Publications by authors named "Ben G L Vanneste"

28 Publications

  • Page 1 of 1

Development of a Management Algorithm for Acute and Chronic Radiation Urethritis and Cystitis.

Urol Int 2021 Jun 15:1-12. Epub 2021 Jun 15.

Department of Urology, St. Antonius Hospital, Gronau, Germany.

Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm.

Material And Methods: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021.

Results: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae.

Conclusions: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.
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http://dx.doi.org/10.1159/000515716DOI Listing
June 2021

Early health economic analysis of 1.5 T MRI-guided radiotherapy for localized prostate cancer: Decision analytic modelling.

Radiother Oncol 2021 Jun 3;161:74-82. Epub 2021 Jun 3.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.

Background And Purpose: 1.5 Tesla magnetic resonance imaging radiotherapy linear accelerator (MR-Linac) is gaining interest for treatment of localized prostate cancer. Clinical evidence is lacking and it therefore remains uncertain whether MR-Linac is cost-effective. An early health economic analysis was performed to calculate the necessary relative reduction in complications and the maximum price of MR-Linac (5 fractions) to be cost-effective compared to 5, 20 and 39 fractionation schedules of external beam radiotherapy (EBRT) and low-dose-rate (LDR) brachytherapy.

Materials And Methods: A state transition model was developed for men with localized prostate cancer. Complication rates such as grade ≥2 urinary, grade ≥2 bowel and sexual complications, and utilities were based on systematic literature searches. Costs were estimated from a Dutch healthcare perspective. Threshold analyses were performed to identify the thresholds of complications and costs for MR-Linac to be cost-effective, while holding other outcomes such as biochemical progression and mortality constant. One-way sensitivity analyses were performed to outline uncertainty outcomes.

Results: At €6460 per patient, no reductions in complications were needed to consider MR-Linac cost-effective compared to EBRT 20 and 39 fractions. Compared to EBRT 5 fractions and LDR brachytherapy, MR-Linac was found to be cost-effective when complications are relatively reduced by 54% and 66% respectively. Results are highly sensitive to the utilities of urinary, bowel and sexual complications and the probability of biochemical progression.

Conclusions: MR-Linac is found to be cost-effective compared to 20 and 39 fractions EBRT at baseline. For MR-Linac to become cost-effective over 5 fractions EBRT and LDR brachytherapy, it has to reduce complications substantially or be offered at lower costs.
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http://dx.doi.org/10.1016/j.radonc.2021.05.022DOI Listing
June 2021

Modeling-Based Decision Support System for Radical Prostatectomy Versus External Beam Radiotherapy for Prostate Cancer Incorporating an Clinical Trial and a Cost-Utility Study.

Cancers (Basel) 2021 May 29;13(11). Epub 2021 May 29.

The D-Lab, Department of Precision Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University, 6229 ER Maastricht, The Netherlands.

The aim of this study is to build a decision support system (DSS) to select radical prostatectomy (RP) or external beam radiotherapy (EBRT) for low- to intermediate-risk prostate cancer patients. We used an individual state-transition model based on predictive models for estimating tumor control and toxicity probabilities. We performed analyses on a synthetically generated dataset of 1000 patients with realistic clinical parameters, externally validated by comparison to randomized clinical trials, and set up an in silico clinical trial for elderly patients. We assessed the cost-effectiveness (CE) of the DSS for treatment selection by comparing it to randomized treatment allotment. Using the DSS, 47.8% of synthetic patients were selected for RP and 52.2% for EBRT. During validation, differences with the simulations of late toxicity and biochemical failure never exceeded 2%. The in silico trial showed that for elderly patients, toxicity has more influence on the decision than TCP, and the predicted QoL depends on the initial erectile function. The DSS is estimated to result in cost savings (EUR 323 (95% CI: EUR 213-433)) and more quality-adjusted life years (QALYs; 0.11 years, 95% CI: 0.00-0.22) than randomized treatment selection.
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http://dx.doi.org/10.3390/cancers13112687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198879PMC
May 2021

An overview of the published and running randomized phase 3 clinical results of radiotherapy in combination with immunotherapy.

Transl Lung Cancer Res 2021 Apr;10(4):2048-2058

Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.

Several studies have established that radiotherapy (RT) in combination with immunotherapy (IO) has a strong synergistic effect. RT changes the tumor microenvironment, generates local inflammation reactions, and enhances immunostimulatory effects, which are able to assist IO with improving local and systemic tumor control. In several pre-clinical reports, RT in combination with IO reveals regression of tumors locally (irradiated sites) and systemically (non-irradiated sites). Several clinical trials are currently running, mostly as phase I and II studies. This article provides an overview of the randomized, prospective reported and recruiting phase 3 clinical trials of RT in combination with IO. To date, three phase 3 trials have been published on RT and sequential IO with variable results, ranging from no significant difference (Kwon , START) to absolute differences in overall survival of 13.5% after 3 years (PACIFIC), respectively. No phase 3 randomized trials have been published on the simultaneous combination of RT with IO. Thirty trials are presently under way, and still recruiting patients to quantify the response to RT with IO. These studies fall into three categories of research interests: (I) to discover an enhancement effect of IO as induction therapy with RT; (II) to determine the additional effect of concurrent IO on the local effect of RT; and (III) to determine the additional effect of adjuvant or consolidation IO on the local effect of RT. Most of the ongoing studies are a combination of these interests, with 15 trials evaluating the concurrent RT+IO with IO consolidation strategy. The results in coming years will provide more insights in the role of RT as an activator of the immune system, the effect of IO as local sensitizer of RT, the optimal sequencing of IO with RT, and the total RT doses needed to obtain the optimal local and systemic effect.
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http://dx.doi.org/10.21037/tlcr-20-304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107766PMC
April 2021

Is prostate cancer radiotherapy using implantable rectum spacers safe and effective in inflammatory bowel disease patients?

Clin Transl Radiat Oncol 2021 Mar 25;27:121-125. Epub 2021 Jan 25.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.

Background: Prostate cancer radiotherapy (RT) in patients with (active) inflammatory bowel disease (IBD) remains controversial. We hypothesized that RT in combination with a biodegradable prostate-rectum spacer balloon implantation, might be a safe treatment approach with acceptable toxicities for these high risk for rectal toxicity patients.

Materials And Methods: We report on a small prospective mono-centric series of 8 patients with all-risk prostate cancer with the comorbidity of an IBD. Four patients had Crohn's disease and 4 patients had ulcerative colitis. One out of four had an active status of IBD. All patients were intended to be treated with curative high-dose RT: 5 patients were treated with external beam RT (70 Gray (Gy) in 28 fractions), and 3 patients were treated with I-implant (145 Gy). Toxicities were scored according to the CTCAE v4.03: acute side effects occur up to 3 months after RT, and late side effects start after 3 months.

Results: Median follow-up was 13 months (range: 3-42 months). Only one acute grade 2 gastro-intestinal (GI) toxicity was observed: an increased diarrhea (4-6 above baseline) during RT, which resolved completely 6 weeks after treatment. No late grade 3 or more GI toxicity was reported, and no acute and late grade ≥2 genitourinary toxicity events were observed.

Conclusion: Prostate cancer patients with IBD are a challenge to treat with RT. Our results suggest that RT in combination with a balloon implant in selective patients with (active) IBD may be promising, however additional validation is needed.
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http://dx.doi.org/10.1016/j.ctro.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875819PMC
March 2021

Immunotherapy as sensitizer for local radiotherapy.

Oncoimmunology 2020 10 30;9(1):1832760. Epub 2020 Oct 30.

Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.

The purpose of this report was to systematically review the radiation enhancement factor (REF) effects of immunotherapy on radiotherapy (RT) to the local tumor in comparison with other traditional radiation sensitizers such as cisplatin. PubMed and Medline databases were searched until February 2019. Reports with abscopal effect in the results were excluded. Graphs of the selected papers were digitized using Plot Digitizer (Sourceforge.net) in order to calculate the tumor growth delay (TGD) caused by immunotherapy. To enable comparison between different studies,the TGD were used to define the REF between RT versus the RT/immunotherapy combination. Thirty-two preclinical papers, and nine clinical series were selected. Different mouse models were exposed to RT doses ranging from 1 to 10 fractions of 1.8 to 20 Gray (Gy) per fraction. Endpoints were heterogeneous, ranging from regression to complete local response. No randomized clinical studies were identified. The median preclinical REF effect of different immunotherapy was varying from 1.7 to 9.1. There was no relationship observed either with subclasses of immunotherapy orRT doses. In the clinical studies, RT doses ranged from 1 to 37 fractions of 1.8 to 24 Gy per fraction. Most clinical trials used ipilimumab and interleukin-2. Local control rate in the clinical series ranged from 66% to 100%. A strong REF of immunotherapy (1.7 to 9.1) was observed, this being higher than traditionally sensitizers such as cisplatin (1.1). This result implies that for the same RT dose, a higher local control was achieved with a combination of immunotherapy and RT in preclinical settings. This study therefore supports the use of combined RT and immunotherapy to improve local tumor control in clinical settings without exacerbation of toxicities.
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http://dx.doi.org/10.1080/2162402X.2020.1832760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605354PMC
October 2020

Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer.

J Clin Oncol 2021 Feb 29;39(4):319-327. Epub 2020 Oct 29.

Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Purpose: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk.

Patients And Methods: The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models.

Results: CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HR, 0.74; 95% CI, 0.64 to 0.85).

Conclusion: Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.
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http://dx.doi.org/10.1200/JCO.20.02352DOI Listing
February 2021

Platinum exposure and cause-specific mortality among patients with testicular cancer.

Cancer 2020 02 15;126(3):628-639. Epub 2019 Nov 15.

Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Background: Although testicular cancer (TC) treatment has been associated with severe late morbidities, including second malignant neoplasms (SMNs) and ischemic heart disease (IHD), cause-specific excess mortality has been rarely studied among patients treated in the platinum era.

Methods: In a large, multicenter cohort including 6042 patients with TC treated between 1976 and 2006, cause-specific mortality was compared with general population mortality rates. Associations with treatment were assessed with proportional hazards analysis.

Results: With a median follow-up of 17.6 years, 800 patients died; 40.3% of these patients died because of TC. The cumulative mortality was 9.6% (95% confidence interval [CI], 8.5%-10.7%) 25 years after TC treatment. In comparison with general population mortality rates, patients with nonseminoma experienced 2.0 to 11.6 times elevated mortality from lung, stomach, pancreatic, rectal, and kidney cancers, soft-tissue sarcomas, and leukemia; 1.9-fold increased mortality (95% CI, 1.3-2.8) from IHD; and 3.9-fold increased mortality (95% CI, 1.5-8.4) from pneumonia. Seminoma patients experienced 2.5 to 4.6 times increased mortality from stomach, pancreatic, bladder cancer and leukemia. Radiotherapy and chemotherapy were associated with 2.1 (95% CI, 1.8-2.5) and 2.5 times higher SMN mortality (95% CI, 2.0-3.1), respectively, in comparison with the general population. In a multivariable analysis, patients treated with platinum-containing chemotherapy had a 2.5-fold increased hazard ratio (HR; 95% CI, 1.8-3.5) for SMN mortality in comparison with patients without platinum-containing chemotherapy. The HR for SMN mortality increased 0.29 (95% CI, 0.19-0.39) per 100 mg/m platinum dose administered (P  < .001). IHD mortality was increased 2.1-fold (95% CI, 1.5-4.2) after platinum-containing chemotherapy in comparison with patients without platinum exposure.

Conclusions: Platinum-containing chemotherapy is associated with a dose-dependent increase in the risk of SMN mortality.
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http://dx.doi.org/10.1002/cncr.32538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004069PMC
February 2020

Development and validation of a patient decision aid for prostate Cancer therapy: from paternalistic towards participative shared decision making.

BMC Med Inform Decis Mak 2019 07 11;19(1):130. Epub 2019 Jul 11.

Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Dr. Tanslaan 12, 6229, ET, Maastricht, The Netherlands.

Background: Patient decision aids (PDAs) can support the treatment decision making process and empower patients to take a proactive role in their treatment pathway while using a shared decision-making (SDM) approach making participatory medicine possible. The aim of this study was to develop a PDA for prostate cancer that is accurate and user-friendly.

Methods: We followed a user-centered design process consisting of five rounds of semi-structured interviews and usability surveys with topics such as informational/decisional needs of users and requirements for PDAs. Our user-base consisted of 8 urologists, 4 radiation oncologists, 2 oncology nurses, 8 general practitioners, 19 former prostate cancer patients, 4 usability experts and 11 healthy volunteers.

Results: Informational needs for patients centered on three key factors: treatment experience, post-treatment quality of life, and the impact of side effects. Patients and clinicians valued a PDA that presents balanced information on these factors through simple understandable language and visual aids. Usability questionnaires revealed that patients were more satisfied overall with the PDA than clinicians; however, both groups had concerns that the PDA might lengthen consultation times (42 and 41%, respectively). The PDA is accessible on http://beslissamen.nl/ .

Conclusions: User-centered design provided valuable insights into PDA requirements but challenges in integrating diverse perspectives as clinicians focus on clinical outcomes while patients also consider quality of life. Nevertheless, it is crucial to involve a broad base of clinical users in order to better understand the decision-making process and to develop a PDA that is accurate, usable, and acceptable.
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http://dx.doi.org/10.1186/s12911-019-0862-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624887PMC
July 2019

Ano-rectal wall dose-surface maps localize the dosimetric benefit of hydrogel rectum spacers in prostate cancer radiotherapy.

Clin Transl Radiat Oncol 2019 Jan 3;14:17-24. Epub 2018 Nov 3.

MAASTRO Clinic, Maastricht, The Netherlands.

Background And Purpose: To evaluate spatial differences in dose distributions of the ano-rectal wall (ARW) using dose-surface maps (DSMs) between prostate cancer patients receiving intensity-modulated radiation therapy with and without implantable rectum spacer (IMRT+IRS; IMRT-IRS, respectively), and to correlate this with late gastro-intestinal (GI) toxicities using validated spatial and non-spatial normal-tissue complication probability (NTCP) models.

Materials And Methods: For 26 patients DSMs of the ARW were generated. From the DSMs various shape-based dose measures were calculated at different dose levels: lateral extent, longitudinal extent, and eccentricity. The contiguity of the ARW dose distribution was assessed by the contiguous-DSH (cDSH). Predicted complication rates between IMRT+IRS and IMRT-IRS plans were assessed using a spatial NTCP model and compared against a non-spatial NTCP model.

Results: Dose surface maps are generated for prostate radiotherapy using an IRS. Lateral extent, longitudinal extent and cDSH were significantly lower in IMRT+IRS than for IMRT-IRS at high-dose levels. Largest significant differences were observed for cDSH at dose levels >50 Gy, followed by lateral extent at doses >57 Gy, and longitudinal extent in anterior and superior-inferior directions. Significant decreases ( = 0.01) in median rectal and anal NTCPs (respectively, Gr 2 late rectal bleeding and subjective sphincter control) were predicted when using an IRS.

Conclusions: Local-dose effects are predicted to be significantly reduced by an IRS. The spatial NTCP model predicts a significant decrease in Gr 2 late rectal bleeding and subjective sphincter control. Dose constraints can be improved for current clinical treatment planning.
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http://dx.doi.org/10.1016/j.ctro.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234617PMC
January 2019

Risk of diabetes after para-aortic radiation for testicular cancer.

Br J Cancer 2018 10 9;119(7):901-907. Epub 2018 Oct 9.

Department of Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Background: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated.

Methods: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates. Treatment-specific risk of diabetes was assessed using a case-cohort design.

Results: With a median follow-up of 13.4 years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not increased compared to general population rates (standardised incidence ratios (SIR): 0.9; 95% confidence interval (95% CI): 0.7-1.1). Adjusted for age, para-aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05-2.62) increased diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31 with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11-0.51, P = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess hazard increased with 0.33 (95% CI: -0.14 to 0.81, P = 0.169) with every 10 Gy increase in radiation dose.

Conclusion: Compared to surgery only, para-aortic irradiation is associated with increased diabetes risk among TC survivors.
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http://dx.doi.org/10.1038/s41416-018-0248-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189211PMC
October 2018

Risk of Solid Cancer After Treatment of Testicular Germ Cell Cancer in the Platinum Era.

J Clin Oncol 2018 08 10;36(24):2504-2513. Epub 2018 Jul 10.

Harmke J. Groot, Jan Martijn Kerst, Katarzyna Jóźwiak, Alexandra W. van den Belt-Dusebout, Simon Horenblas, Flora E. van Leeuwen, and Michael Schaapveld, Netherlands Cancer Institute; Alfons J.M. van den Eertwegh, Vrije Universiteit Medical Center; Heinz-Josef Klümpen, Academic Medical Center, Amsterdam; Sjoukje Lubberts, Igle J. de Jong, Alfons C.M. van den Bergh, and Jourik A. Gietema, University Medical Center Groningen, University of Groningen, Groningen; Ronald de Wit and Luca Incrocci, Erasmus Medical Center Cancer Institute, Rotterdam; Johannes A. Witjes, Radboud University Medical Center, Nijmegen; Gerard Groenewegen, University Medical Center Utrecht Cancer Center, Utrecht; Philip M. Poortmans, Instituut Verbeeten, Tilburg; Hetty A. van den Berg, Catharina Hospital, Eindhoven; Tineke J. Smilde, Jeroen Bosch Hospital, 's-Hertogenbosch; Ben G.L. Vanneste, MAASTRO Clinic; Maureen J. Aarts, Maastricht University Medical Center, Maastricht, the Netherlands; and Philip M. Poortmans, Institut Curie, Paris, France.

Purpose Testicular cancer (TC) treatment increases risk of subsequent malignant neoplasms (SMNs). It is unknown whether changes in TC treatment over time have affected SMN risk. Methods Solid SMN risk was evaluated in a multicenter cohort comprising 5,848 1-year survivors treated for TC before age 50 years between 1976 and 2007. SMN incidence was compared with cancer incidence in the general population. Treatment-specific risks were assessed using multivariable regression in a case-cohort design. Results After a median follow-up of 14.1 years, 350 solid SMNs were observed, translating into a 1.8-fold (95% CI, 1.6-2.0) increased risk compared with general population rates. Solid SMN risk was increased in patients with seminoma and those with nonseminoma (standardized incidence ratio, 1.52 and 2.21, respectively). Patients with nonseminoma experienced increased risk of SMNs of the thyroid, lung, stomach, pancreas, colon, and bladder and of melanoma and soft tissue sarcoma, whereas those with seminoma experienced increased risk of SMNs of the small intestine, pancreas, and urinary bladder. The 25-year cumulative incidence of solid SMNs was 10.3% (95% CI, 9.0% to 11.6%). In multivariable analysis, platinum-based chemotherapy was associated with increased risk of a solid SMN (hazard ratio [HR], 2.40; 95% CI, 1.58 to 3.62), colorectal SMN (HR, 3.85; 95% CI, 1.67 to 8.92), and noncolorectal GI SMN (HR, 5.00; 95% CI, 2.28 to 10.95). Receipt of platinum 400 to 499 and ≥ 500 mg/m increased solid SMN risk compared with surgery only (HR, 2.43; 95% CI, 1.40 to 4.23 and HR, 2.42; 95% CI, 1.50 to 3.90, respectively), whereas risk was not significantly increased with lower doses (HR, 1.75; 95% CI, 0.90 to 3.43). The HR of a GI SMN increased by 53% (95% CI, 26% to 80%) per 100 mg/m of platinum-containing chemotherapy. The HR of an infradiaphragmatic SMN increased by 8% per Gray of radiation dose administered (95% CI, 6% to 9%; P < .001). Conclusion Radiotherapy and platinum-containing chemotherapy are associated with increased solid SMN risk, specifically with GI SMNs.
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http://dx.doi.org/10.1200/JCO.2017.77.4174DOI Listing
August 2018

Development of an isotoxic decision support system integrating genetic markers of toxicity for the implantation of a rectum spacer.

Acta Oncol 2018 Nov 28;57(11):1499-1505. Epub 2018 Jun 28.

a The D-Lab: Decision Support for Precision Medicine, GROW - School for Oncology and Developmental Biology , Maastricht University Medical Centre+ , Maastricht , the Netherlands.

Introduction: Previous studies revealed that dose escalated radiotherapy for prostate cancer patients leads to higher tumor control probabilities (TCP) but also to higher rectal toxicities. An isotoxic model was developed to maximize the given dose while controlling the toxicity level. This was applied to analyze the effect of an implantable rectum spacer (IRS) and extended with a genetic test of normal tissue radio-sensitivity. A virtual IRS (V-IRS) was tested using this method. We hypothesized that the patients with increased risk of toxicity would benefit more from an IRS.

Material And Methods: Sixteen localized prostate cancer patients implanted with an IRS were included in the study. Treatment planning was performed on computed tomography (CT) images before and after the placement of the IRS and with a V-IRS. The normal tissue complication probability (NTCP) was calculated using a QUANTEC reviewed model for Grade > =2 late rectal bleeding and the number of fractions of the plans were adjusted until the NTCP value was under 5%. The resulting treatment plans were used to calculate the TCP before and after placement of an IRS. This was extended by adding the effect of two published genetic single nucleotide polymorphisms (SNP's) for late rectal bleeding.

Results: The median TCP resulting from the optimized plans in patients before the IRS was 75.1% [32.6-90.5%]. With IRS, the median TCP is significantly higher: 98.9% [80.8-99.9%] (p < .01). The difference in TCP between the V-IRS and the real IRS was 1.8% [0.0-18.0%]. Placing an IRS in the patients with SNP's improved the TCP from 49.0% [16.1-80.8%] and 48.9% [16.0-72.8%] to 96.3% [67.0-99.5%] and 90.1% [49.0-99.5%] (p < .01) respectively for either SNP.

Conclusion: This study was a proof-of-concept for an isotoxic model with genetic biomarkers with a V-IRS as a multifactorial decision support system for the decision of a placement of an IRS.
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http://dx.doi.org/10.1080/0284186X.2018.1484156DOI Listing
November 2018

Automated patient-specific transperineal ultrasound probe setups for prostate cancer patients undergoing radiotherapy.

Med Phys 2018 Jul 14;45(7):3185-3195. Epub 2018 Jun 14.

School of Clinical Sciences, Queensland University of Technology, Brisbane, Qld, 4000, Australia.

