METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05).
CONCLUSIONS: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.
MATERIALS AND METHODS: Twenty surviving patients with expandable endoprosthesis from 2006 till 2015 were scored using Musculoskeletal Tumour Society (MSTS) outcomes instrument and reviewed retrospectively for range of motion of respected joints, limb length discrepancy, number of surgeries performed, complications and oncological outcomes. Patients with less than 2 years of follow-up were excluded from this study.
RESULTS: Forty-five percentage patients reached skeletal maturity with initial growing endoprosthesis and 25% of patients were revised to adult modular prosthesis. One hundred fifty-seven surgeries were performed over the 9-year period. The average MSTS score was 90.83%. The mortality rate was 10% within 5 years due to advanced disease. Infection and implant failure rate was 15% each. The event-free survival was 50% and overall survival rate was 90%.
CONCLUSION: There is no single best option for reconstruction in skeletally immature. This study demonstrates a favourable functional and survival outcome of paediatric patients with expandable endoprosthesis. The excellent MSTS functional scores reflect that patients were satisfied and adjusted well to activities of daily living following surgery despite the complications.
AIM: The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen.
METHODS: Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients' recurrence risk.
RESULTS: Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes.
CONCLUSION: Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen.
METHODS: This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia.
RESULTS: A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients.
CONCLUSION: Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients.
MATERIALS AND METHODS: A multicentre, retrospective analysis of prospectively collected robotic bTME resections (July 2015-November 2020). Demographics, clinicopathological features, short-term outcomes, recurrences, and survival were investigated.
RESULTS: One-hundred-sixty-eight patients (eight centres) were included. Median age and BMI were 60.0 (50.0-68.7) years and 24.0 (24.4-27.7) kg/m2. Female sex was prevalent (n = 95, 56.8%). Fifty patients (29.6%) were ASA III-IV. Neoadjuvant chemoradiotherapy was given to 125 (74.4%) patients. Median operative time was 314.0 (260.0-450.0) minutes. Median estimated blood loss was 150.0 (27.5-500.0) ml. Conversion to laparotomy was seen in 4.8%. Postoperative complications occurred in 77 (45.8%) patients; 27.3% and 3.9% were Clavien-Dindo III and IV, respectively. Thirty-day mortality was 1.2% (n = 2). R0 rate was 92.9%. Adjuvant chemotherapy was offered to 72 (42.9%) patients. Median follow-up was 34.0 (10.0-65.7) months. Distant and local recurrences were seen in 35 (20.8%) and 15 patients (8.9%), respectively. Overall survival (OS) at 1, 3, and 5-years was 91.7, 82.1, and 76.8%. Disease-free survival (DFS) at 1, 3, and 5-years was 84.0, 74.5, and 69.2%.
CONCLUSION: Robotic bTME is technically safe with relatively low conversion rate, good OS, and acceptable DFS in the hands of experienced surgeons in high volume centres. In selected cases robotic approach allows for high R0 rates during bTME.
MATERIALS AND METHODS: The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome.
RESULTS: A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001).
CONCLUSIONS: The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.
MATERIALS AND METHODS: This retrospective study looked at patients who had palliative chemotherapy with either cisplatin/5FU or carboplatin/5FU for metastatic and recurrent SCCHN and NPC. It included patients who were treated at UKMMC from 1st January 2004 to 31st December 2009 with either palliative IV cispaltin 75 mg/m2 D1 only plus IV 5FU 750 mg/m2 D1-5 infusion or IV Carboplatin AUC 5 D1 only plus IV 5FU 500 mg/m2 D1-2 infusion plus IV 5FU 500 mg/m2 D1-2 bolus. The specific objectives were to determine the efficacy of palliative chemotherapy in terms of overall response rate (ORR), median progression free survival (PFS) and median overall survival (OS) and to evaluate the toxicities of both regimens.
