Predictive markers for head and neck cancer treatment response: T1rho imaging in nasopharyngeal carcinoma.

OBJECTIVES: To investigate the potential of T1rho, a new quantitative imaging sequence for cancer, for pre and early intra-treatment prediction of treatment response in nasopharyngeal carcinoma (NPC) and compare the results with those of diffusion-weighted imaging (DWI). MATERIALS AND METHODS: T1rho and DWI imaging of primary NPCs were performed pre- and early intra-treatment in 41 prospectively recruited patients. The mean preT1rho, preADC, intraT1rho, intraADC, and % changes in T1rho (ΔT1rho%) and ADC (ΔADC%) were compared between residual and non-residual groups based on biopsy in all patients after chemoradiotherapy (CRT) with (n = 29) or without (n = 12) induction chemotherapy (IC), and between responders and non-responders to IC in the subgroup who received IC, using Mann-Whitney U-test. A p-value of < 0.05 indicated statistical significance. RESULTS: Significant early intra-treatment changes in mean T1rho (p = 0.049) and mean ADC (p < 0.01) were detected (using paired t-test), most showing a decrease in T1rho (63.4%) and an increase in ADC (95.1%). Responders to IC (n = 17), compared to non-responders (n = 12), showed higher preT1rho (64.0 ms vs 66.5 ms) and a greater decrease in ΔT1rho% (- 7.5% vs 1.3%) (p < 0.05). The non-residual group after CRT (n = 35), compared to the residual group (n = 6), showed higher intraADC (0.96 vs 1.09 × 10-3 mm2/s) and greater increase in ΔADC% (11.7% vs 27.0%) (p = 0.02). CONCLUSION: Early intra-treatment changes are detectable on T1rho and show potential to predict tumour shrinkage after IC. T1rho may be complementary to DWI, which, unlike T1rho, did not predict response to IC but did predict non-residual disease after CRT. CLINICAL RELEVANCE STATEMENT: T1rho has the potential to complement DWI in the prediction of treatment response. Unlike DWI, it predicted shrinkage of the primary NPC after IC but not residual disease after CRT. KEY POINTS: Changes in T1rho were detected early during cancer treatment for NPC. Pre-treatment and early intra-treatment change in T1rho predicted response to IC, but not residual disease after CRT. T1rho can be used to complement DWI with DWI predicting residual disease after CRT.

Association of high adherence to vegetables and fruits dietary pattern with quality of life among Chinese women with early-stage breast cancer.

PURPOSE: Dietary intake and patients' quality of life (QoL) are important supportive care issues in breast cancer survivorship. This study aimed to identify dietary pattern before and after breast cancer diagnosis. In addition, the association between dietary patterns and QoL were cross-sectionally and longitudinally investigated. METHODS: A breast cancer cohort which included 1462 Chinese women were longitudinally interviewed at four time-points, namely baseline, 18-, 36-, and 60 months after diagnosis. At each follow-up, validated food frequency questionnaires (FFQ) were used to assess patients' dietary intake, and factor analysis was used to derive dietary patterns. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) were used to measure QoL at each follow-up. This study included 1368, 1226, 1079 and 1095 patients with invasive disease who completed assessment at baseline, 18-, 36- and 60-month follow-up and had detailed data of dietary intake and QoL. RESULTS: Based on data obtained at 18-month follow-up, two major dietary patterns were identified: "grain and animal food pattern" and "vegetables and fruits pattern". Similar dietary patterns were obtained at baseline, 36- and 60- month follow-up. Generalized Estimating Equations (GEE) were used to analyze the longitudinal associations between dietary patterns and QoL over the four follow-ups. High intake of grain and animal food was inversely associated with scores for role functioning (B = - 0.744; 95%CI - 0.147 to - 0.017), dyspnea (B = - 0.092; 95%CI - 0.092 to - 0.092) and constipation (B = - 1.355; 95%CI - 2.174 to - 0.536). Vegetables and fruits intake were positively associated with scores for global health status/QoL (B = 1.282; 95%CI 0.545-2.019), physical functioning (B = 0.545; 95%CI: 0.037-1.053), emotional functioning (B = 1.426; 95%CI 0.653-2.200) and cognitive functioning (B = 0.822; 95%CI 0.007-1.637), while inversely associated with scores for nausea and vomiting (B = - 0.382; 95%CI - 0.694 to - 0.071), dyspnea (B = - 0.570; 95%CI - 0.570 to - 0.570), insomnia (B = - 1.412; 95%CI - 2.647 to - 0.177), loss of appetite (B = - 0.722; 95%CI - 1.311 to - 0.132), constipation (B = - 2.028; 95%CI - 2.775 to - 1.281) and diarrhea (B = - 0.929; 95%CI - 1.481 to - 0.377). CONCLUSION: This study suggested that high adherence to "grain and animal food pattern" or "vegetables and fruits pattern" was significantly associated with several aspects of QoL. For instance, vegetables and fruits pattern appears to have beneficial effect on global health status/QoL among Chinese breast cancer patients. Prospective follow-up data could further confirm whether a specific dietary pattern has impact on cancer outcomes.

Quality of Life Associated with Nausea and Vomiting from Anthracycline-Based Chemotherapy: A Pooled Data Analysis from Three Prospective Trials.

BACKGROUND: There is limited work on the impact of chemotherapy-induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin-cyclophosphamide (AC)-treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients' QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. MATERIALS AND METHODS: This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index-emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included "no significant nausea" (NSN), "significant nausea" (SN), "no vomiting" (NoV), "vomiting" (V), and complete response (CR). RESULTS: Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p < .0001), with lower scores indicating better QoL; the mean scores for the FLIE vomiting domain for patients who experienced NoV versus V were 1.44 versus 19.11, respectively (p < .0001), with similar results across subsequent cycles. Analysis of the effect of the QoL in cycle 1 on the QoL of subsequent cycles revealed the following: for the nausea domain, among patients who had cycle 1 FLIE scores ≥ versus < the mean, the corresponding scores in cycle 2 were 6.87 versus 36.71 (p < .0001); whereas those for cycle 3 were 7.07 versus 36.87 (p < .0001); and those for cycle 4 were 5.92 versus 21.48 (p < .0001). Similar findings were observed for the vomiting domain. Netupitant + palonosetron- or aprepitant/olanzapine-based antiemetics had significantly better QoL outcomes. CONCLUSION: CINV had a significant impact on the QoL of patients with breast cancer treated with AC over multiple cycles. IMPLICATIONS FOR PRACTICE: In this post-hoc analysis of three prospective studies on chemotherapy-induced nausea and vomiting (CINV), quality of life (QoL) using contemporary antiemetic regimens in Chinese breast cancer patients receiving doxorubicin-cyclophosphamide (AC) was evaluated. During the first and subsequent AC cycles, QoL was significantly better for patients who did not experience vomiting or significant nausea. QoL in an earlier cycle affected the QoL in subsequent AC cycles. Furthermore, recent regimens involving olanzapine/aprepitant or netupitant-palonosetron were associated with a positive impact in QoL. Antiemetic guideline-consistent practice and higher clinician awareness of the impact of CINV on QoL can further mitigate the negative effects of CINV on QoL.

Convolutional neural network for discriminating nasopharyngeal carcinoma and benign hyperplasia on MRI.

