Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer

© 2018, Hong Kong Academy of Medicine Press. All rights reserved. Introduction: The management of human epidermal growth factor receptor 2 (HER2)–positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. Methods: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. Results: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3-9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. Conclusions: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.Link_to_subscribed_fulltex

DCE-MRI for pre-treatment prediction and post-treatment assessment of treatment response in sites of squamous cell carcinoma in the head and neck

Background and Purpose It is important to identify patients with head and neck squamous cell carcinoma (SCC) who fail to respond to chemoradiotherapy so that they can undergo post-treatment salvage surgery while the disease is still operable. This study aimed to determine the diagnostic performance of dynamic contrast enhanced (DCE)-MRI using a pharmacokinetic model for pre-treatment predictive imaging, as well as post-treatment diagnosis, of residual SCC at primary and nodal sites in the head and neck. Material and Methods Forty-nine patients with 83 SCC sites (primary and/or nodal) underwent pre-treatment DCEMRI, and 43 patients underwent post-treatment DCE-MRI, of which 33 SCC sites had a residual mass amenable to analysis. Pre-treatment, post-treatment and %change in the mean Ktrans, kep, ve and AUGC were obtained from SCC sites. Logistic regression was used to correlate DCE parameters at each SCC site with treatment response at the same site, based on clinical outcome at that site at a minimum of two years. Results None of the pre-treatment DCE-MRI parameters showed significant correlations with SCC site failure (SF) (29/83 sites) or site control (SC) (54/83 sites). Post-treatment residual masses with SF (14/33) had significantly higher kep (p = 0.05), higher AUGC (p = 0.02), and lower % reduction in AUGC (p = 0.02), than residual masses with SC (19/33), with the% change in AUGC remaining significant on multivariate analysis. Conclusion Pre-treatment DCE-MRI did not predict which SCC sites would fail treatment, but post-treatment DCE-MRI showed potential for identifying residual masses that had failed treatment

DCE-MRI for pre-treatment prediction and post-treatment assessment of treatment response in sites of squamous cell carcinoma in the head and neck

Background and Purpose It is important to identify patients with head and neck squamous cell carcinoma (SCC) who fail to respond to chemoradiotherapy so that they can undergo post-treatment salvage surgery while the disease is still operable. This study aimed to determine the diagnostic performance of dynamic contrast enhanced (DCE)-MRI using a pharmacokinetic model for pre-treatment predictive imaging, as well as post-treatment diagnosis, of residual SCC at primary and nodal sites in the head and neck. Material and Methods Forty-nine patients with 83 SCC sites (primary and/or nodal) underwent pre-treatment DCEMRI, and 43 patients underwent post-treatment DCE-MRI, of which 33 SCC sites had a residual mass amenable to analysis. Pre-treatment, post-treatment and %change in the mean Ktrans, kep, ve and AUGC were obtained from SCC sites. Logistic regression was used to correlate DCE parameters at each SCC site with treatment response at the same site, based on clinical outcome at that site at a minimum of two years. Results None of the pre-treatment DCE-MRI parameters showed significant correlations with SCC site failure (SF) (29/83 sites) or site control (SC) (54/83 sites). Post-treatment residual masses with SF (14/33) had significantly higher kep (p = 0.05), higher AUGC (p = 0.02), and lower % reduction in AUGC (p = 0.02), than residual masses with SC (19/33), with the% change in AUGC remaining significant on multivariate analysis. Conclusion Pre-treatment DCE-MRI did not predict which SCC sites would fail treatment, but post-treatment DCE-MRI showed potential for identifying residual masses that had failed treatment

Impact of disease stage and aetiology on survival in hepatocellular carcinoma::implications for surveillance

Background: Variation in survival in hepatocellular carcinoma (HCC) has been attributed to different aetiologies or disease stages at presentation. While international guidelines recommend surveillance of high-risk groups to permit early diagnosis and curative treatment, the evidence that surveillance decreases disease-specific mortality is weak. Methods: We compared HCC survival figures from Japan (n=1174) and Hong Kong (n=1675) over similar time periods (Japan 2000–2013, Hong Kong, China 2003–2014). The former has an intensive national surveillance programme, while the latter has none. We also analysed changes in survival in Japan over a 50-year period including data from before and after institution of a national HCC surveillance programme. Results: In Japan, over 75% of cases are currently detected by surveillance, whereas in Hong Kong <20% of cases are detected presymptomatically. Median survival was 52 months in Japan and 17.8 months in Hong Kong; this survival advantage persisted after allowance for lead-time bias. Sixty-two per cent of Japanese patients had early disease at diagnosis and 63% received curative treatment. The comparable figures for Hong Kong were 31.7% and 44.1%, respectively. These differences could not be accounted for by disease aetiology, and patients in Hong Kong who were detected at an early stage had a similar survival to the analogous patients in Japan. Conclusions: The variation in survival is largely accounted for by stage at diagnosis, which in turn relates to the intensity of surveillance programmes and the consequent variation in curative therapeutic options

Radiomics for Discrimination between Early-Stage Nasopharyngeal Carcinoma and Benign Hyperplasia with Stable Feature Selection on MRI

Discriminating early-stage nasopharyngeal carcinoma (NPC) from benign hyperplasia (BH) on MRI is a challenging but important task for the early detection of NPC in screening programs. Radiomics models have the potential to meet this challenge, but instability in the feature selection step may reduce their reliability. Therefore, in this study, we aim to discriminate between early-stage T1 NPC and BH on MRI using radiomics and propose a method to improve the stability of the feature selection step in the radiomics pipeline. A radiomics model was trained using data from 442 patients (221 early-stage T1 NPC and 221 with BH) scanned at 3T and tested on 213 patients (99 early-stage T1 NPC and 114 BH) scanned at 1.5T. To verify the improvement in feature selection stability, we compared our proposed ensemble technique, which uses a combination of bagging and boosting (BB-RENT), with the well-established elastic net. The proposed radiomics model achieved an area under the curve of 0.85 (95% confidence interval (CI): 0.82&ndash;0.89) and 0.80 (95% CI: 0.74&ndash;0.86) in discriminating NPC and BH in the 3T training and 1.5T testing cohort, respectively, using 17 features selected from a pool of 422 features by the proposed feature selection technique. BB-RENT showed a better feature selection stability compared to the elastic net (Jaccard index = 0.39 &plusmn; 0.14 and 0.24 &plusmn; 0.06, respectively; p &lt; 0.001)

Higher Level of Sports Activities Participation during Five-Year Survival Is Associated with Better Quality of Life among Chinese Breast Cancer Survivors

Evidence about the association between the level of sports activities participation post-diagnosis and quality of life (QoL) among Chinese women with early-stage breast cancer is limited. A validated modified Chinese Baecke questionnaire was used to prospectively measure sports activities among a breast cancer cohort at four time-points: baseline and 18, 36, and 60 months after diagnosis (sports activities during the previous 12 months before each interview); QoL was measured at the same time. In total, 1289, 1125, and 1116 patients were included in the analyses at 18-, 36- and 60-month follow-up, respectively. The percentages of patients who belonged to no (0 metabolic equivalent of task (MET)-hours per week), low-level (&lt;10 MET-hours/week), and high-level (&ge;10 MET-hours/week) sports activities group were 20.7%, 45.5%, and 33.8% at 18-month follow-up, respectively; the corresponding figures at 36 and 60 months differed slightly. Using data from the three follow-ups, generalized estimating equation (GEE) analyses showed that higher levels of sports activities participation were associated with better QoL in several items as well as fewer symptoms. The present findings in Chinese women with breast cancer provide important evidence on the beneficial effect of regular participation in sports activities following cancer diagnosis on patients&rsquo; QoL

Prospective Randomized Phase II Study of Stereotactic Body Radiotherapy (SBRT) vs. Conventional Fractionated Radiotherapy (CFRT) for Chinese Patients with Early-Stage Localized Prostate Cancer

Background: Stereotactic body radiotherapy (SBRT) has potential radiobiologic and economic advantages over conventional fractionated radiotherapy (CFRT) in localized prostate cancer (PC). This study aimed to compare the effects of these two distinct fractionations on patient-reported quality of life (PRQOL) and tolerability. Methods: In this prospective phase II study, patients with low- and intermediate-risk localized PC were randomly assigned in a 1:1 ratio to the SBRT (36.25 Gy/5 fractions/2 weeks) or CFRT (76 Gy/38 fractions/7.5 weeks) treatment groups. The primary endpoint of variation in PRQOL at 1 year was assessed by changes in the Expanded Prostate Cancer Index Composite (EPIC) questionnaire scores and analysed by z-tests and t-tests. Results: Sixty-four eligible Chinese men were treated (SBRT, n = 31; CFRT, n = 33) with a median follow-up of 2.3 years. At 1 year, 40.0%/46.9% of SBRT/CFRT patients had a &gt;5-point decrease in bowel score (p = 0.08/0.28), respectively, and 53.3%/46.9% had a &gt;2-point decrease in urinary score (p = 0.21/0.07). There were no significant differences in EPIC score changes between the arms at 3, 6, 9 and 12 months, but SBRT was associated with significantly fewer grade &ge; 1 acute and 1-year late gastrointestinal toxicities (acute: 35% vs. 87%, p &lt; 0.0001; 1-year late: 64% vs. 84%, p = 0.03), and grade &ge; 2 acute genitourinary toxicities (3% vs. 24%, p = 0.04) compared with CFRT. Conclusion: SBRT offered similar PRQOL and less toxicity compared with CFRT in Chinese men with localized PC