which have been designed based on planning CT images (and/or MR images) acquired just before the treatments, are adaptively applied for each fraction, taking into account the interfractional location variations. 2D and 3D plans with ATP for 14 patients were simulated for 56 fractions at a prescribed dose of 600 cGy per fraction. The standard deviations (SDs) of location displacements (interfractional location variations) of the target and organs at risk (OARs) with 3D ATP were significantly smaller than those with 2D ATP (P < 0.05). The homogeneity index (HI), conformity index (CI) and tumor control probability (TCP) in 3D ATP were significantly higher for high-risk clinical target volumes than those in 2D ATP. The SDs of the HI, CI, TCP, bladder and rectum D2cc, and the bladder and rectum normal tissue complication probability (NTCP) in 3D ATP were significantly smaller than those in 2D ATP. The results of this study suggest that the interfractional location variations give smaller impacts on the planning evaluation indices in 3D ATP than in 2D ATP. Therefore, the 3D plans with ATP are expected to be robust against interfractional location variations in each treatment fraction.

Simulation analysis of optimized brachytherapy for uterine cervical cancer: Can we select the best brachytherapy modality depending on tumor size?

To choose the optimal brachytherapeutic modality for uterine cervical cancer, we performed simulation analysis. For each high-risk clinical target volume (HR CTV), we compared four modalities [classical conventional intracavitary brachytherapy (ConvICBT), Image-guided ICBT (IGICBT), intracavitary/interstitial brachytherapy (ICISBT), and interstitial brachytherapy (ISBT) with perineal approach] using dose-volume histograms using eight sizes of HR CTV (2×2×2cm to 7×4×4cm) and organs at risk model. In ConvICBT, the doses covered 90% of the HR CTV [D90(HR CTV)] decreased from 197% prescribed dose (PD) for the HR CTV size (2×2×2cm) to 73% PD for 5×4×4cm, whereas the other three modalities could achieve 100% PD for all HR CTV sizes. The minimum doses received by the maximally irradiated 2-cm(3) volumes for organs at risks of IGICBT demonstrated lower values than those of ConvICBT for the HR CTV size of 4×3×3cm or smaller. ICISBT demonstrated lower values than those of IGICBT for 4×3×3cm or larger. ISBT demonstrated lowest values for 5×4×4cm or larger. HR CTV size of 4×3×3cm seems to be a threshold volume in this simulation analysis, and IGICBT is a better choice for smaller HR CTV than the threshold volume. On larger HR CTV, ICISBT or ISBT is the better choice.

Results of Combination Therapy of Interstitial and Intracavitary Brachytherapy for Uterine Cervical Cancer

Results of Combination Therapy of Interstitial and Intracavitary Brachytherapy for Uterine Cervical Cancer

Interfractional change of high-risk CTV D90 during image-guided brachytherapy for uterine cervical cancer

The purpose of this study was to evaluate interfractional changes of the minimum dose delivered to 90% of the high-risk clinical target volume (HR-CTV D90) and D2cc of the bladder and rectum during brachytherapy for uterine cervical cancer patients. A total of 52 patients received external beam radiotherapy and high-dose-rate intracavitary brachytherapy (ICBT). For each of four ICBT applications, a pelvic CT scan was performed and the HR-CTV was delineated. Retrospectively, these patients were divided into two groups: (i) the standard dose group with 6 Gy to point A in each ICBT, and (ii) the adaptive dose group with a modified dose to point A to cover the HR-CTV with the 6-Gy isodose line as much as possible. The HR-CTV D90 was assessed in every session, and analyzed as interfractional changes. In the standard dose group, the interfractional changes of the HR-CTV D90 showed a linear increase from the first to the third of the four ICBT (average 6.1, 6.6, 7.0 and 7.1 Gy, respectively). In contrast, those of the adaptive dose group remained almost constant (average 7.2, 7.2, 7.3 and 7.4 Gy, respectively). Especially, in the case of a large HR-CTV volume (≥35 cm3) at first ICBT, the total HR-CTV D90 of the adaptive dose group with brachytherapy was significantly higher than that of the standard dose group. There were no significant differences in total D2cc in bladder and rectum between the two groups. Image-guided adaptive brachytherapy based on interfractional tumor volume change improves the dose to the HR-CTV while keeping rectal and bladder doses within acceptable levels.

Comparison of dose-volume analysis between standard Manchester plan and magnetic resonance image-based plan of intracavitary brachytherapy for uterine cervical cancer

To investigate the feasibility of image-based intracavitary brachytherapy (IBICBT) for uterine cervical cancer, we evaluated the dose–volume histograms (DVHs) for the tumor and organs at risk (OARs) and compared results from the IBICBT plan and the standard Manchester system (Manchester plan) in eight patients as a simulation experiment. We performed magnetic resonance imaging (MRI) and computed tomography (CT) following MRI-adapted applicator insertion, then superimposed MR images on the planning CT images to describe the contours of high-risk clinical target volume (HR CTV) and OARs. The median volume of HR CTV was 29 cm3 (range, 21–61 cm3). Median D90 (HR CTV) and V100 (HR CTV) were 116.1% prescribed doses (PD) (90.0–150.8%) and 96.7% (84.2–100%), respectively, for the Manchester plan. In comparison, we confirmed that the median D90 (HR CTV) was 100% PD in the IBICBT plan for all patients. Mean D2cc (bladder) was 101.8% PD for the Manchester plan and 83.2% PD for the IBICBT plan. Mean D2cc (rectum) was 80.1% PD for the Manchester plan and 64.2% PD for the IBICBT plan. Mean D2cc (sigmoid) was 75% PD for the Manchester plan and 57.5% PD for the IBICBT plan. One patient with a large tumor (HR CTV, 61 cm3) showed lower D90 (HR CTV) with the Manchester plan than with the IBICBT plan. The Manchester plan may represent overtreatment for small tumors but insufficient dose distribution for larger tumors. The IBICBT plan could reduce OAR dosage while maintaining adequate tumor coverage.