Purpose: The use of ultrasound imaging is not widespread in prostate cancer radiotherapy workflows, despite several advantages (eg, allowing real-time volumetric organ tracking). This can be partially attributed to the need for a trained operator during acquisition and interpretation of the images. We introduce and evaluate an algorithm that can propose a patient-specific transperineal ultrasound probe setup, based on a CT scan and anatomical structure delineations. The use of this setup during the simulation and treatment stage could improve usability of ultrasound imaging for relatively untrained operators (radiotherapists with less than 1 yr experience with ultrasound).

Methods: The internal perineum boundaries of three prostate cancer patients were identified based on bone masks extracted from their CT scans. After projection of these boundaries to the skin and exclusion of specific areas, this resulted in a skin area accessible for transperineal ultrasound probe placement in clinical practice. Several possible probe setups on this area were proposed by the algorithm and the optimal setup was automatically selected. In the end, this optimal setup was evaluated based on a comparison with a corresponding transperineal ultrasound volume acquired by a radiation oncologist.

Results: The algorithm-proposed setups allowed visualization of 100% of the clinically required anatomical structures, including the whole prostate and seminal vesicles, as well as the adjacent edges of the bladder and rectum. In addition, these setups allowed visualization of 94% of the anatomical structures, which were also visualized by the physician during the acquisition of an actual ultrasound volume.

Conclusion: Provided that the ultrasound probe setup proposed by the algorithm, is properly reproduced on the patient, it allows visualization of all clinically required structures for image guided radiotherapy purposes. Future work should validate these results on a patient population and optimize the workflow to enable a relatively untrained operator to perform the procedure.
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http://dx.doi.org/10.1002/mp.12972DOI Listing
July 2018

The Use of Ultrasound Imaging in the External Beam Radiotherapy Workflow of Prostate Cancer Patients.

Biomed Res Int 2018 24;2018:7569590. Epub 2018 Jan 24.

Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht, Netherlands.

External beam radiotherapy (EBRT) is one of the curative treatment options for prostate cancer patients. The aim of this treatment option is to irradiate tumor tissue, while sparing normal tissue as much as possible. Frequent imaging during the course of the treatment (image guided radiotherapy) allows for determination of the location and shape of the prostate (target) and of the organs at risk. This information is used to increase accuracy in radiation dose delivery resulting in better tumor control and lower toxicity. Ultrasound imaging is harmless for the patient, it is cost-effective, and it allows for real-time volumetric organ tracking. For these reasons, it is an ideal technique for image guidance during EBRT workflows. Review papers have been published in which the use of ultrasound imaging in EBRT workflows for different cancer sites (prostate, breast, etc.) was extensively covered. This new review paper aims at providing the readers with an update on the current status for prostate cancer ultrasound guided EBRT treatments.
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http://dx.doi.org/10.1155/2018/7569590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829356PMC
September 2018

A biodegradable rectal balloon implant to protect the rectum during prostate cancer radiotherapy for a patient with active Crohn's disease.

Tech Innov Patient Support Radiat Oncol 2018 Jun 20;6:1-4. Epub 2018 Mar 20.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.

Background: Radiotherapy in patients with active inflammatory bowel disease (IBD) is usually considered an absolute exclusion criterion for prostate cancer radiotherapy treatment.There are no reports available on the use of a biodegradable rectal balloon implantation (RBI) in patients with active IBD for prostate cancer radiotherapy.

Case Presentation: We report on a patient with high-risk prostate cancer with the comorbidity of an active IBD with pancolitis location. He was treated with neo-adjuvant hormonal therapy and high-dose external beam radiotherapy to the prostate and the seminal vesicles. Before radiotherapy treatment, a biodegradable RBI was implanted between the prostate and the anterior rectal wall to push the rectum outside of the high-dose area. This patient at high-risk for rectal toxicity was successfully irradiated to his prostate with only a grade I urinary toxicity, no acute rectal toxicity or toxicity flare of the IBD.

Conclusions: This case describes the use of a RBI implantation in patients with active IBD for prostate cancer radiotherapy. The use of a biodegradable RBI proved to be a promised solution for such patients, and have to be further investigated.
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http://dx.doi.org/10.1016/j.tipsro.2018.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033750PMC
June 2018

Dynamics of rectal balloon implant shrinkage in prostate VMAT : Influence on anorectal dose and late rectal complication risk.

Strahlenther Onkol 2018 01 16;194(1):31-40. Epub 2017 Oct 16.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands.

Purpose: To assess the effect of a shrinking rectal balloon implant (RBI) on the anorectal dose and complication risk during the course of moderately hypofractionated prostate radiotherapy.

Methods: In 15 patients with localized prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and prostate-rectum separation. The absolute anorectal volume encompassed by the 2 Gy equieffective 75 Gy isodose (V) was recalculated as well as the mean anorectal dose. The increase in estimated risk of grade 2-3 late rectal bleeding (LRB) between the start and end of treatment was predicted using nomograms. The observed acute and late toxicities were evaluated.

Results: A significant shrinkage of RBI volumes was observed, with an average volume of 70.4% of baseline at the end of the treatment. Although the prostate-rectum separation significantly decreased over time, it remained at least 1 cm. No significant increase in V of the anorectum was observed, except in one patient whose RBI had completely deflated in the third week of treatment. No correlation between mean anorectal dose and balloon deflation was found. The increase in predicted LRB risk was not significant, except in the one patient whose RBI completely deflated. The observed toxicities confirmed these findings.

Conclusions: Despite significant decrease in RBI volume the high-dose rectal volume and the predicted LRB risk were unaffected due to a persistent spacing between the prostate and the anterior rectal wall.
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http://dx.doi.org/10.1007/s00066-017-1222-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752748PMC
January 2018

Development of a virtual spacer to support the decision for the placement of an implantable rectum spacer for prostate cancer radiotherapy: Comparison of dose, toxicity and cost-effectiveness.

Radiother Oncol 2017 10 16;125(1):107-112. Epub 2017 Aug 16.

Department of Radiation Oncology (MAASTRO, D-lab), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands.

Introduction: Previous studies have shown that the implantable rectum spacer (IRS) is not beneficial for all patients. A virtual IRS (V-IRS) was constructed to help identify the patients for whom it is cost-effective to implant an IRS, and its viability as a tool to tailor the decision of an IRS implantation to be beneficial for the specified patient was assessed. Please watch animation: (https://www.youtube.com/watch?v=tDlagSXMKqw) MATERIALS AND METHODS: The V-IRS was tested on 16 patients: 8 with a rectal balloon implant (RBI) and 8 with a hydrogel spacer. A V-IRS was developed using 7 computed tomography (CT) scans of patients with a RBI. To examine the V-IRS, CT scans before and after the implantation of an IRS were used. IMRT plans were made based on CT scans before the IRS, after IRS and with the V-IRS, prescribing 70 Gray (Gy) to the planning target volume. Toxicity was accessed using externally validated normal tissue complication probability (NTCP) models, and the Cost-effectiveness was analyzed using a published Markov model.

Results: The rectum volume receiving 75Gy (V75) were improved by both the IRS and the V-IRS with on average 4.2% and 4.3% respectively. The largest NTCP reduction resulting from the IRS and the V-IRS was 4.0% and 3.9% respectively. The RBI was cost-effective for 1 out of 8 patients, and the hydrogel was effective for 2 out of 8 patients, and close to effective for a third patient. The classification accuracy of the model, regarding cost-effectiveness, was 100%.

Conclusion: The V-IRS approach in combination with a toxicity prediction model and a cost-effectiveness analyses is a promising basis for a decision support tool for the implantation of either a hydrogel spacer or a rectum balloon implant.
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http://dx.doi.org/10.1016/j.radonc.2017.07.026DOI Listing
October 2017

Online pretreatment verification of high-dose rate brachytherapy using an imaging panel.

Phys Med Biol 2017 Jul;62(13):5440-5461

Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Dr. Tanslaan 12, Maastricht 6229 ET, Netherlands.

Brachytherapy is employed to treat a wide variety of cancers. However, an accurate treatment verification method is currently not available. This study describes a pre-treatment verification system that uses an imaging panel (IP) to verify important aspects of the treatment plan. A detailed modelling of the IP was only possible with an extensive calibration performed using a robotic arm. Irradiations were performed with a high dose rate (HDR) Ir source within a water phantom. An empirical fit was applied to measure the distance between the source and the detector so 3D Cartesian coordinates of the dwell positions can be obtained using a single panel. The IP acquires 7.14 fps to verify the dwell times, dwell positions and air kerma strength (Sk). A gynecological applicator was used to create a treatment plan that was registered with a CT image of the water phantom used during the experiments for verification purposes. Errors (shifts, exchanged connections and wrong dwell times) were simulated to verify the proposed verification system. Cartesian source positions (panel measurement plane) have a standard deviation of about 0.02 cm. The measured distance between the source and the panel (z-coordinate) have a standard deviation up to 0.16 cm and maximum absolute error of  ≈0.6 cm if the signal is close to sensitive limit of the panel. The average response of the panel is very linear with Sk. Therefore, Sk measurements can be performed with relatively small errors. The measured dwell times show a maximum error of 0.2 s which is consistent with the acquisition rate of the panel. All simulated errors were clearly identified by the proposed system. The use of IPs is not common in brachytherapy, however, it provides considerable advantages. It was demonstrated that the IP can accurately measure Sk, dwell times and dwell positions.
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http://dx.doi.org/10.1088/1361-6560/aa7028DOI Listing
July 2017

Implantation of a biodegradable rectum balloon implant: tips, Tricks and Pitfalls.

Int Braz J Urol 2017 Nov-Dec;43(6):1033-1042

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, Netherlands.

Introduction: A rectum balloon implant (RBI) is a new device to spare rectal structures during prostate cancer radiotherapy. The theoretical advantages of a RBI are to reduce the high radiation dose to the anterior rectum wall, the possibility of a post-implant correction, and their predetermined shape with consequent predictable position.

Objective: To describe, step-by-step, our mini-invasive technique for hands-free transperineal implantation of a RBI before start of radiotherapy treatment.

Materials And Methods: We provide step-by-step instructions for optimization of the transperineal implantation procedure performed by urologists and/or radiation oncologists experienced with prostate brachytherapy and the use of the real-time bi-plane transrectal ultrasonography (TRUS) probe. A RBI was performed in 15 patients with localised prostate cancer. Perioperative side-effects were reported.

Results: We provide 'tips and tricks' for optimizing the procedure and proper positioning of the RBI. Please watch the animation, see video in https://vimeo.com/205852376/789df4fae4. The side-effects included mild discomfort to slight pain at the perineal region in 8 out of 15 patients. Seven patients (47%) had no complaints at all. Two patients developed redness of the skin, where prompt antibiotic regimen was started with no further sequelae. One patient revealed a temporary urine retention, which resolved in a few hours following conservative treatment. Further no perioperative complications occurred.

Conclusion: This paper describes in detail the implantation procedure for an RBI. It is a feasible, safe and very well-tolerated procedure.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2016.0494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734065PMC
March 2018

Prostate Cancer Radiation Therapy: What Do Clinicians Have to Know?

Biomed Res Int 2016 28;2016:6829875. Epub 2016 Dec 28.

Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.

Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together () while using patient decision aids.
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http://dx.doi.org/10.1155/2016/6829875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225325PMC
February 2017

Who will benefit most from hydrogel rectum spacer implantation in prostate cancer radiotherapy? A model-based approach for patient selection.

Radiother Oncol 2016 10 16;121(1):118-123. Epub 2016 Sep 16.

Department of Radiation Oncology (MAASTRO Clinic), Maastricht University Medical Center, The Netherlands.

Background And Purpose: Previous studies confirmed that implantable rectum spacers (IRS) decreased acute gastro-intestinal (GI) toxicity in a significant percentage of prostate cancer patients undergoing intensity modulated radiation therapy (IMRT). We developed decision rules based on clinical risk factors (CRFs) to select those patients who are expected to benefit most from IRS implantation.

Materials And Methods: For 26 patients dose distributions with (IMRT+IRS) and without (IMRT-IRS) IRS were calculated. Validated nomograms based on CRFs and dosimetric criteria (anorectal V and V) were used to predict probabilities for grade 2-3 (G2-3) acute GI toxicity, G2-3 late rectal bleeding (LRB), G3 LRB, and G2-3 faecal incontinence (FI) for IMRT+IRS and IMRT-IRS. All permutations of CRFs were generated to identify most benefit scenarios (MBS) in which a predicted toxicity reduction of ⩾5% points in ⩾25% of the cohort was present due to IRS implantation.

Results: IMRT+IRS revealed a significant reduction in V (p=0.0357) and V (p<0.0001) relative to IMRT-IRS. For G2-3 acute GI toxicity and G2-3 LRB, the predicted toxicity rates decreased in 17/26 (65%) and 20/26 (77%) patients, and decision rules were derived for 22/32 (69%) and 12/64 (19%) MBS, respectively. From the decision rules, it follows that diabetes status has no impact on G2-3 acute toxicity, and in absence of pre-RT abdominal surgery, the implantation of an IRS is predicted to show no clinically relevant benefit for G2-3 LRB.

Conclusions: Prostate cancer patients who are expected to benefit most from IRS implantation can be identified prior to IMRT based on their CRFs profile.
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http://dx.doi.org/10.1016/j.radonc.2016.08.026DOI Listing
October 2016

Simulation of pseudo-CT images based on deformable image registration of ultrasound images: A proof of concept for transabdominal ultrasound imaging of the prostate during radiotherapy.

Med Phys 2016 Apr;43(4):1913

Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6201 BN, The Netherlands and Medical Physics Unit, Department of Oncology, McGill University, Montréal, Québec H4A 3J1, Canada.

Purpose: Imaging of patient anatomy during treatment is a necessity for position verification and for adaptive radiotherapy based on daily dose recalculation. Ultrasound (US) image guided radiotherapy systems are currently available to collect US images at the simulation stage (USsim), coregistered with the simulation computed tomography (CT), and during all treatment fractions. The authors hypothesize that a deformation field derived from US-based deformable image registration can be used to create a daily pseudo-CT (CTps) image that is more representative of the patients' geometry during treatment than the CT acquired at simulation stage (CTsim).

Methods: The three prostate patients, considered to evaluate this hypothesis, had coregistered CT and US scans on various days. In particular, two patients had two US-CT datasets each and the third one had five US-CT datasets. Deformation fields were computed between pairs of US images of the same patient and then applied to the corresponding USsim scan to yield a new deformed CTps scan. The original treatment plans were used to recalculate dose distributions in the simulation, deformed and ground truth CT (CTgt) images to compare dice similarity coefficients, maximum absolute distance, and mean absolute distance on CT delineations and gamma index (γ) evaluations on both the Hounsfield units (HUs) and the dose.

Results: In the majority, deformation did improve the results for all three evaluation methods. The change in gamma failure for dose (γDose, 3%, 3 mm) ranged from an improvement of 11.2% in the prostate volume to a deterioration of 1.3% in the prostate and bladder. The change in gamma failure for the CT images (γCT, 50 HU, 3 mm) ranged from an improvement of 20.5% in the anus and rectum to a deterioration of 3.2% in the prostate.

Conclusions: This new technique may generate CTps images that are more representative of the actual patient anatomy than the CTsim scan.
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http://dx.doi.org/10.1118/1.4944064DOI Listing
April 2016

Decision support systems for personalized and participative radiation oncology.

Adv Drug Deliv Rev 2017 01 14;109:131-153. Epub 2016 Jan 14.

Department of Radiation Oncology (MAASTRO), GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands.

A paradigm shift from current population based medicine to personalized and participative medicine is underway. This transition is being supported by the development of clinical decision support systems based on prediction models of treatment outcome. In radiation oncology, these models 'learn' using advanced and innovative information technologies (ideally in a distributed fashion - please watch the animation: http://youtu.be/ZDJFOxpwqEA) from all available/appropriate medical data (clinical, treatment, imaging, biological/genetic, etc.) to achieve the highest possible accuracy with respect to prediction of tumor response and normal tissue toxicity. In this position paper, we deliver an overview of the factors that are associated with outcome in radiation oncology and discuss the methodology behind the development of accurate prediction models, which is a multi-faceted process. Subsequent to initial development/validation and clinical introduction, decision support systems should be constantly re-evaluated (through quality assurance procedures) in different patient datasets in order to refine and re-optimize the models, ensuring the continuous utility of the models. In the reasonably near future, decision support systems will be fully integrated within the clinic, with data and knowledge being shared in a standardized, dynamic, and potentially global manner enabling truly personalized and participative medicine.
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http://dx.doi.org/10.1016/j.addr.2016.01.006DOI Listing
January 2017

Irradiation of localized squamous cell carcinoma of the nasal vestibule.

