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1 A.C.R. and J.D.N. contributed equally to this work.
Affiliations
Department of Radiation Medicine, Northwell Health, Lake Success, New YorkDonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York
Department of Radiation Medicine, Northwell Health, Lake Success, New YorkDonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York
Department of Radiation Medicine, Northwell Health, Lake Success, New YorkDonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York
Intermediate- and high-risk prostate cancer patients undergoing combination external beam radiation therapy (EBRT) and low dose rate (LDR) brachytherapy have demonstrated increased genitourinary (GU) toxicity. We have previously demonstrated a method to combine EBRT and LDR dosimetry. In this work, we use this technique for a sample of patients with intermediate- and high-risk prostate cancer, correlate with clinical toxicity, and suggest preliminary summed organ-at-risk constraints for future investigation.
Methods and Materials
Intensity modulated EBRT and 103Pd-based LDR treatment plans were combined for 138 patients using biological effective dose (BED) and deformable image registration. GU and gastrointestinal (GI) toxicity were compared with combined dosimetry for the urethra, bladder, and rectum. Differences between doses in each toxicity grade were assessed by analysis of variance (α = 0.05). Combined dosimetric constraints are proposed using the mean organ-at-risk dose, subtracting 1 standard deviation for a conservative recommendation.
Results
The majority of our 138-patient cohort experienced grade 0 to 2 GU or GI toxicity. Six grade 3 toxicities were noted. Mean prostate BED D90 (± 1 standard deviation) was 165.5±11.1 Gy. Mean urethra BED D10 was 230.3±33.9 Gy. Mean bladder BED was 35.2±11.0 Gy. Mean rectum BED D2cc was 85.6±24.3 Gy. Significant dosimetric differences between toxicity grades were found for mean bladder BED, bladder D15, and rectum D50, but differences between individual means were not statistically significant. Given the low incidence of grade 3 GU and GI toxicity, we propose urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 <45 Gy as preliminary dose constraints for combined modality therapy.
Conclusions
We successfully applied our dose integration technique to a sample of patients with intermediate- and high-risk prostate cancer. Incidence of grade 3 toxicity was low, suggesting that combined doses observed in this study were safe. We suggest preliminary dose constraints as a conservative starting point to investigate and escalate prospectively in a future study.
Introduction
Prostate cancer is the most common form of cancer among men with nearly 270,000 cases estimated to be diagnosed in 2022.
Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.
The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.
Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
In 2016, Morris et al published the results from the Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) clinical trial comparing biochemical failure and survival for 398 patients with intermediate- and high-risk prostate cancer who received either dose-escalated EBRT to 78 Gy or EBRT with 125I brachytherapy boost.
Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT trial): An analysis of survival endpoints for a randomized trial comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost f.
Both groups received 12 months of androgen-deprivation therapy. While overall survival was the same, patients who received brachytherapy boost were half as likely to experience biochemical failure, with progression-free survival estimates of 89, 86, and 83% versus 84, 75, and 62% at 5, 7, and 9 years, respectively, for the brachytherapy boost and dose-escalated EBRT cohorts.
Though the ASCENDE-RT trial supported the efficacy of brachytherapy boost in combination with EBRT with respect to disease control, the trial also reported significant increases in grade 3 acute GU toxicity and grades 2 and 3 late GU toxicity for combined EBRT and LDR boost compared with dose-escalated EBRT alone.
ASCENDE-RT: An analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
In a separate publication, the authors also identified a significant drop in quality of life with respect to physical and urinary function for patients who received brachytherapy boost.
ASCENDE-RT: An analysis of health-related quality of life for a randomized trial comparing low-dose-rate brachytherapy boost with dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
Late genitourinary and gastrointestinal toxicity after magnetic resonance image-guided prostate brachytherapy with or without neoadjuvant external beam radiation therapy.
Outcomes and toxicities in patients with intermediate-risk prostate cancer treated with brachytherapy alone or brachytherapy and supplemental external beam radiation therapy.
Treatment outcomes and morbidity following definitive brachytherapy with or without external beam radiation for the treatment of localized prostate cancer: 20-year experience at Mount Sinai Medical Center.
What these studies, including ASCENDE-RT, have not examined in detail, however, is the relationship between total organ-at-risk dose (external beam and brachytherapy combined) and subsequent clinical toxicity.