RESULTS: A total of 41 patients were eligible for this study. There were 17 in the cisplatin/5FU arm and 24 in the carboplatin/5FU arm. The ORR was 17.7 % for cisplatin/5FU arm and 37.5 % for carboplatin/5FU arm (p-value=0.304). The median PFS was 7 months for cisplatin/5FU and 9 months for carboplatin/5FU (p-value=1.015). The median OS was 10 months for cisplatin/5FU arm and 12 months for carboplatin/5FU arm (p-value=0.110). There were 6 treatment-related deaths (6/41=14.6%), four in the carboplatin/5FU arm (4/24=16.7%) and 2 in the cisplatin/5FU arm (2/17=11.8%). Grade 3 and 4 hematologic toxicity was also more common with carboplatin/5FU group, this difference being predominantly due to grade 3-4 granulocytopenia (41.6% vs. 0), grade 3-4 anemia (37.5% vs. 0) and grade 3-4 thrombocytopenia (16.6% vs. 0).
CONCLUSIONS: Carboplatin/5FU is not inferior to cisplatin/5FU with regard to its efficacy. However, there was a high rate of treatment-related deaths with both regimens. A better alternative needs to be considered.
METHODS AND MATERIALS: Patients with T3-4, N2 M0 breast cancer diagnosed between January 2005 and December 2008 and who received at least one cycle of neoadjuvant chemotherapy were eligible for this study. Thirty-four patients were identified from the Chemotherapy Daycare Records and their medical records were reviewed retrospectively. The neoadjuvant chemotherapy regimen administered was at the discretion of the treating oncologist. Breast tumour size and nodal status was assessed at diagnosis, at each cycle and before surgery.
RESULTS: All 34 patients had invasive ductal cancer. The median age was 52 years (range 27-69). 65% had T4 disease and 76% were clinically lymph node positive at diagnosis. The median size of the breast tumour at presentation was 80 mm (range 42-200 mm). Estrogen and progesterone receptor positivity was seen in less than 40% and HER2 positivity, by immunohistochemistry, in 27%. The majority (85%) of patients had anthracycline based chemotherapy, without taxanes. The overall response rate (clinical CR+PR) was 67.6% and pathological complete responses were apparent in two (5.9%). 17.6% of patients defaulted part of their planned treatment. Recurrent disease was seen in 44.1% and the median time to relapse was 11.3 months. The three year disease free and overall survival rates were 52.5% and 58% respectively.
CONCLUSION: Neoadjuvant chemotherapy for locally advanced breast cancer in a Malaysian setting confers response and pCR rates comparable to published clinical trials. Patients undergoing neoadjuvant chemotherapy are at risk of defaulting part of their treatment and therefore their concerns need to be identified proactively and addressed in order to improve outcomes.
MATERIALS AND METHODS: Here we reported the initial experience of aflibercept / FOLFIRI in combination. We evaluated treatment-related adverse events (AEs), progression-free survival (PFS) and overall survival (OS).
RESULTS: The majority of the patients experienced gastrointestinal toxicity (grade 1-2), with diarrhea (52%), mucositis (52%), and nausea/vomiting (20%) being largely observed. Neutropenia (16%) and febrile neutropenia (8%) were common grade 3-4 hematological events. Aflibercept-related toxicity was managed as per practice guidelines. No grade 5 event was reported. Median PFS was 6.12 months (95% CI, 4.80-7.20) and OS was 12 months (95% CI, 9.80-14.18). The partial response (PR), stable disease (SD), and progressive disease (PD) rates were 25% (95% CI: 23.4-27.0), 37.5% (95% CI: 31.6-43.3), and 37.5% (95% CI: 22.5-52.5), respectively.
CONCLUSIONS: Aflibercept/FOLFIRI can be administered safely in a second line setting to Malaysian patients with mCRC, as the AEs experienced were generally reversible and manageable. The safety and efficacy outcomes were consistent with those observed in Western populations.
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.
PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.
RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.
CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).