Prognosis of patients with hepatocellular carcinoma (HCC) depends on both tumour extent and hepatic function reserve. Liver function test (LFT) is a basic routine blood test to evaluate hepatic ...function. We first analysed LFT components and their associated scores in a training cohort of 217 patients who underwent curative surgery to identify LFT parameters with high performance (discriminatory capacity, homogeneity, and monotonicity of gradient). We derived a novel index, albumin-to-alkaline phosphatase ratio (AAPR), which had the highest c-index (0.646) and χ2 (24.774) among other liver biochemical parameters. The AAPR was an independent prognostic factor for overall and disease-free survival. The adjusted hazard ratio of death and tumour relapse was 2.36 (P=0.002) and 1.85 (P=0.010), respectively. The independent prognostic significance of AAPR on top of 5 commonly used and well established staging systems was further confirmed in 2 independent cohorts of patients receiving surgical resection (n=256) and palliative therapy (n=425). In summary, the AAPR is a novel index readily derived from a simple low-cost routine blood test and is an independent prognostic indicator for patients with HCC regardless of treatment options.
•Extranodal extension (ENE) is an indicator of outcome in nasopharyngeal cancer (NPC).•Advanced ENE infiltrating to adjacent muscle/skin/salivary glands associated with poor outcome in NPC.•Patients ...with advanced ENE presented similar poor outcome to those with N3 disease.•Study suggested advanced ENE should be included in future staging of NPC.
Extranodal extension (ENE) is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. Our aim was to determine if ENE should be a staging criterion for nasopharyngeal carcinoma (NPC).
MRI of 546 NPC patients were reviewed retrospectively and in 404/546 (74.0%) with metastatic nodes, the nodes were assessed for ENE (grade 0 = absent; grade 1 = infiltration of surrounding fat; grade 2 = infiltration of muscle/skin), size (total volume), site (unilateral/bilateral and upper/lower neck) and necrosis. Associations between nodal features and regional relapse free survival (RRFS), distant metastases free survival (DMFS) and overall survival (OS) were assessed using cox regression. Differences of survival rates were compared using log-rank test. A p-value of < 0.05 indicates statistical significance.
ENE grade was the only determinant of RRFS (p = 0.014) and only independent determinant of DMFS (p = 0.003) and OS (p < 0.001). Grade 2 ENE was associated with significantly poorer RRFS, DMFS and OS compared to grade 0 and 1 (p < 0.05). Addition of grade 2 ENE to N1 and N2 disease showed similar poor RRFS, DMFS and OS to N3 disease (p > 0.05). Compared to the current stage N3 disease, inclusion of grade 2 ENE increased the number of N3 patients from 53/546 (9.7%) to 82/546 (15.0%) with similar hazard ratios for DMFS (6.855 and 7.125, respectively) and OS (3.614 and 4.085, respectively).
Grade 2 ENE (into muscle and/or skin and/or salivary glands) is an independent indicator of poor outcome and may be considered as a new criterion for N3 nodal disease in NPC.
Adjuvant chemotherapy improves outcome of patients with early breast cancer. However, chemotherapy may be associated with long term toxicities. In this retrospective cohort study, the objectives were ...to determine body weight, body mass index (BMI), blood pressure and fasting lipids levels of young premenopausal Chinese breast cancer patients after adjuvant chemotherapy. Potential factors associated with these parameters were identified.
Eligibility criteria include premenopausal Chinese patients who were diagnosed to have stage I-III breast cancer within 3-10 years, age < 45 and having received adjuvant chemotherapy at the time of breast cancer diagnosis. Information at initial breast cancer diagnosis were retrieved from patients' medical records and include age at diagnosis, tumor characteristics, anti-cancer treatments, blood pressure and body weight and height. At study entry, all patients had additional background demographics collected, as well as blood pressure, body weight and fasting serum lipid profiles measured. Incidence of chemotherapy-related amenorrhoea (CRA) and menopause were determined. Factors associated with weight gain, hypertension and dyslipidaemias were analyzed.