OBJECTIVES: A convolutional neural network (CNN) was adapted to automatically detect early-stage nasopharyngeal carcinoma (NPC) and discriminate it from benign hyperplasia on a non-contrast-enhanced MRI sequence for potential use in NPC screening programs. METHODS: We retrospectively analyzed 412 patients who underwent T2-weighted MRI, 203 of whom had biopsy-proven primary NPC confined to the nasopharynx (stage T1) and 209 had benign hyperplasia without NPC. Thirteen patients were sampled randomly to monitor the training process. We applied the Residual Attention Network architecture, adapted for three-dimensional MR images, and incorporated a slice-attention mechanism, to produce a CNN score of 0-1 for NPC probability. Threefold cross-validation was performed in 399 patients. CNN scores between the NPC and benign hyperplasia groups were compared using Student's t test. Receiver operating characteristic with the area under the curve (AUC) was performed to identify the optimal CNN score threshold. RESULTS: In each fold, significant differences were observed in the CNN scores between the NPC and benign hyperplasia groups (p < .01). The AUCs ranged from 0.95 to 0.97 with no significant differences between the folds (p = .35 to .92). The combined AUC from all three folds (n = 399) was 0.96, with an optimal CNN score threshold of > 0.71, producing a sensitivity, specificity, and accuracy of 92.4%, 90.6%, and 91.5%, respectively, for NPC detection. CONCLUSION: Our CNN method applied to T2-weighted MRI could discriminate between malignant and benign tissues in the nasopharynx, suggesting that it as a promising approach for the automated detection of early-stage NPC. KEY POINTS: • The convolutional neural network (CNN)-based algorithm could automatically discriminate between malignant and benign diseases using T2-weighted fat-suppressed MR images. • The CNN-based algorithm had an accuracy of 91.5% with an area under the receiver operator characteristic curve of 0.96 for discriminating early-stage T1 nasopharyngeal carcinoma from benign hyperplasia. • The CNN-based algorithm had a sensitivity of 92.4% and specificity of 90.6% for detecting early-stage nasopharyngeal carcinoma.

Menopausal symptoms in relationship to breast cancer-specific quality of life after adjuvant cytotoxic treatment in young breast cancer survivors.

INTRODUCTIONS: For young premenopausal breast cancer patients, adjuvant chemotherapy may cause menstrual disruptions and premature menopause, which may in turn impair their quality of life (QoL). In this study among young breast cancer survivors who have undergone adjuvant chemotherapy, the objectives were to assess post-treatment menopausal symptoms and their associated factors, and to correlate these symptoms with breast cancer-specific QoL. METHODS: The study population included premenopausal young Chinese women with early-stage breast cancer who had undergone adjuvant chemotherapy between 3 and 10 years prior to enrolling into this study. At study entry, patients' characteristics and clinical features were collected; each patient had detail menstrual history collected and each filled in MENQOL and FACT-B + 4 questionnaires. RESULTS: Two hundred eighty eligible patients were recruited. For adjuvant chemotherapy, 92% received anthracyclines and 28% received taxanes; 76% received adjuvant tamoxifen. At a median of 5.0 years from initial cancer diagnosis, 49 and 11% had become post- and peri-menopausal respectively. MENQOL at study entry revealed that physical domain score was worse in overweight/obese patients (mean scores for underweight/normal vs overweight/obese: 2.65 vs 2.97, p = 0.0162). Vasomotor domain score was worse in those who received taxanes or tamoxifen (taxane vs non-taxane: 2.91 vs. 2.35, p = 0.0140; tamoxifen vs no tamoxifen: 2.75 vs. 2.34, p = 0.0479). Sexual domain score was worse among those who had become peri/post-menopausal (peri/postmenopausal vs premenopausal: 2.82 vs. 2.29, p = 0.0229). On the other hand, patients who utilized traditional Chinese medicine had significantly worse scores for vasomotor, psychosocial and physical domains. Further, there was a significant association between MENQOL scores and FACT-B + 4 scores; less severe symptoms in the MENQOL domains were associated with better QoL scores in FACT-B + 4 physical, functional, psychosocial and emotional well-being, Breast Cancer Subscale, Arm Subscale and FACT-B total score. CONCLUSION: Among premenopausal breast cancer women who had undergone adjuvant chemotherapy, those who had received taxanes or tamoxifen, were overweight/obese and utilized traditional Chinese medicine had more severe menopausal symptoms. Patients who experienced worse menopausal symptoms were found to have worse breast cancer-specific QoL. Interventional studies with an aim to alleviate menopausal symptoms are warranted to assess if overall QoL of these patients could be improved. TRIAL REGISTRATION: Not applicable.

