Renal Cell Carcinoma : Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review

Background: The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA) microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Materials and Methods: Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. Results: The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Conclusion: Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future

Characterization of the first RF coil dedicated to 1.5 T MR guided radiotherapy

The purpose of this study is to investigate the attenuation characteristics of a novel radiofrequency (RF) coil, which is the first coil that is solely dedicated to MR guided radiotherapy with a 1.5 T MR-linac. Additionally, we investigated the impact of the treatment beam on the MRI performance of this RF coil. First, the attenuation characteristics of the RF coil were characterized. Second, we investigated the impact of the treatment beam on the MRI performance of the RF coil. We additionally demonstrated the ability of the anterior coil to attenuate returning electrons and thereby reducing the dose to the skin at the distal side of the treatment beam. Intensity modulated radiation therapy simulation of a clinically viable treatment plan for spinal bone metastasis shows a decrease of the dose to the planned tumor volume of 1.8% as a result of the MR coil around the patient. Ionization chamber and film measurements show that the anterior and posterior coil attenuate the beam homogeneously by 0.4% and 2.2%, respectively. The impact of the radiation resulted in a slight drop of the time-course signal-to-noise ratio and was dependent on imaging parameters. However, we could not observe any image artifacts resulting from this irradiation in any situation. In conclusion, the investigated MR-coil can be utilized for treatments with the 1.5 T-linac system. However, there is still room for improvement when considering both the dosimetric and imaging performance of the coil

Renal Cell Carcinoma : Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review

Background: The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA) microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Materials and Methods: Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. Results: The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Conclusion: Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future

Superior target delineation for stereotactic body radiotherapy of bone metastases from renal cell carcinoma on MRI compared to CT

Background: In metastatic renal cell carcinoma (mRCC) there has been a treatment shift towards targeted therapy, which has resulted in improved overall survival. Therefore, there is a need for better local control of the tumor and its metastases. Image-guided stereotactic body radiotherapy (SBRT) in bone metastases provides improved symptom palliation and local control. With the use of SBRT there is a need for accurate target delineation. The hypothesis is that MRI allows for better visualization of the extend of bone metastases in mRCC and will optimize the accuracy of tumor delineation for stereotactic radiotherapy purposes, compared with CT only. Methods: From 2013 to 2016, patients who underwent SBRT for RCC bone metastases were included. A planning CT and MRI were performed in radiotherapy treatment position. Gross tumor volumes (GTV) in both CT and MRI were delineated. Contouring was performed by a radiation oncologist specialized in bone metastases and verified by a radiologist, based on local consensus contouring guidelines. In both CT and MRI, the GTV volumes, conformity index (CI) and distance between the centers of mass (dCOM) were compared. Results: Nine patients with 11 RCC bone metastases were included. The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT. The median GTV volume on MRI was 33.4 mL (range, 0.2–247.6 mL), compared to 18.1 mL on CT (range, 0.1–195.9 mL) (P=0.013). Conclusions: Contouring of RCC bone metastases on MRI resulted in clinically relevant and statistically significant larger lesions (mean increase 41%) compared with CT. MRI seems to represent the extend of the GTV in RCC bone metastases more accurately. Contouring based on CT-only could result in an underestimation of the actual tumor volume, which may cause underdosage of the GTV in SBRT treatment plans

Trends and variation in the use of radiotherapy in non-metastatic prostate cancer: a 12-year nationwide overview from The Netherlands

Purpose: This population-based study describes nationwide trends and variation in the use of primary radiotherapy for non-metastatic prostate cancer in The Netherlands in 2008-2019. Methods: Prostate cancer patients were selected from the Netherlands Cancer Registry (N=103,059). Treatment trends were studied over time by prognostic risk groups. Multilevel analyses were applied to identify variables associated with external beam radiotherapy (EBRT) and brachy-monotherapy versus no active treatment in low-risk disease, and EBRT versus radical prostatectomy in intermediate and high-risk disease. Results: EBRT use remained stable (5-6%) in low-risk prostate cancer and increased from 21% to 32% in intermediate-risk, 37% to 45% in high-risk localized and 50% to 57% in high-risk locally advanced disease. Brachy-monotherapy decreased from 19% to 6% and from 15% to 10% in low and intermediate-risk disease, respectively, coinciding an increase of no active treatment from 55% to 73% in low-risk disease. Use of EBRT or brachy-monotherapy versus no active treatment in low-risk disease differed by region, T-stage and patient characteristics. Hospital characteristics were not associated with treatment in low-risk disease, except for availability of brachy-monotherapy in 2008-2013. Age, number of comorbidities, travel time for EBRT, prognostic risk group, and hospital characteristics were associated with EBRT versus prostatectomy in intermediate and high-risk disease. Conclusion: Intermediate/high-risk PCa was increasingly managed with EBRT, while brachy-monotherapy in low/intermediate-risk PCa decreased. In low-risk PCa, the no active treatment-approach increased. Variation in treatment suggests treatment decision related to patient/disease characteristics. In intermediate/high-risk disease, variation seems furthermore related to the treatment modalities available in the diagnosing hospitals

An ESTRO-ACROP guideline on quality assurance and medical physics commissioning of online MRI guided radiotherapy systems based on a consensus expert opinion

Objective: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system. Materials and Methods: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected. Only tests and aspects different from commissioning of a CT guided radiotherapy (RT) system were considered. In the following two rounds all twelve participants voted on the importance of the QA tests, their recommended frequency and their suitability for the two oMRgRT systems approved for clinical use as well as on the importance of the aspects to consider during medical physics commissioning. Results: Twenty-four QA tests were identified which are potentially important during commissioning and routine QA on oMRgRT systems compared to online CT guided RT systems. An additional eleven tasks and aspects related to construction, workflow development and training were collected. Consensus was found for most tests on their importance, their recommended frequency and their suitability for the two approved systems. In addition, eight aspects mostly related to the definition of workflows were also found to be important during commissioning. Conclusions: A program for QA and commissioning of oMRgRT systems was developed to support medical physicists to prepare for safe handling of such systems.Elekt

Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer : Toxicity in the FLAME randomized controlled trial

Purpose: To compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the macroscopically visible tumour. Material and methods: FLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures. Results: Ninety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19 95%CI 0.82-1.73p = 0.38), respectively. Conclusions: In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible

Magnetic Resonance Imaging-Guided Adaptive Radiation Therapy: A “Game Changer” for Prostate Treatment?

Radiation therapy to the prostate involves increasingly sophisticated delivery techniques and changing fractionation schedules. With a low estimated α/β ratio, a larger dose per fraction would be beneficial, with moderate fractionation schedules rapidly becoming a standard of care. The integration of a magnetic resonance imaging (MRI) scanner and linear accelerator allows for accurate soft tissue tracking with the capacity to replan for the anatomy of the day. Extreme hypofractionation schedules become a possibility using the potentially automated steps of autosegmentation, MRI-only workflow, and real-time adaptive planning. The present report reviews the steps involved in hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the challenges for implementatio

Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study

Purpose: [177Lu]Lu-PSMA-617 radioligand therapy (177Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of 177Lu-PSMA in pateints with low-volume mHSPC. Patients and Methods: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [68Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of 177Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. Results: All patients received two cycles of 177Lu-PSMA without complications. No treatment-related grade III–IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. Conclusions: 177Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC