Background and purpose
To compare the dosimetric impact of organ and target variations relative to the applicator for intracavitary brachytherapy by a multicentre analysis with different application techniques and fractionation schemes.
Material and methods
DVH data from 363 image/contour sets (120 patients, 6 institutions) were included for 1–6 fractions per patient, with imaging intervals ranging from several hours to ∼20 days. Variations between images acquired within one (intra-application) or between consecutive applicator insertions (inter-application) were evaluated. Dose plans based on a reference MR or CT image series were superimposed onto subsequent image sets and D2cm3 for the bladder, rectum and sigmoid and D90 for HR CTV were recorded.
For the whole sample, the systematic dosimetric variations for all organs at risk, i.e. mean variations of D2cm3, were found to be minor (<5%), while random variations, i.e. standard deviations were found to be high due to large variations in individual cases. The D2cm3 variations (mean ± 1SD) were 0.6 ± 19.5%, 4.1 ± 21.7% and 1.6 ± 26.8%, for the bladder, rectum and sigmoid. For HR CTV, the variations of D90 were found to be −1.1 ± 13.1% for the whole sample.
Grouping of the results by intra- and inter-application variations showed that random uncertainties for bladder and sigmoid were 3–7% larger when re-implanting the applicator for individual fractions. No statistically significant differences between the two groups were detected in dosimetric variations for the HR CTV.
Using 20% uncertainty of physical dose for OAR and 10% for HR CTV, the effects on total treatment dose for a 4 fraction HDR schedule at clinically relevant dose levels were found to be 4–8 Gy EQD2 for OAR and 3 Gy EQD2 for HR CTV.
Substantial variations occur in fractionated cervix cancer BT with higher impact close to clinical threshold levels. The treatment approach has to balance uncertainties for individual cases against the use of repetitive imaging, adaptive planning and dose delivery.
Image guided brachytherapy; Cervix cancer brachytherapy; Interfraction variations; Adaptive brachytherapy
A report of preliminary results and toxicity profiles using image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiation therapy (WP-IMRT) for locally advanced cervical cancer.
Material and methods
Fifteen patients with locally advanced cervical cancer were enrolled into the study. WP-IMRT was used to treat the Clinical Target Volume (CTV) with a dose of 45 Gy in 25 fractions. Concurrent cisplatin (40 mg/m2) was prescribed during radiotherapy (RT) on weekly basis. IGBT using computed tomography was performed at the dose of 7 Gy × 4 fractions to the High-Risk Clinical Target Volume (HR-CTV).
The mean cumulative doses – in terms of equivalent dose of 2 Gy (EQD2) – of IGBT plus WP-IMRT to HR-CTV, bladder, rectum, and sigmoid colon were 88.3, 85.0, 68.2 and 73.6 Gy, respectively. In comparison with standard (point A prescription) dose-volume histograms, volume-based image-guided brachytherapy improved the cumulative doses for bladder of 67%, rectum of 47% and sigmoid of 46%. At the median follow-up time of 14 months, the local control, metastasis-free survival and overall survival rates were 93%, 100% and 93%, respectively. No grade 3-4 acute and late toxicities were observed.
The combination of image-guided brachytherapy and intensity-modulated radiotherapy improved the dose distribution to tumor volumes and avoided overdose in OARs which could be converted in excellent local control and toxicity profiles.
brachytherapy; cervical cancer; IGBT; IMRT
To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy.
Methods and Materials
The rectum, bladder and sigmoid of 14 patients treated with gynecologic interstitial brachytherapy were retrospectively contoured by 13 physicians. Geometric variability was calculated using κ statistics, conformity index (CIgen), and coefficient of variation (CV) of volumes contoured across physicians. Dosimetric variability of the single-fraction D0.1cc and D2cc was assessed through CV across physicians, and the standard deviation of the total EQD2 (equivalent dose in 2 Gy per fraction) brachytherapy dose (SDTOT) was calculated.
The population mean ± 1 standard deviation of κ, CIgen and volume CV were, respectively: 0.77 ± 0.06, 0.70 ± 0.08 and 20% ± 6% for bladder; 0.74 ± 06, 0.67 ± 0.08 and 20% ± 5% for rectum, and 0.33 ± 0.20, 0.26 ± 0.17 and 82% ± 42% for sigmoid. Dosimetric variability was: for bladder, CV = 31% ± 19% (SDTOT = 72 ± 64 Gy) for D0.1cc and CV = 16% + 10% (SDTOT = 9 ± 6 Gy) for D2cc; for rectum, CV = 11% ± 5% (SDTOT = 16 ± 17 Gy) for D0.1cc and CV = 7% ± 2% (SDTOT = 4 ± 3 Gy) for D2cc; for sigmoid, CV = 39% ± 28% (SDTOT = 12 ± 18 Gy) for D0.1cc and CV = 34% ± 19% (SDTOT = 4 ± 4 Gy) for D2cc.
Delineation of bladder and rectum by 13 physicians demonstrated substantial geometric agreement and resulted in good dosimetric agreement for all dose-volume histogram parameters except bladder D0.1cc. Small delineation differences in high-dose regions by the posterior bladder wall may explain these results. The delineation of sigmoid showed fair geometric agreement. The higher dosimetric variability for sigmoid compared with rectum and bladder did not correlate with higher variability in the total brachytherapy dose but rather may be due to the sigmoid being positioned in low-dose regions in the cases analyzed in this study.
Starting in 1999, the University Cooperation Platform (UCP) implemented an exchange program of researchers and clinicians/physicists between the Christian-Albrechts-University Kiel in Germany and Chiang Mai University in Thailand, to initiate a sustainable base for long-term development of image-guided brachytherapy and in general for high-technology radiotherapy in Chiang Mai. A series of UCP protocols, based constructively on each other, were performed and evaluated at intermediate term follow-up. The first protocol, addressing computed tomography (CT)-optimized brachytherapy for advanced cervical cancer (n = 17), showed a significant reduction of D2cc for the bladder and sigmoid (p < 0.001) while maintaining a very high dose in D90 high-risk clinical target volume (HR-CTV) in comparison with standard point-based planning. In addition, after a follow-up of 19 months no tumor relapse was observed. The second UCP protocol, testing the impact of magnetic resonance imaging (MRI) guidance (n = 15) in patients with cervical cancer, proved significantly smaller D2cc doses for the bladder, rectum, and sigmoid (p = 0.003, p = 0.015, and p = 0.012), and secured highly curative mean doses in D90 HR-CTV of 99.2 Gy. The acute and late toxicity was excellent without any observed grade 3 or higher morbidity. In the third protocol, the combination of image-guided brachytherapy (IGBT) and whole pelvis intensity-modulated external beam radiotherapy (WP-IMRT) (n = 15) reaffirmed the significant reduction of D2cc doses for the bladder, rectum, and sigmoid (p = 0.001 or p < 0.001) along with high equivalent dose at 2 Gy (EQD2) in the HR-CTV, and demonstrated very low acute therapy-related toxicity in absence of grade 3 morbidity. The implementation of transabdominal ultrasound (TAUS) was the focus of the fourth UCP project aiming a more generous potential use of image-guidance on long-term, and enhancing the quality of soft tissue assessment complementary to conventionally planned gynecological brachytherapy. Analyses in 29 patients revealed significantly reduced OARs doses in bladder with a total EQD2 > 80 Gy for bladder in only 17.2% versus 62.1% in conventional planning, and in rectum EQD2 > 75 Gy in 44.8% versus 79.3%, respectively.
In conclusion, analyses revealed excellent results for the high-dose-rate IGBT in patients with advanced gynecological cancer both by using CT and MRI, and/or the combination with WP-IMRT. They also define MRI as gold standard for soft tissue assessment and to determine more accurately HR-CTV. The use of TAUS-guidance adds quality aspects to the “classical” conventional X-ray based planning, especially in terms of real-time measures and adequate soft tissue information, and may lower significantly the dose in OARs. The review of all UCP-results reconfirms the importance of the established program that will continue to operate with subsequent projects.
brachytherapy; cervical cancer; computed tomography; gynecological neoplasms; image-guided brachytherapy
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.
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).
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.
cervical cancer; deformable image registration; IMRT; MRI
To evaluate the technique, dosimetry, dose-volume-histograms (DVHs) and acute toxicity for CyberKnife® boost irradiation instead of intra-cervical brachytherapy in patients with cervical cancer.
Methods and materials
Eleven who were not suitable for brachytherapy with FIGO stage IIB-IIIB cervical cancer underwent primary chemoradiation. After fiducial implantation, T2 contrast-enhanced planning MRI and CT scans at 2-mm slice thickness were collected in the treatment position. The clinical target volume was defined as cervix + macroscopic residual tumour on MRI. Five fractions of 6 Gy each were prescribed to the target volume with a covering single dose 6 Gy. DVH parameters were evaluated for the target and organs at risk. Acute toxicity was documented once a week.
