A territory-wide real-world efficacy and toxicity analysis of abiraterone acetate versus docetaxel in 574 Asian patients with metastatic hormone-sensitive prostate cancer.

INTRODUCTION: Abiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. PATIENTS AND METHODS: The medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: A total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a ≥ 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade ≥ 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. CONCLUSION: In Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group.

Frameless versus frame-based stereotactic radiosurgery for intracranial arteriovenous malformations: A propensity-matched analysis.

Objective: The frameless linear accelerator (LINAC) based stereotactic radiosurgery (SRS) has been evolving with a reduction in patient discomfort. However, there was limited evidence comparing frame-based and frameless SRS for intracranial arteriovenous malformations (AVM). We aimed to compare the treatment outcomes between frame-based and frameless LINAC SRS. Materials and Methods: This retrospective cohort compared the outcomes of frame-based LINAC SRS (1998-2009) with frameless LINAC SRS (2010-2020). The primary outcome was the obliteration rate. The other outcomes included the neurological, radiological, and functional outcomes after SRS. A matched cohort was identified by propensity scores for further comparisons. Results: A total of 65 patients were included with a mean follow-up time of 13.2 years (158.5 months). There were 40 patients in the frame-based group and 25 patients in the frameless group. The overall obliteration rate was comparable (Frame-based 82.5% vs Frameless 80.0%, p = 0.310) and not significantly different over time (log-rank p = 0.536). The crude post-SRS hemorrhage rate was 1.5% and the incidence was 0.3 per 100 person-years. There were 67.7% of patients with AVM obliteration without new persistent neurological deficits at the last visit and 56.9% of patients with AVM obliteration without any deficits (transient or persistent) during the entire follow-up period. Four patients (8.0%) developed late onset persistent adverse radiation effects (more than 96 months after SRS) among 50 patients with more than 8-year surveillance. In the propensity-matched cohort of 42 patients, there was no significant difference in AVM obliteration (Frame-based vs Frameless, log-rank p = 0.984). Conclusion: Frameless and frame-based LINAC SRS have comparable efficacy in intracranial AVM obliteration. A longer follow-up duration may further characterize the rate of late adverse radiation effects in frameless SRS.

Outcomes of neoadjuvant chemotherapy using gemcitabine and cisplatin in muscle invasive bladder cancer: A retrospective analysis of the patient and treatment factors in a single institute.

BACKGROUND: Meta-analysis had shown a significant 5% absolute survival benefit in favour of neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy before radical cystectomy (RC) and pelvic lymphadenectomy (PLND) for patients with muscle invasive bladder cancer (MIBC). Those who had pathological complete response (pCR) to NAC could have long-term progression-free survival (PFS) and overall survival (OS). AIM: To identify the treatment and patient factors which could predict a pCR to NAC and the associated PFS and OS in a single institute. METHODS AND RESULTS: We retrospectively reviewed the records of patients who had received NAC with gemcitabine and cisplatin (GC) in our centre from January 2004 to December 2017. The patients' age, tumour stage, baseline estimated glomerular filtration rate (eGFR), chemotherapy chart, and pathological information were recorded. There were 25 men and five women who had received NAC followed by RC. pCR was noted in the surgical specimen of 11 (37%) patients. The mean dose of gemcitabine was significantly higher in the pCR group than the non-pCR group (9850 vs 7852 mg, P = 0.039) as was the dose-intensity of cisplatin (87.4% vs 71.3%, P = 0.044). After a median follow-up of 38 months (range 4.3-154), seven patients had disease progression. The estimated 3-year PFS is 74.9% (95% confidence interval [CI], 66.7%-83.3%). None of the patients who achieved pCR relapsed, while six out of seven patients who had pN1 disease developed distant metastasis (DM). Only two patients died of DM while two other patients died of unrelated causes. The estimated 3-year OS is 88.9% (95% CI 82.8%-95%). CONCLUSIONS: We have demonstrated that the dose intensity of GC is a major determinant of pCR, which predicts longer RFS and OS. Further research in gene expression profiling of MIBC to help selecting patient for NAC is needed.

