To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost.
Materials and methods
Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml.
Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6.
We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.
To investigate the role of low dose rate (LDR) brachytherapy-based multimodal therapy in high-risk prostate cancer (PCa) and analyze its optimal indications.
Materials and Methods
We reviewed the records of 50 high-risk PCa patients [clinical stage ≥T2c, prostate-specific antigen (PSA) >20 ng/mL, or biopsy Gleason score ≥8] who had undergone 125I LDR brachytherapy since April 2007. We excluded those with a follow-up period <3 years. Biochemical recurrence (BCR) followed the Phoenix definition. BCR-free survival rates were compared between the patients with Gleason score ≥9 and Gleason score ≤8.
The mean initial PSA was 22.1 ng/mL, and mean D90 was 244.3 Gy. During a median follow-up of 39.2 months, biochemical control was obtained in 72% (36/50) of the total patients; The estimated 3-year BCR-free survival was 92% for the patients with biopsy Gleason scores ≤8, and 40% for those with Gleason scores ≥9 (p<0.001). In Cox multivariate analysis, only Gleason score ≥9 was observed to be significantly associated with BCR (p=0.021). Acute and late grade ≥3 toxicities were observed in 20% (10/50) and 36% (18/50) patients, respectively.
Our results showed that 125I LDR brachytherapy-based multimodal therapy in high-risk PCa produced encouraging relatively long-term results among the Asian population, especially in patients with Gleason score ≤8. Despite small number of subjects, biopsy Gleason score ≥9 was a significant predictor of BCR among high risk PCa patients after brachytherapy.
Prostate cancer; brachytherapy; high risk group; biochemical recurrence
Prostate brachytherapy can be used as a monotherapy for low- and intermediate-risk patients or in combination with external beam radiation therapy (EBRT) as a form of dose escalation for selected intermediate- and high-risk patients. Prostate brachytherapy with either permanent implants (low dose rate [LDR]) or temporary implants (high dose rate [HDR]) is emerging as the most effective radiation treatment for prostate cancer. Several large Canadian brachytherapy programs were established in the mid- to late-1990s. Prostate brachytherapy is offered in British Columbia, Alberta, Manitoba, Ontario, Quebec and New Brunswick. We anticipate the need for brachytherapy services in Canada will significantly increase in the near future. In this review, we summarize brachytherapy programs across Canada, contemporary eligibility criteria for the procedure, toxicity and prostate-specific antigen recurrence free survival (PRFS), as published from Canadian institutions for both LDR and HDR brachytherapy.
Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.
brachytherapy; oral cancer; high dose rate
Accelerated tumor repopulation has significant implications in low-dose-rate (LDR) brachytherapy. Repopulation onset time remains undetermined for cervical cancer. The purpose of this study was to determine the onset time of accelerated repopulation in cervical cancer using clinical data.
Methods and Materials
The linear-quadratic (LQ) model extended for tumor repopulation was used to analyze the clinical data and MRI-based 3D tumor volumetric regression data of 80 cervical cancer patients who received external beam radiotherapy (EBRT) and low dose rate (LDR) brachytherapy. The LDR dose was converted to EBRT dose in 1.8 Gy fractions using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. The patients were divided into 11 groups according to total dose and treatment time. The tumor control probability (TCP) was calculated for each group. The least χ2 method was used to fit the TCP data with two free parameters: onset time (Tk) of accelerated repopulation and the number of clonogens (K) while other LQ model parameters were adopted from the literature, due to the limited patient data.
Among the 11 patient groups, TCP varied from 33% to 100% as a function of radiation dose and overall treatment time. Higher dose and shorter treatment duration were associated higher TCP. Using the LQ model, the best fit was achieved with the onset time Tk=19 days, K=139, with uncertainty ranges of (11, 22) days for Tk, and (48, 1822) for K, respectively.
This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from the clinical data using the LQ model. Our study verifies that accelerated repopulation does exist in cervical cancer and has a relatively short onset time. Dose escalation may be required to compensate for the effects of tumor repopulation if the radiation therapy course is protracted.
Cervical cancer; Radiation therapy; Tumor control probability; Tumor repopulation onset time; Linear-quadratic model
To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS).
Material and methods
A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest.
The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS.
LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.
brachytherapy; cervical; point A; Fletcher-Suit system
To compare the periodical incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicity in patients who underwent prostate low-dose-rate brachytherapy between the monotherapy group (seed implantation alone) and the boost group (in combination with external beam radiation therapy (EBRT)).
A total of 218 patients with a median follow-up of 42.5 months were enrolled. The patients were divided into 2 groups by treatment modality, namely, the monotherapy group (155 patients) and the boost group (63 patients). The periodical incidence rates of GU and GI toxicity were separately evaluated and compared between the monotherapy group and the boost group using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. To elucidate an independent factor among clinical and postdosimetric parameters to predict grade 2 or higher GU and GI toxicity in the acute and late phases, univariate and multivariate logistic regression analyses were carried out.
Of all patients, 78.0% showed acute GU toxicity, and 7.8% showed acute GI toxicity, while 63.8% showed late GU toxicity, and 21.1% showed late GI toxicity. The incidence rates of late GU and GI toxicity were significantly higher in the boost group. Multivariate analysis showed that the International Prostate Symptom Score (IPSS) before seed implantation was a significant parameter to predict acute GU toxicity, while there were no significant predictive parameters for acute GI toxicity. On the other hand, combination with EBRT was a significant predictive parameter for late GU toxicity, and rectal volume (mL) receiving 100% of the prescribed dose (R100) was a significant predictive parameter for late GI toxicity.
The boost group showed higher incidence rates of both GU and GI toxicity. Higher IPSS before seed implantation, combination with EBRT and a higher R100 were significant predictors for acute GU, late GU and late GI toxicity.
Prostate cancer; LDR-brachytherapy; GU toxicity; GI toxicity
To evaluate predictive factors for PSA bounce after 125I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses.
Materials and methods
Men treated with exclusive permanent 125I seed brachytherapy from November 1999, with at least a 36 months follow-up were included. Bounce was defined as an increase ≥ 0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Biochemical failure (BF) was defined using the criteria of the Phoenix conference: nadir +2 ng/ml.
198 men were included. After a median follow-up of 63.9 months, 21 patients experienced a BF, and 35.9% had at least one bounce which occurred after a median period of 17 months after implantation (4-50). Bounce amplitude was 0.6 ng/ml (0.2-5.1), and duration was 13.6 months (4.0-44.9). In 12.5%, bounce magnitude exceeded the threshold defining BF. Age at the time of treatment and high PSA level assessed at 6 weeks were significantly correlated with bounce but not with BF. Bounce patients had a higher BF free survival than the others (100% versus 92%, p = 0,007). In case of PSA increase, PSA doubling time and velocity were not significantly different between bounce and BF patients. Bounces occurred significantly earlier than relapses and than nadir + 0.2 ng/ml in BF patients (17 vs 27.8 months, p < 0.0001).
High PSA value assessed 6 weeks after brachytherapy and young age were significantly associated to a higher risk of bounces but not to BF. Long delays between brachytherapy and PSA increase are more indicative of BF.
Brachytherapy; 125 iodine permanent seeds; Prostate cancer; PSA; Bounce; Biochemical relapse
To examine the role of brachytherapy for aged patients 80 or more in the trend of rapidly increasing number.
We examined the outcomes for elderly patients with node negative oral tongue cancer (T1-3N0M0) treated with brachytherapy. The 21 patients (2 T1, 14 T2, and 5 T3 cases) ranged in age from 80 to 89 years (median 81), and their cancer was pathologically confirmed. All patients underwent definitive radiation therapy, with low dose rate (LDR) Ra-226 brachytherapy (n = 4; median 70Gy), with Ir-192 (n = 12; 70Gy), with Au-198 (n = 1) or with high dose rate (HDR) Ir-192 brachytherapy (n = 4; 60 Gy). Eight patients also underwent external radiotherapy (median 30 Gy). The period of observation ranged from 13 months to 14 years (median 2.5 years). We selected 226 population matched younger counterpart from our medical chart.
Definitive radiation therapy was completed for all 21 patients (100%), and acute grade 2-3 mucositis related to the therapy was tolerable. Local control (initial complete response) was attained in 19 of 21 patients (90%). The 2-year and 5-year local control rates were 91%, (100% for T1, 83% for T2 and 80% for T3 tumors after 2 years). These figures was not inferior to that of younger counterpart (82% at 5-year, n.s.). The cause-specific survival rate was 83% and the regional control rate 84% at the 2-years follow-up. However, 12 patients died because of intercurrent diseases or senility, resulting in overall survival rates of 55% at 2 years and 34% at 5 years.
Age is not a limiting factor for brachytherapy for appropriately selected elderly patients, and brachytherapy achieved good local control with acceptable morbidity.
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.
The Genitourinary Cancer Disease Site Group (GU DSG) and Cancer Care Ontario’s Program in Evidence-Based Care (PEBC) in Ontario, Canada developed a guideline on low-dose rate brachytherapy (LDR-BT) in patients with early-stage low-grade prostate cancer in 2001. The current updated guideline focuses on the research questions regarding the effect of LDR-BT alone, the effect of LDR-BT with external beam radiation therapy (EBRT) and the selection of an isotope.
This guideline was developed by using the methods of the Practice Guidelines Development Cycle and the core methodology was a systematic review. MEDLINE and EMBASE (from January 1996 to October 2011), the Cochrane Library, main guideline websites, and main annual meeting abstract websites specific for genitourinary diseases were searched. Internal and external reviews of the draft guideline were conducted.
The draft guideline was developed according to a total of 10 systematic reviews and 55 full text articles that met the pre-planned study selection criteria. The quality of evidence was low to moderate. The final report reflects integration of the feedback obtained through the internal review (two oncologists and a methodologist) and external review (five target reviewers and 48 professional consultation reviewers) process, with final approval given by the GU DSG and the PEBC.
The main recommendations are: (1) For patients with newly diagnosed low-risk or intermediate-risk prostate cancer who require or choose active treatment, LDR-BT alone is a treatment option as an alternative to EBRT alone or RP alone; and (2) I-125 and Pd-103 are each reasonable isotope options.
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
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
To determine the incidence and magnitude of the rapid increase in the serum PSA (riPSA) level after high-intensity focused ultrasound (HIFU) therapy for prostate cancer, and its correlation with clinical factors.
A total of 176 patients with localized prostate cancer underwent HIFU therapy. Serum riPSA was determined on the basis of the same criteria as those for “PSA bounce”, ie, an increase of ≥0.2 ng/ml with a spontaneous return to the prebounce level or lower. Patients were stratified according to neoadjuvant PSA level, T stage, risk group, age, Gleason score, pretreatment PSA level, post-treatment PSA nadir, and number of HIFU sessions.
riPSA was seen in 53% of patients during a median follow-up period of 43 months. A PSA nadir was achieved within 3 months for 85.1% of the treatments. In all cases, onset of riPSA was seen two days after HIFU therapy, and the median magnitude was 23.69 ng/ml. A magnitude of >2 ng/ml was seen in 89.4% of cases. Univariate analysis revealed that patients with riPSA were associated with usage of hormonal therapy and the post-treatment PSA nadir level. Multivariate Cox regression analysis revealed that riPSA and the number of HIFU sessions were predictors of biochemical recurrence. A significant statistical association was found between the presence of riPSA and the risk of biochemical failure only in the low- and intermediate-risk group.
Patients treated with HIFU who experience post-treatment riPSA may have an increased risk of biochemical recurrence, especially in non-high-risk patients.
HIFU; prostate cancer; PSA
To compare the efficacy and safety of high dose rate (HDR) and low dose rate (LDR) brachytherapy in treating early-stage oral cancer.
A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies.
Only randomized controlled trials (RCT) and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III) were of interest.
Data Extraction and Synthesis
Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR) met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62–2.01), overall mortality (OR = 1.01, CI 95% 0.61–1.66) and Grade 3/4 complications (OR = 0.86, CI 95% 0.52–1.42).
This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.
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
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
Whole-gland low-dose rate (LDR) brachytherapy has been a well-established modality of treating low-risk prostate cancer. Treatment in a focal manner has the advantages of reduced toxicity to surrounding organs. Focal treatment using LDR brachytherapy has been relatively unexplored, but it may offer advantages over other modalities that have established experiences with a focal approach. This is particularly true as prostate cancer is being detected at an earlier and more localized stage with the advent of better detection methods and newer imaging modalities.
prostate cancer; focal; low dose rate; brachytherapy
The aim of this study was to evaluate the outcome and complications of low-dose-rate brachytherapy (LDR-BT) for oral cancer according to comorbidity.
The records of a total of 180 patients who received LDR-BT for T1-2N0M0 oral cancers between January 2005 and December 2007 were analysed. The comorbidities of the patients were retrospectively graded according to the Adult Comorbidity Evaluation-27, and the relationships between the comorbidity grades and survival, disease control and the incidence of complications were analysed.
The 2 year overall survival rates of patients with no comorbidity, Grade 1, Grade 2 and Grade 3 comorbidity were 87%, 85%, 76% and 65%, respectively, and the reduction in the survival rate according to comorbid severity was significant in a univariate analysis (p = 0.032) but not in a multivariate analysis including other clinical factors. Cause-specific survival, locoregional control and local control were not related to the comorbidity grade, or any other clinical factors. Grade 2 or 3 complications developed in 27% of the patients. The incidence of complications was unrelated to the comorbidity grade.
The disease control of oral cancer and the incidence of complications after LDR-BT were not related to comorbid severity. LDR-BT is a useful and safe treatment for patients regardless of the presence of severe comorbidity.
The present study compared the difference between intraoperative transrectal ultrasound (iTRUS)-based prostate volume and preplan computed tomography (CT), preplan magnetic resonance imaging (MRI)-based prostate volume to estimate the number of seeds needed for appropriate dose coverage in permanent brachytherapy for prostate cancer.
Materials and Methods
Between March 2007 and March 2011, among 112 patients who underwent permanent brachytherapy with 125I, 60 image scans of 56 patients who underwent preplan CT (pCT) or preplan MRI (pMRI) within 2 months before brachytherapy were retrospectively reviewed. Twenty-four cases among 30 cases with pCT and 26 cases among 30 cases with pMRI received neoadjuvant hormone therapy (NHT). In 34 cases, NHT started after acquisition of preplan image. The median duration of NHT after preplan image acquisition was 17 and 21 days for cases with pCT and pMRI, respectively. The prostate volume calculated by different modalities was compared. And retrospective planning with iTRUS image was performed to estimate the number of 125I seed required to obtain recommended dose distribution according to prostate volume.
The mean difference in prostate volume was 9.05 mL between the pCT and iTRUS and 6.84 mL between the pMRI and iTRUS. The prostate volume was roughly overestimated by 1.36 times with pCT and by 1.33 times with pMRI. For 34 cases which received NHT after image acquisition, the prostate volume was roughly overestimated by 1.45 times with pCT and by 1.37 times with pMRI. A statistically significant difference was found between preplan image-based volume and iTRUS-based volume (p < 0.001). The median number of wasted seeds is approximately 13, when the pCT or pMRI volume was accepted without modification to assess the required number of seeds for brachytherapy.
pCT-based volume and pMRI-based volume tended to overestimate prostate volume in comparison to iTRUS-based volume. To reduce wasted seeds and cost of the brachytherapy, we should take the volume discrepancy into account when we estimate the number of 125I seeds for permanent brachytherapy.
Brachytherapy; Prostate cancer; Prostate volume
Background and Purpose
To evaluate the proximity, variance, predictors of dose, and complications to the sigmoid in cervical-cancer brachytherapy using 3D planning.
Materials and Methods
Over 36 months, 50 patients were treated for cervical cancer with either low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy. The distance from the central tandem to the sigmoid, the D0.1cc and the D2cc to the sigmoid, rectum and bladder doses, and toxicity were analyzed.
The median sigmoid EQD2 D0.1cc and D2cc were 84 Gy and 68.3 Gy for HDR versus 71.1 Gy and 65.9 Gy for LDR (p=0.02 and 0.98, respectively). Twenty percent of the HDR fractions required manipulation of the superior dwell positions to decrease the sigmoid dose. The median distance from the sigmoid to the tandem was 1.7 cm (range [rg], 0.1 – 6.16 cm) for HDR and 2.7 cm (rg, 1.17 – 4.52 cm) for LDR; from the sigmoid to the 100% isodose region the median distances were – 0.1 cm (rg, -1.4 – 2.5 cm) and 0.44 cm (rg. -0.73 – 5.2 cm), respectively. The proximity of the sigmoid to the tandem is significantly related to sigmoid dose (p<0.0001). Within-patient (among-fraction) variation in sigmoid-to-tandem distance during HDR was substantial (coefficient of variation = 40%). No grade 3-4 sigmoid toxicity was seen after a median 31-month follow-up period.
3D imaging in cervical cancer brachytherapy shows the sigmoid in close proximity to the tandem. The sigmoid to tandem distance varies substantially between fractions, indicating the importance of sigmoid dose-volume evaluation with each fraction.
cervical cancer; brachytherapy; normal tissue dose
To investigate the possibility of localization of intraprostatic lesions (IL) with contrast-enhanced ultrasound (CEUS) to support the brachytherapy treatment planning of temporary implants.
Material and methods
Two brachytherapy treatment plans were generated for 8 patients treated with external beam radiotherapy and pulsed-dose rate brachytherapy boost for prostate cancer. The first and second brachytherapy treatment plan was without and with knowledge of the localization of the ILs, respectively. Pairwise comparison was performed on prostate, rectum, and urethra dose-volume parameters and total reference air kerma (TRAK)-values.
