A systematic scoping review of group reflection in medical education.

BACKGROUND: Reviewing experiences and recognizing the impact of personal and professional views and emotions upon conduct shapes a physician's professional and personal development, molding their professional identity formation (PIF). Poor appreciation on the role of reflection, shortages in trained tutors and inadequate 'protected time' for reflections in packed medical curricula has hindered its integration into medical education. Group reflection could be a viable alternative to individual reflections; however, this nascent practice requires further study. METHODS: A Systematic Evidence Based Approach guided Systematic Scoping Review (SSR in SEBA) was adopted to guide and structure a review of group reflections in medical education. Independent searches of articles published between 1st January 2000 and 30th June 2022 in bibliographic and grey literature databases were carried out. Included articles were analysed separately using thematic and content analysis, and combined into categories and themes. The themes/categories created were compared with the tabulated summaries of included articles to create domains that framed the synthesis of the discussion. RESULTS: 1141 abstracts were reviewed, 193 full-text articles were appraised and 66 articles were included and the domains identified were theories; indications; types; structure; and benefits and challenges of group reflections. CONCLUSIONS: Scaffolded by current approaches to individual reflections and theories and inculcated with nuanced adaptations from other medical practices, this SSR in SEBA suggests that structured group reflections may fill current gaps in training. However, design and assessment of the evidence-based structuring of group reflections proposed here must be the focus of future study.

Enhancing self-care education amongst medical students: a systematic scoping review.

BACKGROUND: Reports of emotional, existential and moral distress amongst medical students witnessing death and suffering of patients during their clinical postings have raised awareness on the need for better psycho-emotional support during medical school. Furthermore, the stress experienced by medical students stemming from the rigours of their academic curriculum underlines the need for greater awareness on mental health issues and better self-care practices across medical training. With such programmes lacking in most medical schools, we propose a systematic scoping review (SSR) to map and address our research question, "what is known about self-care education interventions amongst medical students?". METHODS: We adopted the Systematic Evidence-Based Approach to guide a systematic scoping review (SSR in SEBA) of relevant articles published between 1st January 2000 and 30th June 2023 in PubMed, Embase, PsycINFO, ERIC, Google Scholar, and Scopus databases. The included articles were independently and concurrently thematically and content analysed, with complementary categories and themes combined using the Jigsaw Approach. The domains created from the Funnelling Process framed the discussion. RESULTS: A total of 6128 abstracts were identified, 429 full-text articles evaluated, and 147 articles included. The 6 domains identified were definition, topics, pedagogy, influences, outcomes and assessment. Most interventions were promising, though peer-led mindfulness-based interventions showed most promise in enhancing engagement, positively impacting personal wellbeing, and improving patient care. Overall, however, self-care education was poorly recognized, adopted and integrated into curricula. CONCLUSION: Greater dedicated time and conducive practice environments within medical school curricula is required to enhance medical student wellbeing. Host organizations must ensure faculty are appropriately selected to instil the importance of self-care, be trained to assess and personalize self-care interventions and provide longitudinal assessment and support. Further study into assessing self-care capabilities is required.

Recent updates on central nervous system prophylaxis in patients with high-risk diffuse large B-cell lymphoma.

The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature, provides mixed conclusions regarding the efficacy of CNS prophylaxis. The utility of CNS prophylaxis has itself been challenged. In this review, we dissect the issues which render the value of CNS prophylaxis uncertain. We first compare international clinical guidelines for CNS prophylaxis. We then interrogate the factors that should be used to identify high-risk patients accurately. We also explore how clinical patterns of CNS relapse have changed in the pre-rituximab and rituximab era. We then discuss the efficacy of CNS-directed approaches, intensification of systemic treatment and other novel approaches in CNS prophylaxis. Improved diagnostics for early detection of CNS relapses and newer therapeutics for CNS prophylaxis are areas of active investigation. In an area where prospective, randomized studies are impracticable and lacking, guidance for the use of CNS prophylaxis will depend on rigorous statistical review of retrospective data.

A Systematic Review and Meta-Analysis of Mapping Biopsy for Primary Extramammary Paget's Disease in Reducing Recurrence Following Surgical Excision.

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD). Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence. Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported. Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results. Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary.

Clinical features and prognostic outcomes of angioimmunoblastic T cell lymphoma in an Asian multicenter study.

In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups.

Evolving therapeutic landscape of diffuse large B-cell lymphoma: challenges and aspirations.

