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Aim: To investigate treatment patterns and outcomes of metastatic colorectal cancer (mCRC) patients beyond second progression (PD2) since regorafenib and TAS-102 became available in Hong Kong., Methods: The clinical records of consecutive mCRC patients who were treated beyond PD2 at Department of Clinical Oncology, Queen Mary Hospital between June 2013 and February 2018, were retrospectively reviewed., Results: Of 176 PD2 patients (76.7% Eastern Cooperative Oncology Group performance status 0/1 and a median follow-up time of 6.6 [range, 0.4-37.2] months), 104 (59%) underwent palliative care only and 72 (41%) received active third-line (3L) treatment: regorafenib (n = 22), TAS-102 (n = 6), chemotherapy + antiepidermal growth factor receptor (n = 12), chemotherapy + antivascular endothelial growth factor (n = 28) or clinical trials (n = 4). Patients on active 3L treatment had significantly longer OS than those on palliative care only: 11.7 versus 5.5 months (adjusted hazard ratio = 0.41, 95% confidence interval: 0.28-0.61, P < 0.001). For those on active treatment, OS was significantly associated with the time from diagnosis of metastasis to PD2 (P < 0.001) and post-3L treatments (P = 0.009). When analyzing treatment eligibility according to trial criteria, half of the eligible patients (54/109) did not receive active treatment, but both eligible and ineligible patients achieved better OS when receiving active 3L treatment versus palliative care only (P < 0.001 and P = 0.002). No unexpected toxicity was reported., Conclusion: Active 3L and beyond treatment significantly prolonged OS versus palliative care, even in selected "trial ineligible" patients. Given a high rate of palliation only care in eligible patients, improved patient access to medicine and counseling may be needed to maximize outcomes., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: 18F-FDG PET-CT is commonly used to monitor treatment response in patients with metastatic colorectal cancer (mCRC). With improvement in systemic therapy, complete metabolic response (CMR) is increasingly encountered but its clinical significance is undefined. The study examined the long-term outcomes and recurrence patterns in these patients., Methods: Consecutive patients with mCRC who achieved CMR on PET-CT during first-line systemic therapy were retrospectively analysed. Measurable and non-measurable lesions identified on baseline PET-CT were compared with Response Criteria in Solid Tumors (RECIST) on CT on a per-lesion basis. Progression free (PFS) and Overall Survival (OS) were compared with clinical parameters and treatment characteristics on a per-patient basis., Results: Between 2008 and 2011, 40 patients with 192 serial PET-CT scans were eligible for analysis involving 44 measurable and 38 non-measurable lesions in 59 metastatic sites. On a per-lesion basis, 46% also achieved Complete Response (CR) on RECIST criteria and sustained CMR was more frequent in these lesions (OR 1.727, p = 0.0031). Progressive metabolic disease (PMD) was seen in 12% of lesions, with liver metastasis the most common. Receiver operating characteristics (ROC) curve analysis revealed the optimal value of SUVmax for predicting PMD of a lesion was 4.4 (AUC 0.734, p = 0.004). On a per-patient basis, 14 patients achieved sustained CMR and their outcomes were better than those with PMD (median OS not reached vs 37.7 months p = 0.0001). No statistical difference was seen in OS between patients who achieved PR or CR (median OS 51.4 vs 44.2 months p = 0.766)., Conclusion: Our results provided additional information of long-term outcomes and recurrence patterns of patients with mCRC after achieving CMR. They had improved survival and sustained CMR using systemic therapy alone is possible. Discordance between morphological and metabolic response was consistent with reported literature but in the presence of CMR the two groups had comparable outcomes.