Integrating dosimetry from EBRT and brachytherapy components is difficult because of the difference in biological effect and the lack of spatial registration between 3-dimensional (3D) dose distributions. Recently, we reported the feasibility of converting physical EBRT and LDR dose distributions to biologically effective dose (BED) and combining the dose distributions voxel-by-voxel using deformable image registration.
Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.
The purpose of the current work was to use our previously reported dose integration technique for a sample of patients with intermediate- and high-risk prostate cancer treated with combination therapy and correlate combined dosimetry with clinical toxicity. In this manuscript, we propose preliminary BED constraints for EBRT and brachytherapy boost treatment for intermediate- and high-risk prostate cancer.
Methods and Materials
Patient sample
We reviewed the charts of all patients with intermediate- and high-risk prostate cancer previously treated at our institution between 2012 and 2020 with combination EBRT and LDR brachytherapy boost. Patients were retrospectively included in the analysis if external beam and brachytherapy treatment planning Digital Imaging and Communications in Medicine data was accessible. These criteria yielded 138 patients, 76 of which had high-risk disease, 11 had favorable intermediate-risk disease, and 51 had unfavorable intermediate-risk disease. All patients received 45 Gy in 1.8 Gy fractions of intensity modulated radiation therapy (IMRT) delivered via multiple static fields or volumetric modulated arc therapy and 100 Gy 103Pd boost. External beam treatment plans were developed in either Pinnacle v.9.2 (Philips Healthcare, Best, Netherlands) or Eclipse v.13.15 (Varian Medical Systems, Palo Alto, CA). Brachytherapy seeds were implanted in a modified peripheral loading pattern under ultrasound guidance and Mick-based dynamic intraoperative technique.
Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.
Briefly, EBRT physical dose distributions were converted to BED voxel-by-voxel using the linear-quadratic model where n is the total number of fractions, d is the dose per fraction, α is the linear cell-kill component coefficient, and β is the quadratic cell-kill component coefficient.
Brachytherapy postimplant physical dose distributions were converted to BED using an in-house Matlab script based on the formalism developed by Dale et al, which used the linear quadratic model and reproduced in AAPM TG 137
AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137.
Where T1/2 is the radioisotope half-life, Tavg is the radioisotope average life, λ is the decay constant, μ is the time constant for sublethal damage repair, Tp is the population doubling time, Teff is the effective treatment time, and is the initial dose rate. Initial dose rate was approximated by the product of physical dose D, and the decay constant λ generalized for each voxel i, j, and k of the 3D dose distribution as per Eq 6.
The variable Teff is the effective treatment time of the implant which is the time point at which cell kill from the continuously decreasing dose rate equals cell repopulation. Values for constants α, β, µ, and Tp for equations 1 to 5 are shown in Table 1. Values for prostate were taken from AAPM TG 137, and values for urethra, rectum, bladder, and unspecified tissue were taken from Pritz et al.
AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137.
AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137.
External beam and brachytherapy BED distributions for the 138 patients were registered either through b-spline deformable image registration (if prostate seed implant occurred after EBRT) or direct Digital Imaging and Communications in Medicine coordinate alignment (if prostate seed implant occurred before EBRT, in which case the postimplant CT and EBRT CT simulation were performed at the same imaging session and were inherently registered). Postimplant CTs were registered to the EBRT CT simulation which served as the “reference” image set. Dose grids were interpolated to the resolution of the EBRT CT simulation (0.97 × 0.97 × 2 mm3) and summed voxel-by-voxel to create a single composite BED distribution. Image registration and dose summation was performed using Velocity version 4.0 (Varian Medical Systems).
Evaluation of toxicity
Acute toxicity was defined as <6 months and chronic toxicity as >6 months. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicity were retrospectively collected and evaluated using Common Terminology Criteria for Advanced Events (CTCAE) Version 4.0 scoring, an internationally standardized system of definitions for identifying and grading adverse events experienced by patients with cancer on treatment. It includes 790 distinct adverse events and grades which are assigned based on the potential effect of each toxicity on the clinical management, activities of daily living, medication discontinuation, and dose modifications for each patient.
Comparison of the NCI-CTCAE version 4.0 and version 3.0 in assessing chemoradiation-induced oral mucositis for locally advanced nasopharyngeal carcinoma.
The CTCAE scoring is a validated and reliable toxicity scoring system approved by the United States Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute and is a product of their collaborative efforts.