Diffuse large B-cell lymphoma (DLBCL) represents the commonest subtype of non-Hodgkin lymphoma and encompasses a group of diverse disease entities, each harboring unique molecular and clinico-pathological features. The understanding of the molecular landscape of DLBCL has improved significantly over the past decade, highlighting unique genomic subtypes with implications on targeted therapy. At the same time, several new treatment modalities have been recently approved both in the frontline and relapsed settings, ending a dearth of negative clinical trials that plagued the past decade. Despite that, in the real-world setting, issues like drug accessibility, reimbursement policies, physician and patient preference, as well as questions regarding optimal sequencing of treatment options present difficulties and challenges in day-to-day oncology practice. Here, we review the recent advances in the therapeutic armamentarium of DLBCL and discuss implications on the practice landscape, with a particular emphasis on the context of the healthcare system in Singapore.

Post-Treatment Neutrophil and Lymphocyte Counts Predict Progression-Free Survival Following First-Line Chemotherapy in Hodgkin's Lymphoma.

Hodgkin's lymphoma carries an excellent prognosis with modern chemotherapy, but a significant proportion of patients remain refractory to or relapse after first-line treatment. Immunological changes post-treatment, such as chemotherapy-induced neutropenia (CIN) or lymphopenia, have shown prognostic significance in multiple tumor types. Our study aims to investigate the prognostic value of immunologic changes in Hodgkin's lymphoma by examining the post-treatment lymphocyte count (pALC), neutrophil count (pANC) and the neutrophil-lymphocyte ratio (pNLR). Patients treated for classical Hodgkin's lymphoma at the National Cancer Centre Singapore using ABVD-based regimens were retrospectively analyzed. An optimal cut-off value for high pANC, low pALC and high pNLR in predicting progression-free survival was determined by receiver operating curve analysis. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional models. Overall OS and PFS were excellent, with a 5-year OS of 99.2% and a 5-year PFS of 88.2%. Poorer PFS was associated with high pANC (HR 2.99, p = 0.0392), low pALC (HR 3.95, p = 0.0038) and high pNLR (p = 0.0078). In conclusion, high pANC, low pALC and high pNLR confer a poorer prognosis for Hodgkin's lymphoma. Future studies should evaluate the potential of improving treatment outcomes by the adjustment of chemotherapy dose intensity based on post-treatment blood counts.

Burkitt lymphoma - no impact of HIV status on outcomes with rituximab-based chemoimmunotherapy.

We analyzed the prognostic factors for treatment outcomes amongst 34 patients with adult Burkitt lymphoma (BL) who received rituximab with standard first-line chemotherapy. Seven patients had human immunodeficiency virus (HIV)-associated BL. Overall, we observed a complete remission (CR) rate of 91.2%, and 10-year progression-free survival (PFS) and overall survival (OS) was 84.8 and 88.2%, respectively. In patients with concomitant HIV, the prognosis was not different with 10-year PFS of 100% and OS of 88.2%. The majority (71.4%) of HIV-associated BL patients received dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and had excellent outcomes with 100% CR and no relapses. Central nervous system (CNS) disease, bone marrow involvement and elevated serum lactate dehydrogenase (LDH) levels more than 3 times upper limit of normal (ULN) were associated with poorer survival outcomes. Patients with refractory disease, whilst uncommon (n = 4), had dismal outcomes. Patients with adult BL, including HIV-related cases, harbor generally good prognosis in the modern era.

An ex vivo platform to guide drug combination treatment in relapsed/refractory lymphoma.

Although combination therapy is the standard of care for relapsed/refractory non-Hodgkin's lymphoma (RR-NHL), combination treatment chosen for an individual patient is empirical, and response rates remain poor in individuals with chemotherapy-resistant disease. Here, we evaluate an experimental-analytic method, quadratic phenotypic optimization platform (QPOP), for prediction of patient-specific drug combination efficacy from a limited quantity of biopsied tumor samples. In this prospective study, we enrolled 71 patients with RR-NHL (39 B cell NHL and 32 NK/T cell NHL) with a median of two prior lines of treatment, at two academic hospitals in Singapore from November 2017 to August 2021. Fresh biopsies underwent ex vivo testing using a panel of 12 drugs with known efficacy against NHL to identify effective single and combination treatments. Individualized QPOP reports were generated for 67 of 75 patient samples, with a median turnaround time of 6 days from sample collection to report generation. Doublet drug combinations containing copanlisib or romidepsin were most effective against B cell NHL and NK/T cell NHL samples, respectively. Off-label QPOP-guided therapy offered at physician discretion in the absence of standard options (n = 17) resulted in five complete responses. Among patients with more than two prior lines of therapy, the rates of progressive disease were lower with QPOP-guided treatments than with conventional chemotherapy. Overall, this study shows that the identification of patient-specific drug combinations through ex vivo analysis was achievable for RR-NHL in a clinically applicable time frame. These data provide the basis for a prospective clinical trial evaluating ex vivo-guided combination therapy in RR-NHL.

Treatment outcomes of T and natural-killer/T-cell lymphoma with ifosfamide, carboplatin and etoposide chemotherapy.