Head Neck 2016 04 26;38 Suppl 1:E1870-5. Epub 2015 Dec 26.

Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands.

Background: The purpose of this study was to evaluate the long-term results of primary radiotherapy treatment for squamous cell carcinoma (SCC) of the nasal vestibule.

Methods: Eighty-one patients were treated with external beam radiotherapy (EBRT) and/or interstitial radiotherapy (IRT) for a primary, localized, Wang classified SCC of the nasal vestibule.

Results: Median follow-up was 38 months. T1 tumors were treated with IRT: we observed 1 local failure (at 13 months) among 48 patients (5-year local control rate of 97%). Most T2 tumors (20 of 26) were treated with EBRT. There were 8 local recurrences among 26 patients (5-year local control rate of 68%). For the T3 tumors (n = 7; all treated with EBRT), we observed local recurrence in 2 patients (5-year local control rate of 53%). The late-term side effects were relatively mild.

Conclusion: Local primary radiotherapy (either IRT for T1 or EBRT for T2/3) is an adequate treatment for SCC of the nasal vestibule with little late sequelae. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1870-E1875, 2016.
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http://dx.doi.org/10.1002/hed.24337DOI Listing
April 2016

Chronic radiation proctitis: tricks to prevent and treat.

Int J Colorectal Dis 2015 Oct 23;30(10):1293-303. Epub 2015 Jul 23.

Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands.

Objective: The purpose of this study was to give an overview of the measures used to prevent chronic radiation proctitis (CRP) and to provide an algorithm for the treatment of CRP.

Methods: Medical literature databases including PubMed and Medline were screened and critically analyzed for relevance in the scope of our purpose.

Results: CRP is a relatively frequent late side effect (5-20%) and mainly dependent on the dose and volume of irradiated rectum. Radiation treatment (RT) techniques to prevent CRP are constantly improving thanks to image-guided RT and intensity-modulated RT. Also, newer techniques like protons and new devices such as rectum spacers and balloons have been developed to spare rectal structures. Biopsies do not contribute to diagnosing CRP and should be avoided because of the risk of severe rectal wall damage, such as necrosis and fistulas. There is no consensus on the optimal treatment of CRP. A variety of possibilities is available and includes topical and oral agents, hyperbaric oxygen therapy, and endoscopic interventions.

Conclusions: CRP has a natural history of improving over time, even without treatment. This is important to take into account when considering these treatments: first be conservative (topical and oral agents) and be aware that invasive treatments can be very toxic.
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http://dx.doi.org/10.1007/s00384-015-2289-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575375PMC
October 2015

Spacers in radiotherapy treatment of prostate cancer: is reduction of toxicity cost-effective?

Radiother Oncol 2015 Feb 20;114(2):276-81. Epub 2015 Jan 20.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, The Netherlands.

Background And Purpose: To compare the cost-effectiveness of treating prostate cancer patients with intensity-modulated radiation therapy and a spacer (IMRT+S) versus IMRT-only without a spacer (IMRT-O).

Materials And Methods: A decision-analytic Markov model was constructed to examine the effect of late rectal toxicity and compare the costs and quality-adjusted Life Years (QALYs) of IMRT-O and IMRT+S. The main assumption of this modeling study was that disease progression, genito-urinary toxicity and survival were equal for both comparators.

Results: For all patients, IMRT+S revealed a lower toxicity than IMRT-O. Treatment follow-up and toxicity costs for IMRT-O and IMRT+S amounted to €1604 and €1444, respectively, thus saving €160 on the complication costs at an extra charge of €1700 for the spacer in IMRT+S. The QALYs yielded for IMRT-O and IMRT+S were 3.542 and 3.570, respectively. This results in an incremental cost-effectiveness ratio (ICER) of €55,880 per QALY gained. For a ceiling ratio of €80,000, IMRT+S had a 77% probability of being cost-effective.

Conclusion: IMRT+S is cost-effective compared to IMRT-O based on its potential to reduce radiotherapy-related toxicity.
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http://dx.doi.org/10.1016/j.radonc.2015.01.005DOI Listing
February 2015

Postoperative brachytherapy for endometrial cancer using a ring applicator.

Brachytherapy 2015 Mar-Apr;14(2):273-8. Epub 2014 Nov 20.

Department of Radiation Oncology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.

Background: To evaluate the rate of vaginal, pelvic, and distant failures and acute toxicity after postoperative vaginal vault brachytherapy (VBT) delivered by a ring applicator in women with high intermediate-risk endometrial cancer.

Methods And Materials: A total of 100 patients were treated with VBT after a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a Stage IA or IB (International Federation of Gynecology and Obstetrics 2009) intermediate-risk endometrial cancer; 26 patients received 30-Gy low-dose-rate, 74 patients received 28-Gy pulsed-dose-rate brachytherapy.

Results: At a median followup of 37 months (range, 1-107), 6 (6%) patients showed failures. Three patients developed an in-field recurrence in the vaginal vault: 1 was isolate, whereas the other 2 showed simultaneous pelvic and/or distant failure. A fourth patient developed an out-of-field recurrence in the posterior vaginal wall of the proximal half of the vagina, including pelvic and distant failure. Two other patients showed only distant failure. The estimated 3-year actuarial rate of any vaginal recurrence was 2.6% (95% confidence interval, 0-6.3%). The 5-year overall survival was 84%, similar to that in the female Dutch population matched for age and date of diagnosis. The acute side effects were low, consisting mainly of the occurrence of temporary diarrhea (2%).

Conclusion: Postoperative VBT by a ring applicator results in a low recurrence risk, survival rates comparable with the normal female population, and a very low risk of acute morbidity.
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http://dx.doi.org/10.1016/j.brachy.2014.10.002DOI Listing
September 2015
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