Trial Participation is Not Associated with Better Biochemical Recurrence-free Survival in a Large Cohort of External Beam Radiotherapy-Treated Intermediate- and High-Risk Prostate Cancer Patients.

AIMS: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT). MATERIALS AND METHODS: We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups. RESULTS: Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts. CONCLUSIONS: Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.

Focal HDR brachytherapy boost to stereotactic radiotherapy (fBTsRT) for prostate cancer: a phase II randomized controlled trial.

BACKGROUND: For patients with a higher burden of localized prostate cancer, radiation dose escalation with brachytherapy boosts have improved cancer control outcomes at the cost of urinary toxicity. We hypothesize that a focal approach to brachytherapy boosts targeting only grossly visualized tumor volumes (GTV) combined with stereotactic radiotherapy will improve quality of life (QoL) outcomes without compromising cancer control. METHODS: 150 patients with intermediate or high-risk prostate cancer will be enrolled and randomized 1:1 in a cohort multiple randomized clinical trial phase 2 design. Patients are eligible if planned for standard-of-care (SOC) high dose rate (HDR) brachytherapy boost to radiotherapy (RT) with GTVs encompassing < 50% of the prostate gland. Those randomly selected will be offered the experimental treatment, consisting of focal HDR brachytherapy boost (fBT) of 13-15 Gy in 1 fraction followed by stereotactic radiotherapy (sRT) 36.25-40 Gy in 5 fractions to the prostate (+/- 25 Gy to the elective pelvis) delivered every other day. The primary endpoint is to determine if fBTsRT is superior to SOC by having fewer patients experience a minimally important decline (MID) in urinary function as measured by EPIC-26 at 1 and 2 years. Secondary endpoints include rates of toxicity measured by Common Terminology Criteria for Adverse Events (CTCAE), and failure-free survival outcomes. DISCUSSION: This study will determine whether a novel approach for the treatment of localized prostate cancer, fBTsRT, improves QoL and merits further evaluation. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04100174 as a companion to registry NCT03378856 on September 24, 2019.

Changes in periprostatic adipose tissue induced by 5α-reductase inhibitors.

There is increasing interest in periprostatic fat and its influence on prostate cancer aggressiveness. In vitro data suggest that adipose stromal/stem cells (ASCs) can increase production of cytokines and growth factors resulting in invasive growth and metastasis in prostate cancer. The objective of the study was to determine the interaction between 5α-reductase inhibitors (5ARIs) and periprostatic adipose tissue (PPAT) and factors of prostate cancer aggressiveness. In this retrospective study, we identified 61 patients treated with 5ARIs for a period of ≥12 months before undergoing radiation therapy (brachytherapy or external beam radiotherapy). The control group consisted of 117 patients without any exposure to 5ARIs. Prior to being treated, all patients underwent abdominal computed tomography (CT). To measure PPAT, we defined the fat pad anteriorly to the prostate, as well as the intra-abdominal visceral adipose tissue (VAT) and subcutaneous tissue (SAT) at the level of L4/L5. All contours were performed manually. These adipose tissue measurements were correlated with the Cancer of the Prostate Risk Assessment (CAPRA) score using Pearson correlation coefficient. Differences in fat contents were evaluated using Student's t-test. Median time on 5ARIs for the 61 patients was 12 months (range 12-96). Patient on 5ARIs had a significantly (p < 0.001) smaller PPAT (0.4, SD 0.5) than patients without a 5ARI (0.6 cc, SD 0.4). There was no significant correlation between the CAPRA score and fat measurements when adjusted for 5ARI use (p = 0.18). In non-5ARI users, BMI was not correlated with PPAT but was correlated with SAT and VAT volume and its density. There were no significant differences in diabetics (p = 0.3), metformin users (p = 0.4) or statin users (p = 0.09) between both groups. 5ARIs taken for at least 12 months induce changes in PPAT volume. Whether these changes or the extent of changes will have an influence on outcome remains unknown.

Prospective Phase II Trial of Once-weekly Hypofractionated Radiation Therapy for Low-risk Adenocarcinoma of the Prostate: Late Toxicities and Outcomes.