BACKGROUND: Contemporary data of peripheral T-cell lymphoma (PTCL) and natural-killer/T-cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited. AIMS: We performed a retrospective analysis to estimate outcomes of ICE-treated PTCL and NKTL patients at three tertiary cancer centres in Singapore. METHODS AND RESULTS: Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first-line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response [CR]). The ORR and CR in the first line were 86% and 64% respectively. At a median follow-up duration of 71.0 months, the median progression-free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7-6.0) and 16 months (95%CI, 8.3-45.4) respectively. CONCLUSION: In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real-world CHOP data and warrants further study.

A Prognostic Model Using Post-Steroid Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Primary Central Nervous System Lymphoma.

Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HIs could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HIs were calculated at three time-points: baseline (pre steroid), pre chemoimmunotherapy (post steroid) and post chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan−Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan−Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR ≥ 4.0, HR 0.42, 95% CI: 0.21−0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR ≥ 241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03), respectively, only. The decision-tree model using age ≤70, post-steroid NLR >4.0, and pre-steroid (baseline) NLR <2.5 and the division of patients into three risk profiles­low, medium, and high­achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusion: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed for accurate and well-calibrated stratification into three risk groups.

Circulating Tumor DNA Mutations in Progressive Gastrointestinal Stromal Tumors Identify Biomarkers of Treatment Resistance and Uncover Potential Therapeutic Strategies.

Liquid biopsy circulating tumor DNA (ctDNA)-based approaches may represent a non-invasive means for molecular interrogation of gastrointestinal stromal tumors (GISTs). We deployed a customized 29-gene Archer® LiquidPlex™ targeted panel on 64 plasma samples from 46 patients. The majority were known to harbor KIT mutations (n = 41, 89.1%), while 3 were PDGFRA exon 18 D842V mutants and the rest (n = 2) were wild type for KIT and PDGFRA. In terms of disease stage, 14 (30.4%) were localized GISTs that had undergone complete surgical resection while the rest (n = 32) were metastatic. Among ten patients, including 7 on tyrosine kinase inhibitors, with evidence of disease progression at study inclusion, mutations in ctDNA were detected in 7 cases (70%). Known somatic mutations in KIT (n = 5) or PDGFRA (n = 1) in ctDNA were identified only among 6 of the 10 patients. These KIT mutants included duplication, indels, and single-nucleotide variants. The median mutant AF in ctDNA was 11.0% (range, 0.38%-45.0%). In patients with metastatic progressive KIT-mutant GIST, tumor burden was higher with detectable KIT ctDNA mutation than in those without (median, 5.97 cm vs. 2.40 cm, p = 0.0195). None of the known tumor mutations were detected in ctDNA for localized cases (n = 14) or metastatic cases without evidence of disease progression (n = 22). In patients with serial samples along progression of disease, secondary acquired mutations, including a potentially actionable PIK3CA exon 9 c.1633G>A mutation, were detected. ctDNA mutations were not detectable when patients responded to a switch in TKI therapy. In conclusion, detection of GIST-related mutations in ctDNA using a customized targeted NGS panel represents an attractive non-invasive means to obtain clinically tractable information at the time of disease progression.

Prognostication of diffuse large B-cell lymphoma patients with Deauville score of 3 or 4 at end-of-treatment PET evaluation: a comparison of the Deauville 5-point scale and the ΔSUVmax method.

Diffuse large B-cell lymphoma is treated with anti-CD 20 and multi-drug chemotherapy for cure. Positron emission tomography (PET) scans are performed at end of treatment (EOT) to assess response. EOT Deauville scores (DS) are equivocal for treatment response in some situations, requiring physicians to determine the need for further investigations or treatment. Studies have suggested the delta maximum standardised uptake value (ΔSUVmax) to be superior to DS for assessment of metabolic response at interim PET, although its use at EOT PET, especially in cases of equivocal response, has yet to be established. We investigated whether ΔSUVmax could better discriminate prognosis than DS 3 or 4 at EOT. ΔSUVmax did not outperform DS. Combination of DS 3 and International Prognostic Index (IPI) <3 selects for patients with extremely low risk of disease progression (HR 0.06, 95% CI 0.01 to 0.62, p 0.018) compared to DS 4 and IPI ≥3.

Cryotherapy in extra-abdominal desmoid tumors: A systematic review and meta-analysis.

