Publications by authors named "Albert Chau"

8 Publications

  • Page 1 of 1

Effect of F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial.

Int J Radiat Oncol Biol Phys 2020 06 14;107(2):316-324. Epub 2020 Feb 14.

Departments of Radiology and Nuclear Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.

Purpose: Early and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of F-fluciclovine on management of men with BCR of prostate cancer.

Methods And Materials: Men with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent F-fluciclovine positron emission tomography/computed tomography (PET/CT) according to standardized procedures. Clinicians documented management plans before and after scanning, recording changes to treatment modality as major and changes within a modality as other. The primary outcome measure was record of a revised management plan postscan. Secondary endpoints were evaluation of optimal prostate specific antigen (PSA) threshold for detection, salvage treatment outcome assessment based on F-fluciclovine-involvement, and safety.

Results: F-Fluciclovine was well tolerated in the 104 scanned patients (median PSA = 0.79 ng/mL). Lesions were detected in 58 out of 104 (56%) patients. Detection was broadly proportional to PSA level; ≤1 ng/mL, 1 out of 3 of scans were positive, and 93% scans were positive at PSA >2.0 ng/mL. Sixty-six (64%) patients had a postscan management change (80% after a positive result). Major changes (43 out of 66; 65%) were salvage or systemic therapy to watchful waiting (16 out of 66; 24%); salvage therapy to systemic therapy (16 out of 66; 24%); and alternative changes to treatment modality (11 out of 66, 17%). The remaining 23 out of 66 (35%) management changes were modifications of the prescan plan: most (22 out of 66; 33%) were adjustments to planned brachytherapy/radiation therapy to include a F-fluciclovine-guided boost. Where F-fluciclovine guided salvage therapy, the PSA response rate was higher than when F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]).

Conclusions: F-Fluciclovine PET/CT located recurrence in the majority of men with BCR, frequently resulting in major management plan changes. Incorporating F-fluciclovine PET/CT into treatment planning may optimize targeting of recurrence sites and avoid futile salvage therapy.
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June 2020

A Nationwide, Population Based Analysis of Patients with Organ Confined, Muscle Invasive Bladder Cancer Not Receiving Curative Intent Therapy in Sweden from 1997 to 2014.

J Urol 2019 11 9;202(5):905-912. Epub 2019 Oct 9.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Purpose: While radical cystectomy remains the standard treatment of muscle invasive bladder cancer, the natural history of patients unable or unwilling to receive therapy with curative intent is not well understood. The study objective was to identify these patients in a population based cohort, investigate the clinical profile and describe time to mortality.

Materials And Methods: We analyzed the Bladder Cancer Data Base Sweden, a database collected from 1997 to 2014, and identified 9,811 patients with stage T2-T4 disease. Median overall and cancer specific survival was estimated by the Kaplan-Meier method. Relative risks due to prognostic factors were estimated using Cox proportional hazards models.

Results: Of the 5,592 patients who did not receive therapy with curative intent 68% were male and 32% were female with a median age of 79 and 81 years, respectively. After 1 year patients had been hospitalized an average of 2.1 times for an average of 18.8 days. Major and minor urological surgeries were the most commonly registered procedures during these hospitalizations. Median overall survival was worse in women than in men (7 vs 8 months). Risk factors for death from bladder cancer were higher tumor stage, age greater than 80 years, later year of diagnosis and female gender. Organ confined disease (T2-T3 M0) was diagnosed in 1,352 patients (24%). These patients had a median of 2.4 hospitalizations per patient during the first 12 months after diagnosis. Half of these hospitalizations were due to cancer or genitourinary symptoms. Median overall survival in the organ confined subgroup was 11 months. Most of these patients had stage N0 disease. They had 2-month longer median overall survival but otherwise similar outcomes.

Conclusions: These patients experience substantial disease specific morbidity. They are hospitalized frequently during the final year of life and primarily die of bladder cancer progression.
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November 2019

The Impact of Positron Emission Tomography with 18F-Fluciclovine on the Treatment of Biochemical Recurrence of Prostate Cancer: Results from the LOCATE Trial.

J Urol 2019 02;201(2):322-331

Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.

Purpose: The prospective, multicenter LOCATE (F Fluciclovine [FACBC] PET/CT in Patients with Rising PSA after Initial Prostate Cancer Treatment) trial assessed the impact of positron emission tomography/computerized tomography with F-fluciclovine on treatment plans in patients with biochemical recurrence of prostate cancer after primary therapy with curative intent.

Materials And Methods: Men who had undergone curative intent treatment of histologically confirmed prostate cancer but who were suspected to have recurrence based on rising prostate specific antigen levels were enrolled prospectively. Each man had negative or equivocal findings on standard of care imaging. F-fluciclovine positron emission tomography/computerized tomography was performed according to standardized protocols. Treating physicians completed a questionnaire regarding the patient treatment plan before and after scanning, recording changes to the treatment modality (eg salvage radiotherapy to systemic androgen deprivation therapy) as major and changes in a modality (eg modified radiotherapy fields) as other.

