Publications by authors named "Henry Sze"

29 Publications

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Consensus statements on the management of metastatic renal cell carcinoma from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology 2019.

Asia Pac J Clin Oncol 2021 Apr;17 Suppl 3:27-38

Specialists Central, Central, Hong Kong.

Background: To establish a set of consensus statements for the management of metastatic renal cell carcinoma, a total of 12 urologists and clinical oncologists from two professional associations in Hong Kong formed an expert consensus panel.

Methods: Through a series of meetings and using the modified Delphi method, the panelists presented recent evidence, discussed clinical experiences, and drafted consensus statements on several areas of focus regarding the management of metastatic renal cell carcinoma. Each statement was eventually voted upon by every panelist based on the practicability of recommendation.

Results: A total of 46 consensus statements were ultimately accepted and established by panel voting.

Conclusions: Derived from recent evidence and expert insights, these consensus statements were aimed at providing practical guidance to optimize metastatic renal cell carcinoma management and promote a higher standard of clinical care.
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http://dx.doi.org/10.1111/ajco.13581DOI Listing
April 2021

NPC-0501 trial on the value of changing chemoradiotherapy sequence, replacing 5-fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma.

Cancer 2020 08 4;126(16):3674-3688. Epub 2020 Jun 4.

Department of Clinical Oncology, The University of Hong Kong, Hong Kong, Hong Kong.

Background: A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy (RT) with concurrent cisplatin followed by adjuvant cisplatin and 5-fluorouracil (PF). This randomized NPC-0501 trial evaluated the therapeutic effect of changing to an induction-concurrent sequence or accelerated-fractionation sequence, and/or replacing 5-fluorouracil with capecitabine (X).

Methods: Patients with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC initially were randomly allocated to 1 of 6 treatment arms (6-arm full-randomization cohort). The protocol was amended in 2009 to permit centers to opt out of randomization regarding fractionation (3-arm chemotherapy cohort).

Results: A total of 803 patients were accrued (1 of whom was nonevaluable) from 2006 to 2012. Based on the overall comparisons, neither changing the chemotherapy sequence nor accelerated fractionation improved treatment outcome. However, secondary analyses demonstrated that when adjusted for RT parameters and other significant factors, the induction-concurrent sequence, especially the induction-PX regimen, achieved significant improvements in progression-free survival (PFS) and overall survival. Efficacy varied among different RT groups: although no impact was observed in the accelerated-fractionation group and the 3-arm chemotherapy cohort, a comparison of the induction-concurrent versus concurrent-adjuvant sequence in the conventional-fractionation group demonstrated a significant benefit in PFS (78% vs 62% at 5 years; P = .015) and a marginal benefit in overall survival (84% vs 72%; P = .042) after adjusting for multiple comparisons. Comparison of the induction-PX versus the adjuvant-PF regimen demonstrated better PFS (78% vs 62%; P = .027) without an increase in overall late toxicity.

Conclusions: For patients irradiated using conventional fractionation, changing the chemotherapy sequence from a concurrent-adjuvant to an induction-concurrent sequence, particularly using induction cisplatin and capecitabine, potentially could improve efficacy without an adverse impact on late toxicity. However, further validation is needed for confirmation of these findings.
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http://dx.doi.org/10.1002/cncr.32972DOI Listing
August 2020

Management of advanced prostate cancer in Hong Kong: Insights from an APCCC-Derived survey.

Asia Pac J Clin Oncol 2019 Oct 23;15 Suppl 6:8-13. Epub 2019 Oct 23.

Specialists Central, Unit 2503-05, The Galleria, No. 9 Queen's Road Central, Central, Hong Kong.

Aim: The 2017 Advanced Prostate Cancer Consensus Conference (APCCC) convened an international multidisciplinary panel to vote on controversial issues in the management of advanced prostate cancer (APC). We aimed to compare their conclusions with the opinions of local specialists and explore the practicability of international recommendations in the healthcare setting in Hong Kong.

Methods: Urologists and clinical oncologists practicing in Hong Kong were invited to complete a survey based on the original APCCC 2017 questionnaire and recently published trials in APC. A joint committee of expert key opinion leaders was convened to discuss and analyze the voting differences between local specialists and the APCCC 2017 panel.

Results: The respondents constituted 21% (28/132) of registered urologists and 21% (31/146) of clinical oncologists in Hong Kong. Discrepancies in three key areas were identified as being the most timely for this analysis: (a) management of metastatic hormone-sensitive/naïve prostate cancer; (b) management of metastatic castration-resistant prostate cancer; and (c) treatment monitoring and initiation of androgen-deprivation therapy. Fears of toxicity and intolerance among patients and physicians (especially urologists) may be driving the relative underuse of chemotherapy in multiple APC patient groups in Hong Kong. Local patients can face long wait times and limited access to contemporary imaging modalities compared with other developed countries.

Conclusion: Increased collaborative efforts by urologists and clinical oncologists could ensure that patients gain wider access to the latest diagnostic, treatment and monitoring modalities for APC in Hong Kong.
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http://dx.doi.org/10.1111/ajco.13247DOI Listing
October 2019

Concurrent-Adjuvant Chemoradiation Therapy for Stage III-IVB Nasopharyngeal Carcinoma-Exploration for Achieving Optimal 10-Year Therapeutic Ratio.

Int J Radiat Oncol Biol Phys 2018 08 2;101(5):1078-1086. Epub 2018 May 2.

Departments of Clinical Oncology, The University of Hong Kong and the University of Hong Kong-Shenzhen Hospital, Hong Kong, China. Electronic address:

Purpose: This is an updated combined analysis of 2 randomized studies (NPC-9901 and NPC-9902 trials) to evaluate the 10-year outcome attributed to the addition of concurrent-adjuvant chemotherapy for advanced locoregional nasopharyngeal carcinoma (NPC).

Patients And Methods: Eligible patients with stage III-IVB nonkeratinizing NPC were randomly assigned to radiation therapy alone (RT: 218 patients) or chemoradiation therapy (CRT: 223 patients) using 3 cycles of cisplatin (100 mg/m) concurrent with RT, followed by 3 cycles of cisplatin (80 mg/m) and fluorouracil (1000 mg/m/day for 4 days). All of the patients were irradiated with conventional fractionation to ≥66 Gy. The median follow-up was 13.9 years.

Results: Intention-to-treat analysis confirmed that the CRT group achieved significant improvement in 10-year failure-free rate (FFR: 62% vs 52%, P = .016), progression-free survival rate (PFS: 56% vs 44%, P = .008), and overall survival rate (OS: 60% vs 50%, P = .044). There was no significant increase in overall late toxicity rate (51% vs 48%, P = .34) or noncancer deaths (19% vs 16%, P = .52). Exploratory studies showed no difference in disease control between 2 or 3 cycles of concurrent cisplatin; however, patients given 3 concurrent cycles had a significant increase in hearing impairment (40% vs 24%, P = .017). Only those who continued to receive 2 or more cycles of adjuvant cisplatin-fluorouracil achieved significant improvement in distant control (73% vs 65%, P = .037) and maximal survival gain.

Conclusion: The addition of concurrent cisplatin plus adjuvant cisplatin-fluorouracil could significantly improve overall survival and disease control without incurring a significant increase in late toxicity or noncancer deaths. Exploratory analyses suggested that both the concurrent and the adjuvant phases contributed to tumor control. Furthermore, the number of concurrent cycles could be reduced from 3 to 2 cycles in order to achieve a similar survival benefit without incurring an excessive increase in hearing impairment. This is a useful hypothesis that warrants further validation.
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http://dx.doi.org/10.1016/j.ijrobp.2018.04.069DOI Listing
August 2018

Differences in clinical outcome between docetaxel and abiraterone acetate as the first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer patients with or without the ineligible clinical factors of the COU-AA-302 study.

Prostate Int 2018 Mar 18;6(1):24-30. Epub 2017 Aug 18.

Department of Clinical Oncology, Queen Mary Hospital, Hong Kong.

Background: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2).

Materials And Methods: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed. The survival time was compared among four subgroups of patients: those with ineligible factors administered AA (Group Ineligible-AA) or T (Group Ineligible-T), and those without ineligible factors and administered AA (Group Eligible-AA) or T (Group Eligible-T).

Results: During the study period, we identified 115 mCRPC patients who received AA or T, among whom 29, 36, 29, and 21 patients were classified as Groups Ineligible-AA, Ineligible-T, Eligible-AA, and Eligible-T, respectively. Both Group Ineligible-AA and Group Eligible-AA had significantly longer progression-free survival (PFS) and similar overall survival (OS) as Group Ineligible-T and Group Eligible-T (Ineligible, PFS: 6.3 vs. 5.9 months,  = 0.0234, OS: 7.8 vs. 15.7 months,  = 0.1601; Eligible, PFS: 9.8 vs. 5.6 months,  = 0.0437, OS: 20.5 vs. 18.2 months,  = 0.7820).

Conclusions: Compared to T, AA treatment resulted in longer PFS and similar OS in chemo-naïve mCRPC patients, irrespective of the presence of ineligible factors, suggesting that the initial treatment by AA may still be beneficial to those with the aforementioned ineligible factors.
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http://dx.doi.org/10.1016/j.prnil.2017.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857184PMC
March 2018

Prospective, Multicenter, Phase 2 Trial of Induction Chemotherapy Followed by Bio-Chemoradiotherapy for Locally Advanced Recurrent Nasopharyngeal Carcinoma.

Int J Radiat Oncol Biol Phys 2018 03 1;100(3):630-638. Epub 2017 Dec 1.

Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China; Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Hong Kong, China.

Purpose: To evaluate, in a phase 2 study, whether induction docetaxel, cisplatin, and fluorouracil (TPF) followed by weekly docetaxel and cetuximab in concurrence with intensity modulated radiation therapy can improve the treatment outcome for patients with advanced locally recurrent nasopharyngeal carcinoma (rNPC).

Methods And Materials: Thirty-three patients with rNPC (T3-T4, N0-N1, M0) were recruited. Of these, 19 patients (57.6%) had stage rT3 recurrence, and the rest had stage rT4. Eight patients also had rN1 at the time of relapse. Treatment outcomes and safety were evaluated.

Results: Among these 33 patients, 1 died after 1 cycle of TPF, 5 patients withdrew from the study during the induction period because of grade ≥3 toxicities; 27 patients completed the whole course of treatment, but 1 died before any assessment could be made. The median follow-up period was 28.5 months. The progression-free survival and overall survival at 3 years for the whole group were 35.7% and 63.8%, respectively. Among the 26 patients who could be assessed after treatment, the complete response rate was 30.8%, and the locoregional control rate at 3 years was 49.2%. Temporal lobe necrosis (TLN) developed in 8 cases. The rates of grade ≥3 hearing loss, soft tissue necrosis, dysphagia, and trismus were 30.8%, 15.4%, 11.5%, and 19.2%, respectively. Overall, 5 patients died owing to acute (1 after cycle 1 TPF and 1 after completion of bio-chemoradiotherapy) or late (2 epistaxis and 1 TLN) treatment-related complications.

Conclusions: The proposed salvage treatment regimen for advanced locally recurrent NPC could achieve a better treatment outcome than seen in previous studies. However, poor tolerability of induction TPF and the high rate of TLN limit its applicability outside clinical trials.
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http://dx.doi.org/10.1016/j.ijrobp.2017.11.038DOI Listing
March 2018

Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: A report of 3328 patients (HKNPCSG 1301 study).

