Association between MRI histogram features and treatment response in locally advanced cervical cancer treated by chemoradiotherapy.

OBJECTIVE: To examine the associations of histogram features of T2-weighted (T2W) images and apparent diffusion coefficient (ADC) with treatment response in locally advanced cervical cancer (LACC) following concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: Fifty-eight patients who underwent a 4-week CCRT regimen with MRI prior to treatment (pre-CCRT) and after treatment (post-CCRT) were retrospectively analysed. Histogram features were calculated from volumes of interest (VOIs) from one radiologist on T2W images and ADC maps. VOIs from two radiologists were used to assess observer repeatability in delineation and feature values at both time-points with the Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC). Treatment response was defined as a 90% reduction in tumour volume. Paired Mann-Whitney U tests were used to determine if features changed significantly between examinations. Two-sample Mann-Whitney U tests were used to identify features that were significantly different between response groups. Receiver operating characteristic (ROC) analysis was done on significantly different MRI features between treatment response groups. RESULTS: Pre-CCRT delineation and feature repeatability were generally good (DSC > 0.700; ICC > 0.750). Post-CCRT repeatability was low (DSC < 0.700; ICC < 0.750), but ADC mean and percentiles retained good ICC scores. All features, except for T2WKurtosis, significantly changed between examinations. Post-CCRT ADC50 was the only feature that demonstrated both good observer variability and significant differences between treatment response groups (p = 0.036) and had an AUC of 0.701 with a cut-off of 1.357 × 10-6 mm2/s. CONCLUSION: ADC and T2W histogram features could be used to track changes in LACC tumours undergoing CCRT. Post-CCRT ADC50 was associated with treatment response with good observer repeatability. KEY POINTS: • Pre-treatment tumour delineation and histogram feature values had good observer repeatability, while these were less repeatable at post-treatment. • MRI histogram analysis could be used to track changes in the tumour as it undergoes concurrent chemoradiotherapy. • Post-treatment median ADC was associated with treatment response and had good repeatability.

Intravoxel incoherent motion MRI assessment of chemoradiation-induced pelvic bone marrow changes in cervical cancer and correlation with hematological toxicity.

PURPOSE: To investigate bone marrow changes after chemoradiation (CRT) using intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) and correlate imaging changes with hematological toxicity (HT) in patients with locally advanced cervical cancer. MATERIALS AND METHODS: Thirty-nine patients with newly diagnosed cervical cancer were prospectively recruited for two sequential 3.0T IVIM-MRI studies: before treatment (MRI-1) and 3-4 weeks after standardized CRT (MRI-2). The irradiated pelvic bone marrow was outlined as the regions of interest to derive the true diffusion coefficient (D) and perfusion fraction (f) based on a biexponential model. The apparent coefficient diffusion (ADC) was derived using the monoexponential model. Changes in these parameters between MRI-1 and MRI-2 were calculated as ΔD, Δf, and ΔADC. HT was defined accordingly to NCI-CTCAE (v. 4.03) of grade 3 and above. Statistical analysis was performed using Mann-Whitney U-test. RESULTS: The median age of patients was 54 years old (range 27-83 years old); 14 patients suffered from HT. Early bone marrow changes (3-4 weeks) of ΔD showed a significant difference between HT and non-HT groups (6.4 ± 19.7% vs. -6.4 ± 19.4%, respectively, P = 0.041). However, no significant changes were noted in Δf (3.7 ± 13.3% vs. 1.5 ± 12.5% respectively, P = 0. 592) and ΔADC (5.5 ± 26.3% vs. -3.3 ± 27.0% respectively, P = 0.303) between the HT and non-HT groups. Δf increased insignificantly for both groups. CONCLUSION: ΔD was the only significant parameter to differentiate early cellular environment changes in bone marrow after CRT, suggestive that ΔD was more sensitive than Δf and ΔADC to reflect the underlying microenvironment injury. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1491-1498.

Perfusion and diffusion characteristics of cervical cancer based on intraxovel incoherent motion MR imaging-a pilot study.