DmeanPTV ranged from 33.6-40 Gy, median 36.7 Gy with a coverage of the PTV calculated to 100% of the prescribed dose ranging from 93.0-99.3% (median 97.7%). For the PTV the median CN was 0.78 (range, 0.66 to 0.87) and the median CI was 1.28 (range 1.15 to 1.52). Gastrointestinal (GI) and genitourinary (GU) toxicity was mild. There was no grade 3 or higher GI and GU toxicity. After 6 months of follow up, there were no local recurrences. For the complete treatment, a median EQD2 to 1 cc and 2 cc of the bladder wall was 98.8 Gy and 87.1 Gy, respectively. Median EQD2 to 1 cc and 2 cc of the rectal wall was 72.3 Gy and 64 Gy, respectively, correlating with a risk < 10% for Grade 2–4 late toxicity.
CyberKnife robotic radiosurgery in patients with cervical cancer provides excellent target coverage with steep dose gradients toward normal tissues and safe DVH parameters for bladder, rectum and sigmoid. Acute toxicity was mild. Longer follow-up is needed to evaluate the oncological equality.
Robotic radiosurgery; Cervical cancer; Boost; Emulating brachytherapy; CyberKnife
To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT) ± chemotherapy (ChT).
Treatment schedule was EBRT with 45–50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90 > 85 Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75 Gy for rectum and sigmoid and 90 Gy for bladder.
Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis.
One hundred and fifty-six consecutive patients (median age 58 years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5 cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42 months for all patients.
Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93 ± 13 Gy, D2cc 86 ± 17 Gy for bladder, 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid.
Complete remission was achieved in 151/156 patients (97%). Overall local control at 3 years was 95%; 98% for tumours 2–5 cm, and 92% for tumours >5 cm (p = 0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3 years was overall 74%, 83% for tumours 2–5 cm, 70% for tumours >5 cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3 years was in total 68%, 72% for tumours 2–5 cm, 65% for tumours >5 cm, 74% for IB, 78% for IIB, 45% for IIIB.
In regard to late morbidity in total 188 grade 1 + 2 and 11 grade 3 + 4 late events were observed in 143 patients. G1 + 2/G3 + 4 events for bladder were n = 32/3, for rectum n = 14/5, for bowel (including sigmoid) n = 3/0, for vagina n = 128/2, respectively.
3D conformal radiotherapy ± chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3 years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings.
Cervical cancer; Image guided adaptive brachytherapy; Clinical outcome; GEC-ESTRO recommendations
To compare the short-term toxicity and dosimetry of tandem and ring (TR), and tandem and ovoid (TO) applicators in treatment of gynecologic malignancy.
Material and methods
Following pelvic external beam radiation therapy (EBRT), a total of 52 computed tomography-based plans from 13 patients with cervical cancer (FIGO IB2-IIIB) were evaluated for HDR brachytherapy. Prescription was 7 Gy to the ICRU point A for four weekly fractions. Gastrointestinal and genitourinary toxicities were evaluated. Clinical target volume (CTV) and organs at risk were delineated on CT scans. Bladder, rectum, and sigmoid mean doses and D2cc were calculated. Treatment time and irradiated tissue volume were compared. Percent of CTV receiving 100% (CTV100%) of the prescribed dose as well as the percent of the prescription dose covering 90% of the CTV (D90) were evaluated.
Gastrointestinal and genitourinary toxicities were not different between TO and TR applicators. No significant differences in the dose to the right and left point A, or the left point B were observed. TO delivered a higher dose to right point B. Organs at risk doses were similar between the two applicators, except mean rectal dose was lower for TO applicator. Overall, TO treats a larger tissue volume than TR. Mean treatment time was shorter for TR. Tumor coverage (D90 and CTV100%) was equivalent between TO and TR applicators.
Although TO treats a larger tissue volume than TR, short-term toxicities and tumor coverage are similar. Long-term clinical outcomes will be elucidated with longer follow up period.
brachytherapy; cervical cancer; dosimetry; radiation toxicity
This report presents the 2011 update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer.
Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder or interstitial applicators for locally advanced cervical cancer were revised based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy.
The Cervical Cancer Committee for Guideline Development affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion prior to treatment delivery. Applicator placement, dose specification and dose fractionation must be documented, quality assurance measures must be performed, and follow-up information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2 Gray (Gy) per fraction radiobiologic equivalence (EQD2) is 80–90 Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed.
These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011.