Intravoxel incoherent motion diffusion-weighted imaging for discrimination of benign and malignant retropharyngeal nodes.

PURPOSE: Anatomical imaging criteria for the diagnosis of malignant head and neck nodes may not always be reliable. This study aimed to evaluate the diagnostic value of conventional diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) DWI in discriminating benign and malignant metastatic retropharyngeal nodes (RPNs). METHODS: IVIM DWI using 14 b-values was performed on RPNs of 30 patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC) and 30 patients with elevated plasma Epstein-Barr virus (EBV)-DNA without NPC who were part of an EBV-based NPC screening program. Histogram measurements of the two groups were compared for pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion volume fraction (f) and apparent diffusion coefficient (ADC) using the Mann-Whitney U test. Area under the curves (AUCs) of significant measurements were calculated from receiver-operating characteristics analysis and compared using the DeLong test. RESULTS: Compared with metastatic RPNs, benign RPNs had lower ADCmean (0.73 vs 0.82 × 10-3 mm2/s) and Dmean (0.60 vs 0.71 × 10-3 mm2/s) and a higher D*mean (35.21 vs 28.66 × 10-3 mm2/s) (all p < 0.05). There was no difference in the f measurements between the two groups (p = 0.204 to 0.301). Dmean achieved the highest AUC of 0.800, but this was not statistically better than the AUCs of the other parameters (p = 0.148 to 0.991). CONCLUSION: Benign RPNs in patients with EBV-DNA showed greater restriction of diffusion compared with malignant metastatic RPNs from NPC. IVIM did not show a significant advantage over conventional DWI in discriminating benign and malignant nodes.

Nasopharyngeal carcinoma: relationship between invasion of the prevertebral space and distant metastases.

PURPOSE: To identify primary sites of nasopharyngeal carcinoma (NPC) invasion on the staging head and neck magnetic resonance imaging (MRI) that correlate with distant metastases (DM). MATERIALS AND METHODS: Staging head and neck MRI examinations of 579 NPC patients were assessed for primary tumour invasion into 16 individual sites, primary stage (T) and nodal stage (N). Results were correlated with distant metastasis-free survival (DMFS) using the Cox regression, and the diagnostic performance of significant independent markers for DM was calculated. In addition, sites of primary tumour invasion were correlated also with involvement of the first echelon of ipsilateral nodes (FEN+) using logistic regression. RESULTS: Distant metastases were present in 128/579 NPC patients (22.1%) after intensity-modulated radiotherapy (IMRT)/chemo-IMRT and 5-year DMFS was 78.8%. Prevertebral space invasion (PVS+) and N stage, but not T stage, were independent prognostic markers of DMFS (p = 0.016, < 0.001, and 0.433, respectively). Compared to stage N3, PVS invasion had a higher sensitivity (28.1 vs. 68.8%), but lower specificity (90.5 vs. 47.4%) and accuracy (76.7 vs. 48.9%) for correlating patients with DM. PVS invasion, together with parapharyngeal fat space invasion (PPFS+), was also an independent predictive marker of FEN+. CONCLUSION: PVS was the only site of primary tumour invasion that independently correlated with DM, and together with PPFS + was an independent prognostic marker of FEN+, but the low specificity and accuracy of PVS invasion limits its use as a prognostic marker of DM.

Incorporating albumin-bilirubin grade into the cancer of the liver Italian program system for hepatocellular carcinoma.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Profiles of lipids, blood pressure and weight changes among premenopausal Chinese breast cancer patients after adjuvant chemotherapy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Integration of albumin-bilirubin (ALBI) score into Barcelona Clinic Liver Cancer (BCLC) system for hepatocellular carcinoma.