OBJECTIVES: To investigate the tissue characteristics of cervical cancer based on the intravoxel incoherent motion (IVIM) model and to assess the IVIM parameters in tissue differentiation in the female pelvis. METHODS: Sixteen treatment-naïve cervical cancer and 17 age-matched healthy subjects were prospectively recruited for diffusion-weighted (b = 0-1,000 s/mm(2)) and standard pelvic MRI. Bi-exponential analysis was performed to derive the perfusion parameters f (perfusion fraction) and D* (pseudodiffusion coefficient) as well as the diffusion parameter D (true molecular diffusion coefficient) in cervical cancer (n = 16), normal cervix (n = 17), myometrium (n = 33) and leiomyoma (n = 14). Apparent diffusion coefficient (ADC) was calculated. Kruskal-Wallis test and receiver operating characteristics (ROC) curves were used. RESULTS: Cervical cancer had the lowest f (14.9 ± 2.6%) and was significantly different from normal cervix and leiomyoma (p < 0.05). The D (0.86 ± 0.16 x 10(-3) mm2/s) was lowest in cervical cancer and was significantly different from normal cervix and myometrium (p < 0.05) but not leiomyoma. No difference was observed in D*. D was consistently lower than ADC in all tissues. ROC curves indicated that f < 16.38%, D < 1.04 × 10(-3) mm(2)/s and ADC < 1.13 × 10(-3) mm(2)/s could differentiate cervical cancer from non-malignant tissues (AUC 0.773-0.908). CONCLUSIONS: Cervical cancer has low perfusion and diffusion IVIM characteristics with promising potential for tissue differentiation. KEY POINTS: • Diffusion-weighted MRI is increasingly applied in evaluation of cervical cancer. • Cervical cancer has distinctive perfusion and diffusion characteristics. • Intravoxel incoherent motion characteristics can differentiate cervical cancer from non-malignant uterine tissues.

Using Virtual Reality to teach ultrasound-guided needling skills for regional anaesthesia: A randomised controlled trial.

STUDY OBJECTIVE: We previously designed and validated a virtual reality-based simulator to help train novices in ultrasound-guided needling skills necessary for safe and competent ultrasound-guided regional anaesthesia. This study was designed to compare the performance and error rates of novices trained by a human faculty aided with the assistance of this virtual reality simulator (virtual reality-assisted training), versus novices trained wholly by humans (conventional training). DESIGN, SETTING, AND PARTICIPANTS: In this single centre, randomised controlled study, we used a standardised teaching protocol, rigorous blinding, iterative training of assessors, and validated global rating scale and composite error score checklists to assess skills learning of novice participants. MAIN RESULTS: We recruited 45 novices and scored 270 assessments of performance and error rates. Inter-rater correlation coefficient of reliability of scoring between assessors for the global rating scale was 0.84 (95%CI 0.68-0.92) and for the composite error score checklist was 0.87 (95%CI 0.73-0.93). After adjustment for age, sex, Depression, Anxiety and Stress-21, and baseline score, there was no statistical difference for virtual reality-assisted training compared to conventional training in final global rating score (average treatment effect -3.30 (95%CI-13.07-6.48), p = 0.51) or in the final composite error score (average treatment effect 1.14 (95%CI -0.60-2.88), p = 0.20). Realism in the virtual reality simulator was similar to real-life when measured by the Presence Questionnaire, all components p > 0.79; and task workload assessed by the NASA-Task Load Index was not statistically different between groups, average treatment effect 5.02 (95%CI -3.51-13.54), p = 0.25. Results were achieved in the virtual reality-assisted group with half the human faculty involvement. CONCLUSION: Novices trained using a hybrid, virtual reality-assisted teaching program showed no superiority to novices trained using a conventional teaching program, but with less burden on teaching resources.

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.

Real-world experience of cabozantinib in Asian patients with advanced renal cell carcinoma following treatment with VEGFR tyrosine kinase inhibitors and/or immune-checkpoint inhibitors.

