Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of ...post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC.
FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies.
The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy.
Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess ...oncological and functional outcomes.
Materials and Methods
This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time‐to‐event outcomes were described using the Kaplan–Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size.
Results
Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow‐up was 24 months. Treatment‐related grade 1–2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4–5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001).
Conclusion
The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune‐mediated response and warrants further investigation.
Background
Despite local therapies, commonly transurethral resection (TUR) followed by adjuvant treatments, non‐muscle‐invasive bladder cancer (NMIBC) has a high rate of recurrence and progression. ...Intravesical Bacillus Calmette‐Guérin (BCG) has been shown to reduce recurrence and progression in people with NMIBC following TUR, however many people do not respond to treatment, have recurrence shortly after, or cannot tolerate standard‐dose therapy. The potential for synergistic antitumour activity of interferon (IFN)‐alpha (α) and BCG provides some rationale for combination therapy for people who do not tolerate or respond to standard‐dose BCG therapy.
Objectives
To assess the effects of intravesically administered BCG plus IFN‐α compared with BCG alone for treating non‐muscle‐invasive bladder cancer.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2016), MEDLINE (OvidSP) (1946 to 2016), Embase (OvidSP) (1974 to 2016), ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) as well as reference lists of retrieved articles and handsearched proceedings of relevant conferences for the past three years. We applied no language restrictions. The date of last search of all databases was 25 August 2016.
Selection criteria
We included randomised controlled trials (RCTs) and pseudo‐randomised trials assessing intravesically administered BCG plus IFN‐α versus BCG alone in adults of either gender with histologically confirmed Ta and T1 superficial bladder cancer, with or without carcinoma in situ, treated with TUR.
Data collection and analysis
Two review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of included studies. We used Review Manager 5 for data synthesis and employed the random‐effects model for meta‐analyses. For prespecified outcomes, where we were unable to derive time‐to‐event information (e.g. time‐to‐recurrence), we assessed dichotomous outcomes (e.g. recurrence) instead. We assessed the quality of the evidence for the main comparisons using the GRADE approach.
Main results
We included five RCTs involving a total of 1231 participants with NMIBC in this review. Due to poor reporting, the risk of bias in the included studies was often unclear. We assessed the studies under two main comparisons: intravesical BCG plus IFN‐α versus intravesical BCG alone (four RCTs), and intravesical BCG alternating with IFN‐α versus intravesical BCG alone (one RCT).
Intravesical BCG plus IFN‐α versus intravesical BCG alone (four RCTs): We observed no clear difference between BCG plus IFN‐α and BCG alone for recurrence (average risk ratio (RR) 0.76, 95% confidence interval (CI) 0.44 to 1.32; 4 RCTs; 925 participants; very low‐quality evidence) or progression (average RR 0.26, 95% CI 0.04 to 1.87; 2 RCTs; 219 participants; low‐quality evidence). The included RCTs did not report on the other primary outcome of this review, discontinuation of therapy due to adverse events. Regarding secondary outcomes, we observed no clear difference for disease‐specific mortality (RR 0.38, 95% CI 0.05 to 3.05; 1 RCT; 99 participants; very low‐quality evidence). Two RCTs reporting contradictory findings for adverse events could not be pooled due to variation in definitions. There were no data from the included RCTs on time‐to‐death or disease‐specific quality of life.
Intravesical BCG alternating with IFN‐α versus intravesical BCG alone (one RCT): We observed shorter time‐to‐recurrence for participants in the BCG alternating with IFN‐α group compared with the BCG alone group (hazard ratio (HR) 2.86, 95% CI 1.98 to 4.13; 1 RCT; 205 participants; low‐quality evidence), but no clear differences in time‐to‐progression (HR 2.39, 95% CI 0.92 to 6.21; 1 RCT; 205 participants; low‐quality evidence) and discontinuation of therapy due to adverse events (RR 2.97, 95% CI 0.31 to 28.09; 1 RCT; 205 participants; low‐quality evidence). Regarding secondary outcomes, there were no clear differences between the BCG alternating with IFN‐α and BCG alone groups for disease‐specific mortality (HR 2.74, 95% CI 0.73 to 10.28; 1 RCT; 205 participants; low‐quality evidence), time‐to‐death (overall survival) (HR 1.00, 95% CI 0.68 to 1.47; 1 RCT; 205 participants; low‐quality evidence), or systemic or local adverse events (RR 1.65, 95% CI 0.41 to 6.73; 1 RCT; 205 participants; low‐quality evidence). There were no data on disease‐specific quality of life.
