A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies.

Purpose: This phase 1 study aims to evaluate the tolerability and the recommended phase 2 dose of selinexor in Asian patients with advanced or metastatic malignancies. Experimental Design: A total of 105 patients with advanced malignancies were enrolled from two sites in Singapore (National University Hospital and the National Cancer Centre, Singapore) from 24 February 2014 to 14 January 2019. We investigated four dosing schedules of selinexor in a 3 + 3 dose escalation design with an additional Phase 1b expansion cohort. Adverse events were graded with the NCI Common Terminology Criteria for Adverse Events v 4.03. Pharmacodynamic assessments included nuclear cytoplasmic localization of p27, XPO1 cargo proteins pre and post selinexor dosing and pharmacokinetic assessments were conducted at doses between 40 and 60 mg/m2. Results: In our Asian patient cohort, dosing at 40 mg/m2 given 2 out of 3 weeks, was the most tolerable for our patients. At this dose level, grade 3 adverse events included fatigue (8%), hyponatremia (23%), vomiting (5%), thrombocytopenia (5%), and anaemia (2%). Selinexor had a rapid oral absorption with median Tmax of 2 h and no PK accumulation after multiple doses of tested regimens. Complete responses were seen in two lymphoma patients. Partial responses were noted in three diffuse large B cell lymphomas, one Hodgkin's lymphoma and thymic carcinoma patient, respectively. Conclusion: Selinexor is tolerated by Asian patients at 40 mg/m2 twice a week given 2 out of 3 weeks. A 1-week drug holiday was needed as our patients could not tolerate the current approved continuous dosing regimens because of persistent grade 3 fatigue, anorexia and hyponatremia.

Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study-An Asian Tertiary Cancer Center Experience.

PURPOSE: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS: One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION: Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.

Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study.

PURPOSE: This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348). PATIENTS AND METHODS: Patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks). Safety was the primary end point. Secondary end points included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors v1.1 and overall survival; exploratory end points included circulating lymphocyte profiles. RESULTS: A total of 332 patients were enrolled (T300 + D, n = 75; durvalumab, n = 104; tremelimumab, n = 69; and T75 + D, n = 84). Tolerability was acceptable across arms, with grade ≥ 3 treatment-related adverse events occurring in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. Confirmed ORRs (95% CI) were 24.0% (14.9 to 35.3), 10.6% (5.4 to 18.1), 7.2% (2.4 to 16.1), and 9.5% (4.2 to 17.9), respectively. An early expansion of CD8+ lymphocytes was associated with response across arms, with highest proliferating CD8+ lymphocyte levels occurring in the T300 + D arm. The median (95% CI) overall survival was 18.7 (10.8 to 27.3), 13.6 (8.7 to 17.6), 15.1 (11.3 to 20.5), and 11.3 (8.4 to 15.0) months in the T300 + D, durvalumab, tremelimumab, and T75 + D arms, respectively. CONCLUSION: All regimens were found to be tolerable and clinically active; however, the T300 + D regimen demonstrated the most encouraging benefit-risk profile. The unique pharmacodynamic activity and association with ORR of the T300 + D regimen further support its continued evaluation in HCC.

Intra-Arterial Therapy for Unresectable Colorectal Liver Metastases: A Meta-Analysis.

PURPOSE: To evaluate the efficacy of hepatic arterial infusion (HAI), conventional transarterial chemoembolization, drug-eluting embolic transarterial chemoembolization (DEE-TACE), transarterial radioembolization, and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases. METHODS: A search was conducted on Embase, Scopus, PubMed, and Web of Science for prospective nonrandomized studies and randomized controlled trials (RCTs) from inception to June 20, 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for the median overall survival (OS), survival rates (SRs), and restricted mean survival time (RMST), whereas two-stage meta-analyses of proportions were conducted to determine response rates (RRs) and conversion to resection rates (CRRs). RESULTS: A total of 71 prospective nonrandomized studies and 21 RCTs were identified, comprising 6,695 patients. Among patients treated beyond the first-line, DEE-TACE + SCT (n = 152) had the best survival outcomes of median OS of 26.5 (95% confidence interval [CI], 22.5-29.1) months and a 3-year RMST of 23.6 (95% CI, 21.8-25.5) months. Upon further stratification by publication year, DEE-TACE + SCT appeared to consistently have the highest pooled SRs at 1 year (81.9%) and 2 years (66.1%) in recent publications (2015-2020). DEE-TACE + SCT and HAI + SCT had the highest pooled RRs of 56.7% (I2 = 0.90) and 62.6% (I2 = 0.87) and pooled CRRs of 35.5% (I2 = 0.00) and 30.3% (I2 = 0.80), respectively. CONCLUSIONS: Albeit significant heterogeneity, the paucity of high-quality evidence, and the noncomparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE + SCT have the best oncological outcomes and greatest potential to be converted for resection.

Molecular Characterization and Clinical Outcomes in RET-Rearranged NSCLC.

INTRODUCTION: RET rearrangements are an emerging targetable oncogenic fusion driver in NSCLC. However, the natural history of disease and activity of different classes of systemic therapy remain to be defined. Furthermore, molecular testing for RET is not yet routine, and the optimal method of testing is unclear. We present a comparative analysis of molecular profiling with fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) and treatment outcomes. METHODS: This study was a retrospective analysis of patients treated at the National Cancer Centre Singapore. Baseline demographics and treatment outcomes were collected. RESULTS: A total of 64 patients were included, with a median age of 62 years (range: 25-85), 56% were women, 77% were of Chinese ethnicity, 95% had adenocarcinoma, and 69% were never smokers. RET rearrangement was detected by FISH in 30 of 34 patients (88%), NGS in 40 of 43 patients (93%), and with discordant results in seven of 13 patients (54%) tested with both methods. Of 61 patients with stage IIIB/IV or recurrent disease, prevalence of central nervous system metastases was 31% and 92% received palliative systemic therapy. Overall survival was prolonged in patients treated with a selective RET tyrosine kinase inhibitor versus untreated patients (median 49.3 versus 15.3 mo; hazard ratio [HR]: 0.16, 95% confidence interval [CI]: 0.06-0.40, p < 0.001). However, it was not different in patients treated with immunotherapy versus untreated patients (median 37.7 versus 49.3 mo; HR: 1.30, 95% CI: 0.53-3.19, p = 0.53). Overall survival was also prolonged in patients with CCDC6-RET fusion versus those with KIF5B-RET fusion (median 113.5 versus 37.7 mo; HR: 0.12, 95% CI: 0.04-0.38, p = 0.009). CONCLUSIONS: In RET-rearranged NSCLC, selective RET tyrosine kinase inhibitor therapy is associated with improved survival outcomes, especially in patients with CCDC6-RET fusion. However, immunotherapy has poor efficacy. NGS and FISH testing methods may also result in substantial discordance.

Systematic review of current prognostication systems for pancreatic neuroendocrine neoplasms.

BACKGROUND: Pancreatic neuroendocrine neoplasms are a heterogenous group of rare tumors whose natural history remains poorly defined. Accurate prognostication of pancreatic neuroendocrine neoplasms is essential for guiding clinical decisions. This paper aims to summarize all the commonly utilized and recently proposed prognostication systems for pancreatic neuroendocrine neoplasms published in the literature to date. METHODS: A systematic review of Pubmed, Scopus, and Embase databases, of the period from January 1, 2000-November 29, 2016, was conducted to identify all published articles reporting on prognostication systems of pancreatic neuroendocrine neoplasms. RESULTS: A total of 23 articles were included in our review, and a total of 25 classification systems were identified. There were 2 modifications of the World Health Organization 2004 criteria, 4 modifications of the World Health Organization 2010 criteria, 2 modifications of the American Joint Committee on Cancer 2010 staging system, 3 modifications of the European Neuroendocrine Tumor Society 2006 tumor, node, metastasis staging system, 7 novel categorial classification systems, and 2 novel proposed continuous classifications. The most commonly included variables included age, size of tumor, presence of distant and lymph node metastases, Ki-67 index, and mitotic count. CONCLUSION: Numerous prognostication systems have been proposed for pancreatic neuroendocrine neoplasms, of which the most commonly used systems presently include the World Health Organization 2010 criteria and the two tumor, node, metastasis staging systems by the European Neuroendocrine Tumor Society and the American Joint Commission on Cancer. However, prognostication systems for pancreatic neuroendocrine neoplasms continue to evolve with time as more prognostication factors are identified. More validation and comparative studies are needed to identify the most effective prognostication system.