Background: There is a lack of real-world data on the use of cabozantinib in Asian patients with metastatic renal cell carcinoma. Methods: We conducted a retrospective study to investigate the toxicity and efficacy of cabozantinib in this patient population who progressed on tyrosine kinase inhibitors and/or immune-checkpoint inhibitors from six oncology centres in Hong Kong. The primary endpoint was the incidence of serious adverse events (AEs) attributed to cabozantinib. Secondary safety endpoints included dose reductions and AE-led treatment terminations. Secondary effectiveness endpoints included overall survival, progression-free survival, and objective response rate. Results: A total of 24 patients were included. Half received cabozantinib as a third-line or later-line treatment, whilst 50% received prior immune-checkpoint inhibitors, primarily nivolumab. Overall, 13 (54.2%) patients reported at least one cabozantinib-related AE of grades 3-4. The most commonly reported AEs were hand-foot skin reactions (9; 37.5%) and anaemia (4; 16.7%). Fifteen (65.2%) patients required dose reductions. Three patients discontinued treatment because of AEs. The median progression-free survival and overall survival were 10.3 months and 13.2 months, respectively; 6 (25%) patients achieved partial responses, and 8 (33.3%) achieved stable disease. Conclusion: Cabozantinib was generally well tolerated and efficacious in Asian patients with metastatic renal cell carcinoma who were heavily pretreated.

Comparing effectiveness of image perturbation and test retest imaging in improving radiomic model reliability.

Image perturbation is a promising technique to assess radiomic feature repeatability, but whether it can achieve the same effect as test-retest imaging on model reliability is unknown. This study aimed to compare radiomic model reliability based on repeatable features determined by the two methods using four different classifiers. A 191-patient public breast cancer dataset with 71 test-retest scans was used with pre-determined 117 training and 74 testing samples. We collected apparent diffusion coefficient images and manual tumor segmentations for radiomic feature extraction. Random translations, rotations, and contour randomizations were performed on the training images, and intra-class correlation coefficient (ICC) was used to filter high repeatable features. We evaluated model reliability in both internal generalizability and robustness, which were quantified by training and testing AUC and prediction ICC. Higher testing performance was found at higher feature ICC thresholds, but it dropped significantly at ICC = 0.95 for the test-retest model. Similar optimal reliability can be achieved with testing AUC = 0.7-0.8 and prediction ICC > 0.9 at the ICC threshold of 0.9. It is recommended to include feature repeatability analysis using image perturbation in any radiomic study when test-retest is not feasible, but care should be taken when deciding the optimal feature repeatability criteria.

A comprehensive systematic review and network meta-analysis: the role of anti-angiogenic agents in advanced epithelial ovarian cancer.

The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis (NMA) to synthesize evidence of their comparative effectiveness for improving overall survival (OS) among EOC patients. We searched six databases for randomized controlled trials (RCTs) from their inception to February 2021. We performed an NMA with hazard ratios (HRs) and 95%-confidence intervals (CIs) to evaluate comparative effectiveness among different AAAs in chemotherapy-naïve and recurrent EOC. P-score was used to provide an effectiveness hierarchy ranking. Sensitivity NMA was carried out by focusing on studies that reported high-risk chemotherapy-naïve, platinum-resistant, and platinum-sensitive EOC. The primary outcome was OS. We identified 23 RCTs that assessed the effectiveness of AAAs. In recurrent EOC, concurrent use of trebananib (10 mg/kg) with chemotherapy was likely to be the best option (P-score: 0.88, HR 1.67, 95% CI 0.94; 2.94). The NMA indicated that bevacizumab plus chemotherapy followed by maintenance bevacizumab (P-score: 0.99) and pazopanib combined with chemotherapy (P-score: 0.79) both had the highest probability of being the best intervention for improving OS in high-risk chemotherapy-naïve and platinum-resistant EOC, respectively. AAAs may not play a significant clinical role in non-high-risk chemotherapy-naïve and platinum-sensitive EOC.

Treatment Outcomes of Computer Tomography-Guided Brachytherapy in Cervical Cancer in Hong Kong: A Retrospective Review.