Authors' conclusions
We found low‐ to very low‐quality evidence suggesting no clear differences in recurrence or progression with BCG plus IFN‐α compared with BCG alone for people with NMIBC; there was no information to determine the effect on discontinuation of therapy due to adverse events. Low‐quality evidence suggests BCG alternating with IFN‐α compared with BCG alone may increase time‐to‐recurrence, however low‐quality evidence also suggests no clear differences for time‐to‐progression or discontinuation of therapy due to adverse events.
Additional high‐quality, adequately powered trials using standardised instillation regimens and doses of both BCG and IFN‐α, reporting outcomes in subgroups stratified by patient and tumour characteristics, and on long‐term outcomes related not only to recurrence but also to progression, discontinuation due to adverse events, and mortality may help to clarify the ideal treatment strategy and provide a more definitive result.
Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial ...investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial.
This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0–2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual.
Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70–82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7–5·5). All patients enrolled had T1–T2a and N0–N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38–60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three 4% patients), abdominal, flank, or tumour pain (four 6%), colonic obstruction (two 3%), and diarrhoea (one 1%). No treatment-related or cancer-related deaths occurred.
To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer.
Cancer Australia Priority-driven Collaborative Cancer Research Scheme.
Comprehensive training in robotic surgery Brook, Nicholas R; Dell’Oglio, Paolo; Barod, Ravi ...
Current opinion in urology,
2019-January, 2019-01-00, 20190101, 2019, Letnik:
29, Številka:
1
Journal Article
PURPOSE OF REVIEWRobotic training in urology can be poorly structured, lack a basic skills foundation, and may not include teaching in important nontechnical human factor skills vital to the safe ...delivery of robotic care. Assessment of acquired skills is not routine. There is a need for structured and standardized curricular to deliver validated training and final assessment. The present reviews the current literature on training methods for robotic surgery, and examines the evidence for their effect on performance, where available.
RECENT FINDINGSThere is good evidence for the beneficial effect of dry lab simulators on robotic skills acquisition, but less for cadaveric and animal models. Two urological authorities have developed comprehensive curricula for robotic training that take a novice robotic surgeon through the full stages of robotic skills acquisition. These are in the early stages of development and validation but have stimulated the development of curricula in other specialties.
SUMMARYThe future landscape for robotic urology training is likely to include structured, mandated, and centralized training, possibly administered by urological organizations. There will be roles for telementoring, advanced education for robotic trainers, and regular revalidation of expert robotic surgeons.
Positive surgical margins (PSMs) after radical prostatectomy (RP) indicate failure of surgery to completely clear cancer. PSMs confer an increased risk of biochemical recurrence (BCR), but how more ...robust outcomes are affected is unclear. This study investigated factors associated with PSMs following RP and determined their impact on clinical outcomes (BCR, second treatment radiotherapy and/or androgen deprivation therapy, and prostate cancer-specific mortality PCSM).
The study cohort included men diagnosed with prostate cancer (pT2-3b/N0/M0) between January 1998 and December 2016 who underwent RP from the South Australian Prostate Cancer Clinical Outcomes Collaborative database. Factors associated with risk of PSMs were identified using Poisson regression. The impact of PSMs on clinical outcomes (BCR, second treatment, and PCSM) was assessed using competing risk regression.
Of the 2827 eligible participants, 28% had PSMs—10% apical, 6% bladder neck, 17% posterolateral, and 5% at multiple locations. Median follow-up was 9.6 years with 81 deaths from prostate cancer recorded. Likelihood of PSM increased with higher pathological grade and pathological T-stage, and greater tumour volume, but decreased with increasing surgeon volume (odds ratio OR: 0.93; 95% confidence interval CI: 0.88–0.98, per 100 previous prostatectomies). PSMs were associated with increased risk of BCR (adjusted sub-distribution hazard ratio sHR 2.5; 95% CI 2.1–3.1) and second treatment (sHR 2.9; 95% CI 2.4–3.5). Risk of BCR was increased similarly for each PSM location, but was higher for multiple margin sites. We found no association between PSMs and PCSM.
Our findings support previous research suggesting that PSMs are not independently associated with PCSM despite strong association with BCR. Reducing PSM rates remains an important objective, given the higher likelihood of secondary treatment with associated comorbidities.
We discuss the differences in cognitive (thinking) and other non-technical skills (NTS) in robotic surgery training compared to other approaches to surgery. Recognition of the importance of NTS and ...cognitive training will aid the development of robotic surgery curricula.
PDF