Results: Between June 2016 and May 2017, 213 evaluable patients with a median age of 67 years and median prostate specific antigen 1.00 ng/ml were enrolled in study. F-fluciclovine avid lesions were detected in 122 of the 213 patients (57%). Overall 126 of the 213 patients (59%) had a change in management after the scan, which were major in 98 of 126 (78%) and in 88 (70%) were informed by positive positron emission tomography/computerized tomography findings. The most frequent major changes were from salvage or noncurative systemic therapy to watchful waiting (32 of 126 cases or 25%), from noncurative systemic therapy to salvage therapy (30 of 126 or 24%) and from salvage therapy to noncurative systemic therapy (11 of 126 or 9%).

Conclusions: F-fluciclovine positron emission tomography/computerized tomography detected 1 or more recurrence sites in the majority of men with biochemical recurrence, frequently resulting in major changes to management plans. Future studies will be planned to determine whether a management change leads to improved outcomes.
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February 2019

Diagnostic Performance of 18F-Fluciclovine in Detection of Prostate Cancer Bone Metastases.

Clin Nucl Med 2018 Jul;43(7):e226-e231

Division of Nuclear Medicine, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA.

Purpose: F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for PET imaging in men with biochemical recurrence (BCR) of prostate cancer after prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer.

Methods: We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of F-fluciclovine PET/CT in an attempt to draw practical and general conclusions on the utility and limitations of F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer.

Results: The cumulative preclinical data and results of some retrospective and 2 prospective clinical studies suggest that F-fluciclovine can detect early bone marrow involvement in patients with BCR of prostate cancer and negative prior bone-specific imaging findings.

Conclusions: F-fluciclovine PET/CT seems to offer useful information for early detection of bone metastases in men with BCR of prostate cancer. Additional investigations will be needed to compare the diagnostic performance of F-fluciclovine PET/CT to other standard and novel imaging methods in initial staging, BCR, and castrate-resistant phases of disease.
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July 2018

Reader Training for the Restaging of Biochemically Recurrent Prostate Cancer Using F-Fluciclovine PET/CT.

J Nucl Med 2017 10 6;58(10):1596-1602. Epub 2017 Apr 6.

Blue Earth Diagnostics (BED), Oxford, United Kingdom.

F-Fluciclovine is a novel PET/CT tracer. This blinded image evaluation (BIE) sought to demonstrate that, after limited training, readers naïve to F-fluciclovine could interpret F-fluciclovine images from subjects with biochemically recurrent prostate cancer with acceptable diagnostic performance and reproducibility. The primary objectives were to establish individual readers' diagnostic performance and the overall interpretation (2/3 reader concordance) compared with standard-of-truth data (histopathology or clinical follow-up) and to evaluate interreader reproducibility. Secondary objectives included comparison to the expert reader and assessment of intrareader reproducibility. F-Fluciclovine PET/CT images ( = 121) and corresponding standard-of-truth data were collected from 110 subjects at Emory University using a single-time-point static acquisition starting 5 min after injection of approximately 370 MBq of F-fluciclovine. Three readers were trained using standardized interpretation methodology and subsequently evaluated the images in a blinded manner. Analyses were conducted at the lesion, region (prostate, including bed and seminal vesicle, or extraprostatic, including all lymph nodes, bone, or soft-tissue metastasis), and subject level. Lesion-level overall positive predictive value was 70.5%. The readers' positive predictive value and negative predictive value were broadly consistent with each other and with the onsite read. Sensitivity was highest for readers 1 and 2 (68.5% and 63.9%, respectively) whereas specificity was highest for reader 3 (83.6%). Overall, prostate-level sensitivity was high (91.4%), but specificity was moderate (48.7%). Interreader agreement was 94.7%, 74.4%, and 70.3% for the lesion, prostate, and extraprostatic levels, respectively, with associated Fleiss' κ-values of 0.54, 0.50, and 0.57. Intrareader agreement was 97.8%, 96.9%, and 99.1% at the lesion level; 100%, 100%, and 91.7% in the prostate region; and 83.3%, 75.0%, and 83.3% in the extraprostatic region for readers 1, 2, and 3, respectively. Concordance between the BIE and the onsite reader exceeded 75% for each reader at the lesion, region, and subject levels. Specific training in the use of standardized interpretation methodology for assessment of F-fluciclovine PET/CT images enables naïve readers to achieve acceptable diagnostic performance and reproducibility when staging recurrent prostate cancer.
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October 2017

Multisite Experience of the Safety, Detection Rate and Diagnostic Performance of Fluciclovine (F) Positron Emission Tomography/Computerized Tomography Imaging in the Staging of Biochemically Recurrent Prostate Cancer.

J Urol 2017 03 13;197(3 Pt 1):676-683. Epub 2016 Oct 13.

Department of Nuclear Medicine and Radiology, Aleris Healthcare, Oslo, Norway; Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

Purpose: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine (F) after biochemical recurrence.