(1) Background: To report the long-term clinical outcomes of computer-tomography (CT)-guided brachytherapy (BT) for locally advanced cervical cancer. (2) Methods: A total of 135 patients with FIGO stage IB-IVA cervical cancer treated with definitive radiotherapy +/- chemotherapy with an IGABT boost at Queen Mary Hospital, Hong Kong, between November 2013 and December 2019 were included. Treatment included pelvic radiotherapy 40 Gy/20 Fr/4 weeks +/- chemotherapy then CT-guided BT (7 Gy × 4 Fr) and a sequential parametrial boost. The primary outcome was local control. Secondary outcomes were pelvic control, distant metastasis-free survival, overall survival (OS) and late toxicities. (3) Results: The median follow-up was 53.6 months (3.0-99.6 months). The five-year local control, pelvic control, distant metastasis-free survival and OS rates were 90.7%, 84.3%, 80.0% and 87.2%, respectively. The incidence of G3/4 long-term toxicities was 6.7%, including proctitis (2.2%), radiation cystitis (1.5%), bowel perforation (0.7%), ureteric stricture (0.7%) and vaginal stenosis and fistula (0.7%). Patients with adenocarcinomas had worse local control (HR 5.82, 95% CI 1.84-18.34, p = 0.003), pelvic control (HR 4.41, 95% CI 1.83-10.60, p = 0.001), distant metastasis-free survival (HR 2.83, 95% CI 1.17-6.84, p = 0.021) and OS (HR 4.38, 95% CI: 1.52-12.67, p = 0.003) rates. Distant metastasis-free survival was associated with HR-CTV volume ≥ 30 cm3 (HR 3.44, 95% CI 1.18-9.42, p = 0.025) and the presence of pelvic lymph node (HR 3.44, 95% CI 1.18-9.42, p = 0.025). OS was better in patients with concurrent chemotherapy (HR 4.33, 95% CI: 1.40-13.33, p = 0.011). (4) Conclusions: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes. (4) Conclusion: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes.

Prevention of docetaxel-associated febrile neutropenia with primary granulocyte colony-stimulating factor in Chinese metastatic hormone-sensitive and castration-resistant prostate cancer patients.

INTRODUCTION: Asian prostate cancer (PC) patients are particularly susceptible to docetaxel-related febrile neutropenia (FN). We evaluated primary granulocyte colony-stimulating factor (GCSF) for preventing FN in Chinese patients with metastatic hormone-sensitive PC (mHSPC) and castration-resistant PC (mCRPC). PATIENTS AND METHODS: Data from two cohorts of 377 Chinese patients with mHSPC (100; 26.5%) and mCRPC (277; 73.5%) treated with docetaxel at six public oncology centres were analysed with multivariate regression. Primary GCSF prophylaxis was defined as administration within 5 days of starting docetaxel. The primary outcome was FN within 21 days of the first docetaxel cycle (1st FN). RESULTS: Primary GCSF was given to 71 (18.8%) patients. FN occurred in 61 patients (16.2%) including 37 (9.8%) during the first cycle. Among patients who developed 1st cycle FN (n = 37) or not (n = 340), 2 and 69 received primary GCSF (5.4 vs. 20.3%, P = .03). Primary GCSF was associated with an overall reduced risk of 1st cycle FN (odds ratio [OR] = 0.22; 95% confidence interval [CI]: 0.05-0.96, P = .04), and similar trends were observed in the mHSPC (OR = 0.36, P = .35) and mCRPC (OR = 0.16, P = .08) subgroups. Poor Eastern Cooperative Oncology Group performance status (>1) was associated with an increased risk of 1st FN (OR = 3.90; 95% CI: 1.66-9.13, P = .002). CONCLUSIONS: To alleviate the risk of docetaxel-related FN, primary GCSF prophylaxis is suggested for Asian mCRPC and mHSPC patients, particularly those with poor performance status.

A cross-sectional study on the attitudes and perceptions of outpatients towards palliative care at the Hong Kong Queen Mary Hospital Hospice Centre.

