Salvage brachytherapy in combination with interstitial hyperthermia for locally recurrent prostate carcinoma following external beam radiation therapy: a prospective phase II study.

Optimal treatment for patients with only local prostate cancer recurrence after external beam radiation therapy (EBRT) failure remains unclear. Possible curative treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several single institution series proved that high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of patients with acceptable levels of genitourinary and gastrointestinal toxicity. A standard dose prescription and scheme have not been established yet, and the literature presents a wide range of fractionation protocols. Furthermore, hyperthermia has shown the potential to enhance the efficacy of re-irradiation. Consequently, a prospective trial is urgently needed to attain clear structured prospective data regarding the efficacy of salvage brachytherapy with adjuvant hyperthermia for locally recurrent prostate cancer. The purpose of this report is to introduce a new prospective phase II trial that would meet this need. The primary aim of this prospective phase II study combining Iridium-192 brachytherapy with interstitial hyperthermia (IHT) is to analyze toxicity of the combined treatment; a secondary aim is to define the efficacy (bNED, DFS, OS) of salvage brachytherapy. The dose prescribed to PTV will be 30 Gy in 3 fractions for HDRBT, and 60 Gy in 2 fractions for PDRBT. During IHT, the prostate will be heated to the range of 40-47°C for 60 minutes prior to brachytherapy dose delivery. The protocol plans for treatment of 77 patients

What do we know about the α/β for prostate cancer?

Since last decade, the debate on the parameter which reflects prostate cancer sensitivity to fractionation in a radiotherapy treatment, the α/β, has become extensive. Unlike most tumors, the low labeling indices (LI) and large potential doubling time that characterize the prostate tumor led some authors to consider that it may behave as a late responding tissue. So far, the existing studies with regard to this subject point to a low value of α/β, around 2.7 Gy, which may be considered as a therapeutic gain in relation to surrounding normal tissues by using fewer and larger fractions. The aim of this paper is to review several estimates that have been made in the last few years regarding the prostate cancer α/β both from clinical and experimental data, as well as the set of factors that have potentially influenced these evaluations

Comparisons of oncological and functional outcomes among radical retropubic prostatectomy, high dose rate brachytherapy, cryoablation and high-intensity focused ultrasound for localized prostate cancer

PURPOSE: To conduct a retrospective, single institutional and comparative study for radical retropubic prostatectomy (RRP), high dose rate brachytherapy (HDRBT), cryoablation and high-intensity focused ultrasound (HIFU) in localized prostate cancer with respect to oncological and functional outcomes. METHODS: We reviewed 97, 161, 114 and 120 patients of RRP, HDRBT, cryoablation and HIFU respectively for localized prostate cancer from May 2008 to December 2013. PSA biochemical recurrence, salvage treatment-free rate, metastasis-free rate, and biochemical recurrence-free survival were analyzed for oncological outcomes. Functional outcomes included complications and serial IIEF-5 scores, IPSS and related QoL scores. RESULTS: During nearly 3 years of follow-up, the patients of HDRBT experienced higher PSA biochemical recurrence rate overall (54.7%), as well as D’Amico intermediate-risk (34.4%) and high-risk (61.8%) groups, lower salvage treatment-free rate (46.7%), and metastasis-free rate (90.7%). Besides, the patients of RRP demonstrated higher urethral stricture (29.9%) and urinary incontinence (11.3%). The patients of HIFU revealed lower de novo erectile dysfunction rate at 1 year (65.6%), higher serial IIEF-5 scores, lower IPSS and related QoL scores. CONCLUSIONS: The patients of HDRBT demonstrated worse oncological outcomes in D’Amico intermediate and high-risk groups. Besides, the patients of RRP had more complications rate in urethral stricture and urinary incontinence. Moreover, the patients of HIFU experienced better urinary function improvement and more possible sexual function preservation. In consideration of trifecta, HIFU may provide equivalent cancer control and better quality of life for patients of localized prostate cancer

Comparisons of oncological and functional outcomes among radical retropubic prostatectomy, high dose rate brachytherapy, cryoablation and high-intensity focused ultrasound for localized prostate cancer: A prospective, controlled, nonrandomized trial

Background: Several clinical decision rules (CDRs) are available to exclude acute pulmonary embolism (PE), but they have not been directly compared. Objective: To directly compare the performance of 4 CDRs (Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score) in combination with D-dimer testing to exclude PE. Design: Prospective cohort study. Setting: 7 hospitals in the Netherlands. Patients: 807 consecutive patients with suspected acute PE. Intervention: The clinical probability of PE was assessed by using a computer program that calculated all CDRs and indicated the next diagnostic step. Results of the CDRs and D-dimer tests guided clinical care. Measurements: Results of the CDRs were compared with the prevalence of PE identified by computed tomography or venous thromboembolism at 3-month follow-up. Results: Prevalence of PE was 23%. The proportion of patients categorized as PE-unlikely ranged from 62% (simplified Wells rule) to 72% (Wells rule). Combined with a normal D-dimer result, the CDRs excluded PE in 22% to 24% of patients. The total failure rates of the CDR and D-dimer combinations were similar (1 failure, 0.5% to 0.6% [upper-limit 95% CI, 2.9% to 3.1%]). Even though 30% of patients had discordant CDR outcomes, PE was not detected in any patient with discordant CDRs and a normal D-dimer result. Limitation: Management was based on a combination of decision rules and D-dimer testing rather than only 1 CDR combined with D-dimer testing. Conclusion: All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal D-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice. Primary Funding Source: Academic Medical Center, VU University Medical Center, Rijnstate Hospital, Leiden University Medical Center, Maastricht University Medical Center, Erasmus Medical Center, and Maasstad Hospital. © 2011 American College of Physicians

EBRT And HDRBT in Rectal Cancer Patients Who Are Medically Unfit Or Refuse Surgery

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Image-guided high-dose-rate brachytherapy: preliminary outcomes and toxicity of a joint interventional radiology and radiation oncology technique for achieving local control in challenging cases.

PurposeTo determine the ability of image-guided high-dose-rate brachytherapy (IG-HDR) to provide local control (LC) of lesions in non-traditional locations for patients with heavily pre-treated malignancies.Material and methodsThis retrospective series included 18 patients treated between 2012 and 2014 with IG-HDR, either in combination with external beam radiotherapy (EBRT; n = 9) or as monotherapy (n = 9). Lesions were located in the pelvis (n = 5), extremity (n = 2), abdomen/retroperitoneum (n = 9), and head/neck (n = 2). All cases were performed in conjunction between interventional radiology and radiation oncology. Toxicity was graded based on CTCAE v4.0 and local failure was determined by RECIST criteria. Kaplan-Meier analysis was performed for LC and overall survival.ResultsThe median follow-up was 11.9 months. Two patients had localized disease at presentation; the remainder had recurrent and/or metastatic disease. Seven patients had prior EBRT, with a median equivalent dose in 2 Gy fractions (EQD2) of 47.0 Gy. The median total EQD2s were 34 Gy and 60.9 Gy for patients treated with monotherapy or combination therapy, respectively. Image-guided high-dose rate brachytherapy was delivered in one to six fractions. Six patients had local failures at a median interval of 5.27 months with a one-year LC rate of 59.3% and a one-year overall survival of 40.7%. Six patients died from their disease at a median interval of 6.85 months from the end of treatment. There were no grade ≥ 3 acute toxicities but two patients had serious long term toxicities.ConclusionsWe demonstrate a good one year LC rate of nearly 60%, and a favorable toxicity profile when utilizing IG-HDR to deliver high doses of radiation with high precision into targets not readily accessible by other forms of local therapy. These preliminary results suggest that further studies utilizing this approach may be considered for patients with difficult to access lesions that require LC

High-dose-rate brachytherapy boost in prostate cancer: clinical outcomes, late rectal toxicity and uncertainties in organ at risk delineation