Purpose of the Study: To evaluate the benefits and tolerability of regorafenib in the real-world setting, we performed a multicentre analysis in Hong Kong., Study Design: Individual patient data were retrieved from three leading oncology centres in Hong Kong for analyses. All patients with metastatic colorectal cancer (mCRC) treated with regorafenib after failure of all standard systemic options were included., Results: From July 2013 to December 2015, 45 consecutive patients treated with regorafenib for mCRC were analysed. The median age was 63. Twenty patients were started at 160 mg, while the other 25 patients were started at a lower dose. The median progression-free survival was 15.6 weeks (95% CI 13.1 to 18.1 weeks) and the median overall survival was 30.4 weeks (95% CI 16.6 to 44.3 weeks). Among the 31 evaluable patients, only 1 patient (3.2%) achieved partial response and another 10 patients (32.3%) had stable disease. The commonest grade 3 non-haematological adverse event (AE) was hand-foot skin reaction (26.7%) and the commonest grade 3 or 4 haematological AE was anaemia (8.9%). Notably, patients who were started on a lower dose of regorafenib had significantly lower risk of grade 3 treatment-emergent AEs. Overall, 78.3% of the patients had dose reduction during the first and second cycles. Patients older than 65 years were more likely to experience cycle suspension and require dose reduction., Conclusions: Our study confirmed the efficacy and tolerability of regorafenib in the real-world setting. It also suggested that individualised dosing of regorafenib in patients with mCRC might result in better clinical outcomes., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: Definitive concurrent chemoradiotherapy is the standard treatment for stage III non-small cell lung cancer (NSCLC). Previous studies showed that the tumor size and its metabolic activity are predictors of treatment outcome. We investigated whether there are new metabolic prognostic factors of survival for stage III NSCLC after definitive concurrent chemoradiotherapy., Patients and Methods: A total of 57 consecutive patients treated with definitive concurrent chemoradiotherapy for their stage IIIA (n=22) and stage IIIB (n=35) (AJCC 7th edition) unresectable NSCLC were identified. A total of 43 (75.4%) patients had positron emission tomography with integrated computed tomography (PET-CT) scan performed at diagnosis that were subsequently reviewed and analyzed. Prognosticators of progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed., Results: The median PFS, DMFS, and OS were 14.1, 12.6, and 37.8 months, respectively, after a median follow-up of 41.5 months. PFS advantage was demonstrated in stage IIIA versus stage IIIB (median 38.6 vs. 13.5 mo, P=0.020), N-stage N0-N2 versus N3 (median 16.7 vs. 8.1 mo, P<0.001), planning target volume (PTV) <500 versus ≥500 cm (median 23.6 vs. 11.3 mo, P=0.008), and the maximum standardized uptake value (SUVmax) nodes <8 versus ≥8 (median 16.1 vs. 10.7 mo, P=0.048). DMFS advantage was noted in those with PTV<500 versus PTV≥500 cm (median 13.0 vs. 11.3 mo, P=0.045) and SUVmax nodes <8 versus ≥8 (median 13.5 vs. 8.0 mo, P=0.050). OS advantage was revealed in stage IIIA versus stage IIIB (median 56.5 vs. 22.7 mo, P=0.013) and SUVmax nodes <8 versus ≥8 (42.3 vs. 12.8 mo, P=0.009). Multivariate analysis demonstrated that SUVmax nodes <8 was the only prognostic factor of PFS, DMFS, and OS. Metabolic tumor volume and total lesion glycolysis were not prognostic factors., Conclusions: SUVmax nodes <8 was the only prognostic factor of PFS, DMFS, and OS in our study. PET-CT scan at the time of diagnosis is useful in stratifying patients into favorable and unfavorable groups in stage III NSCLC treated with definitive concurrent chemoradiotherapy.