The purpose of this study was to evaluate the efficacy and safety of high-dose-rate (HDR) brachytherapy of a single implant with two fractions plus external beam radiotherapy (EBRT) for hormone-naïve prostate cancer in comparison with radical prostatectomy. Of 150 patients with localized prostate cancer (T1c–T2c), 59 underwent HDR brachytherapy plus EBRT, and 91 received radical prostatectomy. The median follow-up of patients was 62 months for HDR brachytherapy plus EBRT, and 64 months for radical prostatectomy. In patient backgrounds between the two cohorts, the frequency of T2b plus T2c was greater in HDR brachytherapy cohort than in prostatectomy cohort (27% versus 12%, p = 0.029). Patients in HDR brachytherapy cohort first underwent 3D conformal RT with four beams to the prostate to an isocentric dose of 50 Gy in 25 fractions and then, a total of 15–18 Gy in two fractions at least 5 hours apart. We prescribed 9 Gy/fraction for target (prostate gland plus 3 mm lateral outside margin and seminal vesicle) using CT image method for radiation planning. The total biochemical failure-free control rates (BF-FCR) at 3 and 5 years for the HDR brachytherapy cohort, and for the prostatectomy cohort were 92% and 85%, and 72% and 72%, respectively (significant difference, p = 0.0012). The 3-and 5-year BF-FCR in the HDR brachytherapy cohort and in the prostatectomy cohort by risk group was 100 and 100%, and 80 and 80%, respectively, for the low-risk group (p = 0.1418); 92 and 92%, 73 and 73%, respectively, for the intermediate-risk group (p = 0.0492); and 94 and 72%, 45 and 45%, respectively, for the high-risk group (p = 0.0073). After HDR brachytherapy plus EBRT, no patient experienced Grade 2 or greater genitourinay toxicity. The rate of late Grade 1 and 2 GI toxicity was 6% (n = 4). No patient experienced Grade 3 GI toxicity. HDR brachytherapy plus EBRT is useful for treating patients with hormone-naïve localized prostate cancer, and has low GU and GI toxicities.
prostate cancer; high dose rate brachytherapy; external beam radiation therapy; radical prostatectomy
Permanent low-dose-rate (LDR-BT) and temporary high-dose-rate (HDR-BT) brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never to be conducted comparing these two forms of brachytherapy, a comparative analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. The aim of this paper is to look for possible similarities and differences between both brachytherapy modalities. Indications and contraindications for monotherapy and for brachytherapy as a boost to external beam radiation therapy (EBRT) are presented. It is suggested that each of these techniques has attributes that advocates for one or the other. First, they represent the extreme ends of the spectrum with respect to dose rate and fractionation, and therefore have inherently different radiobiological properties. Low-dose-rate brachytherapy has the great advantage of being practically a one-time procedure, and enjoys a long-term follow-up database supporting its excellent outcomes and low morbidity. Low-dose-rate brachytherapy has been a gold standard for prostate brachytherapy in low risk patients since many years. On the other hand, HDR is a fairly invasive procedure requiring several sessions associated with a brief hospital stay. Although lacking in significant long-term data, it possesses the technical advantage of control over its postimplant dosimetry (by modulating the source dwell time and position), which is absent in LDR brachytherapy. This important difference in dosimetric control allows HDR doses to be escalated safely, a flexibility that does not exist for LDR brachytherapy.
Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy, using current dose regimens. At present, all available clinical data regarding these two techniques suggests that they are equally effective, stage for stage, in providing high tumor control rates.
brachytherapy; HDR; LDR; prostate cancer; seeds
This study was designed to evaluate the dosimetric feasibility of definitive stereotactic body radiation therapy (SBRT) for the treatment of medically inoperable early stage endometrial cancer.
CT simulation scans from 10 medically inoperable early stage endometrial cancer patients previously treated with high dose-rate (HDR) intracavitary brachytherapy were used to generate Helical Tomotherapy (HT) plans using the IMRT mode with clinical target volumes (CTVs) that included the uterus plus cervix. A prescription dose of 34 Gy in 4 fractions was used. The SBRT dosimetry was compared to the 10 prior intracavitary brachytherapy plans normalized to a standard dose. Organs at risk (OARs) evaluated were the bladder, rectum, sigmoid, femoral heads, and other bowel, including both large and small bowel. The simulation CT and daily image guidance for 4 patients treated with this technique were evaluated to assess for interfraction variation in the uterine position and effects on dosimetry.
Compared to intracavitary brachytherapy, HT SBRT produced significantly greater overall target coverage to the uterus, boost CTV, and PTV, with exception of the V150% of the uterus. HT SBRT significantly increased dose to the rectum, bowel, and femoral heads compared to intracavitary brachytherapy, though not outside of dose tolerance limits. Review of daily image guidance for patients treated with this technique demonstrated good reproducibility with a mean overlap index of 0.87 (range, 0.74 – 0.99).
Definitive SBRT for medically inoperable early stage endometrial cancer appears to be a feasible treatment option. Future studies are warranted to evaluate long-term clinical outcomes with this technique, compared to HDR intracavitary brachytherapy.
SBRT; Medically inoperable; Endometrial cancer; Intracavitary brachytherapy
We perform a clinical retrospective study to determine whether a vaginal balloon-packing system provides a dosimetric reduction to organs at risk (OARs) versus traditional gauze packing for gynecological high-dose-rate brachytherapy (HDR-BT). We also test various balloon filling materials for optimizing imaging quality.