Prostate cancer is one of the most commonly diagnosed cancers in the developed world, having caused 293,000 deaths in 2013 (Global Burden of Disease Cancer, et al., 2013). According to the Spanish Network of Cancer Registries (REDECAN), 33,370 new cases were diagnosed in 2015 in Spain. In 2014, prostate cancer was ranked fifth in terms of cancer deaths among Spanish men (Instituto de Salud Carlos III, 2014). High-risk prostate cancer is an aggressive form of the disease with a higher risk of distant metastasis and mortality. This classification represents a significant portion of the nearly 28,000 prostate cancer deaths per year in the United States and the 5,855 deaths in Spain (American Cancer Society 2015; Instituto de Salud Carlos III, 2014). There are different treatment options for locally advanced prostate cancer, such as active surveillance, radical prostatectomy, and radiotherapy. The use of radiotherapy in the radical treatment of intermediate- and high-risk prostate cancer has been well studied in several prospective randomized trials (Zelefsky et al., 2008; Coen et al., 2002). This option can be administered through EBRT, BT, and either HDRBT or LDRBT given alone or combined with EBRT. HDRBT is a brachytherapy technique, and when combined with EBRT, it allows for dose escalation, administration of the complete dose to the target (the prostate), and minimisation of the dose received by the surrounding normal tissues. Current international treatment guidelines recommend the use of HDRBT combined with EBRT, which is also known as “HDRBT boost”. According to the ABS, GEC/ESTRO, and ESTRO/EUA/EORTC, this treatment modality improves local control compared with monotherapy, as well as the outcomes in certain patients with intermediate- and high-risk disease (Zaorsky et al., 2017). There are no specific recommendations about the best dose fractionation scheme for HDRBT boost. Several studies have reported various treatment schemes, which has made it difficult to compare the results of acute and late toxicity. In recent years, there has been a transition in the number of fractions delivered. Initially, as many as four boost fractions were used, but currently, the evidence supports large boost fractions with a single HDRBT boost (Morton et al., 2013). This trend has been accompanied by important biological effects, as well as practical and cost-saving advantages. Furthermore, virtually all-geometric uncertainty is eliminated, as there is no risk of inter-fraction variability. For these reasons, there has been much interest in this technique, which has also been adopted by several centres for high-risk patients. This thesis is motivated by the need for clinical outcomes, including improvements in prevention and decrease of rectal toxicity. The purpose of this thesis was threefold. Firstly, to determine the clinical outcomes of a cohort of patients diagnosed with prostate cancer and treated with HDRBT boost using real-time TRUS based planning in combination with EBRT (see Chapter IV, Paper I). Secondly, determining the occurrence of late rectal toxicity in our patients’ cohort and evaluating its potential relationship with D2cc parameter. This was based in the rectal constraint recommended by GEC/ESTRO, given the absence of another rectal dose constraints from similar studies of HDRBT combined with EBRT for prostate cancer (see Chapter IV, Paper I). Thirdly, we proposed to evaluate the D 2cc robustness in HDRBT for prostate cancer using the interobserver variability in the rectum contouring. A first pilot study was performed with a limited number of patients and physicians of the same center (see Chapter IV, Paper II). Lastly, in order to evaluate the outcomes from the pilot study, a multicentre prospective study was performed (see Chapter IV, Paper III). Below is a summary of the information contained in each of the papers of this thesis. Chapter I provides a summary describing the findings of the research that were carried out by the doctoral candidate. Chapter II provides a general introduction and justification of the thesis. Chapter III contains the general aim, specific objectives and the study design of the thesis. In Chapter IV (Paper I), we review our institution´s experience with HDRBT boost for localized prostate cancer. The first purpose of this study was to analyse the clinical outcomes, particularly local control, overall survival, and late rectal toxicity. The second purpose was to determine the significance of dose-volume histogram parameters for predicting LRT after single-fraction HDRBT boost and EBRT in prostate cancer patients. A cohort of 300 patients diagnosed with locally advanced prostate cancer and treated with HDRBT boost plus EBRT were followed prospectively. The patient data were used for both purposes. The treatment comprised a single-fraction HDRBT boost of 15 Gy plus EBRT ...MedicinaCiencias de la Salu