Oral Oncol 2018 02 12;77:16-21. Epub 2017 Dec 12.

Hong Kong Cancer Registry, Hospital Authority, Hong Kong, China.

Purpose: To evaluate treatment outcomes, failure patterns and late toxicities in patients with nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) in 6 public hospitals in Hong Kong over a 10-year period from 2001 to 2010.

Material And Methods: Eligible patients were identified through the Hong Kong Cancer Registry data base. Clinical information was retrieved and verified by oncologists working in the individual centers. Treatment details, survival outcomes and late toxicities were analyzed.

Results: A total of 3328 patients were recruited. The median follow-up time was 80.2 months. The 8-year actuarial overall survival (OS), local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure free survival (DFFS), progression-free survival (PFS) for the whole group was 68.5%, 85.8%, 91.5%, 81.5% and 62.6% respectively. Male gender, older age, advanced T and N stage were adverse prognostic factors for OS, DFFS and PFS, whereas use of chemotherapy in form of concurrent chemo-irradiation (CRT), neoadjuvant + CRT, or CRT + adjuvant chemotherapy were favorable prognostic factors for OS and PFS. The local control was adversely affected by advanced T stage. N stage remained as the single adverse prognostic factor for regional control. Distant metastasis was the commonest site of failure.

Conclusion: IMRT is an effective treatment for NPC with excellent overall loco-regional control. Distant metastasis is the major site of failure. Concurrent chemotherapy with cisplatin has an established role in NPC patients treated by IMRT.
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http://dx.doi.org/10.1016/j.oraloncology.2017.12.004DOI Listing
February 2018

Reirradiation with intensity-modulated radiotherapy for locally recurrent T3 to T4 nasopharyngeal carcinoma.

Head Neck 2017 03 29;39(3):533-540. Epub 2016 Nov 29.

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong.

Background: The purpose of this study was to assess the efficacy and toxicities of reirradiation using intensity-modulated radiotherapy (IMRT) in patients with locally advanced recurrent nasopharyngeal carcinoma (NPC).

Methods: Thirty-eight patients with consecutive rT3 to rT4 NPC treated between 2005 and 2013 were retrospectively analyzed.

Results: The 3-year overall survival (OS), progression-free survival (PFS), and local control rate were 47.2%, 17.5%, and 44.3%, respectively. Gross target volume (GTV) D , GTV D , and age were all important prognostic factors for OS and PFS, but only GTV D was an important determinant for local control. A total of 73.7% patients experienced ≥1 grade 3 late toxicities and 3 patients died of massive epistaxis. Temporal lobe necrosis (TLN) developed sooner with a higher total biological equivalent dose.

Conclusion: Adequate tumor dose coverage was important for treating rT3 to rT4 NPC. Although late complications were common, treatment-related mortality was solely vascular in nature. Dose constraints of neurologic structures for reirradiation should be revised with the latest information on late toxicities. © 2016 Wiley Periodicals, Inc. Head Neck 39: 533-540, 2017.
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http://dx.doi.org/10.1002/hed.24645DOI Listing
March 2017

Prognostic nomogram for refining the prognostication of the proposed 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy.

Cancer 2016 Nov 19;122(21):3307-3315. Epub 2016 Jul 19.

Department of Clinical Oncology, University of Hong Kong/University of Hong Kong-Shenzhen Hospital, Hong Kong, China.

Background: The objective of this study was to develop a nomogram for refining prognostication for patients with nondisseminated nasopharyngeal cancer (NPC) staged with the proposed 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system.

Methods: Consecutive patients who had been investigated with magnetic resonance imaging, staged with the proposed 8th edition of the AJCC/UICC staging system, and irradiated with intensity-modulated radiotherapy from June 2005 to December 2010 were analyzed. A cohort of 1197 patients treated at Fujian Provincial Cancer Hospital was used as the training set, and the results were validated with 412 patients from Pamela Youde Nethersole Eastern Hospital. Cox regression analyses were performed to identify significant prognostic factors for developing a nomogram to predict overall survival (OS). The discriminative ability was assessed with the concordance index (c-index). A recursive partitioning algorithm was applied to the survival scores of the combined set to categorize the patients into 3 risk groups.

Results: A multivariate analysis showed that age, gross primary tumor volume, and lactate dehydrogenase were independent prognostic factors for OS in addition to the stage group. The OS nomogram based on all these factors had a statistically higher bias-corrected c-index than prognostication based on the stage group alone (0.712 vs 0.622, P <.01). These results were consistent for both the training cohort and the validation cohort. Patients with <135 points were categorized as low-risk, patients with 135 to <160 points were categorized as intermediate-risk, and patients with ≥160 points were categorized as high-risk. Their 5-year OS rates were 92%, 84%, and 58%, respectively.

Conclusions: The proposed nomogram could improve prognostication in comparison with the TNM stage group. This could aid in risk stratification for individual NPC patients. Cancer 2016;122:3307-3315. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524130PMC
November 2016

Global Pattern of Nasopharyngeal Cancer: Correlation of Outcome With Access to Radiation Therapy.

Int J Radiat Oncol Biol Phys 2016 Apr 14;94(5):1106-12. Epub 2015 Dec 14.

International Atomic Energy Agency, Vienna, Austria.

Purpose: This study aimed to estimate the treatment outcome of nasopharyngeal cancer (NPC) across the world and its correlation with access to radiation therapy (RT).

Methods And Materials: The age-standardized mortality (ASM) and age-standardized incidence (ASI) rates of NPC from GLOBOCAN (2012) were summarized, and [1-(ASM/ASI)] was computed to give the proxy relative survival (RS). Data from the International Atomic Energy Agency (IAEA) and the World Bank were used to assess the availability of RT in surrogate terms: the number of RT equipment units and radiation oncologists per million population.