AIMS: To report the long-term toxicities and sexual quality of life of a once-weekly hypofractionated radiation therapy schedule for low-risk prostate cancer. MATERIALS AND METHODS: A multi-institutional phase II trial was conducted, using a three-dimensional conformal radiation therapy (3D-CRT) approach for low-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and prostate-specific antigen ≤ 10 ng/ml). Forty-five Gray (Gy) were delivered in nine fractions of 5 Gy given on a weekly basis. Acute and late genitourinary and gastrointestinal toxicities were graded according to the Radiation Therapy Oncology Group toxicity scale. Sexual function and sexual bother were assessed with the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. RESULTS: Between March 2006 and August 2008, 80 patients were treated, with a median age of 69 years (interquartile range 64-72). The median follow-up was 83 months (interquartile range 73-85 months). At 7 years, overall survival was 88%. No patients died of prostate cancer. Cumulative grade ≥2 genitourinary and gastrointestinal late toxicity was reported for 31.3% and 30% of our patients, respectively. Cumulative grade ≥3 genitourinary and gastrointestinal late toxicity was seen in 3.8% and 12.5% of cases, respectively. Late genitourinary grade 2 toxicity was correlated with the occurrence of acute genitourinary grade 2 toxicity (P = 0.006). The occurrence of late gastrointestinal toxicity was not correlated with acute gastrointestinal toxicity. Pre-treatment EPIC sexual function was low (37.5%) and the mean EPIC sexual function score at 7 years after treatment was 14%. On the other hand, pre-treatment EPIC sexual bother reached 80.5%, meaning little bother, and remained stable during follow-up. CONCLUSIONS: Once-weekly 3D-CRT leads to excellent biochemical disease-free survival and acceptable toxicities. Pre-treatment EPIC sexual function dropped by 42% at 5 years of follow-up. This functional deficit did not bother patients, possibly due to the already low sexual function at baseline.

Publication rates of abstracts presented at the 2007 and 2010 Canadian Association of Radiation Oncology meetings.

BACKGROUND: We set out to determine the rate, time-trend, and defining factors associated with publication of abstracts presented at two annual scientific meetings of the Canadian Association of Radiation Oncology (caro). METHODS: All abstracts accepted for oral presentation in 2007 and 2010 were obtained from the caro program archives and searched using the PubMed database. Variables in the dataset included the year of presentation at caro and of publication in a scientific journal, time to publication (in months), publishing journal, impact factor of publishing journal, abstract research type (clinical, technical, or basic science) and disease site, country of origin, and university of the first author. RESULTS: Overall, 88 of 172 abstracts from the 2007 (n = 102) and 2010 (n = 70) caro meetings were published in peer-reviewed journals (publication rate: 51.2%). Mean time to publication was 18.5 months. Among research types, clinical research (62.5%) and, among disease sites, prostate cancer (40.4%) were most likely to be published. Of all the abstracts, 50.1% were contributed by only 2 universities, a proportion that resembles the overall abstract publication rate of 51.2%. The conversion rate for those 2 universities (51.1%) is very similar to that for all abstracts presented at the two meetings. CONCLUSIONS: Half the abstracts presented at the 2007 and 2010 caro meetings were ultimately published in journals indexed in PubMed by about 1.5 years after presentation. Half the abstracts and publications came from just 2 universities; more must to be done to close the gap.

Using fiducial markers in the prostate bed in postprostatectomy external beam radiation therapy improves accuracy over surgical clips.

BACKGROUND AND PURPOSE: The purpose of this work was to assess the stability of fiducial markers in the prostate bed and compared their use to surgical clips. PATIENTS AND METHODS: In this study, 3-4 gold fiducial markers were transrectally implanted in the prostate bed of 14 patients. The stability of the fiducial markers position (fiducial markers fixity) over an EBRT course was assessed. Furthermore, the advantages of the fiducial markers compared to the surgical clips were assessed and the interobserver variation between the two technologies was compared. RESULTS: The mean fiducial marker migration during a course of EBRT was small with 1.2 mm (SD ± 0.8 mm). Compared to fiducial markers, the matches with surgical clips were mismatched ≥ 2 mm in 68% of treatments. This discrepancy of > 2 mm was on average 3.7 ± 1.3 mm. There was less interobserver variability for matching of fiducial markers (0.8 ± 0.7 mm) than for surgical clips (2.0 ± 1.6 mm). CONCLUSION: Fiducial markers showed less interobserver variability in matching and less variation in position than surgical clips. Fiducial markers could ultimately help in reducing treatment margins.

Prognostic impact of abdominal adiposity, waist circumference and body mass index in patients with intermediate-risk prostate cancer treated with radiotherapy.

OBJECTIVE: We tested the potential role of abdominal visceral (VAT) and subcutaneous (SAT) adipose tissues, waist circumference (WC) and body mass index (BMI) as prognostic factors in patients with intermediate-risk prostate cancer (clinical stage T1b-2b, and Gleason Score (GS)=7 and prostate-specific antigen PSA level <15 ng ml(-1), or GS ≤ 6 and PSA between 10 and 20 ng ml(-1)) treated with ultrasound-based image-guided radiotherapy. METHODS: VAT, SAT and WC (measured from planning abdominal computed tomography) and BMI were compared with clinical and pathologic factors using univariate analyses. Cox regression analyses were performed to evaluate whether obesity indices significantly predicted biochemical disease free-survival (bDFS). RESULTS: Of the 112 eligible patients, 30 (27%) were obese. Median BMI at baseline was 27.5 kg m(-2) (range, 19.2-51.5 kg m(-2)). Greater abdominal adiposity, WC and BMI were significantly associated with younger age at diagnosis and increased prostate volume (P=0.003 and P=0.002, respectively). No significant correlation between obesity measures and T-stage, GS, PSA or percentage of positive cores at biopsy was found. On Cox regression analyses, none of the obesity measures predicted for bDFS. No association was observed between obesity indices and surrogate markers of biochemical failure as PSA nadir (nPSA) or time to nPSA. CONCLUSIONS: Abdominal adiposity, WC and BMI are associated with younger age at diagnosis and greater prostate volume but not with an increased risk of biochemical failure in patients with intermediate-risk prostate cancer.

Sci-Sat AM(2): Brachy-07: Tomosynthesis-based seed reconstruction in LDR prostate brachytherapy: A clinical study.

To develop a tomosynthesis-based dose assessment procedure that can be performed after an I-125 prostate seed implantation, while the patient is still under anaesthesia on the treatment table. Our seed detection procedure involves the reconstruction of a volume of interest based on the backprojection of 7 seed-only binary images acquired over an angle of 60° with an isocentric imaging system. A binary seed-only volume is generated by a simple thresholding of the volume of interest. Seeds positions are extracted from this volume with a 3D connected component analysis and a statistical classifier that determines the number of seeds in each cluster of connected voxels. A graphical user interface (GUI) allows to visualize the result and to introduce corrections, if needed. A phantom and a clinical study (24 patients) were carried out to validate the technique. A phantom study demonstrated a very good localization accuracy of (0.4+/-0.4) mm when compared to CT-based reconstruction. This leads to dosimetric error on D90 and V100 of respectively 0.5% and 0.1%. In a patient study with an average of 56 seeds per implant, the automatic tomosynthesis-based reconstruction yields a detection rate of 96% of the seeds and less than 1.5% of false-positives. With the help of the GUI, the user can achieve a 100% detection rate in an average of 3 minutes. This technique would allow to identify possible underdosage and to correct it by potentially reimplanting additional seeds. A more uniform dose coverage could then be achieved in LDR prostate brachytherapy.

Preoperative radiotherapy without femoral shielding for prevention of heterotopic ossification in hydroxyapatite-coated hip prostheses.

Twenty-seven consecutive patients at high risk of developing heterotopic ossifications (HO) after implantation of a hydroxyapatite (HA)-coated hip prosthesis were irradiated with a single dose of 7 Gy, at least 4 h before the operation. The femoral stem was not shielded during radiotherapy (RT). After a median follow-up of 14.8 months, no clinically significant HO could be found, while 12 (52%) patients in this high-risk population had only minor HO (grade I). No reoperation was needed, and no evidence of prosthesis migration was observed. We conclude that single-dose, preoperative RT for HA-coated hip prosthesis can effectively inhibit HO. Not blocking the femoral stem does not result in prosthesis migration.

Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study.

To assess the prognostic factors in patients with transitional-cell carcinoma of the renal pelvis and/or ureter, a series of 138 patients with transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicentre study. 12 patients with distant metastases were excluded from the statistical evaluation. All but 3 patients underwent radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 10), and ureterectomy (n = 5). Sixty-one per cent (n = 77) of the tumours were located in the renal pelvis, and 21% (n = 27) in the ureter (both in 22 [17%]). Following surgery, residual tumour was still present in 33 patients (16 microscopic and 17 macroscopic). Postoperative radiotherapy was given to 45 (36%) patients. The median follow-up period was 39 months. In a median period of 9 months, 66% of the patients relapsed (34 local, 7 locoregional, 16 regional, and 24 distant). The 5- and 10-year survival were 29% and 19%, respectively, in all patients. In univariate analyses, statistically significant factors influencing the outcome were Karnofsky index, pT-classification, pN-classification, tumour localisation, grade, and residual tumour after surgery. Multivariate analysis revealed that independent prognostic factors influencing outcome were pT-classification, the existence of residual tumour, and tumour localisation. In patients with urothelial renal pelvis and/or ureter tumours, a radical surgical attitude is mandatory; and the presence of tumour in the ureter is associated with a poorer prognosis.

Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy: the importance of the target volume.

PURPOSE: To assess the health-related quality of life (QOL) of long-term survivors of carcinomas of different subsites of the head and neck following curative radiotherapy (RT). PATIENTS AND METHODS: Patients continuously free from recurrence or second primary tumors treated 1988-1994 were contacted 5.1 to 5.9 years after RT and asked to fill in the EORTC QLQ-C30 core questionnaire and the H&N cancer module. RT had been restricted to the glottis (group A; carcinomas of the vocal cord T1-2 N0), or had included bilateral neck nodes and the primary tumor outside the nasopharynx (group B; AJC Stage II to IV) or within the nasopharynx, respectively (group C; Stage II to IV). Response rate was 97% (group A; n = 41), 69% (group B; n = 26) and 71% (group C; n = 12), respectively. The groups were different with respect to age (older in group A), alcohol consumption (absent in group C) and proportion of females (more in group C). RESULTS: Patients with nasopharyngeal cancer reported the highest morbidity on the H&N module (dry mouth, sticky saliva, trismus, problems with teeth, trouble eating). However, these symptoms did not have a high impact on global QOL or function scores on the QLQ-C30 core questionnaire. Patients in group B reported a lower global QOL but less severe symptoms on the module. CONCLUSION: The high morbidity of patients treated for a nasopharyngeal cancer may be explained by the location of the target volume which included the bilateral temporo-mandibular joints and the salivary glands. These patients require appropriate care during follow-up and will probably profit most from new RT techniques with sparing of normal tissues.

Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and -IV carcinomas of the head and neck. Long-term results including functional outcome.

PURPOSE: To assess the survival rate, the probability of local control, the patterns of relapse and late sequelae including self-reported quality of life in patients treated with hyperfractionated radiotherapy (RT) and simultaneous CDDP chemotherapy for stage-III to stage-IV carcinomas of the head and neck. METHODS: From 1988 to 1994, 64 patients (median age 55.5 years) with carcinomas of different subsites, excluding the nasopharynx, were treated in a pilot study with 1.2 Gy bid (6 h interval; total dose 74.4 Gy) and simultaneous CDDP (20 mg/m2 daily, 5 days in week 1 and 5) and followed at regular intervals. Overall survival and local control, as well as the rates of late toxicity, were estimated using the actuarial method. Median follow-up was 3.3 years for all and 5.2 years for surviving patients. To assess the quality of life, the EORTC QLQ-C 30 questionnaire and the H&N35 module questionnaire were sent to the patients surviving with no evidence of disease or second primary tumors; they were answered by 15/23 (67%). RESULTS: Overall survival was 37% at 5 years, whereas disease-specific survival was 59%. Twenty-three patients died from uncontrolled head and neck cancer. Second primary tumors were observed in 13 patients, most frequently in the lung. Local control without salvage surgery was 74% at 5 years for all subsites and stages, and loco-regional disease-free survival was 72%. Eleven patients developed distant metastases, which was the only site of failure in 6 cases. Salvage surgery was successful in 2 cases. The actuarial estimates of > or = grade-3 late toxicity was 4% for the mandibular bone and 23% for dysphagia, and 50% of the patients experienced a permanent xerostomy. Self-reported global quality of life in surviving patients was good (mean 68 points on a scale 0 to 100); consequences of impaired salivary function had most impact on nutritional and social aspects. CONCLUSIONS: Hyperfractionated RT with concomitant CDDP is well tolerated and highly efficient in controlling moderately advanced to advanced cancers of the head and neck. Second primary tumors are the main cause of death after 3 years and were observed outside of the irradiated area, most frequently in the lung. Even after RT of large volumes to a high dose, salvage surgery can be successfully performed in individual cases. Self-reported quality of life of surviving patients is good, despite xerostomy-associated nutritional difficulties.