Material and methods
Filling materials for balloon-packing were evaluated based on imaging quality with X-ray, computerized tomography, and magnetic resonance imaging modalities. We then retrospectively reviewed 45 HDR-BT plans of 18 patients performed with gauze packing and 39 plans of 16 patients performed with balloon-packing. Twelve patients received both gauze and balloon-packing. HDR-BT was delivered with an iridium-192 afterloader and a Fletcher-Suit-Declos-style T&O applicator. At each fraction, 3D imaging was obtained. The D2cc values of OARs were calculated, as well as ICRU-defined point doses.
In the 84 HDR fractions reviewed, vaginal balloon-packing provides statistically equivalent doses to rectum, bladder, and sigmoid compared to gauze packing. On average balloon-packing produced average reductions of 3.3% and 6.9% in the rectal and sigmoid D2cc doses and an increase of 3.2% to the bladder D2cc dose (normalized to prescription dose), although none of these values were statistically significant for the twelve patients who received both gauze and balloon-packing (32 and 40 total fractions, respectively).
In the 84 HDR fractions analyzed, vaginal balloon-packing is as effective as gauze packing for dose sparing to the rectum, bladder, and sigmoid. A 1: 1 solution of saline and contrast for filling material enables easy contouring for image-guided HDR with minimal artefacts.
brachytherapy; gynecological cancer; high-dose-rate brachytherapy; vaginal balloon packing
Distension and shape of urinary bladder may vary during intracavitary brachytherapy (ICBT) for cervical cancer, significantly affecting doses to bladder, rectum, sigmoid colon and small intestine and consequently late radiation toxicities. This study is to evaluate the effects of different fixed volume bladder distention on dosimetry, assessed by three dimensional image based planning, in different organs at risk during the treatment of cervical cancer with ICBT.
Material and methods
Forty seven cervical cancer patients (stage IB to IVA) were qualified for ICBT following external beam radiotherapy. Urinary bladder was distended with different volumes of normal saline instilled by a Foley's catheter. Planning CT scans were performed after insertion of applicators and three dimensional treatment planning was done on Brachyvision® treatment planning system (Varian Medical Systems, Palo Alto, CA). Dose volume histograms were analyzed. Bladder, rectum, sigmoid colon and small intestine doses were collected for individual plans and compared, based on the amount of bladder filling.
Mean dose to the bladder significantly decreased with increased bladder filling. However, doses to the small volumes (0.1 cc, 1 cc, 2 cc) which are relevant for brachytherapy, did not change significantly with bladder filling for bladder, rectum or sigmoid colon. Nevertheless, all dose values of small intestine are decreased significantly with bladder filling.
Bladder distension has no significant effect on doses received during brachytherapy by relevant volumes of bladder, rectum and sigmoid colon except intestine where values are decreased with bladder distension. A larger study with clinical correlation of late toxicities is essential for proper evaluation of this strategy.
bladder distension; cervical cancer; dosimetric comparison; intracavitary brachytherapy
The efficacy and safety results of treatment with low-dose-rate vaginal brachytherapy for grade 3 vaginal intraepithelial neoplasia over a 25-year period at Gustave Roussy Institute are presented. This treatment was found to be both safe and effective.
After completing this course, the reader will be able to:
Utilize data supporting the efficacy of low-dose definitive brachytherapy to inform clinical decisions about treating women with high-grade vaginal intraepithelial neoplasia.Implement methods for delivering low-dose definitive brachytherapy that minimize toxicity.Communicate to patients the type and incidence of toxic events associated with low-dose definitive brachytherapy.
This article is available for continuing medical education credit at CME.TheOncologist.com
Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute.
Patients and Methods.
We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear.
Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up <2 years, and the median follow-up for the remaining 21 patients was 79 months. The median age at brachytherapy was 63 years (range, 38–80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm3. Only one “in field” recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%–99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported.
LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia.
Vaginal neoplasms; Carcinoma in situ; Cervical intraepithelial neoplasia; Brachytherapy
An evaluation of CT plan data, using cylinder applicators, in fractionated HDR treatments of cervical cancers has been investigated in this clinical study. Critical and statistical analysis of the data, for each patient and fraction, for plan dose, doses for bladder and rectum have been enumerated and reported. Plans were done for each patient, following CT scans after insertion of the applicator in the respective cases. This process involved time for CT-scan and re-plan, in each fraction, adding cost of treatments for the poor patients.