BACKGROUND: Palliative care aims to improve the quality of life for patients and their families, by helping them to cope with problems associated with illness. It targets four aspects of health: physical, psychological, social, and spiritual. Most of the current literature on palliative care is limited to the perspectives of health professionals. This study aims to investigate the views of outpatients receiving palliative care at the Hong Kong Queen Mary Hospital Hospice Centre (HKQMHHC), which offers palliative care services to cancer patients. METHODS: This observational cross-sectional study was performed with the completion of a single paper- based original questionnaire over 18 afternoon clinic sessions on Thursdays and Fridays from December 2017 to February 2018 at the HKQMHHC. The questionnaire was designed to examine patients' perspectives; in particular, the Edmonton Symptom Assessment Scale (ESAS) was used to assess their symptoms. Descriptive and univariate analyses were performed. RESULTS: One hundred patients attending HKQMHHC were included in the study. The study revealed that all the mean scores for aspects of care offered at the centre were above 8, on a scale of 0-10 with 0 being extremely inadequate and 10 being extremely adequate. Each respondent was able to identify an average of 1.82 of the 4 aspects of palliative care. Eighty-seven percent of respondents perceived the physical aspect of this care to be of the highest priority. A negative correlation (P<0.05) was found between the extent of symptoms experienced by the patient and their satisfaction towards the services offered. CONCLUSIONS: Patients generally held very positive attitudes, reflecting that the services sufficiently met their needs. However, owing to their rather limited knowledge, this may have restricted their perspectives to a largely superficial level, as many discerned palliative care to be simply targeting physical health with medical consultations. Considering the implications of the results, the addition of accessibility and education components to Hong Kong's current system of palliative care is crucial in the betterment of such services for patients. There should also be increased local coverage of palliative care services to facilitate convenience of access. With reference to the World Health Organisation (WHO) palliative care model, the inclusion of a continued spectrum of services, such as physical and mental health activities and psychosocial counselling, should be reinforced throughout the progression of disease so as to better help patients to cope with illness. The discovery of the relationship between extent of symptoms experienced and patients' satisfaction towards services provided is a new direction for further study.

Third-line systemic treatment versus best supportive care for advanced/metastatic gastric cancer: A systematic review and meta-analysis.

This review evaluated the efficacy, toxicities and quality of life of third-line systemic treatment (TLT) versus best supportive care (BSC) in metastatic gastric cancer patients after failing two lines of systemic treatment. Six studies were included, involving 890 participants (TLT: 587, BSC: 303, Asian: 679, 76.3%), median 53-61 years old, ECOG 0-1 with no major co-morbidities. Compared with BSC, TLT improved overall survival (HR 0.63; 95% CI 0.46-0.87, corresponding to an improvement in medial OS from 3.20 to 4.80 months), progression-free survival (HR 0.29; 95% CI 0.18-0.45), objective response rate (RR 5.28; 95% CI 1.00-27.83) and disease control rate (RR 4.51; 95% CI 2.64-7.71). The efficacy results favoring TLT should be interpreted with caution for the substantial heterogeneities, wide confidence intervals and selection bias. More toxicities occurred in the TLT arms. This review highlighted the paucity of QOL data. Future studies should focus more on QOL-related outcomes. PROSPERO registration: 2015 CRD42015017873.

Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC).

OBJECTIVES: This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone. METHODS: Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile. RESULTS: A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm. CONCLUSION: AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.

Use of methylphenidate for the management of fatigue in Chinese patients with cancer.

UNLABELLED: REASON FOR THE STUDY: Studies on methylphenidate for cancer-related fatigue showed conflicting results. This prospective study aims to determine whether methylphenidate is useful for relieving fatigue in Chinese patients with cancer. Chinese Version of Brief Fatigue Inventory (BFI-C) was administered on days 1, 8, and 29. Methylphenidate dose on day 1 was 5 mg daily then adjusted after day 8 according to response and side effects tolerance. MAIN FINDINGS: Only 48% of the 25 recruited patients were on methylphenidate by day 29. Overall, no significant improvement in fatigue level was observed after methylphenidate, though benefits were shown in subgroups with age ≤ 65 and higher baseline BFI-C values. PRINCIPAL CONCLUSIONS: Methylphenidate may be useful for management of cancer-related fatigue in selected Chinese patients.

Patients' views on failure to gain expected clinical beneficial outcomes from participation in palliative medicine clinical trials.

UNLABELLED: REASON FOR THE STUDY: This study aims to understand patients' views on failing to gain expected beneficial outcomes from palliative medicine clinical trials. This is a qualitative study involving semistructured interviews. MAIN FINDINGS: Seven patients were interviewed. Despite loss of initial hope in benefiting themselves in terms of better disease or symptom control, patients interviewed still found joining clinical trials meaningful experience in terms of benefiting future patients and being valuable life experience. Experience in interacting with research staff partly formulated final impressions on clinical trial participation experience. PRINCIPAL CONCLUSIONS: Joining well-designed clinical trials unlikely causes harm to patients. Caring attitudes of researchers and maintaining good researcher-patient relationships can help patients in meaning-finding process, especially if they have failed to gain anticipated clinical benefits.