The following dosimetric parameters were extracted from the composite BED dose volume histograms: mean urethral dose, urethra D10, mean rectal dose, rectal D50, rectal D2cc, mean bladder dose, bladder D50, bladder D15, mean prostate dose, and prostate D90. Descriptive statistics for each organ-at-risk parameter were calculated and correlated with observed clinical toxicity grades. Statistically significant dose differences between toxicity grades were tested using analysis of variance and Tukey's honestly significant difference tests for individual mean differences (α= 0.05). Hypothesis testing was performed via VassarStats software.
The distribution of acute and chronic GU and GI toxicity is shown in Figure 1. Acute GU toxicity was recorded for 135 of 138 patients (97.8%), chronic GU toxicity was recorded for 134 of 138 patients (97.1%), and acute and chronic GI toxicity were recorded for 132 of 138 patients (95.6%). Nearly all patients in the sample demonstrated some form of acute GU toxicity, with the majority experiencing grade 1. Over two-thirds of patients experienced chronic GU toxicity, nearly half with grade 1. Rectal toxicity was much less common, with 81 and 91% demonstrating no acute or chronic rectal toxicity respectively. Only 5 grade 3 GU and 1 grade 3 GI toxicities were noted, and there were no grade 4 to 5 toxicities.
Figure 1Bar graph showing the distribution of recorded toxicity grades for each Common Terminology Criteria for Advanced Events (CTCAE) category.
Acute genitourinary (GU) data were not available for 3 patients. Chronic GU data were not available for 4 patients. Acute and chronic gastrointestinal (GI) data were not available for 6 patients each.
The combined BED distribution and composite dose-volume histogram for a single representative patient are shown in Figure 2. For the entire sample, mean prostate BED, and D90 (± 1 standard deviation) were 265.4±17.9 Gy and 165.5±11.1 Gy, respectively. Figure 3 illustrates prostate doses and outliers in a box and whisker plot with individual data points superimposed and outliers defined as doses more than 1.5 times the interquartile range away from the upper or lower quartile. Mean urethra BED and D10 were 181.8±22.7 Gy and 230.3±33.9 Gy respectively. Mean bladder BED, D50, and D15 were 35.2±11.0, 29.6±13.4, and 58.3±13.9 Gy, respectively. Mean rectum BED, D50, and D2cc were 32.7±7.6, 26.2±8.1, and 85.6±24.3 Gy, respectively. Figure 4, Figure 5, Figure 6 are box and whisker plots for each dosimetric parameter and each toxicity grade for urethra, bladder, and rectum. Analysis of variance revealed significant differences in mean dose between toxicity grades for 3 dosimetric parameters: Bladder mean (acute and chronic GU toxicity P = .05 and P = 0.03, respectively), bladder D15 (acute and chronic GU toxicity P = .02 and P = 0.03, respectively), and rectum D50 (chronic GI toxicity, P = .04). Tukey's honestly significant difference tests did not detect individual mean differences, indicating little correlation between organ dose and observed toxicity.
Figure 2Transverse computed tomography slice, composite dosimetry, and dose-volume histogram for a representative patient treated with combined modality therapy to the prostate.
Figure 3Box and whisker plots for mean prostate biological effective dose (BED) and D90. Plots illustrate the median, upper and lower quartiles, minimum and maximum values, and any outliers as defined by 1.5 times the intraquartile range. Statistical significance between toxicity grades was assessed using analysis of variance and Tukey's honestly significant difference tests (α = 0.05).
Figure 4Box and whisker plots for mean urethral biological effective dose (BED) and D10 versus Common Terminology Criteria for Advanced Events (CTCAE) toxicity grade (acute and chronic genitourinary [GU] toxicity).
Plots illustrate the median, upper and lower quartiles, minimum and maximum values, plus any outliers as defined by 1.5 times the intraquartile range. Statistical significance between toxicity grades was assessed using analysis of variance and Tukey's honestly significant difference tests (α = 0.05).
Figure 5Box and whisker plots for mean bladder biological effective dose (BED), D15, and D50 versus Common Terminology Criteria for Advanced Events (CTCAE) toxicity grade (acute and chronic genitourinary [GU] toxicity).
Plots illustrate the median, upper and lower quartiles, minimum and maximum values, plus any outliers as defined by 1.5 times the intraquartile range. Statistical significance between toxicity grades was assessed using analysis of variance and Tukey's honestly significant difference tests (α = 0.05).
Figure 6Box and whisker plots for mean rectum biological effective dose (BED), D50, and D2cc versus Common Terminology Criteria for Advanced Events (CTCAE) toxicity grade (acute and chronic gastrointestinal [GI] toxicity).
Plots illustrate the median, upper and lower quartiles, minimum and maximum values, plus any outliers as defined by 1.5 times the intraquartile range. Statistical significance between toxicity grades was assessed using analysis of variance and Tukey's honestly significant difference tests (α = 0.05).
Given the low incidence of grade 3 GU and GI toxicity, we propose the following BED constraints for combined modality therapy: urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 >45 Gy. These values were determined by the mean BED measured in our sample minus 1 standard deviation, serving as a conservative starting point to investigate and escalate prospectively in a future study.
Discussion
Combined modality radiation therapy is effective for intermediate- and high-risk prostate cancer, but accurate dosimetry between different modalities of radiation therapy remains elusive. Most studies that have examined toxicity associated with EBRT and LDR combined modality therapy have not attempted to correlate toxicity with dose received,
Preliminary toxicity and prostate-specific antigen response of a Phase I/II trial of neoadjuvant hormonal therapy, 103Pd brachytherapy, and three-dimensional conformal external beam irradiation in the treatment of locally advanced prostate cancer.
Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.
Previously, we developed a technique to spatially and biologically combine contributions of radiation dose from intensity modulated EBRT and LDR brachytherapy for patients with prostate cancer.
Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.
AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137.
spatially registered, and summed to generate composite dosimetry. In the current work, we used this technique to correlate combined BED received by a sample of patients with intermediate- and high-risk prostate cancer with toxicity to propose feasible combined BED dose constraints for pelvic organs at risk.
Though novel in prostate radiation therapy, there is precedent for combined modality dosimetric constraints in treatment of gynecologic malignancies.
Several studies have investigated the utility of deformable image registration and dose summation of external beam and brachytherapy dose contributions for cervical cancer.
Comparative analysis of image-guided adaptive interstitial brachytherapy and intensity-modulated arc therapy versus conventional treatment techniques in cervical cancer using biological dose summation.
Assessing cumulative dose distributions in combined external beam radiotherapy and intracavitary brachytherapy for cervical cancer by treatment planning based on deformable image registration.
Deformable image registration for cervical cancer brachytherapy dose accumulation: Organ at risk dose–volume histogram parameter reproducibility and anatomic position stability.
Appropriate methodology for EBRT and HDR intracavitary/interstitial brachytherapy dose composite and clinical plan evaluation for patients with cervical cancer.
Fewer studies have applied this technique to prostate cancer and fewer still to LDR boost. Fröhlich et al used deformable image registration to combine volumetric modulated arc therapy and high-dose rate (HDR) brachytherapy dose contributions for 25 patients with intermediate- and high-risk prostate cancer.
Biological dose summation of external beam radiotherapy for the whole breast and image-guided high-dose-rate interstitial brachytherapy boost in early-stage breast cancer.
The authors demonstrated superior BED of brachytherapy boost versus external beam boost but did not examine clinical toxicity. Moulton et al summed 4-field 3D conformal dose distributions with HDR for 118 patients with prostate cancer and found significant correlations between dose strata and GI toxicity such as rectal bleeding and stool frequency.
Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: Dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications.
Generation of composite dose and biological effective dose (BED) over multiple treatment modalities and multistage planning using deformable image registration.
Biological effective dose for comparison and combination of external beam and low-dose rate interstitial brachytherapy prostate cancer treatment plans.
Kikuchi et al combined 4-field 3D conformal dose distributions with 125I LDR seed implants for 37 patients with prostate cancer and correlated with rectal toxicity.
In this study, image registration was not required as the postimplant CT was used for external beam treatment planning. Similar to the current work, BED conversion was performed via the Dale/TG-137 formalism.
AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137.
The authors examined the relationship between several dosimetric parameters and rectal toxicity and, though the sample size was small, found V150 >1.2 cc was associated with incidence of grade 2 or 3 rectal toxicity. To our knowledge, the current work is the first to examine dosimetric integration of intensity modulated external beam and 103Pd-based LDR brachytherapy for prostate cancer with BED and deformable image registration. Given the sharp dose gradients caused by intensity modulation and the lower energy of 103Pd, accurate image registration is a vital precursor to accurate composite dosimetry. As demonstrated in our prior work, deformable image registration performed the best in both phantom and patient studies.
Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.