Coverage of the ILs by the 140% isodose was increased from mean 66.0-67.7% for the standard plan to mean 92.5-95.7% for the adapted plan. The mean D90 of the ILs increased from 1.49-1.57 Gy/pulse to 1.76-1.81 Gy/pulse. Dose-volume parameters for the prostate, rectum, and urethra and the TRAK did not change.
CEUS technique is a promising method for IL localization to aid in brachytherapy treatment planning. Dose coverage on the IL could be improved without any increase of dose in organs at risk.
contrast-media; ultrasonography; image-processing; brachytherapy planning; prostate
Prostate cancer, due to wide availability of PSA tests, is very often diagnosed in early stage, nowadays. This makes management of this disease even harder in every day oncology care. There is a wide range of treatment options including surgery, radiotherapy and active surveillance, but essential question is which treatment patient and oncologist should decide for. Due to recent publication of Prostate Cancer Results Study Group, in which brachytherapy is one of supreme curative options for prostate cancer, we decided to overview most present european and north american recommendations. National Comprehensive Cancer Network, American Society for Radiation Oncology, American Brachytherapy Society, European Association of Urology and Groupe Européen de Curiethérapie of European Society for Therapeutic Radiation Oncology guidelines are overviewed, particularly focusing on HDR and LDR brachytherapy.
temporary implant; permanent seeds; dose prescription; dose constrains; follow-up
To determine whether higher intensity of prostate-specific antigen (PSA) surveillance was associated with earlier detection of biochemical recurrence (BCR) or survival.
Patients and Methods
We identified a population-based cohort of 832 men diagnosed with nonmetastatic prostate cancer between January 1, 1995, and July 31, 2006. These men were treated with radical prostatectomy (RP), brachytherapy or external beam radiation therapy (RT), or primary androgen deprivation therapy or chose watchful waiting. To test the associations of intensity in PSA surveillance with study outcomes, we used a 2-year landmark analysis to assess whether the number of PSA tests during the first 2 years after treatment was associated with earlier detection of BCR, prostate cancer–related mortality, and all-cause mortality. We used landmark analysis to assess the association of PSA intensity, adjusting for clinicopathologic covariate, with outcome.
Median follow-up time for the entire cohort was 6.7 years. Higher Gleason score was the only clinicopathologic variable associated with higher PSA frequency in multivariable analysis for both the RP and RT groups (P value of .001 and .05, respectively). After adjustment for other covariates, the frequency of PSA tests during the first 2 years after RP did not increase the ability to detect BCR (hazard ratio, 1.00; 95% confidence interval, 0.84-1.19) or all-cause mortality (hazard ratio, 0.95; 95% confidence interval, 0.70-1.30) in the landmark analysis.
Higher intensity of PSA surveillance during the 2 years after RP or RT did not improve earlier detection of BCR or survival. Evidence-based guidelines for PSA surveillance after primary treatment are needed.
ACM, all-cause mortality; ADT, androgen deprivation therapy; BCR, biochemical recurrence; HR, hazard ratio; PCSM, prostate cancer–specific mortality; PSA, prostatic-specific antigen; RP, radical prostatectomy; RT, radiation therapy; WW, watchful waiting
The aim was to identify preimplant factors affecting postimplant prostate volume and the increase in prostate volume after transperineal interstitial prostate brachytherapy with 125I free seeds.
We reviewed the records of 180 patients who underwent prostate brachytherapy with 125I free seeds for clinical T1/T2 prostate cancer. Eighty-one (45%) of the 180 patients underwent neoadjuvant hormonal therapy. No patient received supplemental external beam radiotherapy. Postimplant computed tomography was undertaken, and postimplant dosimetric analysis was performed. Univariate and multivariate analyses were performed to identify preimplant factors affecting postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.
Preimplant prostate volume by transrectal ultrasound, serum prostate-specific antigen, number of needles, and number of seeds implanted were significantly correlated with postimplant prostate volume by computed tomography. The increase in prostate volume after implantation was significantly higher in patients with neoadjuvant hormonal therapy than in those without. Preimplant prostate volume by transrectal ultrasound, number of needles, and number of seeds implanted were significantly correlated with the increase in prostate volume after implantation. Stepwise multiple linear regression analysis showed that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy were significant independent factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.
The results of the present study show that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy are significant preimplant factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.