Background: Afaitnib has shown anti-tumor activity against metastatic EGFR-mutated NSCLC after prior failure to first generation EGFR-TKI and chemotherapy. We prospectively evaluated the efficacy and safety of afatinib in Chinese patients who previously failed first-generation TKI and chemotherapy under a compassionate use program (CUP) and compared to the erlotinib cohort., Methods: Patients who suffered from metastatic EGFR-mutated NSCLC previously responsive to first-generation TKI and chemotherapy received afatinib until progression, loss of clinical benefits or intolerable toxicity. Treatment response, survival and safety were evaluated and compared to the erlotinib cohort., Results: Twenty-five and 28 patients received afatinib and erlotinib respectively. More patients in the afatinib group had worse performance status (ECOG 2) than the erlotinib group (p = 0.008). After a median follow-up of 12.1 months, afatinib demonstrated comparable objective response rate (ORR) (20.0% vs. 7.1%, p = 0.17) but significantly higher disease control rate (DCR) (68.0% vs. 39.3%, p = 0.04) compared to erlotinib. Median progression-free survival (PFS) (4.1 months [95% CI, 2.7-5.5 months] vs. 3.3 months [95% CI, 2.2-4.3 months], p = 0.97) and overall survival (OS) were not different between the two groups (10.3 months [95% CI, 7.5-13.0 months] vs. 10.8 months [95% CI, 7.4-14.2 months], p = 0.51). Multivariate analyses revealed that age ≤ 70 years and time to progression (TTP) ≥ 18 months for the 1st TKI therapy were prognostic of PFS (p = 0.006 and p = 0.008 respectively). Afatinib caused less rash (60.0% vs. 67.9%, p = 0.04) but more diarrhea (60.0% vs. 10.7%, p = 0.002) compared to erlotinib., Conclusion: Afatinib produced encouraging clinical efficacy as 2nd TKI therapy with manageable safety profiles in our Chinese patients after failure to another TKI and systemic chemotherapy. This study was registered at ClinicalTrials.gov (NCT02625168) on 3rd December 2015.

Background: This study investigated whether there were differential survival outcomes to first-line tyrosine kinase inhibitors (TKI) in patients with metastatic non-small-cell lung cancer harboring different subtypes of exon 19 and exon 21 mutations on epidermal growth factor receptor (EGFR)., Methods: Of 452 patients with stage IIIB and IV non-small-cell lung cancer, 192 patients (42.5%) harbored EGFR mutation and 170 (37.5%) received TKI as first-line treatment. EGFR mutation analysis was performed by direct sequencing. Survival and response outcome were compared among different subtypes of exon 19 and exon 21 EGFR mutations in these 170 patients., Results: Patients harboring exon 19 18-nucleotide deletion (delL747&#95;P753insS) had the shortest median progression-free survival (PFS) (6.5 months), followed by those with 15-nucleotide deletion (delE746&#95;A750) (12.4 months) and mixed insertion/substitution mutations (22.3 months; p = 0.012). However, patients who had exon 19 deletions starting on codon E746 had better median PFS (14.2 months) than those starting on L747 (6.5 months; hazard ratio, 0.445; 95% confidence interval [0.219-0.903]; p = 0.021). Besides, exon 21 L858R derived a longer median PFS than L861R/L861Q (11.4 months versus 2.1 months, respectively; hazard ratio, 0.298; 95% confidence interval [0.090-0.980]; p = 0.034)., Conclusions: Different subtypes of EGFR exon 19 and 21 mutations exhibited differential survival to first-line TKI therapy. Detailed sequence evaluation of exon 19 deletions may provide important prognostic information on survival outcome after TKI.

To meet the requirement of World Health Organization for zero tolerance of E. coli cell in 100mL drinking water, a new procedure based on photodeposition of nano-Ag at TiO(2)-coated piezoelectric quartz crystal (PQC) electrode was developed to fabricate a highly sensitive PQC/DNA biosensor. Enhancement of 3.3 times for binding of complementary DNA has been shown and attributed to the following effects arising from the nano-Ag coating. First, a large increase in the active surface area and packing density of neutravidin enhances the maximum neutravidin load to 1.8 times of a normal electrode. Second, the functional activity of neutravidin is enhanced by chemical interaction with nano-Ag to give rise to an increase in the binding ratio between neutravidin and biotinylated DNA probe from 1.00:1.76 to 1.00:3.01. Third, the stronger binding leads to a higher stability of the biotinylated DNA probes bound and increase in hybridization with the complementary DNA. Under the optimized conditions for flow analysis with online PCR product denaturing and hybridization, a detection limit of eight E. coli cells are obtained which require sampling at least 800mL water to detect a single E. coli cell in 100mL water.

Purpose: The Xeloda in Adjuvant Cancer Therapy trial, conducted in a white population of patients, established capecitabine (Xeloda) as adjuvant chemotherapy for Stage III colon cancer. Given the ethnical difference in toxicity of adjuvant chemotherapy in colon cancer, this study was designed to evaluate the safety and efficacy of adjuvant capecitabine in Chinese patients with colon cancer., Methods: Chinese patients with curatively resected Stage III colon adenocarcinoma, who received adjuvant capecitabine, were entered into a prospective database. Oral capecitabine was given at 1,250 mg/m(2) twice daily, Days 1 to 14, every 21 days, for 8 cycles. Toxicities, laboratory abnormalities, and survival outcomes were evaluated., Results: Fifty-eight patients were entered into the database between August 2004 and October 2005. The median age was 63.9 years with a male-to-female ratio of 1.15:1. With a median follow-up duration of 20.9 months, 14 patients relapsed and 3 patients died. Disease-free and overall survival at two years was 69 and 97 percent, respectively. Grade 3 toxicities occurred as follows: stomatitis (1.7 percent), diarrhea (0 percent), hand-foot syndrome (41.4 percent), leucopenia (1.7 percent), neutropenia (3.4 percent), and hyperbilirubinemia (1.7 percent). No Grade 4 or 5 toxicity was noted. Compared with the Xeloda in the Adjuvant Cancer Therapy trial, a much higher incidence of serious hand-foot syndrome and a lower rate of severe diarrhea were found in this study., Conclusions: A different toxicity profile of adjuvant capecitabine was noted in this study on Chinese patients with colon cancer compared with that reported in the Xeloda in Adjuvant Cancer Therapy trial, whereas the efficacy outcomes were comparable.

Objectives/hypothesis: The authors studied the change of health-related quality of life (HR-QOL) in patients with differentiated thyroid carcinoma (DTC) with thyroxine (T4) withdrawal in preparation for whole body radioactive iodine scanning., Study Design: Seventy-eight patients with DTC and history of radioactive iodine (RAI) ablation were prospectively recruited. They completed the Functional Assessment of Cancer Treatment-General (FACT-G) questionnaire on weeks 0, 2, and 4 after T4 withdrawal with corresponding checking of serum thyroid-stimulating hormone (TSH)., Results: Overall, 74.5% (58 of 78) of patients completed all FACT-G. Comparing FACT-G scores at weeks 0 and 4, "physical" (P < .001), "social" (P = .04), and "emotional" (P = .047) aspects were lowered as well as "total" HR-QOL (P = .001). However, the "functional" domain of HR-QOL was not affected (P = .14). Comparing FACT-G scores at week 0 and 2, we found that "physical" (P = .049) and "total" (P = .05) HR-QOL were affected early (in the first 2 weeks) in T4 withdrawal. Comparison of week 2 and 4 showed that in the later half of the withdrawal period, "physical" (P = .001), "emotional" (P = .02), and "total" FACT-G scores (P = .002) were affected. Mean TSH level (in mIU/L) increased gradually: 2.8 (week 0), 42.8 (week 2), 97 (week 3), and 153 (week 4). The percentage of patients attaining TSH level of >30 mIU/L were 55% (week 2), 96.2% (week 3), and 100% (week 4)., Conclusions: HR-QOL declines with time of T4 withdrawal. The impact is more severe in the later period of T4 withdrawal. In 3 weeks, 96.2% of our patients attained TSH level of 30 mIU/L. To minimize the impact on HR-QOL, duration of T4 withdrawal can be decreased to 3 weeks.