Radiation sigmoiditis mimicking sigmoid colon cancer after radiation therapy for cervical cancer: the implications of three-dimensional image-based brachytherapy planning

External-beam radiation therapy with intracavitary high-dose-rate brachytherapy is the standard treatment modality for advanced cervical cancer; however, late gastrointestinal complications are a major concern after radiotherapy. While radiation proctitis is a well-known side effect and radiation oncologists make an effort to reduce it, the sigmoid colon is often neglected as an organ at risk. Herein, we report two cases of radiation sigmoiditis mimicking sigmoid colon cancer after external-beam radiation therapy with intracavitary high-dose-rate brachytherapy for uterine cervical cancer with dosimetric consideration.

A Dose–Volume Analysis of Magnetic Resonance Imaging-Aided High-Dose-Rate Image-Based Interstitial Brachytherapy for Uterine Cervical Cancer

To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.

Quality Assurance in the Prospective Multi-institutional Trial on Definitive Radiotherapy Using High-dose-rate Intracavitary Brachytherapy for Uterine Cervical Cancer: The Individual Case Review

To assess compliance with the radiotherapy protocol of a multi-institutional prospective study (JAROG0401/JROSG04-2), which investigated the efficacy and toxicity of definitive radiotherapy using high-dose-rate intracavitary brachytherapy (HDR-ICBT) for early-stage uterine cervical cancer patients. Individual case reviews (ICRs) were performed on all 60 study participants. Radiotherapy data were submitted to the quality assurance (QA) committee, which performed ICRs on 16 QA items according to previously selected criteria. The items focused on quality of external beam radiotherapy (EBRT), HDR-ICBT and both. Each item was determined to be either acceptable or a deviation. The QA committee performed ICR three times as planned, two during the patient accrual and the final one just after the final patient accrued. The QA results of the first and second reviews were reported back to the investigators after each ICR. In 40 cases (67%), all 16 QA items were classified as acceptable. One deviation was found in 16 cases, two deviations were identified in 3 cases and three deviations were noted in 1 case. The most frequently observed deviation was missing the rules for determining point A (10 cases). The items described by quantitative values, such as prescribed doses, certain time intervals and overall treatment time, were well followed. The proportion of deviations gradually decreased during the ICR process. The present ICR demonstrated the favorable radiotherapy compliance with the JAROG0401/JROSG04-2 protocol. The QA process using ICRs can potentially be used to improve the quality of radiotherapy, including HDR-ICBT in the multi-institutional prospective studies for cervical cancer.

Concurrent chemoradiotherapy using high-dose rate intracavitary brachytherapy for uterine cervical cancer

16568 Background: We retrospectively reviewed our experience with concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) to assess its feasibility and effic...

High-dose-rate 3D image-based brachytherapy for uterine cervical cancer – evaluation of Japanese cervical cancer protocol based on gynecologic GEC-ESTRO recommendations

High-dose-rate 3D image-based brachytherapy for uterine cervical cancer – evaluation of Japanese cervical cancer protocol based on gynecologic GEC-ESTRO recommendations

Computed Tomography-Based High-Dose-Rate Intracavitary Brachytherapy for Uterine Cervical Cancer: Preliminary Demonstration of Correlation Between Dose–Volume Parameters and Rectal Mucosal Changes Observed by Flexible Sigmoidoscopy

To compare the dose-volume histogram (DVH) parameters obtained by three-dimensional gynecologic brachytherapy planning with the rectosigmoid mucosal changes observed by flexible sigmoidoscopy. Between January 2004 and July 2005, 71 patients with International Federation of Gynecology and Obstetrics Stage IB-IIIB uterine cervical cancer underwent computed tomography-based high-dose-rate intracavitary brachytherapy. The total dose (external beam radiotherapy [RT] plus intracavitary brachytherapy) to the International Commission of Radiation Units and Measurements rectal point (ICRU(RP)) and DVH parameters for rectosigmoid colon were calculated using the equivalent dose in 2-Gy fractions (alpha/beta = 3 Gy). Sigmoidoscopy was performed every 6 months after RT, with the 6-scale scoring system used to determine mucosal changes. The mean values of the DVH parameters and ICRU(RP) were significantly greater in patients with a score of > or =2 than in those with a score <2 at 12 months after RT (ICRU(RP), 71 Gy(alpha/beta3) vs. 66 Gy(alpha/beta3), p = 0.02; D(0.1cc), 93 Gy(alpha/beta3) vs. 85 Gy(alpha/beta3), p = 0.04; D(1cc), 80 Gy(alpha/beta3) vs. 73 Gy(alpha/beta3), p = 0.02; D(2cc), 75 Gy(alpha/beta3) vs. 69 Gy(alpha/beta3), p = 0.02). The probability of a score of > or =2 showed a significant relationship with the DVH parameters and ICRU(RP) (ICRU(RP), p = 0.03; D(0.1cc), p = 0.05; D(1cc), p = 0.02; D(2cc), p = 0.02). Our preliminary data have shown that DVH values of the rectosigmoid colon obtained by computed tomography-based three-dimensional brachytherapy planning are reliable and predictive of score > or =2 rectosigmoid mucosal changes.

1397 POSTER Optimal dose and fractionation for combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer

1397 POSTER Optimal dose and fractionation for combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer