Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer

PurposeThe recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer.Methods and materialsA multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data.ResultsThe estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions.ConclusionsIMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.     

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone

PurposeHigh-dose-rate (HDR) brachytherapy boost is a treatment of intermediate- to high-risk prostate cancer, but long-term clinical outcome data are sparse. We report long-term survival and toxicity data in a cohort of patients treated in a single institution.MethodsBetween 1998 and 2004, 654 patients with localized prostate cancer received either 3-dimensional conformal radiotherapy (median 46 Gy) with an HDR (median 18 Gy in three fractions) boost (“3-D conformal radiotherapy [3DCRT] + HDR”; 215 patients) or 3DCRT alone (“3DCRT”; median 70 Gy; 439 patients) with curative intent. Men with National Comprehensive Cancer Network intermediate risk were offered neoadjuvant androgen deprivation and with high risk were also offered adjuvant androgen deprivation. Data collection included patient-reported outcome measures.ResultsThe 3DCRT + HDR group was older (72.3 vs. 68.9 yrs), had higher presenting PSAs (iPSA) (15.66 and 12.57 ng/mL, respectively), higher proportion of Gleason scores >7 (15.3% vs. 12.4%), and higher proportions of extracapsular disease (29.3% vs. 25.5%). 3DCRT + HDR men had lower proportions of low-risk patients (3.3% vs. 19.4%) and higher proportions of high-risk patients (50.7% vs. 37.4%) than the 3DCRT group. The 5-, 10-, and 15-year overall survival was superior at 92%, 81%, and 67%, respectively, for the 3DCRT + HDR group, compared with 88%, 71%, and 53%, respectively, in the 3DCRT group (p < 0.001). The 5-, 10-, and 15-year cause specific survival also favored the HDR boost group with survival of 96%, 93%, and 87% (3DCRT + HDR) and 95% 88% and 79% (3DCRT), respectively (p < 0.037).ConclusionsHDR brachytherapy boost in conjunction with 3DCRT offered superior overall survival and cause-specific survival in our patient population.     

Interstitial brachytherapy as boost for locally advanced T4 head and neck cancer

PurposeLocally advanced squamous cell cancers of the head and neck (SCCHN) with bone and cartilage invasion (BCI) or those with soft-tissue invasion (STI) have been treated with resection followedup with chemoradiotherapy (CRT) or definitive CRT. However, locoregional recurrence remained a large component of treatment failure. High-dose-rate interstitial brachytherapy (BT) has been used for dose escalation to further prevent local relapse. This is a review of our experience.Methods and MaterialsT4N0-3M0 locally advanced oral cavity and oropharyngeal squamous cell carcinoma (SCCA) patients underwent definitive CRT or radiotherapy (RT) followedup with brachytherapy (BT). RT doses ranged from 45 to 50.4 Gy. The patients were reassessed at this dose and if response was inadequate, patients underwent BT. BT doses ranged from 24 to 30 Gy at 3–4 Gy per fraction BID with 6 h in between fractions. Concurrent chemotherapy was platinum based.ResultsTwenty patients were treated with CRT or RT alone followed by BT. Thirteen patients had STI and 7 had BCI; 14 patients were treated with CRT followed by BT; and 6 patients were treated with RT alone followed by BT. Five-year locoregional control was 61%. Five-year overall survival was 29%. When we excluded the patients treated with RT alone, 5-year overall survival was 36%. Nodal status was the only prognostic factor.ConclusionsThis study suggests CRT followedup with BT for patients with T4 locally advanced SCCHN of the oral cavity, and oropharynx is a feasible treatment option. In patients with poor response to CRT, BT may be used for dose escalation to increase locoregional control.     

External beam radiotherapy plus high-dose-rate brachytherapy for treatment of locally advanced prostate cancer: The initial experience of the Catalan Institute of Oncology

PurposeThe objective of this study was to report initial outcomes in patients with locally advanced prostate cancer (CaP) who underwent external beam radiation therapy (EBRT) treatment combined with high-dose-rate brachytherapy (HDR-BT) as a boost.Methods and MaterialsFrom 2002 to 2007, 114 CaP patients underwent EBRT followed by ¹⁹²I HDR-BT. The patients were classified into intermediate- (Group 1) or high- (Group 2) risk groups. The mean total EBRT dose was 60.0 Gy (95% confidence interval [CI]: 59.9–60.1) at 2 Gy per fraction. After a mean of 20.6 days (95% CI: 18.4–22.8), all the patients received a single-fraction 9-Gy dose of HDR-BT boost. Of the 114 patients in the study, 103 (90.4%) underwent up to 3 years of complete androgen deprivation therapy after diagnosis.ResultsThe mean followup for the entire group was 32.1 months (95% CI: 29.9–34.4). The 4-year biochemical failure-free survival rate was 97.4% and treatment was well-tolerated.ConclusionsPreliminary biochemical control rates after EBRT plus one fraction of 9-Gy HDR-BT are encouraging. This atypical fractionation schedule is cost-effective and reduces patient discomfort and treatment-related risks. More followup is required to confirm these findings.     