Reduction of intra-fraction prostate motion - Determining optimal bladder volume and filling for prostate radiotherapy using daily 4D TPUS and CBCT.

BACKGROUND AND PURPOSE: Inconsistent bladder and rectal volumes have been associated with motion uncertainties during prostate radiotherapy. This study investigates the impact of these volumes to determine the optimal bladder volume. MATERIALS AND METHODS: 60 patients from two Asian hospitals were recruited prospectively. 1887 daily cone-beam computed tomography (CBCT) images were analysed. Intra-fraction motion of the prostate was monitored real-time using a four-dimension transperineal ultrasound (4D TPUS) Clarity® system. The impact of planned bladder volume, adequacy of daily bladder filling, and rectum volume on mean intra-fraction motion of the prostate was analysed. Patients' ability to comply with the full bladder hydration protocol and level of frustration was assessed using a questionaire. Acute side effects were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and quality of life (QoL) assessed using the International Prostate Symptom Score (IPSS). RESULTS: The mean (SD) bladder and rectum volumes achieved during daily treatment were 139.7 cm3 (82.4 cm3) and 53.3 cm3 (18 cm3) respectively. Mean (SD) percentage change from planned CT volumes in bladder volume was reduced by 8.2% (48.7%) and rectum volume was increased by 12.4% (42.2%). Linear Mixed effect model analysis revealed a reduction in intra-fraction motion in both the Sup/Inf (p = 0.008) and Ant/Post (p = 0.0001) directions when the daily bladder was filled between 82 and 113% (3rd Quartiles) of the planned CT volumes. A reduction in intra-fraction motion of the prostate in the Ant/Post direction (z-plane) (p = 0.03) was observed when the planned bladder volume was greater than 200 ml. Patients complied well with the hydration protocol with minimal frustration (mean (SD) scores of 2.1 (1.4) and 1.8 (1.2) respectively). There was a moderate positive correlation (0.496) between mean bladder volume and IPSS reported post-treatment urinary straining (p = 0.001). CONCLUSIONS: A planned bladder volume >200 cm3 and daily filling between 82 and 113%, reduced intra-fraction motion of the prostate. The hydration protocol was well tolerated.

Analysis of intra-fraction prostate motion and derivation of duration-dependent margins for radiotherapy using real-time 4D ultrasound.

BACKGROUND AND PURPOSE: During radiotherapy, prostate motion changes over time. Quantifying and accounting for this motion is essential. This study aimed to assess intra-fraction prostate motion and derive duration-dependent planning margins for two treatment techniques. MATERIAL AND METHODS: A four-dimension (4D) transperineal ultrasound Clarity® system was used to track prostate motion. We analysed 1913 fractions from 60 patients undergoing volumetric-modulated arc therapy (VMAT) to the prostate. The mean VMAT treatment duration was 3.4 min. Extended monitoring was conducted weekly to simulate motion during intensity-modulated radiation therapy (IMRT) treatment (an additional seven minutes). A motion-time trend analysis was conducted and the mean intra-fraction motion between VMAT and IMRT treatments compared. Duration-dependent margins were calculated and anisotropic margins for VMAT and IMRT treatments were derived. RESULTS: There were statistically significant differences in the mean intra-fraction motion between VMAT and the simulated IMRT duration in the inferior (0.1 mm versus 0.3 mm) and posterior (-0.2 versus -0.4 mm) directions respectively (p ≪ 0.01). An intra-fraction motion trend inferiorly and posteriorly was observed. The recommended minimum anisotropic margins are 1.7 mm/2.7 mm (superior/inferior); 0.8 mm (left/right), 1.7 mm/2.9 mm (anterior/posterior) for VMAT treatments and 2.9 mm/4.3 mm (superior/inferior), 1.5 mm (left/right), 2.8 mm/4.8 mm (anterior/posterior) for IMRT treatments. Smaller anisotropic margins were required for VMAT compared to IMRT (differences ranging from 1.2 to 1.6 mm superiorly/inferiorly, 0.7 mm laterally and 1.1-1.9 mm anteriorly/posteriorly). CONCLUSIONS: VMAT treatment is preferred over IMRT as prostate motion increases with time. Larger margins should be employed in the inferior and posterior directions for both treatment durations. Duration-dependent margins should be applied in the presence of prolonged imaging and verification time.

Survival analysis of malignant epidural spinal cord compression after palliative radiotherapy using Tokuhashi scoring system and the impact of systemic therapy.

BACKGROUND: Previous studies have shown similar clinical outcomes of both single and multi-fraction (Fr) radiation therapy among malignant epidural spinal cord compression (MSCC) patients with poor prognosis; whereas, patients expected to have longer survival may require long-course radiotherapy to prevent local failure. However, such a poor prognosis risk group has not yet been clearly identified for use in daily clinical practice. We examined if the known predictive Tokuhashi scoring system could be adapted in MSCC patients treated with palliative radiation therapy. METHODS: A retrospective review of the treatment outcomes of MSCC patients who received palliative radiotherapy from January 2014 to May 2015 was conducted. The patients were stratified into two groups according to the Tokuhashi scoring system: group 1 (score <9), expected survival <6 months, and group 2 (score >8), expected survival >6 months. Their survival was tested against subsequent systemic therapy (chemotherapy, targeted or hormonal therapy) and other risk factors including age, primary site, visceral metastasis, baseline motor function, prior radiotherapy and radiotherapy fractionation (single or multiple). RESULTS: The outcomes of 119 patients were studied, 116 (97.5%) patients had already succumbed. The overall median survival was 55 days (range, 4-576 days). Ninety-three patients (78.2%) belonged to group 1. The median dose delivered was 25 Gy in 5 Frs [range, 7 Gy in 2 Frs-40 Gy in 10 Frs (to the cauda equina)]. Only nine patients (7.6%) received single-Fr radiotherapy, all belonging to Tokuhashi group 1. Patients belonging to group 1 had shorter median survival than group 2; 49 and 108 days, respectively (P=0.003). Among all the patients, subsequent systemic treatment [hazard ratio (HR) =0.407; 95% confidence interval (CI), 0.236-0.702; P=0.001], non-visceral metastasis (HR =0.608; 95% CI, 0.387-0.956; P=0.031) and primary lung or breast or prostate cancer (P=0.029) were associated with better survival in multivariate analysis. For patients in group 1, primary breast or prostate cancer (HR =0.264; 95% CI, 0.122-0.572; P=0.001) or lung cancer (HR =0.421; 95% CI, 0.246-0.719; P=0.002), non-visceral metastasis (HR =0.453; 95% CI, 0.264-0.777; P=0.004), multi-Fr (HR =0.455; 95% CI, 0.217-0.956; P=0.038) and subsequent systemic therapy (HR =0.460; 95% CI, 0.252-0.842; P=0.012) were associated with better survival. The survival of a subset of patients in group 1 without subsequent systemic therapy was dismal (median survival only 40 days) and not altered by radiotherapy schedule (P=0.189). CONCLUSIONS: MSCC comprises a very heterogenous group of patients, even under the Tokuhashi grouping. Systemic therapy or visceral metastasis may be more important prognostic factors. Further studies are necessary to better select the poor prognosis risk group. In clinical practice, single-Fr radiotherapy could be considered in Tokuhashi group 1 patients due to their expected short survival, especially for those without reasonable systemic treatment options.

Primary yolk sac tumour of the urinary bladder: A case report and review of the literature.

We present a case of rare primary yolk sac tumour of the urinary bladder in adulthood. A 31-year-old female patient presented with a history of chronic ketamine abuse, which has not previously been shown to be associated with malignancy development. The final diagnosis was established only after radical cystectomy. A computed tomography (CT) scan showed paraaortic lymph node metastasis. The patient was treated with systemic chemotherapy. A review of the literature revealed that surgical excision and cisplatin-based chemotherapy remain to be the standard of care for extragonadal yolk sac tumours.