BACKGROUND AND AIMS: The albumin-bilirubin (ALBI) grade is a recently reported, simpler, more objective, and evidence-based alternative to the Child-Pugh (CP) score for hepatocellular carcinoma (HCC). We aimed to study whether ALBI grade could substitute for CP score in Barcelona Clinic Liver Cancer (BCLC) for HCC. METHODS: An international multicentre cohort (n = 3696) was accrued to compare the prognostic performance of the CP-based and ALBI-based BCLC system, in terms of homogeneity, discriminatory ability, and monotonicity of gradients that were numerically reflected by homogeneity likelihood, linear trend chi-squares, and c-indices, respectively. RESULTS: The ALBI grade performed as well as CP score when integrated into the BCLC staging system in terms of predicting clinical outcome of HCC regardless of regions, etiology, and treatment options. CP-based and ALBI-based BCLC systems were highly concordant with weighted kappa value of 0.917. All restaged patients showed significantly different clinical outcomes compared with their original stage classification. In particular, ALBI-based BCLC upstaged 83 (2.2%) patients from lower CP-based BC LC stages to ALBI-based BCLC stage D, whose median overall survival was only 3 months. CONCLUSIONS: The overall prognostic performance of ALBI-based and CP-based BCLC systems was similar. It also potentially allows more precise patient selection for clinical trials on systemic agents.

Applicability of albumin-bilirubin-based Japan integrated staging score in hepatitis B-associated hepatocellular carcinoma.

BACKGROUND AND AIM: The Japan Integrated Staging (JIS) for hepatocellular carcinoma (HCC) has been extensively studied in hepatitis virus C-endemic Japanese population but seldom evaluated outside Japan, while albumin-bilirubin (ALBI)-based JIS (ALBI-T) has never been externally validated. We evaluate the prognostic significance of the ALBI-T score among Chinese patients with hepatitis virus B (HBV)-related HCC, and to explore its potential therapeutic application in selecting patients for appropriate treatments in addition to the Barcelona Clinic Liver Cancer (BCLC) recommendation. METHODS: A cohort of 1222 HBV-associated HCC patients was evaluated to compare the prognostic performance of JIS and ALBI-T scores by homogeneity likelihood chi-square and corrected Akaike information criterion. In the subgroup analysis of each BCLC stage, Kaplan-Meier method and log-rank statistics were used to compare overall survival of patients undergoing different treatment options. RESULTS: The ALBI-T score showed better prognostic performance than the JIS score, which were indicated by homogeneity likelihood chi-squares (ALBI-T 580.12 vs JIS 536.35) and Akaike information criteria (ALBI-T 9836.57 vs JIS 9880.23). Treatment options significantly influenced prognosis among patients of the same BCLC stage. With the use of ALBI-T score 4 as the cutoff, the current study identified that a portion of patients (14.7%, 25.2% and 28.6% of BCLC stage B, C and D, respectively) undergoing unnecessary therapy without survival advantage. CONCLUSIONS: The ALBI-T score is applicable to Chinese patients with HBV-related HCC to provide reasonable prognostic information as well as potentially helping clinicians to avoid offering non-beneficial aggressive treatments.

Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response.

BACKGROUND: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC. Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with concomitant chronic liver disease. The objectives of this study were: (1) In phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and (3) to explore potential biomarkers for response. METHODS: Major eligibility criteria included histologically confirmed advanced HCC and adequate organ function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The MTD was used in the subsequent phase II part; the primary endpoint was PFS and secondary endpoints were response and OS. In addition, exploratory analysis was conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p-AKT expressions as potential biomarkers for response. Overall survival and PFS were calculated using the Kaplan-Meier method. Reassessment CT scans were done every 6 weeks. All adverse events were reported using CTCAE v3. RESULTS: The Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36 patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD. Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was 8.89 months (95% C.I. 5.89-13.30). Grade ≥ 3 that occurred in > 10% of patients included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR 5.667, 95% CI 1.129-28.454, p = 0.035). CONCLUSIONS: In HCC patients with chronic liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The targeted PFS endpoint was not reached. However, further studies to identify appropriate patient subgroup are warranted. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.