INTRODUCTION: Desmoid tumor is a locally-invasive neoplasm that causes significant morbidity. There is recent interest in cryotherapy for treatment of extra-abdominal desmoid tumors. This systematic review assesses evidence on safety and efficacy of cryotherapy in the treatment of extra-abdominal desmoid tumors. MATERIALS AND METHODS: The systematic review was conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials. 9 full text papers were reviewed and meta-analysis was performed for measures of safety, efficacy and symptom relief. RESULTS: The estimated pooled proportion of major and minor complications was 4.2% (95% CI, 1.8-9.6; I 2 = 0%) and 10.2% (95% CI, 5.7-17.8; I 2 = 0%) respectively. The estimated pooled proportion of non-progressive disease rate of all studies was 85.8% (95% CI, 73.4-93.0; I 2 = 32.9%). The estimated progression free survival rate at 1 year was 84.5% (95% CI:74.6-95.8) and 78.0% at 3 years (95% CI: 63.8-95.3). As for pain control, the estimated pooled proportion of patients with decrease in visual analogue scale (VAS) > = 3 for those with VAS > = 3 before treatment for 2 studies was 87.5% (95% CI, 0.06-100; I 2 = 71.5%) while 37.5% to 96.9% of patients were reported to have experienced partial or complete symptom relief in the other studies. CONCLUSION: Cryotherapy is a safe and effective treatment modality for extra-abdominal desmoid tumors with efficacy similar to those treated with traditional strategies in the short to medium term.

Treatment Outcomes and Survival Patterns of Asian Patients With Relapsed/Refractory Mantle Cell Lymphoma.

Background: Mantle cell lymphoma (MCL) is widely considered an incurable malignancy even with current therapies and relapsed/refractory (R/R) disease to primary treatment remains common. With improved treatment guidelines and the advent of novel agents, patients are increasingly being treated with more lines of regimens. However, outcomes after each line of treatment remain poorly characterized, especially in the Asian population. In this paper, we described the survival outcomes in a group of R/R MCL patients. Methods: We retrospectively studied 35 patients with R/R MCL between 1998 and 2020 at the National Cancer Centre Singapore. Patients were followed longitudinally throughout their disease course. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method. Results: The median OS and PFS from diagnosis were 105 and 40 months, respectively. After first relapse, the median OS and PFS were 52 and 19 months, post-second relapse 32 and 8 months, and post-third relapse 12 and 6 months, respectively. Patients older than 65 years at first relapse had shorter survival (median OS: 22 vs. 55 months, P = 0.0417; median PFS: 9 vs. 29 months, P = 0.001). Early treatment failure after first line therapy was also associated with worse survival outcomes (median OS: 13 vs. 55 months, P < 0.001; median PFS: 9 vs. 26 months, P < 0.001). Conclusion: With each relapse, survival outcomes for patients with MCL are worse. Novel treatment and contemporary outcomes of R/R MCL are encouraging and support the need for continued research in this area.

A systematic scoping review of approaches to teaching and assessing empathy in medicine.

BACKGROUND: Empathy is pivotal to effective clinical care. Yet, the art of nurturing and assessing empathy in medical schools is rarely consistent and poorly studied. To inform future design of programs aimed at nurturing empathy in medical students and doctors, a review is proposed. METHODS: This systematic scoping review (SSR) employs a novel approach called the Systematic Evidence Based Approach (SEBA) to enhance the reproducibility and transparency of the process. This 6-stage SSR in SEBA involved three teams of independent researchers who reviewed eight bibliographic and grey literature databases and performed concurrent thematic and content analysis to evaluate the data. RESULTS: In total, 24429 abstracts were identified, 1188 reviewed, and 136 included for analysis. Thematic and content analysis revealed five similar themes/categories. These comprised the 1) definition of empathy, 2) approaches to nurturing empathy, 3) methods to assessing empathy, 4) outcome measures, and 5) enablers/barriers to a successful curriculum. CONCLUSIONS: Nurturing empathy in medicine occurs in stages, thus underlining the need for it to be integrated into a formal program built around a spiralled curriculum. We forward a framework built upon these stages and focus attention on effective assessments at each stage of the program. Tellingly, there is also a clear need to consider the link between nurturing empathy and one's professional identity formation. This foregrounds the need for more effective tools to assess empathy and to better understand their role in longitudinal and portfolio based learning programs.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Clinical and economic evaluation of a surveillance protocol to manage hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

STUDY OBJECTIVE: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. DESIGN: Prospective, single-arm study. SETTING: National Cancer Centre, Singapore. PATIENTS: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment. INTERVENTION: Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment. MEASUREMENTS: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. MAIN RESULTS: A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. CONCLUSIONS: The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven patients with a median age of 60 were enrolled; 6 at DL1 and 5 at DL2. Patients had received a median of 2 (range 1-4) prior lines of treatment and 7 had primary refractory disease at study entry. Patients received a median of 3 cycles (range 1-6) of selinexor-DICE. The most common grade (G) 1/2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common G 3/4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed doselimiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the 10 evaluable patients, the overall and complete response rates were 91% and 82% respectively. The MTD of selinexor was 40mg when combined with DICE. The combination showed promising CR rates in patients with R/R TCL and NKTL but was poorly tolerated.