Results: A total of 112 countries with complete valid data were analyzed, and the proxy RS varied widely from 0% to 83% (median, 50%). Countries were categorized into Good, Median, and Poor outcome groups on the basis of their proxy RS (<45%, 45%-55%, and >55%). Eighty percent of new cases occurred in the Poor outcome group. Univariable linear regression showed a significant correlation between outcome and the availability of RT: proxy RS increased at 3.4% (P<.001) and 1.5% (P=.001) per unit increase in RT equipment and oncologist per million population, respectively. The median number of RT equipment units per million population increased significantly from 0.5 in the Poor, to 1.5 in the Median, to 4.6 in the Good outcome groups, and the corresponding number of oncologists increased from 1.1 to 3.3 to 7.1 (P<.001).

Conclusions: Nasopharyngeal cancer is a highly treatable disease, but the outcome varies widely across the world. The current study shows a significant correlation between survival and access to RT based on available surrogate indicators. However, the possible reasons for poor outcome are likely to be multifactorial and complex. Concerted international efforts are needed not only to address the fundamental requirement for adequate RT access but also to obtain more comprehensive and accurate data for research to improve cancer outcome.
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http://dx.doi.org/10.1016/j.ijrobp.2015.11.047DOI Listing
April 2016

Abiraterone acetate in metastatic castration-resistant prostate cancer - the unanticipated real-world clinical experience.

BMC Urol 2016 Mar 22;16:12. Epub 2016 Mar 22.

Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, Hong Kong.

Background: There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real-life clinical practice.

Methods: The clinical records of mCRPC patients treated with AA from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. The treatment efficacy and its determinants, and toxicities were determined.

Results: A total of 110 patients with mCRPC were treated with AA in the review period, of whom 58 were chemo-naive and 52 had received prior chemotherapy (post-chemo). The median follow-up time was 7.5/11.4 months for chemo-naive/post-chemo patients. 6.9/15.4 % of chemo-naive/post-chemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 18.1/15.5 months and 6.7/6.4 months for chemo-naive/post-chemo patients, respectively. Among chemo-naive patients, those with visceral diseases had significantly inferior OS (2.8 vs 18.0 p = 0.0007) and PFS (2.8 vs 6.8 months, p = 0.0088) than those without. Pain control was comparable in both groups of patients. The most common grade 3 or above toxicities were hypertension (6.9/5.8 %) and hypokalemia (3.4/3.8 %) in chemo-naive/post-chemo patients. In multivariate analysis, the presence of prostate-specific antigen (PSA) response (≥50 % drop of PSA from baseline) within the first 3 months of therapy was associated with favorable OS and PFS in both chemo-naive and post-chemo group.

Conclusions: In clinical practice outside the trial setting, OS after AA in our chemo-naive patient cohort (18.1 months) was considerably shorter than that reported in the COU-AA-302 trial (34.7 months), and the OS was particularly short in those with visceral metastases (2.8 months). Conversely, AA was efficacious in post-chemo patients. AA resulted in comparable pain control in both groups of patients. The presence of PSA response within the first 3 months of treatment was a significant determinant of survival.
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http://dx.doi.org/10.1186/s12894-016-0132-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802641PMC
March 2016

Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy.

Cancer 2016 Feb 20;122(4):546-58. Epub 2015 Nov 20.

Clinical Oncology Center, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Background: An accurate staging system is crucial for cancer management. Evaluations for continual suitability and improvement are needed as staging and treatment methods evolve.

Methods: This was a retrospective study of 1609 patients with nasopharyngeal carcinoma investigated by magnetic resonance imaging, staged with the 7th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system, and irradiated by intensity-modulated radiotherapy at 2 centers in Hong Kong and mainland China.

Results: Among the patients without other T3/T4 involvement, there were no significant differences in overall survival (OS) between medial pterygoid muscle (MP) ± lateral pterygoid muscle (LP), prevertebral muscle, and parapharyngeal space involvement. Patients with extensive soft tissue involvement beyond the aforementioned structures had poor OS similar to that of patients with intracranial extension and/or cranial nerve palsy. Only 2% of the patients had lymph nodes > 6 cm above the supraclavicular fossa (SCF), and their outcomes resembled the outcomes of those with low extension. Replacing SCF with the lower neck (extension below the caudal border of the cricoid cartilage) did not affect the hazard distinction between different N categories. With the proposed T and N categories, there were no significant differences in outcome between T4N0-2 and T1-4N3 disease.

Conclusions: After a review by AJCC/UICC preparatory committees, the changes recommended for the 8th edition include changing MP/LP involvement from T4 to T2, adding prevertebral muscle involvement as T2, replacing SCF with the lower neck and merging this with a maximum nodal diameter > 6 cm as N3, and merging T4 and N3 as stage IVA criteria. These changes will lead not only to a better distinction of hazards between adjacent stages/categories but also to optimal balance in clinical practicability and global applicability.
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http://dx.doi.org/10.1002/cncr.29795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968037PMC
February 2016

Chemotherapy for Nasopharyngeal Carcinoma - Current Recommendation and Controversies.

Hematol Oncol Clin North Am 2015 Dec 20;29(6):1107-22. Epub 2015 Oct 20.

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China; Department of Clinical Oncology, The University of Hong Kong - Shenzhen Hospital, 1 Haiyuan First Road, Futian District, Shenzhen, Guangdong 518053, China.

Radiotherapy is the primary treatment of nasopharyngeal carcinoma and combination chemotherapy can enhance treatment outcomes for locoregionally advanced disease. The Intergroup 0099 study using concurrent-adjuvant cisplatin-based chemoradiotherapy was the first trial to demonstrate a survival benefit. Since then, there have been attempts to further improve the treatment results by altering the chemotherapy sequence, using different chemotherapeutic agents or schedules, and extending the use of chemotherapy to early-stage disease. This review provides an overview of the data and highlights the current controversies behind international guidelines.
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http://dx.doi.org/10.1016/j.hoc.2015.07.004DOI Listing
December 2015

Chemotherapy for Nasopharyngeal Cancer: Neoadjuvant, Concomitant, and/or Adjuvant.

Curr Treat Options Oncol 2015 Sep;16(9):44

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong.

Nasopharyngeal cancers are unique among other head and neck cancers, not only in epidemiology and histological characteristics, but also on treatment strategies as well. Radiotherapy is the primary treatment due to its radiosensitivity. In locally advanced stages, concurrent chemoradiation has been established to be effective to eradicate the disease and improve survival, in favor of radiotherapy alone. While increasing studies have explored the potential benefit of adding more chemotherapy to the concurrent regimen, whether adjuvant or neoadjuvant, it is generally agreed that proper patient selection is needed to stratify high-risk groups to intensify treatment and to optimize the disease outcome. Future studies are ongoing, possibly with the addition of biomarkers such as EBV DNA for risk group stratification. Refinement of patient groups that should be selected for combined modality treatment in stage II disease is also warranted.
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http://dx.doi.org/10.1007/s11864-015-0361-5DOI Listing
September 2015

Intravoxel water diffusion heterogeneity MR imaging of nasopharyngeal carcinoma using stretched exponential diffusion model.

Eur Radiol 2015 Jun 23;25(6):1708-13. Epub 2014 Dec 23.

Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Room 406, Block K, Pok Fu Lam, Hong Kong,

Purpose: To determine the utility of stretched exponential diffusion model in characterisation of the water diffusion heterogeneity in different tumour stages of nasopharyngeal carcinoma (NPC).

Materials And Methods: Fifty patients with newly diagnosed NPC were prospectively recruited. Diffusion-weighted MR imaging was performed using five b values (0-2,500 s/mm(2)). Respective stretched exponential parameters (DDC, distributed diffusion coefficient; and alpha (α), water heterogeneity) were calculated. Patients were stratified into low and high tumour stage groups based on the American Joint Committee on Cancer (AJCC) staging for determination of the predictive powers of DDC and α using t test and ROC curve analyses.

Results: The mean ± standard deviation values were DDC = 0.692 ± 0.199 (×10(-3) mm(2)/s) for low stage group vs 0.794 ± 0.253 (×10(-3) mm(2)/s) for high stage group; α = 0.792 ± 0.145 for low stage group vs 0.698 ± 0.155 for high stage group. α was significantly lower in the high stage group while DDC was negatively correlated. DDC and α were both reliable independent predictors (p < 0.001), with α being more powerful. Optimal cut-off values were (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) DDC = 0.692 × 10(-3) mm(2)/s (94.4 %, 64.3 %, 2.64, 0.09), α = 0.720 (72.2 %, 100 %, -, 0.28).

Conclusion: The heterogeneity index α is robust and can potentially help in staging and grading prediction in NPC.

Key Points: • Stretched exponential diffusion models can help in tissue characterisation in nasopharyngeal carcinoma • α and distributed diffusion coefficient (DDC) are negatively correlated • α is a robust heterogeneity index marker • α can potentially help in staging and grading prediction.
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http://dx.doi.org/10.1007/s00330-014-3535-9DOI Listing
June 2015

Should all nasopharyngeal carcinoma with masticator space involvement be staged as T4?

Oral Oncol 2014 Dec 30;50(12):1188-95. Epub 2014 Sep 30.

Clinical Oncology Center, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.

Introduction: The prognostic significance of the involvement of anatomical masticator space (MS) in nasopharyngeal carcinoma (NPC) was retrospectively reviewed.

Material And Methods: 1104 Patients with non-metastatic NPC treated with radical radiotherapy between 1998 and 2010 were re-staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system; tumors with medial pterygoid muscle (MP) and/or lateral pterygoid muscle (LP) involvement but did not fulfill the criteria for T3 or T4 were staged as TX. The tumor volume data, dosimetric data and survival endpoints of different T stage diseases were analyzed and compared to study the significance of MS involvement.

Results: The overall MS involvement rate was 61.0%. The median volumes of the primary gross tumor volume were 9.6ml, 15.2ml, 19.9ml, 32.6ml and 77.3ml for T1, T2, TX, T3 and T4, respectively (p<0.001). T1, T2 and TX tumors received higher minimum dose to the gross tumor volume and planning target volume than T3 and T4. Multivariate analysis showed that age, gender, T-/N-classification and the use of chemotherapy were significant prognostic factors for various survival end-points. Patients with TX disease had similar survival rates as with T1-T2; and had a significantly better 5-year overall survival rate (86.6% vs. 76.6%; p=0.013) and a trend of higher 5-year distant failure-free survival rate (91.5% vs. 81.3%; p=0.09) than patients with T3 disease.

Conclusion: NPC with the involvement of MP and/or LP alone should be classified as T2 disease.
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http://dx.doi.org/10.1016/j.oraloncology.2014.09.001DOI Listing
December 2014

A tale of two cities in China: Hong Kong and Shenzhen.

Int J Radiat Oncol Biol Phys 2014 Jul;89(4):704-8

Clinical Oncology Center, University of Hong Kong - Shenzhen Hospital, Shenzhen, China.

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http://dx.doi.org/10.1016/j.ijrobp.2013.12.053DOI Listing
July 2014

Evolution of treatment for nasopharyngeal cancer--success and setback in the intensity-modulated radiotherapy era.

Radiother Oncol 2014 Mar 11;110(3):377-84. Epub 2014 Mar 11.

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong.

Background And Purpose: To assess the therapeutic gains and setbacks as we evolved from the 2-dimensional radiotherapy (2DRT) to conformal 3-dimensional (3DRT) and to intensity-modulated (IMRT) era.

Materials And Methods: 1593 consecutive patients from 1994 to 2010 were retrospectively analyzed. Evolving changes in the different era included advances in staging investigation, radiotherapy technique, dose escalation, and use of chemotherapy.

Results: The 3DRT era achieved significant improvement in local failure-free rate (L-FFR), disease-specific survival (DSS) and overall survival (OS). Neurological damage and bone/soft tissue necrosis were significantly reduced. However, the improvement in distant failure-free rate (D-FFR) was insignificant, and more hearing impairment occurred due to chemotherapy. Significantly higher D-FFR was achieved in the IMRT era, but L-FFR did not show further improvement. 5-Year DSS increased from 78% in the 2DRT, to 81% in the 3DRT, and 85% in the IMRT era, while the corresponding neurological toxicity rate decreased from 7.4% to 3.5% and 1.8%.

Conclusions: Significant improvement in survival and reduction of serious toxicity was achieved as we evolved from 2DRT to 3DRT and IMRT era; the therapeutic ratio for all T-categories improved with more conformal techniques. Improvements in tumor control were attributed not only to advances in RT technique, but also to better imaging and increasing use of potent chemotherapy. However, it should also be noted that hearing impairment significantly increased due to chemotherapy, L-FFR reached a plateau in the 3DRT era, and it is worrisome that the result for T4 remained unsatisfactory. Besides exploring for more potent chemotherapy and innovative methods, the guideline on dose constraint should be re-visited to optimize the therapeutic ratio.
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http://dx.doi.org/10.1016/j.radonc.2014.02.003DOI Listing
March 2014

Treatment outcomes of postradiation second head and neck malignancies managed by a multidisciplinary approach.

Head Neck 2015 Jun 19;37(6):815-22. Epub 2014 Jun 19.

Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.

Background: The purpose of this study was to report on the treatment outcomes of patients with postradiation second head and neck malignancies.

Methods: Fifty-seven consecutive patients with postradiation second malignancy were reviewed. Progression-free survival (PFS), overall survival (OS), and prognostic factors were analyzed.

Results: Mean time interval between first course of radiation therapy to the development of postradiation second malignancy was 13.2 years. Median PFS and OS for the whole group were 12.0 and 67.0 months, respectively. Postradiation sarcoma conferred a worse PFS (p = .003) and OS (p = .001) as compared to postradiation carcinoma. Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (p = .034), postradiation sarcoma (p = .007), and lack of radical surgery (p = .044) are prognostic of PFS, whereas postradiation sarcoma (p = .002), lack of postprogression surgery (p < .001), and lack of postprogression systemic therapy (p = .011) were prognostic factors of OS.

Conclusion: Treatment outcomes of postradiation second malignancy seemed promising under a multidisciplinary management.
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http://dx.doi.org/10.1002/hed.23674DOI Listing
June 2015

Current controversies in radiotherapy for nasopharyngeal carcinoma (NPC).

Oral Oncol 2014 Oct 11;50(10):907-12. Epub 2013 Oct 11.

Center of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, China.

Radiotherapy has a good track record in the treatment of NPC, yet the late toxicity profile and local failure rate for locally advanced disease remain a concern. Modern RT techniques incorporating IMRT and IGRT have widened our potential in treating NPC more effectively, and shall be regarded as the standard of care. Out of the various dose fractionation regimens in IMRT, 70 Gy in 35 fractions or the mini-SIB proves to be safe in combination with chemotherapy, but any further attempt of dose escalation must be tried out with extreme caution to avoid severe toxicities. CT-MRI image fusion improves the accuracy of GTV delineation, whereas the role of PET-CT has yet to be verified. RTOG definition of the CTV provides a reasonable template for the inclusion of sites at risk of microscopic involvement, and fine tuning has to be made in the future based on careful analysis of the pattern of local failure with long term follow-up. Toxicity reduction via radiation volume or dose reduction is tempting, but once again it has to be tested under scrutiny. Retrospective data have emerged that suggest a benefit of using adaptive IMRT replanning in NPC, however the optimal timing or frequency of replanning is still unclear. Future prospective studies are thus required to evaluate the cost-effectiveness of adaptive RT and streamline the workflow logistics before it can be widely accepted in routine practice.
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http://dx.doi.org/10.1016/j.oraloncology.2013.09.013DOI Listing
October 2014

The battle against nasopharyngeal cancer.

Radiother Oncol 2012 Sep 30;104(3):272-8. Epub 2012 Aug 30.

Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.

This is a review of the evolving efforts to understand and combat nasopharyngeal carcinoma (NPC), a most peculiar cancer with a distinctly skewed geographic and ethnic distribution. Multifactorial etiology with dynamic interplay of genetic predisposition, Epstein-Barr virus (EBV) infection and environmental carcinogens is suggested. With changing lifestyle in Hong Kong, the age-standardized incidence rate has decreased by more than 50% during the past 30 years. The advent of megavoltage radiotherapy has transformed this once lethal cancer into one that is readily curable. Advances in technology and addition of chemotherapy have led to gratifying improvements. Overall survival exceeding 75% at 5 years could now be achieved; series using advanced technique with intensity-modulation consistently achieved excellent locoregional control. Studies are on-going to develop more potent systemic therapy for distant control. Serious late toxicities remain a serious concern demanding further improvement in radiotherapy technique and optimization of dose fractionation. Translational researches are increasingly important for the ideal goals of prevention, early detection and more accurate prognostication/prediction to work toward personalized medicine. The battle against NPC is one of the most fascinating successes in oncology, it is highly hopeful that with international collaborations and concerted efforts, we can totally conquer this cancer.
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http://dx.doi.org/10.1016/j.radonc.2012.08.001DOI Listing
September 2012

Predictive factors and radiological features of radiation-induced cranial nerve palsy in patients with nasopharyngeal carcinoma following radical radiotherapy.

Oral Oncol 2013 Jan 11;49(1):49-54. Epub 2012 Aug 11.

Department of Radiology, Pamela Youde Nethersole Eastern Hospital, Hong Kong.

Objectives: To identify the key predictive factors of radiation-induced cranial nerve palsy in patients with nasopharyngeal carcinoma (NPC).

Method And Materials: From November 1998 to December 2007, all consecutive patients with newly diagnosed NPC who were curatively treated with radiotherapy and subsequently developed radiation-induced cranial nerve palsy (RICNP) were included in our study. Patients with cranial nerve palsy due to disease recurrence were excluded. Their records were retrospectively reviewed.

Results: Amongst 965 patients with NPC treated with radical radiotherapy, 41 developed new cranial nerve palsy. After exclusion of 5 patients with cranial nerve palsy due to recurrence, 36 (3.7%) developed RICNP. The median follow-up was 8.9 years (range, 3.2-11.3 years). Ten of the 36 patients had cranial nerve palsy at presentation. Twenty-seven patients had single cranial nerve palsy and 9 patients had multiple cranial nerve palsy. The most commonly involved cranial nerve was cranial nerve XII, with 30 patients having palsy of cranial nerve XII and 6 of them having bilateral cranial nerve XII palsies. Magnetic resonance imaging features of radiation-induced hypoglossal nerve palsy were demonstrated in our study. Multivariate analysis revealed that cranial nerve palsy at presentation was an independent prognostic factor for the development of RICNP. Other factors including T staging, N staging, gender, age, radiotherapy technique and the use of chemotherapy have no significant relationship with the risk of developing RICNP.

Conclusion: RICNP in patients with NPC is not a rare complication, and cranial nerve palsy at presentation is an important prognostic factor.
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http://dx.doi.org/10.1016/j.oraloncology.2012.07.011DOI Listing
January 2013

The strength/weakness of the AJCC/UICC staging system (7th edition) for nasopharyngeal cancer and suggestions for future improvement.

Oral Oncol 2012 Oct 22;48(10):1007-1013. Epub 2012 Apr 22.

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.

Background And Purpose: To evaluate the current AJCC/UICC staging system (7th edition) for nasopharyngeal carcinoma and to explore for future improvement.

Materials And Methods: A total of 985 patients, initially staged with preceding 5-6th edition, were retrospectively re-staged with the 7th edition. All were assessed by magnetic resonance imaging, and all 945 non-disseminated patients were irradiated with conformal/intensity-modulated technique.

Results: Staging factors by both the 5-6th edition and the 7th edition were strongly significance for important endpoints (p<0.001). Down-staging of the previous T2a to T1 and, stages IIA to I in the 7th edition was appropriate. However, the impacts on overall stage distribution and prognostication were minimal. Further down-staging of the current T2 to T1, N2 to N1, stages II to I, and merging of N3a and N3b, stages IVA and IVB were suggested. With the 7th edition, the 5-year disease-specific survival (DSS) was 100% for stage I, 95% for II, 90% for III, 67% for IVA, 68% for IVB and 18% for IVC. The corresponding DSS for the proposed stages I, II, III and IV were 95%, 86%, 67% and 18%, respectively.

Conclusions: The changes introduced in the 7th edition were appropriate, but the magnitude of improvement was minimal. With improving results by modern management, further simplification of the staging system is suggested. The proposed system could lead to more accurate prognostication, further validation is warranted.
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http://dx.doi.org/10.1016/j.oraloncology.2012.03.022DOI Listing
October 2012

Radical radiotherapy for nasopharyngeal carcinoma in elderly patients: the importance of co-morbidity assessment.

Oral Oncol 2012 Feb 16;48(2):162-7. Epub 2011 Sep 16.

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region.

Elderly patients represent a unique challenge for radical treatment in nasopharyngeal carcinoma (NPC) because of age and co-morbid conditions. We sought to evaluate the outcome of this particular group of patients and to identify key factors affecting treatment outcome. From 1998 to 2008, 990 consecutive NPC patients without distant metastasis were treated with radical radiotherapy with planned total dose >66 Gy. Among them, 103 (10.4%) patients were elderly aged >70 (group A). Their clinical characteristics and outcome were compared with those aged <70 (group B). Mortality at 90 days was used as a proxy of early deaths related to treatment. Co-morbidities were measured by the Adult Co-morbidity Evaluation 27 (ACE-27). Group A presented more commonly with poorer performance status. They showed higher rates of acute reaction, radiotherapy incompletion and mortality at 90 days (7.8% vs. 1.2%, p<0.001). The 5-year overall survival rates were 43.9% and 78.1% for groups A and B, respectively (p<0.001). No difference in failure free survival rates was noted. For group A, ACE-27 was the only predicting factor for mortality at 90 days [ACE-27 2-3 vs. 0-1: HR 15.86 (2.68-93.95), p=0.002], and the most important prognostic factors for overall survival included age, presenting stage and ACE-27 (p<0.05). Elderly NPC patients had poorer tolerance to radiotherapy. Early deaths related to treatment were not uncommon. A reasonable disease control can still be attained after radical radiotherapy for those who were able to survive through the peri-radiotherapy period. Patient selection and treatment approach with reference to ACE-27 should be considered.
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http://dx.doi.org/10.1016/j.oraloncology.2011.08.019DOI Listing
February 2012

RapidArc radiotherapy planning for prostate cancer: single-arc and double-arc techniques vs. intensity-modulated radiotherapy.

Med Dosim 2012 16;37(1):87-91. Epub 2011 Sep 16.

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.

RapidArc is a novel technique using arc radiotherapy aiming to achieve intensity-modulated radiotherapy (IMRT)-quality radiotherapy plans with shorter treatment time. This study compared the dosimetric quality and treatment efficiency of single-arc (SA) vs. double-arc (DA) and IMRT in the treatment of prostate cancer. Fourteen patients were included in the analysis. The planning target volume (PTV), which contained the prostate gland and proximal seminal vesicles, received 76 Gy in 38 fractions. Seven-field IMRT, SA, and DA plans were generated for each patient. Dosimetric quality in terms of the minimum PTV dose, PTV hotspot, inhomogeneity, and conformity index; and sparing of rectum, bladder, and femoral heads as measured by V70, V-40, and V20 (% of volume receiving >70 Gy, 40 Gy, and 20 Gy, respectively), treatment efficiency as assessed by monitor units (MU) and treatment time were compared. All plan objectives were met satisfactorily by all techniques. DA achieved the best dosimetric quality with the highest minimum PTV dose, lowest hotspot, and the best homogeneity and conformity. It was also more efficient than IMRT. SA achieved the highest treatment efficiency with the lowest MU and shortest treatment time. The mean treatment time for a 2-Gy fraction was 4.80 min, 2.78 min, and 1.30 min for IMRT, DA, and SA, respectively. However, SA also resulted in the highest rectal dose. DA could improve target volume coverage and reduce treatment time and MU while maintaining equivalent normal tissue sparing when compared with IMRT. SA achieved the greatest treatment efficiency but with the highest rectal dose, which was nonetheless within tolerable limits. For busy units with high patient throughput, SA could be an acceptable option.
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http://dx.doi.org/10.1016/j.meddos.2011.01.005DOI Listing
June 2012

Fibromatosis of the neck causing airway obstruction managed effectively with weekly low-dose methotrexate and vinblastine.

Authors:
Henry Sze M W Yeung

Hong Kong Med J 2009 Jun;15(3):221-3

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong.

Fibromatosis is a rare disease with benign histology. Its infiltrative growth pattern may prevent complete resection. We report a case of a 40-year-old woman with fibromatosis of the neck requiring an emergency operation for acute upper airway obstruction. Gross residual tumour was left behind but excellent tumour shrinkage was achieved by using weekly low-dose methotrexate and vinblastine. Despite the use of newer agents such as imatinib, cytotoxic chemotherapy remains an efficacious treatment for inoperable fibromatosis.
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June 2009

Should young age be a contra-indication to breast conservation treatment in Chinese women? Twelve-year experience from a public cancer centre in Hong Kong.

Hong Kong Med J 2009 Apr;15(2):94-9

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong.

Objective: It has been proposed that young women should not be treated by breast conservation treatment because of a higher risk of local recurrences and worse survival. We therefore examined whether breast conservation treatment in young Chinese women yielded inferior clinical outcomes compared to modified radical mastectomy.

Design: Retrospective study.

Setting: Clinical oncology department in a public hospital in Hong Kong.

Patients: A total of 258 Chinese women with invasive breast cancer, aged below 40 years, and referred between January 1994 and July 2006.

Results: A total of 124 (48%) and 134 (52%) patients were treated by breast conservation treatment and modified radical mastectomy, respectively. Mastectomy patients tended to have larger primary tumours (P<0.001) and more nodal involvement (P<0.001). At a median follow-up of 6.5 years, there was no significant difference in the local failure-free survival rate (92% vs 93%, P=0.324) and loco-regional failure-free survival rate (89% vs 88%, P=0.721) in patients having breast conservation treatment and mastectomy. Probably due to their earlier presentation with disease, the former actually had better 6-year distant failure-free survival (88% vs 71%, P=0.002) and overall survival (92% vs 81%, P=0.173) rates. Multivariate analyses showed that both the resection margin status (hazard ratio=2.77, P=0.050) and the presence of peritumoural vascular invasion (hazard ratio=3.01, P=0.038) were independent predictors of local recurrence; the nodal status (hazard ratio=3.91, P<0.001) was the only predictive factor for overall survival. The choice of breast conservation treatment (vs modified radical mastectomy) had no apparent adverse impact on all the clinical outcome parameters analysed.

Conclusion: Breast conservation treatment is a reasonable option for many suitably selected young Chinese women.
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April 2009

Trends and patterns of breast conservation treatment in Hong Kong: 1994-2007.

Int J Radiat Oncol Biol Phys 2009 May 26;74(1):98-103. Epub 2008 Dec 26.

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.

Purpose: Breast conservation treatment (BCT) was quite unpopular in Hong Kong until the early 1990s, but the trends and patterns of BCT use in the past 14 years have not been studied since. The purpose of this study was to identify the latest trends and patterns.

Methods And Materials: All consecutive cases of female breast cancer referred to a community oncology center in Hong Kong between 1994 and 2007 were retrospectively reviewed. Of the 2,375 women with T1-2 invasive breast cancer who underwent surgery, 1,137 (48%) had T1 (2 cm-
Results: Of the total patient cohort, 2,153 (91%) patients presented with palpable breast masses and only 104 (4%) with mammographically detected cancers. Overall, 721 (30%) and 1,654 (70%) patients underwent BCT and mastectomy, respectively. There was no significant increase in the BCT rates (31%, SD 5%; p = 0.804) or mammographic detection rates (5%, SD 1%; p = 0.125) in Hong Kong between 1994 and 2007. In multivariate analyses, age
Conclusions: Our results indicate a satisfactory acceptance of BCT by patients who are young and have small tumors, node-negative disease, or surgery in private hospitals. However, the continuing unpopularity of breast screening is likely a major factor limiting the broad use of BCT.
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http://dx.doi.org/10.1016/j.ijrobp.2008.07.066DOI Listing
May 2009
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