METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
MATERIALS AND METHODS: Medical records of 407 cervical cancer patients between 1st January 2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were identified to have received definitive extended field radiotherapy with or without chemotherapy. Treatment outcomes, clinicopathological factors affecting survival and radiotherapy related acute and late effects were analyzed.
RESULTS: Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the period of review. The median follow-up was 70 months. The 5-year overall survival (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients who had EFRT alone, with median survival sof 29 months and 13 months, respectively. The 5-years progression free survival (PFS) for patients who underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18 months and 12 months, respectively. Overall treatment time (OTT) less than 8 weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four patients (12.5%) developed radiotherapy late toxicity and there was no treatment-related death observed.
CONCLUSIONS: CCEFRT is associated with higher 5-years OS and median OS compared to EFRT and with tolerable level of acute and late toxicities in selected patients with cervical cancer and PALN metastasis.
MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.
RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.
CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.
OBJECTIVES: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC.
MATERIALS AND METHODS: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records.
RESULTS: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC.
CONCLUSIONS: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.
MATERIALS AND METHODS: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
RESULTS: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated.
CONCLUSION: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.
RESULTS: In the present cross-sectional descriptive study, analysis of ZAP-70 expression showed that 36/110 (32.7%) patients positively expressed ZAP-70 and insignificant higher presentation in intermediate and at advanced stages as well as no correlation was seen with hematological parameters and clinical features compared with negatively ZAP-70, on the other hand, 41/110 (37.3%) were CD38+ and no significant correlation was shown with the stage at presentation, clinical characteristics (except Splenomegaly, P = 0.02) and hematological parameters. However, in combined expressions of both ZAP-70 and CD38 together, 20/110 (18.2%) were concordantly ZAP-70+/CD38+, 53/110 (48.2%) concordantly ZAP-70-/CD38- and 37/110 (33.6%) either ZAP-70+ or CD38+, and these three groups showed insignificant correlation with clinical (except Splenomegaly, P = 0.03) and hematological parameters, and the stage at presentation. Our data showed the combined analysis of these two markers, lead to classify our patients into three subgroups (either concordant positive, negative or discordant expressions) with statistically insignificant correlation with clinical presentation (except Splenomegaly), hematological parameters and stage at presentation of B-CLL patients.
METHODS: A prospective, non-randomised longitudinal study was conducted in two government integrated hospitals over an 8-month period. Early-stage breast cancer patients who were (1) either already using complementary and alternative medicine (CAM) or not and (2) who were on a regime of 5-fluorouracil, epirubicin, and cyclophosphamide were included in the study. Patients who agreed to receive CHM were assigned to receive individualised CHM prescriptions deemed suitable for the individual at a particular time. Those who were not willing to take Chinese herbal medicines (CHM) were assigned to the non-CHM control group. Blood profile and chemotherapy-induced AE were recorded whilst HRQOL assessment was done using the EORTC QLQ-C30 questionnaire on first, third, and sixth cycles.
RESULTS: Forty-seven patients [32 female vs. 1 male, p = 0.31; mean year of age: 52.2(SD = 7.6), p = 0.28)}] were recruited during the study period. Demographics of both groups were comparable. Fifty percent of respondents reported using some kind of CAM before chemotherapy. Diet supplements (40.6%) were the most common CAM used by the respondents. The study showed that patients using CHM had significantly less fatigue (p = 0.012), nausea (p = 0.04), and anorexia (p = 0.005) during chemotherapy. There were no significant differences in patients' HRQOL (p = 0.79). There were no AEs reported during the study.
CONCLUSION: The use of CHM as an adjunct treatment with conventional chemotherapy have been shown to reduce fatigue, nausea, and anorexia in breast cancer patients but did not reduce chemotherapy-associated hematologic toxicity. The sample size of this study was not powered to assess the significance of HRQOL between two groups of patients.