Registration artifacts can occur, however, in cases of extreme anatomic changes between external beam CT simulation and postimplant scanning or in the presence of significant high-density artifact.
While the ASCENDE-RT trial reported significant GU and GI events,
ASCENDE-RT: An analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
our 138-patient cohort yielded only 2 grade 3 acute GU toxicities (1.4%), 3 grade 3 late GU toxicities (2.2%), 0 grade 3 acute GI toxicities (0%), and 1 grade 3 late rectal toxicity (0.8%). Several studies have demonstrated similar findings, contradicting the results of ASCENDE-RT.
Treatment outcomes and morbidity following definitive brachytherapy with or without external beam radiation for the treatment of localized prostate cancer: 20-year experience at Mount Sinai Medical Center.
There was no correlation between urethral, bladder, or rectal dose with GU and GI toxicity grades, implying that the range of doses delivered to these organs at risk was reasonably safe and will not result in considerable dose-limiting toxicity. We therefore propose combined BED constraints equal to the mean values minus 1 standard deviation of the D10, D2cc, and D15 of the urethra, rectum, and bladder, respectively, as a conservative starting point to investigate and escalate prospectively in a future study.
These values are, of course, preliminary and serve as a starting point for further investigation and validation. Our study was a retrospective analysis on a relatively small sample. A larger sample may yield a stronger correlation between toxicity and total BED. We are currently designing a prospective study where the aforementioned dose constraints guide treatment planning by incorporating dose from one modality into the optimization of the other modality. Cao et al examined this motivation in a 2011 feasibility study where the authors used intensity modulated radiation therapy to fill in cold spots of an 125I LDR implant.
Reductions in prostatic doses are associated with less acute morbidity in patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for focal therapy.
Combining dosimetric contributions from intensity modulated EBRT and LDR brachytherapy is feasible. From the limited toxicities observed in our 138-patient sample, we suggest preliminary BED constraints of urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 <45 Gy for combined modality therapy of EBRT and 103Pd LDR brachytherapy. These constraints should be validated before clinical use and our future work is aimed at using these constraints to optimize external beam and brachytherapy treatment planning.
Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.
Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT trial): An analysis of survival endpoints for a randomized trial comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost f.
ASCENDE-RT: An analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
ASCENDE-RT: An analysis of health-related quality of life for a randomized trial comparing low-dose-rate brachytherapy boost with dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
Late genitourinary and gastrointestinal toxicity after magnetic resonance image-guided prostate brachytherapy with or without neoadjuvant external beam radiation therapy.
Outcomes and toxicities in patients with intermediate-risk prostate cancer treated with brachytherapy alone or brachytherapy and supplemental external beam radiation therapy.
Treatment outcomes and morbidity following definitive brachytherapy with or without external beam radiation for the treatment of localized prostate cancer: 20-year experience at Mount Sinai Medical Center.
Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.
AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137.
Comparison of the NCI-CTCAE version 4.0 and version 3.0 in assessing chemoradiation-induced oral mucositis for locally advanced nasopharyngeal carcinoma.
Preliminary toxicity and prostate-specific antigen response of a Phase I/II trial of neoadjuvant hormonal therapy, 103Pd brachytherapy, and three-dimensional conformal external beam irradiation in the treatment of locally advanced prostate cancer.
Comparative analysis of image-guided adaptive interstitial brachytherapy and intensity-modulated arc therapy versus conventional treatment techniques in cervical cancer using biological dose summation.
Assessing cumulative dose distributions in combined external beam radiotherapy and intracavitary brachytherapy for cervical cancer by treatment planning based on deformable image registration.
Deformable image registration for cervical cancer brachytherapy dose accumulation: Organ at risk dose–volume histogram parameter reproducibility and anatomic position stability.
Appropriate methodology for EBRT and HDR intracavitary/interstitial brachytherapy dose composite and clinical plan evaluation for patients with cervical cancer.
Biological dose summation of external beam radiotherapy for the whole breast and image-guided high-dose-rate interstitial brachytherapy boost in early-stage breast cancer.
Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: Dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications.
Generation of composite dose and biological effective dose (BED) over multiple treatment modalities and multistage planning using deformable image registration.
Biological effective dose for comparison and combination of external beam and low-dose rate interstitial brachytherapy prostate cancer treatment plans.
Reductions in prostatic doses are associated with less acute morbidity in patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for focal therapy.
From Nath et al (2009).
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