Radiobiological optimization comparison between pulse-dose-rate and high-dose-rate brachytherapy in patients with locally advanced cervical cancer

PurposeOnly scarce data are available on the possibility to include radiobiological optimization as part of the dosimetric process in cervical cancer treated with brachytherapy (BT). We compared dosimetric outcomes of pulse-dose-rate (PDR) and high-dose-rate (HDR)-BT, according to linear-quadratic model.Methods and MaterialsThree-dimensional dosimetric data of 10 consecutive patients with cervical cancer undergoing intracavitary image-guided adaptive PDR-BT after external beam radiation therapy were examined. A new HDR plan was generated for each patient using the same method as for the PDR plan. The procedure was intended to achieve the same D₉₀ high-risk clinical target volume with HDR as with PDR planning after conversion into dose equivalent per 2 Gy fractions (EQD2) following linear-quadratic model. Plans were compared for dosimetric variables.ResultsAs per study's methodology, the D₉₀ high-risk clinical target volume was strictly identical between PDR and HDR plans: 91.0 Gy (interquartile: 86.0–94.6 Gy). The median D₉₈ intermediate-risk clinical target volume was 62.9 Gy_EQD2 with HDR vs. 65.0 Gy_EQD2 with PDR (p < 0.001). The median bladder D_2cc was 65.6 Gy_EQD2 with HDR, vs. 62 Gy_EQD2 with PDR (p = 0.004). Doses to the rectum, sigmoid, and small bowel were higher with HDR plans with a median D_2cc of 55.6 Gy_EQD2 (vs. 55.1 Gy_EQD2, p = 0.027), 67.2 Gy_EQD2 (vs. S 64.7 Gy_EQD2, p = 0.002), and 69.4 Gy_EQD2 (vs. 66.8 Gy_EQD2, p = 0.014), respectively. For organs at risk (OARs), the effect of radiobiological weighting depended on the dose delivered. When OARs BT contribution to D_2cc doses was <20 Gy_EQD2, both BT modalities were equivalent. OARs EQD2 doses were all higher with HDR when BT contribution to D_2cc was ≥20 Gy_EQD2.ConclusionBoth BT modalities provided satisfactory target volume coverage with a slightly higher value with the HDR technique for OARs D2_cc while intermediate-risk clinical target volume received higher dose in the PDR plan. The radiobiological benefit of PDR over HDR was predominant when BT contribution dose to OARs was >20 Gy.     

Palliative treatment by high-dose-rate intraluminal brachytherapy in patients with advanced esophageal cancer

PURPOSE: The aim of this work was to analyze the results of palliative HDR brachytherapy in patients with advanced esophageal cancer. METHODS AND MATERIALS: Ninety-one patients with unresectable, advanced esophageal cancer were treated palliatively by HDR brachytherapy. All patients received a total dose of 22.5 Gy in three fractions per week. Remissions of dysphagia and other clinical and radiological factors were assessed in the first month posttreatment, and then in the third, sixth, and twelfth months. The survival rate was compared with some chosen clinical factors using a log-rank test and the Kaplan-Meier method. RESULTS: The median survival time among all patients was 8.2 months. The median survival time according to the obtained remission was 14.6, 7.2, and 3.8 months (log-rank p = 00001, F Cox p = 0.00001) for complete remission (CR), partial remission (PR), and lack of remission (NR), respectively. A longer median survival time was observed when tumor size was less then 5 cm (12.1 months), than between 5 and 10 cm (7.8 months), or longer than 10 cm (6.4 months) (log-rank p = 0.002). Longer median survival times were observed in clinical stage II (14.1 months), compared with clinical stage III (7.7 months) and IV (7.2 months) (log-rank p = 0.01). Significant correlations were found between survival and the Karnofsky Performance Status, grade of dysphagia, and age. CONCLUSIONS: HDR brachytherapy for advanced esophageal cancer allowed for improvement of dysphagia in most patients. The complete or partial remission, the older age of patients, and the lower grade of dysphagia observed in first month posttreatment were the most important prognostic factors allowing for prolonged survival (confirmed by a multivariate analysis). In the univariate analysis, important prognostic factors for prolonged survival were: a higher Karnofsky Performance Status, a lower clinical stage and a small tumor size.     

Endoluminal high-dose-rate brachytherapy for locally recurrent or persistent esophageal cancer

PurposeManagement of locally recurrent or persistent esophageal cancer (EC) after standard chemoradiation is challenging. This study updates our experience of treating medically inoperable EC patients with endoluminal high-dose-rate brachytherapy (EHDRBT) including the patients treated with a novel multiballoon channel centering esophageal applicator.Methods and MaterialsThirty-three consecutive patients with early-stage primary (n = 7), posttreatment persistent (n = 7), and recurrent (n = 19) EC treated with EHDRBT at our institution were included. Median dose and treatment lengths were 14 Gy (range 10–17.5 Gy) and 6 cm (3.5–9.0 cm), respectively. Endoscopy and biopsy were performed 3 months after EHDRBT and then every 3–6 months thereafter.ResultsMedian followup was 17.4 months (range 5.0–88.3). Grade 1 and 2 toxicities were observed in 13 (44.8%) and 11 (37.9%) patients, respectively. Grade 3 toxicity (tracheoesophageal fistula) was observed in 1 patient who had previously received two courses of external beam radiotherapy as well as a stent insertion. Median overall survival (OS) for entire cohort was 20.9 months, and 1-year OS was 78%. Complete response was achieved in 58.6% of patients with median time to failure and 1-year disease-free survival of 10.3 months (range 5.4–28.2) and 27%, respectively.ConclusionsFor medically inoperable patients with early-stage primary or local posttreatment residual or recurrent EC, EHDRBT is a well-tolerated treatment option with minimal Grade ≥3 toxicity. Brachytherapy in our hands continues to be a safe treatment option. Although 58.6% of patients achieved a complete response and the OS of this cohort is relatively good, long-term local control and cure remains a challenge.     

Image-guided interstitial high-dose-rate brachytherapy for dose escalation in the radiotherapy treatment of locally advanced lung cancer: A single-institute experience

PurposeTo evaluate the clinical outcome after CT-guided interstitial high-dose-rate (HDR) brachytherapy for dose escalation in the radiotherapy treatment of inoperable locally advanced non–small-cell lung cancer (NSCLC).Methods and MaterialsFrom 2005 to 2015, 16 patients with unresectable NSCLC were treated. Median age was 65.7 years (range, 52–86). The median tumor volume was 95.3 cm³ (range, 20.0–2000.0). The median prescribed HDR was 15.0 Gy (range, 7.0–32.0) delivered in twice-daily fractions of 6.0–8.0 Gy in 4 patients and in once-daily fractions of 7.0–15.0 Gy in 12 patients, respectively.ResultsAfter a median followup of 12.5 months, median overall survival and local control was 12.9 and 24.9 months, respectively. The corresponding median overall survival and local control rates at 1, 2, and 3 years were 56.2%, 37.5%, and 12.5% as well as 68.9%, 57.4%, and 43%, respectively. Apart from one Grade 1 cough episode persisting for 1 week and one patient developing a minor hemopneumothorax requiring no postprocedural drainage, no other adverse events were recorded.ConclusionsCT-guided interstitial HDR brachytherapy is a safe modality for radiation dose escalation which may play a role in the definitive radiotherapy treatment of locally advanced NSCLC.     

Dosimetry of anal radiation in high-dose-rate brachytherapy for prostate cancer

PURPOSE: The objective of this study is to determine the radiation dose to the anus during brachytherapy using high-dose-rate Ir-192 sources. METHODS AND MATERIALS: Thermoluminescence dosimeters were used for measuring the dose to the distal part of the anus in 10 patients, and in a prostate phantom to measure the radiation dose during the transport of the radiation source. RESULTS: The measured dose to the anus in vivo was on average 0.85 Gy (range, 0.48-1.37 Gy) per treatment. The transport dose using 15 and 19 needles in the prostate phantom was 0.07 and 0.08 Gy, respectively. CONCLUSIONS: The dose delivered to the anus using high-dose-rate brachytherapy with Ir-192 sources is quite low. There is a contribution to the anal radiation dose during the transport of the Ir-192 source into the needles. However, in clinical practice when using 15-20 needles, the dose from transporting the Ir-192 source can be ignored.     

Needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer

PurposeTo introduce an effective ambulatory technique in high-dose-rate interstitial brachytherapy (HDR-ISBT) for prostate cancer, we investigated the displacement distance using our novel calculation method.Methods and MaterialsSixty-four patients treated with HDR-ISBT as monotherapy were examined. Of these, 4, 17, and 43 patients were administered treatment doses of 38 Gy (3 days), 49 Gy (4 days), and 54 Gy (5 days), respectively. For dose administration, we used 776 flexible applicators with a removable template (ambulatory technique).Using CT images, we calculated the relative coordinates of the metal markers and applicators. From these coordinates, to analyze displacement during treatment, we measured the distance between the tip of the needle applicator and the center of gravity of the markers along the average applicator vector.ResultsThe median displacement distance for all applicators was 7 mm (range, ?14 to 24), and that of each treatment schedule was 4, 6, and 9 mm for 38, 49, and 54 Gy, respectively. Of the 776 applicators, displacement of >10 mm was seen in 198 (26%) applicators and >15 mm in 57 (7%) applicators.Body height (p < 0.0001) and anticoagulant usage (p < 0.0001) were significant factors influencing displacement.ConclusionsWe investigated needle applicator displacement using our unique method. Additional cranial margins are necessary if there is no repositioning of the dwell position. CT scanning should be performed daily during treatment for checking the position of the applicator to detect and rectify the issue of displacement.     

The impact of body mass index on rectal dose in locally advanced cervical cancer treated with high-dose-rate brachytherapy

PurposeThe impact of body mass index (BMI) on rectal dose in brachytherapy for cervical cancer is unknown. We assessed the association of BMI on rectal dose and lower gastrointestinal (GI) toxicity.Methods and MaterialsBetween 2007 and 2010, 51 patients with 97 brachytherapy planning images were reviewed. Volumetric measurements of the maximum percentage, mean percentage, dose to 2cc (D2cc), and dose to 1cc (D1cc) of the rectum, and the Internal Commission on Radiation Units and Measurement (ICRU) rectal point were recorded. Linear mixed effect models, analysis of variance, and regression analyses were used to determine the correlation between multiple observations or to detect a difference in the mean. The GI acute and late toxicity were prospectively recorded and retrospectively analyzed.ResultsThe average BMI (kg/m²) was 27.7 with a range of 17.4–46.6. Among the patients, 8% were morbidly obese, 25% obese, 25% overweight, 40% normal weight, and 2% underweight. The mean D1cc, D2cc, mean rectal dose (%), maximum rectal dose (%), and ICRU rectum was 3.03 Gy, 2.78 Gy, 20%, 60%, and 2.99 Gy, respectively. On multivariate analysis, there was a significant decrease in the D1cc and D2cc rectal dose (p = 0.016), ICRU rectal point dose (p = 0.022), and mean rectal dose percentage (p = 0.021) with an increase in BMI. There was, however, no statistically significant relationship between BMI and GI toxicity.ConclusionsObesity decreases the rectal dose given in high-dose-rate brachytherapy for locally advanced cervical cancer because of an increase in fatty tissue in the recto-uterine space. There is no significant correlation between BMI and acute or late GI toxicity.     

Dosimetry modeling for focal high-dose-rate prostate brachytherapy

PurposeThe dosimetry of focal high-dose-rate prostate brachytherapy was assessed. Dose volume histogram parameters, robustness to source position errors, and Monte Carlo (MC) simulations were compared for whole-gland (WG), hemi-gland (HEMI), and ultra-focal (UF) treatment plans.Methods and MaterialsTumor volumes were delineated based on MRI and template biopsy results for 9 patients. WG, HEMI, and UF plans were produced assuming 19 Gy single fraction monotherapy treatments. For UF plans, a 6-mm margin was applied to the visible tumor to create a focal-planning target volume (F-PTV). Systematic source position shifts of 1–4 mm were applied to assess plan robustness. The dosimetric impact of steel catheters was assessed using MC simulation.ResultsMean D₉₀ and V₁₀₀ were 20.4 Gy and 97.9% for prostate in WG plans, 22.2 Gy and 98.1% for hemi-prostate in HEMI plans, and 23.0 Gy and 98.2% for F-PTV in UF plans. Mean urethra D₁₀ was 20.3, 19.7, and 9.2 Gy in WG, HEMI, and UF plans, respectively. Mean rectal D_2cc was 12.5, 9.8, and 4.6 Gy in WG, HEMI, and UF plans, respectively. Focal treatment plans were sensitive to source position errors—2 mm systematic shifts reduced mean prostate D₉₀ by 0.7%, hemi-prostate D₉₀ by 2.6%, and F-PTV D₉₀ by 8.3% in WG, HEMI, and UF plans, respectively. MC simulation results were similar for all plan types with most dose volume histogram parameters reduced by <2%.ConclusionsHEMI and UF treatments can achieve higher D₉₀ values compared with WG treatments with reduced organ at risk dose. Focal treatments are more sensitive to systematic source position errors than WG treatments.