Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available.
To determine the safety and ...feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response.
In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo.
A single fraction of 20-Gy SABR to each lesion.
Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval CI: 91–100) and 93% (95% CI: 84–100), and DPFS was 58% (95% CI: 43–77) and 39% (95% CI: 25–60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm.
A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy.
This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.
For patients with one to three oligometastases from prostate cancer, single fraction 20-Gy stereotactic ablative body radiotherapy was both safe and feasible. Local and distant progression-free survival at 2 yr were 93% and 39%, respectively. Quality of life was maintained at baseline levels using this treatment strategy.
To evaluate the outcomes of patients treated for intermediate- and high-risk prostate cancer with a single schedule of either external beam radiation therapy (EBRT) and high-dose-rate brachytherapy ...(HDRB) boost or EBRT alone.
From 2001-2006, 344 patients received EBRT with HDRB boost for definitive treatment of intermediate- or high-risk prostate cancer. The prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3 fractions. This cohort was compared to a contemporaneously treated cohort who received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three-dimensional conformal EBRT was used. Matching was performed using a propensity score matching technique. High-risk patients constituted 41% of the matched cohorts. Five-year clinical and biochemical outcomes were analyzed.
Initial significant differences in prognostic indicators between the unmatched treatment cohorts were rendered negligible after matching, providing a total of 688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom from biochemical failure was 79.8% (95% confidence interval CI, 74.3%-85.0%) and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively, equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction analyses showed no alteration in HDR efficacy when planned androgen deprivation therapy was administered (P=.95), but a strong trend toward reduced efficacy was shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and HDRB, respectively (P<.0001). No differences in clinical outcomes were observed.
This comparison of 2 individual contemporaneously treated HDRB and EBRT approaches showed improved freedom from biochemical progression with the HDR approach. The benefit was more pronounced in intermediate- risk patients but needs to be weighed against an increased risk of urethral toxicity.
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.
There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was ...undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer.
This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml.
Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval CI, 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time.
HDR brachytherapy as a monotherapy for favorable-risk prostate cancer, administered using a single implant over 2 days, is feasible and has acceptable acute and late toxicities. Further follow-up is still required to better evaluate the efficacy of such treatment.
To develop a high-resolution target volume atlas with intensity-modulated radiotherapy (IMRT) planning guidelines for the conformal treatment of anal cancer.
A draft contouring atlas and planning ...guidelines for anal cancer IMRT were prepared at the Australasian Gastrointestinal Trials Group (AGITG) annual meeting in September 2010. An expert panel of radiation oncologists contoured an anal cancer case to generate discussion on recommendations regarding target definition for gross disease, elective nodal volumes, and organs at risk (OARs). Clinical target volume (CTV) and planning target volume (PTV) margins, dose fractionation, and other IMRT-specific issues were also addressed. A steering committee produced the final consensus guidelines.
Detailed contouring and planning guidelines and a high-resolution atlas are provided. Gross tumor and elective target volumes are described and pictorially depicted. All elective regions should be routinely contoured for all disease stages, with the possible exception of the inguinal and high pelvic nodes for select, early-stage T1N0. A 20-mm CTV margin for the primary, 10- to 20-mm CTV margin for involved nodes and a 7-mm CTV margin for the elective pelvic nodal groups are recommended, while respecting anatomical boundaries. A 5- to 10-mm PTV margin is suggested. When using a simultaneous integrated boost technique, a dose of 54 Gy in 30 fractions to gross disease and 45 Gy to elective nodes with chemotherapy is appropriate. Guidelines are provided for OAR delineation.
These consensus planning guidelines and high-resolution atlas complement the existing Radiation Therapy Oncology Group (RTOG) elective nodal ano-rectal atlas and provide additional anatomic, clinical, and technical instructions to guide radiation oncologists in the planning and delivery of IMRT for anal cancer.
Abstract Background and purpose To evaluate renal dysfunction after stereotactic ablative body radiotherapy (SABR) for inoperable primary renal cell carcinoma (RCC) using nuclear medicine ...assessments. Materials and methods In a prospective clinical trial, patients received single fraction renal SABR (26 Gy) for tumours <5 cm, or fractionated SABR (3 × 14 Gy) for tumours ⩾5 cm. Global and regional glomerular filtration rate (GFR) was calculated through51 Cr-EDTA and99m Tc-DMSA SPECT/CT, respectively, at baseline and post-treatment (14, 90 days and at 1-year). Regional loss in function was correlated to the absolute and biologically effective doses (BED) delivered. Results In 21 patients the mean (range) tumour size was 48 mm (21–75 mm). The mean ± SD GFR at baseline was 52 ± 24 ml/min. Net change in mean GFR was +0.6 ± 11.3, +3.2 ± 14.5 and −8.7 ± 13.4 ml/min ( p = 0.03) at 2 weeks, 3 months and 1 year, respectively. For every 10 Gy of physical dose delivered, an exponential decline in affected kidney GFR was observed at 39% for 26 Gy/1 fraction and 25% for 42 Gy/3 fractions. When normalised to BED3Gy , the dose–response relationship for each treatment prescription was similar with a plateau beyond 100 Gy. The R50% conformity index correlated with GFR loss ( p = 0.04). No patient required dialysis. Conclusions SABR results in clinically acceptable and dose-dependent renal dysfunction at 1-year. Sparing functional kidney from high-dose regions (>50% isodoses) may help reduce risk of functional loss.
To explore the utility of diffusion and perfusion changes in primary renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR) as an early biomarker of treatment response, using ...diffusion weighted (DWI) and dynamic contrast enhanced (DCE) MRI.
Patients enrolled in a prospective pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter received a single fraction of 26 Gy and larger tumours received three fractions of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour volumes were contoured and statistics extracted. Spearman's rank correlation coefficients were computed between MRI parameter changes versus the percentage tumour volume change from CT at 6, 12 and 24 months and the last follow-up relative to baseline CT.
Twelve patients were eligible for DWI analysis, and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow-up MRI scan showed correlations between the change in percentage voxels with washout contrast enhancement behaviour and the change in tumour volume (ρ = 0.84, p = 0.004 at 12 month CT, ρ = 0.81, p = 0.02 at 24 month CT, and ρ = 0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of enhancement and mean Ktrans at the second follow-up MRI scan were positively correlated with percent tumour volume change at the 12 month CT onwards (ρ = 0.65, p = 0.05 and ρ = 0.66, p = 0.04 at 12 month CT respectively). Changes in ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed positive correlations with the percentage tumour volume change (ρ = 0.66, p = 0.02 at 12 month CT, ρ = 0.69, p = 0.02 at last follow-up CT), but these results are possibly confounded by inflammation.
DWI and DCE MRI parameters show potential as early response biomarkers after SABR for primary RCC. Further prospective validation using larger patient cohorts is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC). However, its impact on renal function is unclear. This study aimed to ...evaluate incidence and clinical factors predictive of severe to end-stage chronic kidney disease (CKD) after SABR for RCC.
This was a Single institutional retrospective analysis of patients with diagnosed primary RCC receiving SABR between 2012-2020. Adult patients with no metastatic disease, baseline estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m
, and at least one post-SABR eGFR at six months or later were included in this analysis. Patients with upper tract urothelial carcinoma were excluded. Primary outcome was freedom from severe to end-stage CKD, determined using the Kaplan-Meier estimator. The impact of baseline CKD, age, hypertension, diabetes, tumor size and fractionation schedule were assessed by Cox proportional hazard models.
Seventy-eight consecutive patients were included, with median age of 77.8 years (IQR 70-83), tumor size of 4.5 cm (IQR 3.9-5.8) and follow-up of 42.2 months (IQR 23-60). Baseline median eGFR was 58 mls/min; 55% (n = 43) of patients had baseline CKD stage 3 and the remainder stage 1-2. By last follow-up, 1/35 (2.8%) of baseline CKD 1-2, 7/27 (25.9%) CKD 3a and 11/16 (68.8%) CKD 3b had developed CKD stage 4-5. The estimated probability of freedom from CKD stage 4-5 at 1 and 5 years was 89.6% (CI 83.0-97.6) and 65% (CI 51.4-81.7) respectively. On univariable analysis, worse baseline CKD (p < 0.0001) and multi-fraction SABR (p = 0.005) were predictive for development of stage 4-5 CKD though only the former remained significant in multivariable model.
In this elderly cohort with pre-existing renal dysfunction, SABR achieved satisfactory nephron sparing with acceptable rates of severe to end-stage CKD. It can be an attractive option in patients who are medically inoperable.
To study the management of a woman who returned to conceive after high-dose radiation treatment, with documentation of uterine dosimetry, and the efficacy of ovarian tissue grafted into an irradiated ...pelvis.
Case report.
Private and public In Vitro Fertilization units.
A 26-year-old woman underwent radiation treatment for rectal cancer, with half of the uterus and the fundus being exposed to radiation doses of 50 and 25 Gy, respectively. We report the details of the uterine assessment, determining suitability of conception with her own uterus, pregnancy surveillance, and reproductive outcome.
In Vitro Fertilization stimulation grafted ovarian tissue to assist with pregnancy.
Successful conception and live birth, pregnancy complications and management of high risk pregnancy.
The results of magnetic resonance imaging and pelvic ultrasound showed a small uterus with preserved junctional zone anatomy, and although the endometrium was initially thin after high-dose estrogen administration, endometrial thickness increased with time. Twelve grafted ovarian tissue stimulation cycles led to 4 embryo transfers, the last of which resulted in a live birth. She had 2 cervical cerclage procedures because of cervical shortening and delivered a 3.3-kg healthy female neonate at 38 weeks of gestation via lower-segment cesarean section.
Successful pregnancy is possible from ovarian tissue grafted into an irradiated pelvis, with high-dose uterine exposure. Careful uterine assessment needs to be undertaken to determine suitability of conception attempt with a patient’s own uterus, in consultation with the medical team. Further studies are needed to correlate imaging and biopsy findings with reproductive outcomes.
BackgroundLittle is known about the learning curve characteristics of residents undertaking simulation-based education. It is important to understand the time for acquisition and decay of knowledge ...and skills needed to manage rare and difficult clinical situations.MethodTen anaesthesiology residents underwent simulation-based education to manage a cannot intubate cannot ventilate scenario during general anaesthesia for caesarean section. Their performance was measured using an assessment tool and debriefed by two experienced anaesthesiologists. The parameters against which the performance was judged were grouped into preoperative assessment, preoperative patient care, equipment availability, induction sequence, communication and adherence to airway algorithm protocol. The scenario was repeated at 6 and 12 months thereafter. The residents’ acquisition of knowledge, technical and non-technical skills were assessed and compared at baseline, 6 months and end of 12 months.ResultThe skills of preoperative assessment, preoperative care and communication quickly improved but the specific skill of managing a difficult airway as measured by adherence to an airway algorithm required more than 6 months (CI at 6 vs 12 months: −3.4 to –0.81, p=0.016). The skills of preoperative assessment and preoperative care improved to a higher level quickly and were retained at this improved level. Communication (CI at 0 vs 6 months: −3.78 to −0.22, p=0.045 and at 6 vs 12 months : −3.39 to −1.49, p=0.007) and difficult airway management skill were slower to improve but continued to do so over the 12 months. The compliance to machine check was more gradual and showed an improvement at 12 months.ConclusionOur study is unique in analysing the learning curve characteristics of different components of a failed obstetric airway management skill. Repeated simulations over a longer period of time help in better reinforcement, retention of knowledge, recapitulation and implementation of technical and non-technical skills.
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