Consensus Statements on Precision Oncology in the China Greater Bay Area.

BACKGROUND: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA. METHODS: Thirty experts used a modified Delphi method. The evidence extracted to support the statements was graded according to the GRADE system and reported according to the Revised Standards for Quality Improvement Reporting Excellence guidelines, version 2.0. RESULTS: The POWG reached consensus in six key statements: harmonization of reporting and quality assurance of NGS; molecular tumor board and clinical decision support systems for PO; education and training; research and real-world data collection, patient engagement, regulations, and financial reimbursement of PO treatment strategies; and clinical recommendations and implementation of PO in clinical practice. CONCLUSION: POWG consensus statements standardize the clinical application of NGS CGPs, streamline the interpretation of clinically significant genomic alterations, and align actionable mutations with sequence-directed therapies. The POWG consensus statements may harmonize the utility and delivery of PO in China's GBA.

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.

Prostate cancer management in the era of COVID-19: Recommendations from the Hong Kong Urological Association and Hong Kong Society of Uro-oncology.

AIM: In response to the fast-developing coronavirus disease 2019 (COVID-19) pandemic, special arrangement and coordination are urgently required in the interdisciplinary care of patients across different medical specialties. This article provides recommendations on the management of different stages of localized or metastatic prostate cancer (PC) amid this pandemic. METHODS: The Hong Kong Urological Association and Hong Kong Society of Uro-oncology formed a joint discussion panel, which consisted of six urologists and six clinical oncologists with extensive experience in the public and private sectors. Following an evidence-based approach, the latest relevant publications were searched and reviewed, before proceeding to a structured discussion of relevant clinical issues. RESULTS: The joint panel provided recommendations for PC management during the pandemic, in terms of general considerations, diagnostic procedures, different disease stages, treatment modules, patient support, and interdisciplinary collaboration. The overall goal was to minimize the risk of infection while avoiding unnecessary delays and compromises in management outcomes. Practical issues during the pandemic were addressed such as the use of invasive diagnostic procedures, robotic-assisted laparoscopic prostatectomy, hypofractionated radiotherapy, and prolonged androgen deprivation therapy. The recommendations were explicated in the context of Hong Kong, a highly populated international city, in relation to the latest international guidelines and evidence. CONCLUSION: A range of recommendations on the management of PC patients during the COVID-19 pandemic was developed. Urologists, oncologists, and physicians treating PC patients may refer to them as practical guidance.

Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer-2019 Updates.

BACKGROUND: To update the Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer, the same panelists as in the previous consensus panel held a series of meetings to discuss updated clinical evidence and experiences. METHODS: The previous consensus statements were retained, deleted, or revised, and new statements were added. At the final meeting, all statements were reviewed and amended as appropriate, followed by panel voting. RESULTS: There were significant changes and additions to the previous consensus statements, primarily driven by the advances in androgen receptor signaling inhibitors, treatment sequencing in metastatic castration-resistant prostate cancer, and increasing recognition of oligometastatic prostate cancer since the introduction of prostate-specific membrane antigen positron emission tomography. In this update, a total of 59 consensus statements were accepted and established. CONCLUSIONS: The consensus panel updated consensus statements on the management of advanced prostate cancer, aiming to allow physicians in the region to keep abreast of the recent evidence on optimal clinical practices.

Consensus statements on the management of clinically localized prostate cancer from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

OBJECTIVE: To formulate consensus statements to facilitate physician management strategies for patients with clinically localized prostate cancer (PCa) in Hong Kong by jointly convening a panel of 12 experts from the two local professional organizations representing PCa specialists, who had previously established consensus statements on the management of metastatic PCa for the locality. METHODS: Through a series of meetings, the panellists discussed their clinical experience and the published evidence regarding various areas of the management of localized PCa, then drafted consensus statements. At the final meeting, each drafted statement was voted on by every panellist based on its practicability of recommendation in the locality. RESULTS: A total of 76 consensus statements were ultimately accepted and established by panel voting. CONCLUSION: Derived from the recent evidence and major overseas guidelines, along with local clinical experience and practicability, the consensus statements were aimed to serve as a practical reference for physicians in Hong Kong for the management of localized PCa.

Revisiting the role of bone-modifying agents in the management of metastatic prostate cancer.

Bone metastases are a hallmark of advanced prostate cancer and may drive the morbidity and mortality of the disease in patients with a poor prognosis. The pathogenesis of bone metastasis involves the interaction between cancer cells, normal bone cells and the bone microenvironment. Targeting the bone microenvironment has become a promising therapy for patients with advanced prostate cancer and bone metastasis. This article reviews the use of the antiresorptive bone-targeted agents zoledronic acid and denosumab in the management of skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastasis. In real-world clinical practice, these agents have been widely prescribed as a concomitant medication to novel mCRPC therapies, such as abiraterone, enzalutamide and radium-223. International guidelines have recommended zoledronic acid or denosumab for the prevention of SREs in patients with bone metastasis from mCRPC. Although there is currently no consensus regarding the optimal sequencing between the bone-targeted agents and novel anti-cancer therapies, future optimal treatments for patients with bone metastasis from prostate cancer may involve the combination of these agents.

Consensus statements on the management of metastatic prostate cancer from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

To establish a set of consensus statements to facilitate physician management strategies for patients with metastatic prostate cancer (mPCa) in Hong Kong. A local expert consensus was organized jointly by the two main professional organizations representing prostate cancer specialists in Hong Kong. A total of 12 experts were included in the consensus panel. Six of the most crucial and relevant areas of debate regarding the management of mPCa were identified. With the use of a modified Delphi method, several panel meetings were held for the members to discuss their clinical experience and the published literature relevant to the areas of debate. At the final meeting, each drafted statement was voted on by every member based on its practicability of recommendation in the locality. After the panel voting, a total of 45 consensus statements regarding the management of mPCa were ultimately accepted and established. The consensus statements were primarily derived from the latest clinical evidence and major overseas guidelines, with the consideration of local clinical experience and practicability. These are considered applicable recommendations for Hong Kong physicians for the management of mPCa patients.

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.

Hong Kong consensus recommendations on the management of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is particularly prevalent in Hong Kong because of the high prevalence of chronic hepatitis B (CHB) infection; HCC is the fourth commonest cancer in men and the seventh commonest in women, and it is the third leading cause of cancer death in Hong Kong. The full spectrum of treatment modalities for HCC is available locally; however, there is currently no local consensus document detailing how these modalities should be used. SUMMARY: In a series of meetings held between May and October 2013, a multidisciplinary group of Hong Kong clinicians - liver surgeons, medical oncologists, clinical oncologists, hepatologists, and interventional radiologists - convened to formulate local recommendations on HCC management. These recommendations consolidate the most current evidence pertaining to HCC treatment modalities, together with the latest thinking of practicing clinicians engaged in HCC management, and give detailed guidance on how to deploy these modalities effectively for patients in various disease stages. KEY MESSAGES: Distinct from other regional guidelines, these recommendations provide guidance on the use of antiviral therapy to reduce the incidence of HCC in CHB patients with cirrhosis and to reduce recurrence of CHB-related HCC.

Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. METHODS: Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. RESULTS: In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). CONCLUSIONS: Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.

Risk factors and natural history of breast cancer in younger Chinese women.

AIM: To investigate the age differences in the risk factors, clinicopathological characteristics and patterns of treatment of female breast cancer patients. METHODS: Seven thousand one hundred and fifty-two women with primary breast cancer from the Hong Kong Breast Cancer Registry were recruited after receiving patients' consent, they were asked to complete standardized questionnaires which captured their sociodemographic characteristics and risk factors associated with breast cancer development. Among them, clinicopathological data and patterns of treatment were further collected from medical records of 5523 patients with invasive breast cancers. Patients were divided into two groups according to the age at diagnosis: younger (< 40 years old) vs older patients (≥ 40 years old) for subsequent analyses. RESULTS: Analysis on the sociodemographic characteristics and exposure to risk factors were performed on 7152 women with primary breast cancer and the results revealed that younger patients were more likely to have unhealthy lifestyles; these include a lack of exercise (85.4% vs 73.2%, P < 0.001), having high stress in life (46.1% vs 35.5%, P < 0.001), having dairy/meat-rich diets (20.2% vs 12.9%, P < 0.001), having alcohol drinking habit (7.7% vs 5.2%, P = 0.002). Younger patients were also more likely to have hormone-related risk factors including nulliparity (43.3% vs 17.8%, P < 0.001) and an early age at menarche (20.7% vs 13.2%, P < 0.001). Analyses on clinicopathological characteristics and patterns of treatment were performed on 5523 women diagnosed with invasive breast cancer. The invasive tumours in younger patients showed more aggressive pathological features such as having a higher percentage of grade 3 histology (45.7% vs 36.5%, P < 0.001), having a higher proportion of tumours with lymphovascular invasion (39.6% vs 33.2%, P = 0.003), and having multifocal disease (15.7% vs 10.3%, P < 0.001); they received different patterns of treatment than their older counterparts. CONCLUSION: Younger patients in Hong Kong are more likely to encounter risk factors associated with breast cancer development and have more aggressive tumours than their older counterparts.

Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma.

PURPOSE: A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety. RESULTS: Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively). CONCLUSION: Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

The impact of dosimetric inadequacy on treatment outcome of nasopharyngeal carcinoma with IMRT.

BACKGROUND AND PURPOSE: This study aims to address the relationship between tumor size and dosimetric inadequacy in treating nasopharyngeal carcinoma (NPC), and how it subsequently affects the local control. MATERIAL AND METHODS: 444 NPC patients treated with IMRT from 2005 to 2010 were included in the study. The planning aim was to deliver at least 66.5 Gy (i.e. 95% of 70 Gy) to 95% of the primary gross tumor volume (GTV_P) while keeping all the critical neurological organs at risk (OAR) within dose tolerance. Treatment outcome were analyzed according to T stage, GTV_P volume and the degree of under-dosing. RESULTS: Disease outcome was related to T stage, GTV_P volume and the degree of under-dosing. The 5-year local failure free survival (LFFS), disease free survival (DFS) and overall survival (OS) for T4 disease were 74%, 50.4% and 63.6% respectively. 48 cm(3) was identified as the critical cut-off GTV_P volume, the large volume group (GTV_P ≥ 48 cm(3)) had lower 5-year DFS (50.4% vs. 76.6%) and OS (65.2% vs. 86.3%, p < 0.001). Most T4 diseases (and some T3) were under-dosed (<66.5 Gy) and an under-dosed GTV_P volume of 3.4 cm(3) was found to be prognostically important. Multivariate analyses showed that the effect of GTV_P volume on LFFR and DFS was outweighed by the degree of under-dosing. CONCLUSIONS: Treatment outcome of locally advanced NPC was significantly affected by the volume of under-dosed (<66.5 Gy) GTV_P due to the neighboring neurological structures. A new set of OAR dose constraint and specification is proposed.

Definitive radiotherapy for early stage glottic cancer by 6 MV photons.

PURPOSE: To evaluate the clinical outcome of early glottic cancer (GC) treated by primary radiotherapy (RT) with 6 MV photons. METHODS AND MATERIALS: We retrospectively reviewed the medical records of 695 consecutive patients with T1N0 and T2N0 GC treated between 1983 and 2005 by RT in our institution. Clinical outcome in terms of local control (LC), overall survival (OS) and cause- specific survival (CSS) rate were evaluated. RESULTS: The median follow-up time was 10.5 years. The 10-year actuarial LC rates were as follows: T1A, 91%; T1B, 87%; T2, 77%. The 10-year OS were as follows: T1, 74.2%; T2, 70.7%. The 10-year CSS were as follows: T1, 97.7%; T2, 97.1%.Poorly differentiated histology and tumor biologically effective dose<65 Gy15 were adverse factors in both LC of T1 and T2 disease. Involvement of anterior commissure was an adverse factor in both LC and CSS of T1 disease. Subglottic extension was associated with poor LC in T2 disease whereas hemoglobin <13.0 was associated with poor LC and CSS of T2 disease. CONCLUSION: Primary RT remains an option among the various standard treatments for early GC. Clinical treatment outcome by 6MV photons is similar and comparable to historic data of Cobalt-60 and 2 MV photons.

Impact and relationship of anterior commissure and time-dose factor on the local control of T1N0 glottic cancer treated by 6 MV photons.

BACKGROUND: To evaluate prognostic factors that may influence local control (LC) of T1N0 glottic cancer treated by primary radiotherapy (RT) with 6 MV photons. METHODS: We retrospectively reviewed the medical records of 433 consecutive patients with T1N0 glottic cancer treated between 1983 and 2005 by RT in our institution. All patients were treated with 6 MV photons. One hundred and seventy seven (41%) patients received 52.5 Gy in 23 fractions with 2.5 Gy/fraction, and 256 (59%) patients received 66 Gy in 33 fractions with 2 Gy/fraction. RESULTS: The median follow-up time was 10.5 years. The 10-year LC rates were 91% and 87% for T1a and T1b respectively. Multivariate analysis showed LC rate was adversely affected by poorly differentiated histology (Hazard Ratio [HR]: 7.5, p = 0.035); involvement of anterior commissure (HR: 2.34, p = 0.011); fraction size of 2.0 Gy (HR: 2.17, p = 0.035) and tumor biologically effective dose (BED) < 65 Gy15 (HR: 3.38, p = 0.017). CONCLUSIONS: The negative impact of anterior commissure involvement could be overcome by delivering a higher tumor BED through using fraction size of > 2.0 Gy. We recommend that fraction size > 2.0 Gy should be utilized, for radiation schedules with five daily fractions each week.