Validation and comparison between current prognostication systems for pancreatic neuroendocrine neoplasms: A single-institution experience with 176 patients.

BACKGROUND: This article aims to validate and compare the performance of 6 prognostication systems-the World Health Organization 2010 grading criteria, the European Neuroendocrine Tumour Society and the American Joint Committee for Cancer staging systems, the Memorial Sloan Kettering Cancer Center staging and grading systems, as well as the Bilimoria criteria in a cohort of patients with pancreatic neuroendocrine neoplasms at a single institution. METHODS: A retrospective review of 176 patients with histologically proven pancreatic neuroendocrine neoplasm was performed. The prognostic ability of the various prognostication systems for pancreatic neuroendocrine neoplasm was assessed by analyzing the homogeneity, discriminatory ability, monotonicity of gradient, and Akaike information criteria. RESULTS: The 5-year overall survival for the 176 patients was 69% and 5-year recurrence-free survival in 119 patients who underwent curative resection was 78%. Comparison between the 6 prognostication systems demonstrated that the World Health Organization 2010 system had the lowest Akaike information criteria score and was hence the best prognostication system in predicting overall survival and recurrence-free survival rates in our cohort of patients. The European Neuroendocrine Tumour Society was superior to the American Joint Committee for Cancer in prognosticating overall survival rates for pancreatic neuroendocrine neoplasms, as there was a statistically significant difference in overall survival across the different stages when stratified by the European Neuroendocrine Tumour Society, while the use of the American Joint Committee for Cancer was limited to distinguishing between patients in stages I and II versus stages III and IV only. CONCLUSION: All 6 prognostication systems were useful in the prognostication of pancreatic neuroendocrine neoplasm. The World Health Organization 2010 grading system was the best prognostication system in predicting both overall survival in our entire cohort of patients and recurrence-free survival in the subset of patients who underwent curative resection.

Preoperative platelet-to-lymphocyte ratio improves the performance of the international consensus guidelines in predicting malignant pancreatic cystic neoplasms.

INTRODUCTION: To determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in pancreatic cystic neoplasms (PCN) and if these improved the performance of the international consensus guidelines (ICG) in the initial triage of these patients. METHODS: 318 patients with surgically-treated suspected PCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma. The optimal cut-off for NLR and PLR were determined by plotting the receiver operating characteristics (ROC) curves of NLR/PLR in predicting malignant PCN and utilizing the Youden index. RESULTS: The optimal NLR and PLR cut-offs were determined to be 3.33 and 205, respectively. Univariate analyses demonstrated that symptomatic PCNs, age, obstructive jaundice, presence of solid component, dilatation of main pancreatic duct ≥10 mm, high NLR and high PLR were predictive of a malignant PCN. Multivariate analyses demonstrated that obstructive jaundice, presence of solid component, MPD ≥10 mm and high PLR but not NLR were independent predictors of a malignant PCN. A high PLR significantly predicted invasive carcinoma in patients classified within the ICG(HR) group. Comparison between the ROC curves of the ICG versus ICG plus high PLR in predicting malignant PCN demonstrated a significant improvement in the accuracy of the ICG when PLR was included [AUC 0.784 (95% CI: 0.740-0.829) vs AUC 0.822 (95% CI: 0.772-0.872) (p = 0.0032)]. CONCLUSIONS: High PLR is an independent predictor of malignancy in PCN. The addition of PLR as a criterion to the ICG improved the accuracy of these guidelines in detecting invasive neoplasms.

National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.

A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90.

BACKGROUND: Curative liver resection is the treatment of choice for both primary and secondary liver malignancies. However, an inadequate future liver remnant (FLR) frequently precludes successful surgery. Portal vein embolization is the gold-standard modality for inducing hypertrophy of the FLR. In recent times, unilobar Yttrium-90 selective internal radiation therapy (SIRT) has been reported to induce hypertrophy of the contralateral, untreated liver lobe. The aim of this study is to review the current literature reporting on contralateral liver hypertrophy induced by unilobar SIRT. METHODS: A systematic review of the English-language literature between 2000 and 2014 was performed using the search terms "Yttrium 90" OR "selective internal radiation therapy" OR "radioembolization" AND "hypertrophy". RESULTS: Seven studies, reporting on 312 patients, were included. Two hundred and eighty four patients (91.0%) received treatment to the right lobe. Two hundred and fifteen patients had hepatocellular carcinoma (HCC), 12 had intrahepatic cholangiocarcinoma, and 85 had liver metastases from mixed primaries. Y90 SIRT resulted in contralateral liver hypertrophy which ranged from 26 to 47% at 44 days-9 months. All studies were retrospective in nature, and heterogeneous, with substantial variations relative to pathology treated, underlying liver disease, dosage and delivery of Y90, number of treatment sessions and time to measurement of hypertrophy. CONCLUSION: Unilobar Y90 SIRT results in significant hypertrophy of the contralateral liver lobe. The rate of hypertrophy seems to be slower than that achieved by other methods.

A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90.

BACKGROUND: A curative liver resection is the treatment of choice for both primary and secondary liver malignancies. However, an inadequate future liver remnant (FLR) frequently precludes successful surgery. Portal vein embolization is the gold-standard modality for inducing hypertrophy of the FLR. In recent times, unilobar Yttrium-90 selective internal radiation therapy (SIRT) has been reported to induce hypertrophy of the contralateral, untreated liver lobe. The aim of this study was to review the current literature reporting on contralateral liver hypertrophy induced by unilobar SIRT. METHODS: A systematic review of the English-language literature between 2000 and 2014 was performed using the search terms 'Yttrium 90' OR 'selective internal radiation therapy' OR 'radioembolization' AND 'hypertrophy'. RESULTS: Seven studies, reporting on 312 patients, were included. Two hundred and eighty-four patients (91.0%) received treatment to the right lobe. Two hundred and fifteen patients had hepatocellular carcinoma (HCC), 12 had intrahepatic cholangiocarcinoma and 85 had liver metastases from mixed primaries. Y90 SIRT resulted in contralateral liver hypertrophy that ranged from 26% to 47% at 44 days to 9 months. All studies were retrospective in nature, and heterogeneous, with substantial variations relative to pathology treated, underlying liver disease, dosage and delivery of Y90, the number of treatment sessions and time to measurement of hypertrophy. CONCLUSION: Unilobar Y90 SIRT results in significant hypertrophy of the contralateral liver lobe. The rate of hypertrophy seems to be slower than that achieved by other methods.

Are preoperative blood neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios useful in predicting malignancy in surgically-treated mucin-producing pancreatic cystic neoplasms?

INTRODUCTION: The aim of this study was to determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in mucin-producing pancreatic cystic neoplasms (MpPCN). METHODS: One hundred and twenty patients with MpPCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma or high grade dysplasia. A high NLR and PLR were defined as ≥2.551 and ≥208.1, respectively. RESULTS: High NLR was significantly associated with symptomatic tumors, larger tumors, solid component, main-duct IPMN, and Sendai high risk category. High PLR was significantly associated with jaundice and Sendai high risk category. On univariate analyses, symptomatic tumors, jaundice, solid component, dilated pancreatic duct, and both a high NLR and PLR were significant predictors of malignant and invasive MpPCN. On multivariate analyses, solid component and dilated pancreatic duct were independent predictors of malignant and invasive MpPCN. PLR was an independent predictor for invasive MpPCN. When MpPCN were stratified by the Fukuoka and Sendai Guidelines, both a high NLR and PLR were significantly associated with malignant neoplasms within the high risk categories. CONCLUSIONS: PLR is an independent predictor of invasive carcinoma. The addition of PLR as a criterion to the FCG and SCG significantly improved the predictive value of these guidelines in detecting invasive neoplasms.

Phase II study of trastuzumab in combination with S-1 and cisplatin in the first-line treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer.

PURPOSE: The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer. METHODS: We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m(2) on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses. RESULTS: All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months. CONCLUSION: The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.

Effect of concomitant statin, metformin, or aspirin on rituximab treatment for diffuse large B-cell lymphoma.

Several pre-clinical studies report that statins interfere with the surface binding of rituximab to CD20. This study investigated the effects of statins in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-based chemoimmunotherapy, and the impact of commonly used drugs, metformin and aspirin, on the clinical outcomes of patients receiving chemoimmunotherapy. We included 213 patients with DLBCL who received rituximab-based chemoimmunotherapy. Details of statin, metformin, and aspirin use and initiation of chemoimmunotherapy were abstracted from medical records. All patients received rituximab, and 47 (22.1%) were taking statins. The median age of patients receiving statins was significantly higher compared to those who did not (p <0.001). Response rates between patients receiving and not receiving statins were not significantly different (85.1% vs. 87.3%; p = 0.688). Event-free survival (EFS) was not significantly different (p = 0.352). Overall survival was lower in patients receiving statins compared to those who did not (p = 0.036). However, it was no longer significant after adjustment for age (p = 0.140). Metformin had no impact on the response rate (p = 0.268), EFS (p = 0.574), and overall survival (p = 0.141). Aspirin had no impact on the response rate (p = 0.784), EFS (p = 0.836), and overall survival (p = 0.779). Statins do not interfere with rituximab, and need not be withheld during rituximab administration. Larger studies are needed to confirm the impact of metformin and aspirin on patients with DLBCL receiving chemoimmunotherapy.

Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis.

The use of rituximab has been associated with increased risk of hepatitis B virus (HBV) reactivation in patients who are hepatitis B surface antigen (HBsAg) negative and antihepatitis B core antibody (anti-HBc) positive. We aim to determine the rate of HBV reactivation in this group of patients who received rituximab-containing combination chemotherapy without concomitant antiviral prophylaxis and to identify potential risk factors for reactivation. Sixty-two HBsAg negative/anti-HBc positive patients with B-cell lymphoma treated with rituximab-based immunochemotherapy from 2006 to 2009 were included. None of the patients received concomitant antiviral prophylaxis. In this cohort, 48 (77%) patients received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), eight (13%) received rituximab with cyclophosphamide, vincristine and prednisolone, and six (10%) received other chemotherapy regimens. Two patients suffered HBV reactivation; both were above 70 years of age, received R-CHOP chemotherapy and were negative for antihepatitis B surface antibody (anti-HBs) at baseline. One of the two patients reactivated shortly after completion of R-CHOP chemotherapy while the other reactivated during rituximab maintenance treatment. Thus, the overall reactivation rate in this cohort of patients is 3% (2/62), 4% (2/48), and 25% (1/4) in patients who received R-CHOP chemotherapy and who received rituximab maintenance, respectively. The rate of HBV reactivation is low in patients who are HBsAg negative/anti-HBc positive receiving rituximab-based combination chemotherapy without concomitant antiviral prophylaxis. However, elderly patients, particularly those without anti-HBs, seemed particularly at risk.