Aim
To evaluate the safety and efficacy of the combination therapy of fluorouracil, leucovorin and irinotecan (FOLFIRI) and aflibercept in Asian patients with metastatic colorectal cancer (mCRC), who ...had progressed after oxaliplatin‐based chemotherapy.
Methods
This is a retrospective analysis of 19 mCRC patients who received FOLFIRI and aflibercept (4 mg/kg intravenously) every 2 weeks via a Named Patient Program (supported by Sanofi Aventis) in Singapore. Treatment was administered until disease progression or unacceptable toxicities. Kaplan–Meier method was used to estimate progression‐free survival (PFS) and overall survival (OS). Efficacy and toxicities were summarized using descriptive statistics. Statistical analysis was performed using STATA 12.0 software.
Results
The majority (84%) of the patients were of chinese ethnicity. The median age was 59 years, with 63.2% of the patients having an Eastern Cooperative Oncology Group status of 1. Four patients (21.1%) achieved partial response and 8 patients (42.1%) achieved stable disease. After a median follow‐up of 9.6 months 95% confidence interval (CI), 2.2–13.1 months, the median OS was 11.6 months (95% CI, 6.1 to not‐estimable), and median PFS was 4.1 months (95% CI, 2.2–5.9). Majority of the toxicities were grade 1–2, and include leucopenia (84.2%), anemia (73.7%), liver enzyme elevation (68.4%) and fatigue (68.4%). The most frequently reported grade 3 toxicities were neutropenia and neutropenic complications (both 15.8%). All adverse events resolved with supportive management.
Conclusion
The clinical benefit and safety profile of the combination of FOLFIRI/aflibercept in Asian patients with mCRC are consistent with that of Western population. FOLFIRI/aflibercept may be an appropriate therapeutic option in Asian patients with mCRC previously treated with an oxaliplatin‐based regimen.
While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of ...intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type.
The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression.
Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR
= 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR
= 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR
= 0.77, 95% CI: 0.67-0.89; HR
= 0.57, 95% CI: 0.44-0.73; HR
= 0.71, 95% CI: 0.58-0.87), but not ICC.
These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.
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Background: The majority (78%) of cancer deaths in Asia arise from cancers with no existing screening recommendations. Earlier cancer detection is associated with improved outcomes. While ...single-cancer screening by liquid biopsy (notably plasma EBV DNA for nasopharyngeal cancer) is recognized in Asia, multi-cancer screening (MCS) liquid biopsy testing is a potential opportunity to address this key need. We developed a ctDNA mutation-based testing workflow based on targeted amplicon-based next generation sequencing testing of plasma and matched buffy coat as required to exclude clonal hematopoiesis, with a custom pipeline incorporating clinico-demographic factors for tissue-of-origin (TOO) calling. Methods: Primary objectives were to evaluate assay performance for detection of cancer-associated alterations, as well as TOO prediction accuracy. Validation was performed on a sample cohort of 476 untreated patients, each with 1 of 10 different cancers (lung, liver, breast, colorectal, prostate, nasopharyngeal, pancreas, bile duct, acute and chronic myeloid leukemia). 50 initial age-matched healthy controls were also used. A weighted sum model was used for TOO prediction, which was evaluated in an expanded 1478-sample cohort. Weights assigned to each cancer-associated alteration and its co-occurring combinations represent the importance or contribution of each alteration to each potential TOO. The impact of inclusion of clinico-demographic data (where available) on TOO prediction was also evaluated. Results: Overall sensitivity for detection of cancer-associated alterations was 72.7% (346/476). Sensitivity is higher in metastatic cases (82.5%) compared to localized cases (41.8%). Sample-level specificity for cancer-associated alterations/EBV detection was 96% (48/50), also comparable to previous series. Cancer-associated alterations/EBV were detected in approximately 50% of localized cases for 3 cancer types with no established screening recommendations in Asia (lung - 54.6%; bile duct - 50.0%; pancreas - 48.6%). In the expanded cohort, a high confidence call for TOO was obtained in 55.4% (818/1478) of samples with positive findings. Clinico-demographic data inclusion as a model variable improved overall TOO prediction accuracy in 10 cancer types to 93.8% (767/818), compared to an accuracy of 90.2% without factoring in clinico-demographic data. Conclusions: The MCS ctDNA assay shows reasonable sensitivity and specificity for detection of cancer-associated alterations, based on a retrospective study cohort. Tumor TOO can also be correctly classified in the majority of patients. Incorporation of clinico-demographic data to personalize TOO recommendations also improved accuracy of calls. Further prospective studies and the addition of multi-omic capabilities will continue to be helpful to determine MCS performance in an Asian multi-ethnic environment.
Background: Primary intracranial germinomas are a rare subset of intracranial tumors derived from mis-incorporated germ cells within the folding neural plate during embryogenesis. Though known to ...arise from midline structures in the central nervous system (CNS), occurrence within the corpus callosum is exceedingly rare. Case Description: We present a rare case of secreting primary intracranial germinoma with extensive intraventricular metastasis presenting as a multi-cystic butterfly lesion in the genu of the corpus callosum in a young boy. Conclusion: Intracranial germ cell tumors must be considered for any multi-cystic lesion arising from midline structures in the CNS in the preadult population.
Background and Aims
In almost all countries, incidence rates of liver cancer (LC) are 100%‐200% higher in males than in females. However, this difference is predominantly driven by hepatocellular ...carcinoma (HCC), which accounts for 75% of LC cases. Intrahepatic cholangiocarcinoma (ICC) accounts for 12% of cases and has rates only 30% higher in males. Hormones are hypothesized to underlie observed sex differences. We investigated whether prediagnostic circulating hormone and sex hormone binding globulin (SHBG) levels were associated with LC risk, overall and by histology, by leveraging resources from five prospective cohorts.
Approach and Results
Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC cases (HCC, n = 83; ICC, n = 56) and 426 controls, matched on sex, cohort, age, race/ethnicity, and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between a one‐unit increase in log2 hormone value (approximate doubling of circulating concentration) and LC were calculated using multivariable‐adjusted conditional logistic regression. A doubling in the concentration of 4‐androstenedione (4‐dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30‐0.82), whereas SHBG was associated with a 31% increased risk (OR = 1.31; 95% CI = 1.05‐1.63). Examining histology, a doubling of estradiol was associated with a 40% increased risk of ICC (OR = 1.40; 95% CI = 1.05‐1.89), but not HCC (OR = 1.12; 95% CI = 0.81‐1.54).
Conclusions
This study provides evidence that higher levels of 4‐dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk.
Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and ...-β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC.
We harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases).
Hysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors.
This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.
Abstract
Worldwide, hepatocellular carcinoma (HCC) is the fifth most common cancer and the second-leading cause of cancer-related death worldwide. In the U.S., the incidence rate of HCC has tripled ...since 1975. Although preliminary evidence suggesting a biological impact of diet on multiple inflammatory pathways implicated in hepatocarcinogenesis, the most comprehensive review by the WCRF/AICR concluded that the relationship between diet and HCC remains largely unknown. HCC is an inflammation-related cancer but few studies have investigated diet quality based on its inflammatory potential in relation to HCC risk. The empirical dietary inflammatory pattern scores (EDIP) score were calculated from validated food frequency questionnaires. It characterized dietary inflammatory potential based on circulating levels of inflammatory bio-markers. We prospectively followed 49,674 men in the Health Professionals Follow-up Study (1986-2012), and 74,139 women in the Nurses' Health Study (1984-2012). Cox regression analyses were used to calculate hazards ratios (HR) for HCC risk adjusting for body mass index, smoking, history of diabetes, race, physical activity, and regular aspirin use. We documented a total of 89 incident HCC cases (44 in women and 45 in men) over 28 years, encompassing 1,522,972 person-years of follow-up. Compared to the lowest tertile, the highest tertile of the EDIP score was associated with a multivariable HR for HCC of 2.86 (95%CI, 1.20-6.81) among women (P-trend=0.01) and of 0.68 (95%CI, 0.31-1.50) among men (P-trend=0.35). Future study is warranted to confirm this finding and elucidate the potential biological basis.
Key words: inflammation, dietary patterns, HCC
A. T. C. and X. Z contributed equally to this work.
Citation Format: Yanan Ma, Tracey G. Simon, Fred K Tabung, Lindsay Y. King, Dawn Q. Chong, Long Nguyen, Trang VoPham, Charles S. Fuchs, Jeffrey A. Meyerhardt, Kathleen E. Corey, Hamed Khalili, Stephanie Smith-Warner, Raymond T. Chung, Edward L. Giovannucci, Andrew T. Chan, Xuehong Zhang. A prospective study of inflammatory diet potential and risk of hepatocellular carcinoma (HCC) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5256.
Abstract only
526
Background: Adiponectin is a hormone secreted by adipose tissue and has been demonstrated to possess anticarcinogenic, anti-inflammatory and insulin-sensitizing effects. Circulating ...adiponectin has been shown to be inversely associated with the risk of colorectal cancer (CRC) in prospective studies. However, the association of prediagnostic adiponectin with survival among patients with established colorectal cancer is unclear. Methods: We conducted a prospective study of 621 incident colorectal cancer cases from the Nurses’ Health Study and Health Professionals Follow-up Study to evaluate the association between prediagnostic plasma adiponectin and mortality. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay from ALPCO Diagnostics. The interbatch coefficient of variation from quality control samples randomly interspersed among the case samples was 8.6%. We examined the associations between quartiles of plasma adiponectin and mortality using a Cox proportional hazards model adjusted for established and putative risk factors. All statistical tests were two sided. Results: After a median follow-up of 9 years, there were 267 (43%) total deaths and 130 (21%) CRC deaths in the total study cohort. Compared with patients in the lowest quartile of adiponectin, patients in the highest quartile had a multivariate hazard ratio (HR) for CRC-specific mortality of 2.70 95% confidence interval (CI), 1.54-4.75; P
trend
= 0.001. The corresponding multivariate HR for overall mortality was 1.64 (95% CI, 1.14-2.36; P
trend
= 0.007). These associations were reasonably consistent in analyses according to subgroups defined by age, gender, body mass index, stage, grade and site of primary cancer. Similar results were yielded after excluding patients diagnosed within 4 years of blood collection (P
trend
= 0.027). Conclusions: Prediagnostic adiponectin is associated with an increased risk of colorectal cancer- specific and overall mortality. Further studies are needed to elucidate the mechanistic basis for these findings and determine the potential role of adiponectin as a prognostic marker in colorectal cancer.
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