Materials And Methods: A total of 596 patients underwent fluciclovine (F) positron emission tomography/computerized tomography at 4 clinical sites. Detection rate determinations were stratified by the baseline prostate specific antigen value. Diagnostic performance was assessed against a histological reference standard in 143 scans.

Results: The subject level fluciclovine (F) positron emission tomography/computer tomography detection rate was 67.7% (403 of 595 scans). Positive findings were detected in the prostate/bed and pelvic lymph node regions in 38.7% (232 of 599) and 32.6% of scans (194 of 596), respectively. Metastatic involvement outside the pelvis was detected in 26.2% of scans (155 of 591). The subject level detection rate in patients in the lowest quartile for baseline prostate specific antigen (0.79 ng/ml or less) was 41.4% (53 of 128). Of these patients 13 had involvement in the prostate/bed only, 16 had pelvic lymph node involvement without distant disease and 24 had distant metastases. The positive predictive value of fluciclovine (F) positron emission tomography/computerized tomography scanning for all sampled lesions was 62.2%, and it was 92.3% and 71.8% for extraprostatic and prostate/bed involvement, respectively. Fluciclovine (F) was well tolerated and the safety profile was not altered following repeat administration.

Conclusions: Fluciclovine (F) is well tolerated and able to detect local and distant prostate cancer recurrence across a wide range of prostate specific antigen values.
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March 2017

Randomized phase II trial of letrozole plus anti-MUC1 antibody AS1402 in hormone receptor-positive locally advanced or metastatic breast cancer.

Clin Cancer Res 2011 Nov 30;17(21):6822-30. Epub 2011 Aug 30.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Purpose: AS1402 is a humanized immunoglobulin G1 antibody that targets the aberrantly glycosylated antigen MUC1, which is overexpressed in 90% of breast tumors and contributes to estrogen-mediated growth and survival of breast cancer cells in vitro by modulating estrogen receptor (ER) activity. Aromatase inhibitors have been reported to enhance antibody-dependent cell-mediated cytotoxicity elicited by antibodies in vitro. We compared the outcomes of patients with breast cancer treated with letrozole with or without AS1402.

Experimental Design: The study population included 110 patients with locally advanced or metastatic hormone receptor-positive breast cancer randomized to receive 2.5 mg letrozole only once daily or with a weekly 9 mg/kg AS1402 infusion. The primary endpoint was overall response rate. Secondary endpoints included progression-free survival, time to progression, and safety. AS1402 exposure and influence of allotypes of FcγRIIIa, FcγRIIa, and MUC1 were evaluated.

Results: The study was stopped early because of a trend toward worse response rates and a higher rate of early disease progression in the AS1402 + letrozole arm. Final analysis revealed no significant difference in efficacy between the study arms. Evaluated gene polymorphisms did not define patient subgroups with improved outcomes. Addition of AS1402 to letrozole was associated with manageable toxicity.

Conclusions: Because adding AS1402 to letrozole did not improve outcomes compared with letrozole only, blocking ER may be a better strategy for harnessing MUC1 modulation of the ER to a clinical advantage. FcγRIIIa, FcγRIIa, and MUC1 allotype did not predict outcome for patients treated with letrozole with or without AS1402.
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November 2011

The effect of pre-operative information in relieving anxiety in oral surgery patients.

Community Dent Oral Epidemiol 2004 Jun;32(3):227-35

Department of Psychiatry, Tuen Mun Hospital, Hong Kong SAR, PR China.

Unlabelled: Appropriate stress management of patients is essential for smooth running of invasive or surgical dental procedures conducted under local anaesthesia.

Objective: The current study analysed the effectiveness of pre-operative information provision for anxiety reduction during dentoalveolar surgery in patients with high- or low-trait anxiety.

Methods: Patients scheduled for oral surgical procedures performed by six private dental practitioners were invited to participate in the study. They were randomly assigned to four groups and received the following pre-operative information: (i) basic information only, (ii) basic information with details of the operative procedures, (iii) basic information with details of the expected recovery, and (iv) basic information with details of both the operative procedures and recovery. The participants' trait anxiety level was measured with the Depression Anxiety Stress Scales (DASS), then they were divided into high- or low-trait anxiety groups with the method of median-split on the basis of the DASS score. Self-rated anxiety was recorded immediately before, during and 10 min after the surgical procedures.

Results: High-trait anxiety subjects gave higher self-reported anxiety levels (repeated-measures ANOVA, P < 0.05). Pre-operative provision of details about the expected recovery only or details concerning both the operative procedures and recovery led to significant reduction in self-reported anxiety among the participants throughout the procedure (P < 0.01). However, information on operative procedures led to anxiety reduction in low (P < 0.05) but not high-trait anxiety participants.

Conclusion: Provision of pre-operative information of the recovery process leads to significant anxiety reduction in all patients who undergo surgical/invasive procedures with local anaesthesia.
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June 2004