Comprehensive assessment of HER2 alteration in a colorectal cancer cohort: from next-generation sequencing to clinical significance.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in colorectal cancer (CRC). Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been used to determine HER2-positive CRCs; however, the clinical utility of next-generation sequencing (NGS)-based techniques for determining HER2 status in CRC has been limited. Here, we detail our experience regarding the assessment of HER2 alterations in a CRC cohort. MATERIALS AND METHODS: We prospectively enrolled 73 CRC patients who underwent surgery and received adjuvant oxaliplatin treatment. We then examined HER2 alterations using the Oncomine Comprehensive Assay version 1, as well as clinical outcomes, in this cohort. RESULTS: Using the NGS-based assay, HER2 copy number gains in 12 of 73 CRCs were determined to range from 2.74 to 92.62. Of these 12 tumors, 6 had HER2 high-level copy number gain (92.6, 57.9, 57.0, 52.0, 35.2, and 8.42) and were all defined as HER2-positive CRC using HERACLES Diagnostic Criteria. Nevertheless, other 6 patients with low-level copy number gain (ranging from 2.74 to 3.04) and the remaining 61 patients without increase in HER2 copy number were all HER2-negative. Among the 6 HER2-positive CRCs, KRAS and PIK3CA mutations were detected in 1 (17%; G13D) and 2 (33.3%; 1 Q546R and 1 H1047R) patients, respectively. Moreover, 2 of the 6 (33.3%) HER2-positive patients had recurrent disease, while one patient had a partial response after anti-HER2 therapy. CONCLUSION: NGS-based tools could assist in the simultaneous detection of HER2 and other genomic alterations in patients with CRC. Only CRCs with HER2 high-level copy number gain were HER2-postive by current diagnostic criteria.

Cost effectiveness of cancer treatment in Taiwan.

BACKGROUND/PURPOSE: This study aims to examine the cost effectiveness of treating major cancers compared with other major illnesses in Taiwan. METHODS: We collected data on 395,330 patients with cancer, 125,277 patients with end-stage renal disease, and 50,481 patients under prolonged mechanical ventilation during 1998-2007. They were followed for 10-13 years to estimate lifetime survival functions using a semiparametric method. EuroQol five-dimension was used to measure the quality of life for 6189 cancer patients and 1401 patients with other illnesses. The mean utility values and healthcare costs reimbursed by the National Health Insurance were multiplied with the corresponding survival probabilities to estimate quality-adjusted life expectancies and lifetime costs, respectively. Data of 22,344 cancer patients under hospice care (considered as a comparison group) were used to conduct a cost-effectiveness analysis. Sensitivity analysis was conducted by assuming patients without treatment survived for 2 years with a quality of life value of 0.5. RESULTS: The costs of care for patients under prolonged mechanical ventilation and those with end-stage renal disease were US$41,780-53,708 per quality-adjusted life year (QALY) and US$18,222-18,465 per QALY, respectively, which are equivalent to 2.17-2.79 gross domestic product (GDP) per capita per QALY and 1.18-1.25 GDP per capita per QALY. The costs of care for the nine different cancers were less than 1 GDP per capita per QALY, with those of lung, esophagus, and liver cancers being the highest. Sensitivity analysis showed the same conclusion. Lifetime risks of six out of nine cancer sites show an increased trend. CONCLUSION: Cancer care in Taiwan seemed cost effective compared with that of other illnesses, but prevention is necessary to make the National Health Insurance more sustainable.

Estimation of Life-Year Loss and Lifetime Costs for Different Stages of Colon Adenocarcinoma in Taiwan.

BACKGROUNDS AND AIMS: Life-expectancy of colon cancer patients cannot be accurately answered due to the lack of both large datasets and long-term follow-ups, which impedes accurate estimation of lifetime cost to treat colon cancer patients. In this study, we applied a method to estimate life-expectancy of colon cancer patients in Taiwan and calculate the lifetime costs by different stages and age groups. METHODS: A total of 17,526 cases with pathologically verified colon adenocarcinoma between 2002 and 2009 were extracted from Taiwan Cancer Registry database for analysis. All patients were followed-up until the end of 2011. Life-expectancy, expected-years-of-life-lost and lifetime costs were estimated, using a semi-parametric survival extrapolation method and borrowing information from life tables of vital statistics. RESULTS: Patients with more advanced stages of colon cancer were generally younger and less co-morbid with major chronic diseases than those with stages I and II. The LE of stage I was not significantly different from that of the age- and sex-matched general population, whereas those of stages II, III, and IV colon cancer patients after diagnosis were 16.57 ± 0.07, 13.35 ± 0.07, and 4.05 ± 0.05 years, respectively; the corresponding expected-years-of-life-lost were 1.28 ± 0.07, 5.93 ± 0.07 and 16.42 ± 0.06 years, significantly shorter than the general population after accounting for lead time bias. Besides, the lifetime cost of managing stage II colon cancer patients would be US $8,416 ± 1939, 14,334 ± 1,755, and 21,837 ± 1,698, respectively, indicating a big saving for early diagnosis and treatment after stratification for age and sex. CONCLUSIONS: Treating colon cancer at younger age and earlier stage saves more life-years and healthcare costs. Future studies are indicated to apply these quantitative results into the cost-effectiveness evaluation of screening program for colon cancers.