Postoperative endometrial cancer treatments with electronic brachytherapy source

Purpose This study is a dosimetric and acute toxicity comparison of endometrial cancer patients treated with either Axxent (Xoft, Inc., San José, CA, USA) electronic and interstitial brachytherapy versus interstitial high dose rate brachytherapy (HDRBT). Materials and Methods Between 2015 and 2017, 94 patients with postoperative endometrial cancer were treated in our centre with the Axxent electronic brachytherapy (eBT) system. The V 150 and V 200 are evaluated prospectively for each plan. The mean age of patients was 65.9 years (age range 33-84 years), with different tumour staging. Of the 94 patients, 37 received exclusive adjuvant brachytherapy (25 Gy in five sessions); the remaining patients received external beam radiotherapy (EBRT) with a regimen of 23 sessions of 2 Gy each to the entire pelvis, followed by eBT (15 Gy in three sessions). Additionally, the absorbed doses received by the organs at risk (OAR), urinary bladder, rectum and sigmoid colon were compared with HDRBT plans, evaluating D 2cc, V 50% and V 35%. Median follow-up was done for each of the 94 patients to assess the toxicity of the treatment: vaginal mucosa toxicity, rectal and urinary toxicity; and results are presented for acute toxicity, toxicity at 1 month after the end of treatment and follow-up after 12 months for a portion of patients according to the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Results The doses in OAR for eBT plans were lower than that for HDRBT plans, both Ir-192 and Co-60 plans, whose doses were similar. The dose in bladder with eBT was 63.8% of the prescribed dose for D 2cc versus 70.1% for HDRBT Ir-192, for V 50% was 7.2% versus 12.7% and for V 35% was 15.2% versus 28.2%. In rectum the D 2cc was 61.2% versus 68.4%, for V 50% was 7.9% versus 14.3% and for V 35% was 16.7% versus 32%. Results demonstrated lower doses to OAR in all eBT plans. Acute toxicity in eBT was very low in cases of mucositis, with only one case of toxicity greater than grade 1, rectal toxicity and urinary toxicity; results at 1 month are equally good, toxicity symptoms disappeared and no relapses have occurred to date. Conclusions The results of treatment with the Axxent eBT unit for 94 patients are very good, as no recurrence has been observed and the toxicity of the treatment is very low. The increase in V 150 and V 200 has not produced an increase in vaginal mucosa toxicity, and the doses in the OAR are lower than in the plans implemented for HDRBT with Ir-192 or Co-60. eBT is a good alternative to treat endometrial cancer in centres without conventional HDR availability. To date, there are limited published studies reporting on outcomes from patients treated with eBT

Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma

cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease. During the last decade, locoregional therapies usually performed by interventional radiologists and its established role in HCC treatment have gained an increasing role in CCA treatment as well. These comprise a wide range of options from tumor ablation procedures such as radiofrequency ablation (RFA), microwave ablation (MWA), computed tomography high-dose rate brachytherapy (CT-HDRBT), and cryoablation to transarterial chemoembolization (TACE), including the option of intra-arterial administration of radioactive spheres (transarterial radioembolization-TARE), and much attention has focused on the potential of individual concepts in recent years. The purpose of this review is to provide an overview of current radiologic interventions for CCA (excluding options for eCCA), to review and appraise the existing literature on the topic, and to provide an outlook on whether such interventions may have a role as treatment for cHCC-CCA in the future

Hepatocellular carcinoma tumor thrombus entering the right atrium treated with combining percutaneous and intravenous high-dose-rate brachytherapy: a case report

The presented report describes a case of a Hepatocellular carcinoma (HCC) tumor thrombus (TT) infiltrating the inferior vena cava (IVC) and the right atrium (RA) in a 66-year old male patient who initially presented with TT related symptoms. CT-guided high-dose-rate brachytherapy (HDRBT) was performed for both, the intraparenchymal primary and the TT. A marked improvement of the tumor-related symptoms and shrinkage of the tumor mass were achieved six months after treatment initiation. The combination of intravascular and percutaneous HDRBT demonstrating a promising approach to palliate tumor-related symptoms in advanced HCC with macrovascular invasion