Material and methods
This study on HDR brachytherapy for cervical cancer patients has applied the Co-60 BEBIG Multisource Unit. Cylinder applicators have been applied for treatments. A selection of twenty nine patients, out of a few hundred representative female patients, in the age group of 40-70 years, has been analyzed and presented in this paper. Radiation oncologists inserted the applicator and fixed it in more than 600 treatments. This study, therefore, aimed at their insertion technique, CT-planning by radiation oncology physicists and the delivery of the treatments. Details of set up and technique has been explained, where bladder and rectum doses has been assessed within the tolerance limit .
Statistical analysis of data from the treatment plans, substantiates the conclusion of the argument that there is no need to do CT-plans for each subsequently prescribed number of fractions as the doses in plan, bladder and rectum are restricted within the limits of tolerance. Data in Table 1 are analyzed in various graphs. This utilized the Empirical Null Distribution of Group Differences. A graphic study of dose distribution is reported to assure the expected variation of dose from the central tandem. This analysis proves to substantiate a protocol that no re-plan for fractionated delivery is essential following the approval of the first plan.
The goal of this study was to critically evaluate the outcome of fractionated cylinder treatments of cervical cancers. This resulted in the set up technique for insertion of applicators and treatment plan, following a CT-scan and the assertion of the argument that re-plans are not necessary for multiple HDR cylinder treatments for the same patient [2, 3].
HDR; cervical cancer; cylinder plan; null distribution
The literature supporting high-dose rate brachytherapy (HDR) in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR) brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial.
A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations.
Pooled results from five randomized trials (2,065 patients) of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52), local recurrence (p = 0.68), or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06) rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages.
Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix cancer.
We investigated the rectal dose-sparing effect and tumor control of a point A dose-reduced plan in patients with Stage I–II cervical cancer (≤4 cm) arising from a small-sized uterus. Between October 2008 and August 2011, 19 patients with Stage I–II cervical cancer (≤4 cm) were treated with external beam radiotherapy (EBRT) for the pelvis and CT-guided brachytherapy. Seven patients were treated with brachytherapy with standard loading of source-dwell positions and a fraction dose of 6 Gy at point A (conventional brachy-plan). The other 12 patients with a small uterus close to the rectum or small intestine were treated with brachytherapy with a point A dose-reduction to match D2cc of the rectum and <6 Gy as the dose constraint (‘point A dose-reduced plan’) instead of the 6-Gy plan at point A (‘tentative 6-Gy plan’). The total doses from EBRT and brachytherapy were added up and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2). The median doses to the high-risk clinical target volume (HR-CTV) D90 in the conventional brachy-plan, tentative 6-Gy plan and point A dose-reduced plan were 62 GyEQD2, 80 GyEQD2 and 64 GyEQD2, respectively. The median doses of rectal D2cc in the corresponding three plans were 42 GyEQD2, 62 GyEQD2 and 51 GyEQD2, respectively. With a median follow-up period of 35 months, three patients developed Grade-1 late rectal complications and no patients developed local recurrence. Our preliminary results suggested that CT-guided brachytherapy using an individualized point A dose-reduced plan might be useful for reducing late rectal complications while maintaining primary tumor control.
cervical cancer; CT-guided brachytherapy; small-sized uterus; late rectal complication; point A dose
Iridium-192 is widely used for high-dose rate brachytherapy. Co-60 source with similar geometric and dosimetric properties are now available. It has a longer half life but higher energy than Iridium-192. If Co-60 source can produce similar results, it will be more economical for low resource settings.
To evaluate the acute gastrointestinal and genitourinary toxicity associated with Co-60 source in the brachytherapy of cervical cancer.
Seventy patients with cervical cancer received 45 Gy in 22 fractions of pelvic external beam radiotherapy and 19.5 Gy in 3 fractions of HDR with Co-60 source using tandem and ring applicators with 6 courses of cisplatin 50 mg/m2 and 5 fluorouracil 1000 mg/m2 every 3 weeks Toxicity was scored using NCI-CTC version 4.0.
The median total BED (Gy10) for tumor was 86.2 (84.4–88.8) while that for rectum (BED Gy3) was 124.4 (120–133). Two patients (3%) had grade 3 gastrointestinal toxicity while all others had ≤grade 2 toxicity and this is comparable with previous results.
Co-60 as HDR brachytherapy source is tolerable and is economical for low resource settings.
HDR brachytherapy; Co-60 source; cervical cancer; acute toxicity
The purpose of this work was the biological comparison between Low Dose Rate (LDR) and Pulsed Dose Rate (PDR) in cervical cancer regarding the discontinuation of the afterloading system used for the LDR treatments at our Institution since December 2009.