Radiologic extranodal extension for nodal staging in nasopharyngeal carcinoma.

PURPOSE: Extranodal extension (ENE) has the potential to add value to the current nodal staging system (N8th) for predicting outcome in nasopharyngeal carcinoma (NPC). This study aimed to incorporate ENE, as well as cervical nodal necrosis (CNN) to the current stage N3 and evaluated their impact on outcome prediction. The findings were validated on an external cohort. METHODS & MATERIALS: Pre-treatment MRI of 750 patients from the internal cohort were retrospectively reviewed. Predictive values of six modified nodal staging systems that incorporated four patterns of ENE and two patterns of CNN to the current stage N3 for disease-free survival (DFS) were compared with that of N8th using multivariate cox-regression and concordance statistics in the internal cohort. Performance of stage N3 for predicting disease recurrence was calculated. An external cohort of 179 patients was used to validate the findings. RESULTS: Incorporation of advanced ENE, which infiltrates into adjacent muscle/skin/salivary glands outperformed the other five modifications for predicting outcomes (p < 0.01) and achieved a significantly higher c-index for 5-year DFS (0.69 vs 0.72) (p < 0.01) when compared with that of N8th staging system. By adding advanced ENE to the current N3 increased the sensitivity for predicting disease recurrence from 22.4 % to 47.1 %. The finding was validated in the external cohort (5-year DFS 0.65 vs. 0.72, p < 0.01; sensitivity of stage N3 increased from 14.0 % to 41.9 % for disease recurrence). CONCLUSION: Results from two centre cohorts confirmed that the radiological advanced ENE should be considered as a criterion for stage N3 disease in NPC.

Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Discriminating between benign and malignant salivary gland tumors using diffusion-weighted imaging and intravoxel incoherent motion at 3 Tesla.

PURPOSE: The purpose of this study was to retrospectively evaluate the diagnostic performances of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) for discriminating between benign and malignant salivary gland tumors (SGTs). MATERIALS AND METHODS: Sixty-seven patients with 71 SGTs who underwent MRI examination at 3 Tesla were included. There were 34 men and 37 women with a mean age of 57 ± 17 (SD) years (age range: 20-90 years). SGTs included 21 malignant tumors (MTs) and 50 benign SGTs (33 pleomorphic adenomas [PAs] and 17 Warthin's tumors [WTs]). For each SGT, DWI and IVIM parameters, mean, skewness, and kurtosis of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion volume fraction (f) were calculated and further compared between SGTs using univariable analysis. Areas under the curves (AUC) of receiver operating characteristic of significant parameters were compared using the Delong test. RESULTS: Significant differences in ADCmean, Dmean and D*mean were found between SGTs (P < 0.001). The highest AUC values were obtained for ADCmean (0.949) for identifying PAs and D*mean (0.985) for identifying WTs and skewness and kurtosis did not outperform mean. To discriminate benign from malignant SGTs with thresholds set to maximize Youden index, IVIM and DWI produced accuracies of 85.9% (61/71; 95% CI: 75.6-93.0) and 77.5% (55/71; 95% CI: 66.0-86.5) but misdiagnosed MTs as benign in 28.6% (6/21) and 61.9% (13/21) of SGTs, respectively. After maximizing specificity to 100% for benign SGTs, the accuracies of IVIM and DWI decreased to 76.1% (54/71; 95% CI: 64.5-85.4) and 64.8% (46/71; 95% CI: 52.5-75.8) but no MTs were misdiagnosed as benign. IVIM and DWI correctly diagnosed 66.0% (33/50) and 50.0% (25/50) of benign SGTs and 46.5% (33/71) and 35.2% (25/71) of all SGTs, respectively. CONCLUSION: IVIM is more accurate than DWI for discriminating between benign and malignant SGTs because of its advantage in detecting WTs. Thresholds set by maximizing specificity for benign SGTs may be advantageous in a clinical setting.