Two hundred and eighty patients were studied. The median age at breast cancer diagnosis was 41 years (range: 24-45). The median time from breast cancer diagnosis to study entry was 5.0 years. The median age at study entry was 46.5 years (range: 28-54). 91.1% developed CRA; 48.9% had become menopausal and 10% were peri-menopausal. Between initial breast cancer diagnosis and the time of study entry, the median weight gain was 1.8 kg; 63.2% gained weight by >2%; 52.1% were overweight/obese; 30.7% had hypertension. Abnormal total-cholesterol and LDL-cholesterol occurred in 34.3% and 56.1% respectively. On multivariate analyses, older age was associated with reduced risk while occurrence of CRA and having received taxane-containing regimens were associated with increased risk of weight gain. Oestrogen-receptor positivity was associated with reduced risk while overweight/obese statuses were associated with increased risk of hypertension. Use of tamoxifen was associated with reduced risk of abnormal LDL-cholesterol. Weight gain, overweight/obese, older age, progression to post/peri-menopausal status at study entry, having received corticosteroid premedication before adjuvant chemotherapy and having received taxane-containing adjuvant chemotherapy were associated with increased risk of dyslipidaemias.
Among young premenopausal Chinese breast cancer patients who had received adjuvant chemotherapy, the current study has revealed that although there was only a median weight gain of 1.8 kg, there was a nearly 60% increase in abnormal BMI. Further, a significant proportion of patients were detected to have hypertension and dyslipidaemias. Interventional studies with lifestyle modifications are warranted.
This post-hoc analysis retrospectively assessed data from two recent studies of antiemetic regimens for chemotherapy-induced nausea and vomiting (CINV). The primary objective was to compare ...olanzapine-based versus netupitant/palonosetron (NEPA)-based regimens in terms of controlling CINV during cycle 1 of doxorubicin/cyclophosphamide (AC) chemotherapy; secondary objectives were to assess quality of life (QOL) and emesis outcomes over four cycles of AC.
This study included 120 Chinese patients with early-stage breast cancer who were receiving AC; 60 patients received the olanzapine-based antiemetic regimen, whereas 60 patients received the NEPA-based antiemetic regimen. The olanzapine-based regimen comprised aprepitant, ondansetron, dexamethasone, and olanzapine; the NEPA-based regimen comprised NEPA and dexamethasone. Patient outcomes were compared in terms of emesis control and QOL.
During cycle 1 of AC, the olanzapine group exhibited a higher rate of 'no use of rescue therapy' in the acute phase (olanzapine vs NEPA: 96.7% vs 85.0%, P=0.0225). No parameters differed between groups in the delayed phase. The olanzapine group had significantly higher rates of 'no use of rescue therapy' (91.7% vs 76.7%, P=0.0244) and 'no significant nausea' (91.7% vs 78.3%, P=0.0408) in the overall phase. There were no differences in QOL between groups. Multiple cycle assessment revealed that the NEPA group had higher rates of total control in the acute phase (cycles 2 and 4) and the overall phase (cycles 3 and 4).
These results do not conclusively support the superiority of either regimen for patients with breast cancer who are receiving AC.
•Quantitative T1rho imaging had a good test-retest repeatability for head and neck.•Repeatability of T1rho imaging varied among tissues in the head and neck.•Quantitative T1rho imaging has potential ...to characterise head and neck tumours.
T1rho imaging is a new quantitative MRI sequence for head and neck cancer and the repeatability for this region is unknown. This study aimed to evaluate the repeatability of quantitative T1rho imaging in the head and neck.
T1rho imaging of the head and neck was prospectively performed in 15 healthy participants on three occasions. Scan 1 and 2 were performed with a time interval of 30 minutes (intra-session) and scan 3 was performed 14 days later (inter-session). T1rho values for normal tissues (parotid glands, palatine tonsils, pterygoid muscles, and tongue) were obtained on each scan. Intra-class coefficients (ICCs), within-subject coefficient of variances (wCoVs), and repeatability coefficient (RCs) of the intra-session scan (scan 1 vs 2) and inter-session scan (scan 1 vs 3) for the normal tissues were calculated.
The ICCs of T1rho values for normal tissues were almost perfect (0.83–0.97) for intra-session scans and were substantial (0.71–0.80) for inter-session scans. The wCoVs showed a small range (2.46%–3.30%) for intra-session scans, and slightly greater range (3.27%–6.51%) for inter-session scan. The greatest and lowest wCoVs of T1rho were found in the parotid gland and muscles, respectively. The T1rho RCs varied for all tissues between intra- and inter- sessions, and the greatest RC of 10.07 msec was observed for parotid gland on inter-session scan.
T1rho imaging is a repeatable quantitative MRI sequence in the head and neck but variances of T1rho values among tissues should be take into account during analysis.
This study assessed menopausal symptoms (MPS) after breast cancer in relation to quality of life (QoL) during the first 5 years of survival.
An ongoing prospective study enrolled 1,462 Chinese women ...with early-stage breast cancer. They were longitudinally followed up at four time-points, namely baseline, 18-, 36-, and 60-month after diagnosis. At each follow-up, Menopause Rating Scale (MRS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were used to assess MPS and QoL, respectively.
In total, 1,462, 1,289, 1,125, and 1,116 patients were included into the analyses at baseline, 18-, 36-, and 60-months, respectively. The percentages of patients with no or little, mild, moderate, and severe MPS at baseline were 31.8%, 30.0%, 30.4%, and 7.7%, respectively; the corresponding figures at 18-, 36-, and 60-month follow-up were similar. Using data from four follow-ups, Generalized Estimating Equations analyses showed that MPS was inversely associated with QoL. Higher MRS scores were related to lower QoL scores. For instance, every 1 point increase in MRS score was associated with a 1.5 point decrease in global health status/QoL score (P < 0.01). In terms of symptoms, higher MRS scores were related to more severe symptoms.
This study highlighted patients with more severe MPS tend to have worse QoL. Future investigation should be conducted to assess different means of alleviating MPS to improve patient's QoL.
To systematically review and perform meta-analysis to evaluate the prognostic value of cervical nodal necrosis (CNN) on the staging computed tomography/magnetic resonance imaging (MRI) of ...nasopharyngeal carcinoma (NPC) in era of intensity-modulated radiotherapy.
Literature search through PubMed, EMBASE, and Cochrane Library was conducted. The hazard ratios (HRs) with 95% confidence intervals (CIs) of CNN for distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were extracted from the eligible studies and meta-analysis was performed to evaluate the pooled HRs with 95%CI.
Nine studies, which investigated the prognostic values of 6 CNN patterns on MRI were included. Six/9 studies were eligible for meta-analysis, which investigated the CNN presence/absence in any nodal group among 4359 patients. The pooled unadjusted HRs showed that the CNN presence predicted poor DMFS (HR =1.89, 95%CI =1.72-2.08), DFS (HR =1.57, 95%CI =1.08-2.26), and OS (HR =1.87, 95%CI =1.69-2.06). The pooled adjusted HRs also showed the consistent results for DMFS (HR =1.34, 95%CI =1.17-1.54), DFS (HR =1.30, 95%CI =1.08-1.56), and OS (HR =1.61, 95%CI =1.27-2.04). Results shown in the other studies analysing different CNN patterns indicated the high grade of CNN predicted poor outcome, but meta-analysis was unable to perform because of the heterogeneity of the analysed CNN patterns.
The CNN observed on the staging MRI is a negative factor for NPC outcome, suggesting that the inclusion of CNN is important in the future survival analysis. However, whether and how should CNN be included in the staging system warrant further evaluation.
Background
Breast cancer patients regularly undergo adjuvant chemotherapies following surgery. However, these treatments are largely associated with chemotherapeutic toxicities ranging from nausea to ...severe myelosuppression. In this investigation, we examined the effects of four SNPs in
NR1I2
,
CYP3A4
and
CYP3A5
genes on chemotherapy-induced severe neutropenia in 311 female Chinese breast cancer patients undergoing a standard adjuvant chemotherapy regimen.
Methods
Patients were monitored for adverse reactions throughout the treatment, then divided into “none or mild” (80 %) or “severe” (20 %) toxicity groups according to whether they suffered grade 4 neutropenia defined as having an absolute neutrophil counts (ANC) of less than 0.5 × 10
9
/L anytime during the treatment. DNA was extracted from patients’ peripheral blood samples, then genotyped using allele-specific Tm-shift PCR and melting analysis.
Results
Logistic regression revealed that rs776746 or
CYP3A5*3
strongly associated with grade 4 neutropenia (OR = 2.56,
P
= 0.023) after adjustment for covariates, one of which more significant factor was baseline ANC (OR = 0.68,
P
= 0.020). Although univariate analysis in all patients did not reveal any association at first, further analysis indicated that rs776746 is significantly associated with severe neutropenia in subgroup of breast cancer patients with normal baseline ANC (≥2.0 × 10
9
/L). These carriers of A-allele have 3.14-fold increased risk of developing severe neutropenia (
P
= 0.004).
Conclusion
Our results suggested that polymorphisms in
CYP3A5
might be useful pharmacogenetic markers for the prediction of severe neutropenia during chemotherapy, however, only after screening patients by their baseline ANC in the presence of gene–environmental interaction. We demonstrate an approach of pharmacogenetic analysis, in which the genetic data should be analyzed in the perspective of other clinical parameters.
Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine.
Eligible ...patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored.
120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of “Complete Response” than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of “No significant nausea” and “No nausea” during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment.
The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.
•Olanzapine is reported to reduce nausea and vomiting after highly emetogenic chemotherapy.•Reported studies are limited by heterogeneous populations receiving diverse cytotoxic regimes.•This study enrolled Chinese breast cancer patients undergoing doxorubicin/cyclophosphamide.•Adding olanzapine to aprepitant/ondansetron/dexamethasone is superior in controlling nausea and vomiting.•Baseline investigations shows a surprisingly high rate of glucose and lipids abnormalities.
The albumin-bilirubin (ALBI) grade is a recently emerging alternative of the Child-Pugh (CP) grade. The Cancer of the Liver Italian Program (CLIP) was demonstrated to be a useful prognostic model for ...hepatocellular carcinoma (HCC) in large prospective cohorts. We aimed to investigate the feasibility of substituting the CP grade by the ALBI grade in the CLIP system and compare the prognostic performance with other existing staging systems.
A large cohort of 1973 Chinese patients with HCC was recruited to evaluate the prognostic performance of CP-based CLIP (CP-CLIP) and ALBI-based CLIP (ALBI-CLIP) systems and nine other staging systems by homogeneity likelihood chi-square, c-index, and corrected Akaike information criterion.
The ALBI-CLIP system provided comparable prognostic performance than the CP-CLIP system, which was indicated by homogeneity likelihood chi-squares (ALBI-CLIP 1186.35 vs CP-CLIP 1145.54), c-indices (ALBI-CLIP 0.789 vs CP-CLIP 0.785) and AICs (ALBI-CLIP 15 493.47 vs CP-CLIP 15 534.28). Among 11 staging systems, ALBI-CLIP and CP-CLIP systems were associated with the highest homogeneity chi-squares and c-indices, and the lowest corrected Akaike information criterion. Patients in ALBI-CLIP score 0-4 had better median survival than those in corresponding CP-CLIP score.
The ALBI grade performs as well as the CP grade when integrating into the CLIP system. ALBI-CLIP and CP-CLIP systems are the most accurate prognostic models among 11 existing staging systems.
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