Material and methods
In the first phase we studied the influence of the pulse dose and the pulse time in the biological equivalence between LDR and PDR treatments using the Linear Quadratic Model (LQM). In the second phase, the equivalent dose in 2 Gy/fraction (EQD2) for the tumor, rectum and bladder in treatments performed with both techniques was evaluated and statistically compared. All evaluated patients had stage IIB cervical cancer and were treated with External Beam Radiotherapy (EBRT) plus two Brachytherapy (BT) applications. Data were collected from 48 patients (26 patients treated with LDR and 22 patients with PDR).
In the analyses of the influence of PDR parameters in the biological equivalence between LDR and PDR treatments (Phase 1), it was calculated that if the pulse dose in PDR was kept equal to the LDR dose rate, a small the-rapeutic loss was expected. If the pulse dose was decreased, the therapeutic window became larger, but a correction in the prescribed dose was necessary. In PDR schemes with 1 hour interval between pulses, the pulse time did not influence significantly the equivalent dose. In the comparison between the groups treated with LDR and PDR (Phase 2) we concluded that they were not equivalent, because in the PDR group the total EQD2 for the tumor, rectum and bladder was smaller than in the LDR group; the LQM estimated that a correction in the prescribed dose of 6% to 10% was ne-cessary to avoid therapeutic loss.
A correction in the prescribed dose was necessary; this correction should be achieved by calculating the PDR dose equivalent to the desired LDR total dose.
brachytherapy; cervical cancer; LDR; PDR; EQD2; LQM
Purpose: Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered “Virtual HDR” treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients.
Methods: Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create “HDR-like” PTV dose distribution.
Results: Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient’s potent pre-SBRT, 65% remained so at 5 years.
Conclusion: Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.
CyberKnife; prostate cancer; dosimetry; HDR; brachytherapy; image guided; stereotactic body radiotherapy
The goal of this study was to determine the dose contributions from image guided adaptive brachytherapy (IGABT) to individual suspicious pelvic lymph nodes (pLNN) in cervical cancer patients. Data were collected in two cancer centers, University of Pittsburgh Cancer Institute (UPCI) and University Medical Center Utrecht (UMCU).
Material and methods
27 and 15 patients with node positive cervical cancer treated with HDR (high dose rate) or PDR (pulsed dose rate)-IGABT were analyzed. HDR-IGABT (UPCI) was delivered with CT/MRI compatible tandem-ring applicators with 5.0-6.0 Gy × five fractions. PDR-IGABT (UMCU) dose was delivered with Utrecht tandem-ovoid applicators with 32 × 0.6 Gy × two fractions. Pelvic lymph nodes with short axis diameter of ≥ 5 mm on pre-treatment MRI or PET-CT were contoured for all BT-plans. Dose contributions to individual pLNN expressed as D90 (dose to 90% of the volume) were calculated from dose-volume histograms as absolute and relative physical dose (% of the reference dose) for each fraction. For each node, the total dose from all fractions was calculated, expressed in EQD2 (equivalent total dose in 2 Gy fractions).
Fifty-seven (UPCI) and 40 (UMCU) individual pLNN were contoured. The mean D90 pLNN was 10.8% (range 5.7-25.1%) and 20.5% (range 6.8-93.3%), respectively, and therefore different in the two centers. These values translate into 2.7 Gy (1.3-6.6 Gy) EQD2 and 7.1 Gy (2.2-36.7 Gy) EQD2, respectively. Differences are caused by the location of the individual nodes in relation to the spatial dose distribution of IGABT, differences in total dose administered and radiobiology (HDR versus PDR).
The IGABT dose contribution to individual pelvic nodes depends on patient and treatment related factors, and varies considerably.
brachytherapy; cervical cancer; dosimetry; HDR; MRI-guidance; PDR
To investigate dosimetric effects of bladder distention on organs at risk (OARs) during treatment of endometrial cancer using 3D image-based planning of postoperative vaginal vault brachytherapy (BRT).
Material and methods
Fifteen patients with early-stage endometrial cancer were studied, each undergoing adjuvant BRT of vaginal vault via 3.5 cm diameter cylinder. As treatment, 25 Gy in 5 fractions were delivered to 5 mm depth of the vaginal mucosa. Dose-volume histograms of OARs were generated individually with bladder empty and with bladder inflated by sterile saline (180 ml), to compare doses received.
Bladder distention appreciably impacted dosimetry of bladder, sigmoid colon, and small bowel, but dosimetry of rectum was unaffected. With bladder inflated, mean cylinder-to-bowel distance increased significantly (1.69 cm vs. 1.20 cm; p = 0.006). Mean minimum dose to most exposed 2 cc (D2cc) volume also rose significantly at bladder (5.40 Gy vs. 4.55 Gy [18.7%]; p < 0.001), as opposed to near-significant reductions in D2cc at sigmoid colon (15.1%; p = 0.11) and at small bowel (10.5%; p = 0.14). A full bladder had no effect on dose to 50% volume (D50%) of bladder or rectum, and declines seen in mean D50% values of sigmoid colon (22.7%; p = 0.12) and small bowel (19.0%; p = 0.13) again fell short of statistical significance.
The combination of a full bladder and an empty rectum may cause significant unwanted increases in BRT dosing of bladder, without significantly impacting sigmoid colon and small bowel exposures. These findings should be validated through further clinical studies.
bladder distention; brachytherapy; dosimetry; endometrial cancer; vaginal vault
Currently, image-based 3-dimentional (3D) planning brachytherapy allows for a better assessment of gross tumor volume (GTV) and the definition and delineation of target volume in cervix cancer. In this study, we investigated the feasibility of our novel computed tomography (CT)-guided free-hand high-dose-rate interstitial brachytherapy (HDRISBT) technique for cervical cancer by evaluating the dosimetry and preliminary clinical outcome of this approach. Dose-volume histogram (DVH) parameters were analyzed according to the Gynecological GEC-ESTRO Working Group recommendations for image-based 3D treatment in cervical cancer. Twenty cervical cancer patients who underwent CT-guided free-hand HDRISBT between March 2009 and June 2010 were studied. With a median of 5 (range, 4–7) implanted needles for each patient, the median dose of brachytherapy alone delivered to 90% of the target volume (D90) was 45 (range, 33–54) Gyα/β10 for high-risk clinical target volume (HR-CTV) and 30 (range, 20–36) Gyα/β10 for intermediate-risk clinical target volume (IR-CTV). The percentage of the CTV covered by the prescribed dose (V100) of HR-CTV with brachytherapy alone was 81.9%–99.2% (median, 96.7%). With an additional dose of external beam radiotherapy (EBRT), the median D90 was 94 (range, 83–104) Gyα/β10 for HR-CTV and 77 (range, 70–87) Gyα/β10 for IR-CTV; the median dose delivered to 100% of the target volume (D100) was 75 (range, 66–84) Gyα/β10 for HR-CTV and 65 (range, 57–73) Gyα/β10 for IR-CTV. The minimum dose to the most irradiated 2 cc volume (D2cc) was 73–96 (median, 83) Gyα/β3 for the bladder, 64–98 (median, 73) Gyα/β3 for the rectum, and 52–69 (median, 61) Gyα/β3 for the sigmoid colon. After a median follow-up of 15 months (range, 3–24 months), two patients experienced local failure, and 1 showed internal iliac nodal metastasis. Despite the relatively small number of needles used, CT-guided HDRISBT for cervical cancer showed favorable DVH parameters and clinical outcome.
Cervical carcinoma; radiotherapy; high-dose-rate; brachytherapy; dose-volume histogram
To retrospectively assess the incidence of sub-serosal and uterine perforation of intra-uterine tandem in intracavitary high-dose-rate (HDR) brachytherapy for cervical cancer, and to evaluate its dosimetric implications on computed tomography (CT)-based treatment planning.
Material and methods
Computed tomography images and brachytherapy plans of cervical cancer patients treated from February 2006 to December 2012 were reviewed for sub-optimal implants (sub-serosal and uterine perforation), and their correlation with cancer FIGO stage and patients’ age. For each patient, the plans showing sub-optimal insertion of intra-uterine tandem were analyzed and compared to plans with adequate insertion. The difference in dose coverage of clinical-target-volume (CTV) and variation of the dose delivered to organs-at-risk (OARs) rectum and bladder were evaluated.
A total of 231 brachytherapy plans for 82 patients were reviewed. We identified 12 (14.6%) patients and 14 (6%) applications with uterine perforation, and 12 (14.6%) patients and 20 (8.6%) applications with sub-serosal insertion of tandem. Data analysis showed that advanced stage correlates with higher incidence of sub-optimal implants (p = 0.005) but not the age (p = 0.18). Dose-volume-histograms (DVHs) analysis showed large variations for CTV dose coverage: D90 significantly decreased with average of –115.7% ± 134.9% for uterine perforation and –65.2% ± 82.8% for sub-serosal insertion (p = 0.025). The rectum and bladder dose assessed by D2cc increased up to 70.3% and 43.8%, respectively, when sub-optimal insertion of uterine tandem occurred.
We report a low incidence of uterine perforation and sub-serosal insertion of uterine tandem in intracavitary HDR brachytherapy for cervical cancer. However, the effects on treatment plan dosimetry can be considerably detrimental. Therefore, we recommend image-guided insertion, at least for the challenging cases.
cervix brachytherapy; cervical cancer; uterine perforation