A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma.

BACKGROUND: The level of circulating interleukin 10 (IL-10) is elevated in a proportion of patients with hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the prognostic significance of serum the IL-10 level in patients with unresectable HCC. METHODS: Patients with unresectable HCC who provided serum at the time of diagnosis were enrolled prospectively in the study. The level of circulating IL-10 in serum samples was determined by enzyme-linked immunosorbent assay. The association of the IL-10 level with overall survival was evaluated in relation to sociodemographics, liver function, hepatitis B viral load, and tumor staging. RESULTS: In total, 222 patients were recruited; of these, 82.4% were positive for hepatitis B virus surface antigen, and 65.8% had Barcelona Clinic Liver Cancer stage C disease. The mean log IL-10 level was 1.1 pg/mL, and 146 patients had an IL-10 level >1 pg/mL (high IL-10 group). The high IL-10 group had worse overall survival than the low IL-10 group (5.0 months vs 14.9 months; hazard ratio, 2.192; P < .0001). The IL-10 level was associated with worse hepatic function and with a high alanine transaminase (ALT) level. The IL-10 level remained an independent prognostic factor (hazard ratio, 1.824; P = .0005) after adjustment for sociodemographics, tumor staging, treatment, Child-Pugh stage, and ALT level. The IL-10 level also subdivided patients into 2 populations with distinct survival (10.2 months vs 3.5 months; P = .0027). CONCLUSIONS: The serum IL-10 level was identified as an independent prognostic factor for unresectable HCC. The current findings suggested that an elevated IL-10 level may be related to hepatic injury caused by cirrhotic processes rather than tumor load. The authors concluded that the IL-10 level offers additional prognostic value to the existing tumor staging systems.

Use of antiviral therapy in surveillance: impact on outcome of hepatitis B-related hepatocellular carcinoma.

BACKGROUND: Antiviral therapy for hepatitis B virus (HBV) infection is frequently prescribed for patients with chronic HBV infection during surveillance for hepatocellular carcinoma (HCC). In patients who subsequently develop HCC, the impact of antiviral therapy on the outcome of HCC remains unclear. AIMS: We aimed to study the impact of antiviral therapy on the survival of patients who developed HCC. METHODS: From two prospective surveillance cohorts, the use of antiviral therapy for patients with HCC was retrospectively reviewed. We compared the overall survival, liver function and tumour characteristics between patients with and without antiviral therapy during surveillance. Multivariate analysis was conducted to determine the independent prognostication of antiviral therapy. RESULTS: During a median follow-up of 10.1 years of 1429 patients, 148 cases of HCC were diagnosed and followed up for a median of 5.7 years. Twenty-nine patients were given antiviral therapy during surveillance and continued treatment after diagnosis of HCC. The median survival of this group of patients was better than the rest of cohorts (hazard ratio: 0.472; 95% CI: 0.25-0.89; P = 0.0191). Use of antiviral therapy remained an independent prognostic factor after adjustment for demographic factors and tumour staging on multivariate analysis. Exploratory analysis revealed that patients who commenced antiviral therapy during surveillance had lower HBV DNA, lower serum alanine transaminase, better hepatic reserves and higher rate of local treatment at diagnosis of HCC. CONCLUSION: This study provides evidence that commencement of antiviral therapy during the surveillance period is associated with improvement in overall survival in HBV-related HCC.

Prognostic value of cervical nodal necrosis on staging imaging of nasopharyngeal carcinoma in era of intensity-modulated radiotherapy: a systematic review and meta-analysis.

PURPOSES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population.

BACKGROUND AND AIM: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems. METHODS: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor-node-metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared. RESULTS: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow-up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child-Pugh-stage, alpha-fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3-month survival while CLIP performed better in predicting the outcome of 6- and 12-month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance. CONCLUSION: We have validated CUPI in a population composed of predominant HBV-related HCC. CUPI is an appropriate staging system for HBV-related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification.