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Self-administration at home and decreased visits to see health care professionals bring patients on oral anticancer medication (OAM) and their caregivers to become experts in handling medication, managing adverse events, and making sure that they adhere to treatment. This project aimed to implement a standardized education group session for patients starting an OAM regimen and their caregivers that would build new knowledge, validate comprehension of information, increase satisfaction, and empower participants in self-management. A group session led by an oncology nurse was developed. The theoretical section consisted of short videos that include both verbal and visual explanations. The practical component consisted of quizzes with electronic recordings and instant answers. Turning Point technology was used to compile and analyze the data. Over a 2-year period, 124 patients and 79 caregivers participated in the group sessions. More than 111 h were saved by giving standardized group sessions instead of individual teachings. The participants’ level of confidence regarding the essential concepts to master significantly increased following the group sessions. The results ranged from 18% of participants who answered 4 or 5 on a five-point Likert-type scale before the session to 100% who answered 4 or 5 after the group session. 94% of participants responded with a rating of 4 or 5 when asked if they were satisfied with the overall interactive group session. It is crucial that caregivers participate in the initial OAM teaching. The involvement of the interdisciplinary team was crucial in meeting the informational needs of patients. A standardized group session accessible for viewing and use by all health care professionals and patients simplifies the process of sharing high-quality learning materials in a technological society.

Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.

Background Chemotherapy has been associated with a theoretical risk of hepatitis C virus (HCV) reactivation. However, little is known about the amplitude of viral replication and the incidence of subsequent hepatic exacerbation. Method We aimed to describe the occurrence of hepatitis flare and HCV reactivation at our center. We included, over a period of 5 years, adult patients with chronic HCV receiving intravenous chemotherapy. We excluded patients with undetectable HCV RNA, hepatocellular carcinoma, liver metastases or other etiologies of hepatic disease. The primary objective was to identify hepatic flares (elevation of alanine aminotransferase 3 times above the upper limit of normal). Secondary objectives were to assess viral reactivation (HCVr, HCV-RNA ≥1 log10 IU/mL when compared to baseline value), hepatic decompensation, mortality and the impact on the chemotherapy. Descriptive statistics were used. Results A total of 11 patients with chronic HCV were identified among the 5761 oncology patients. Five patients experienced a hepatic flare with median maximal ALT value of 139 U/L (IQR 133-237). Only 2 patients met criteria for HCVr with a median RNA increase of 1.16 log IU/mL (IQR 1.1-1.2). One patient presented with both HCVr and a hepatic flare. Only one patient required chemotherapy discontinuation following hepatic flare. No hepatic decompensation or related mortality were observed. Conclusion We identified a very small number of HCV cases among our population. We observed HCVr and hepatic flares, but only one consequence on cancer treatment. Nonetheless, HCV screening is encouraged among patients undergoing chemotherapy to allow close follow-up of hepatic function.

Introduction Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centers have undertaken efforts to care for patients with cancer in COVID-free units. Nevertheless, the frequency and relevance of nosocomial transmission of COVID-19 in patients with cancer remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify predictive factors for COVID-19 severity in patients with cancer. Methods Patients with cancer and a laboratory-confirmed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3rd and May 23rd, 2020 in the provinces of Quebec and British Columbia in Canada. Patient’s baseline characteristics including age, sex, comorbidities, cancer type, and type of anti-cancer treatment were collected. The exposure of interest was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 ≥ 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalization, supplemental oxygen, intensive-care unit (ICU) admission and/or mechanical ventilation. Results A total of 252 patients (N=249 adult, and N=3 pediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N=233). One-hundred-and-six patients (42.1%) received active anti-cancer treatment in the last 3 months prior to COVID-19 diagnosis. During a median follow-up of 25 days, 33 (13.1%) required admission to the ICU, and 71 (28.2%) died. Forty-seven (19.1%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection, compared to a contemporary community-acquired population (27 days vs unreached, HR 2.3, 95% CI 1.2-4.4, p=0.0006). Multivariate analysis demonstrated that hospital-acquired COVID-19, age, ECOG status, and advanced stage of cancer were independently associated with death. Interpretation Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free units. We also validated that age and advanced cancer were negative predictive factors for COVID-19 severity in patients with cancer., Highlights • We found a high rate of nosocomial transmission of COVID-19 in patients with cancer. • Nosocomial COVID-19 increased mortality compared to community-acquired infection. • Nosocomial COVID-19, age, ECOG, and stage were independently associated with death. • COVID-free units and infection control procedures are required to protect patients.

Background: TAK-981 is the first small-molecule inhibitor of SUMOylation to enter clinical trials. SUMOylation is a post-translational modification in which small ubiquitin-like modifier (SUMO) proteins are activated and covalently attached to substrate proteins. SUMOylation has a central role in constraining type I interferon (IFN-I)-dependent responses (Decque Nat Immunol 2016). By blocking SUMOylation, TAK-981 promotes IFN-I production and increases innate immunity. The ability of TAK-981 to promote activation of macrophages and NK cells and increase their cytotoxic/phagocytic activity provides a mechanistic rationale for its use in combination with monoclonal antibodies (mAbs) reliant on antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical studies have demonstrated synergistic antitumor activity between TAK-981 and the anti-CD20 monoclonal antibody rituximab in xenograft models of human B cell lymphoma (Nakamura AACR 2019). Based on these data, and a single-agent TAK-981 study (TAK-981-1002), this phase 1b/2, open-label, dose-escalation and expansion study is investigating the safety and efficacy of TAK-981 plus rituximab in adults with CD20-positive R/R NHL (NCT04074330); here, we report data from the phase 1b dose-escalation part of the study. Methods: Eligible pts were aged ≥18 years with CD20-positive, R/R aggressive B-cell NHL (aNHL) or indolent NHL (iNHL). aNHL included diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and grade 3b follicular lymphoma (FL); iNHL included grade 1-3a FL and marginal zone lymphoma. aNHL pts had to have received prior R-CHOP or equivalent plus 1 additional line of therapy in the R/R setting; iNHL pts had to be refractory to rituximab or another anti-CD20 mAb, and to have received at least 1 prior therapy for R/R disease. TAK-981 IV was given at increasing doses (starting: 10 mg) on days 1 and 8 (QW) or days 1, 4, 8, and 11 (BIW) of 21-day cycles. Rituximab 375 mg/m 2 IV was given on days 1, 8, and 15 of cycle 1 and on day 1 thereafter. Dose escalation was based on adaptive Bayesian logistic regression modelling with overdose control based on the posterior probability of having a dose-limiting toxicity (DLT). Primary phase 1b objectives were safety, tolerability, and recommended phase 2 dose (RP2D) of TAK-981 in combination with rituximab; data cutoff was 28 June 2021. Results: 24 pts have been enrolled and treated: 19 QW (10-120 mg) and 5 BIW (90 mg); 4 are currently on treatment. Enrollment continues in the 90 mg BIW and 120 mg QW cohorts. Median age was 65 years (range 29-80); 67% were male. No DLTs have been reported to date. RP2D and schedule will be determined based on safety, pharmacokinetic (PK), and pharmacodynamic (PD) data. Treatment-emergent adverse events (TEAEs) are shown in the Table. Most common TEAEs (≥15%) were similar between the QW/BIW schedules with the exception of dizziness (2 pts at 10 mg, 2 at 40 mg, and 1 at 90 mg) and hypokalemia (1 pt at 40 mg, 2 at 90 mg, and 1 at 120 mg); all QW. TEAEs were consistent with induction of IFN signalling (transient flu-like symptoms: fever, chills, fatigue) and with those observed in the single-agent study (data on file); no further TAK-981- or immune-related TEAEs were observed. Grade ≥3 TEAEs related to TAK-981 were reported in 2 pts: grade 3 atrial fibrillation (ongoing cardiac history) and grade 4 neutropenia; both in the 40 mg QW cohort and transient. In this population of rituximab-refractory pts, there were 5 objective responses in 17 response-evaluable pts: 4 partial responses (2 at 10 mg, FL and DLBCL; 1 at 60 mg, DLBCL; 1 at 90 mg, primary mediastinal thymic large B-cell lymphoma) and 1 complete response (40 mg, MCL), all in the QW cohort. TAK-981 PK was linear and declined in a tri-phasic manner. TAK-981 exhibited PD activity in peripheral blood including target engagement, decreased SUMOylation, and increased IFN-regulated gene expression (Figure). Conclusion: The combination of TAK-981 and rituximab was well tolerated in pts across each dose level and schedule. TAK-981 PK showed minimal accumulation after repeat dosing and PD assays confirmed inhibition of SUMOylation and activation of IFN-I signalling. More importantly, the combination of TAK-981 and rituximab resulted in promising clinical activity (ORR 29%) in the R/R setting, supporting the continued development of this combination in pts with NHL. Figure 1 Figure 1. Disclosures Assouline: Johnson&Johnson: Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Roche/Genentech: Research Funding; Eli Lilly: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Current equity holder in publicly-traded company, Research Funding; Gilead: Speakers Bureau; Jewish General Hospital, Montreal, Quebec: Current Employment. Mehta: Affirmed; Kite/Gilead; Roche-Genetech; Celgene/BMS; Oncotartis; Innate Pharmaceuticals; Seattle Genetics; Incyte; Takeda; Fortyseven Inc/Gilead; TG Therapeutics; Merck; Juno Pharmaceuticals/Bristol Myers Squibb: Research Funding; Seattle Genetics; Incyte; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics; Incyte; TG Therapeutics: Consultancy. Phillips: Bayer: Consultancy, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding. Danilov: Rigel Pharm: Honoraria; Bristol-Meyers-Squibb: Honoraria, Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TG Therapeutics: Consultancy, Research Funding; Takeda Oncology: Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria, Research Funding; SecuraBio: Research Funding; Bayer Oncology: Consultancy, Honoraria, Research Funding. Doucet: Amgen: Consultancy; Novartis: Consultancy; Astra-Zeneca: Consultancy; BMS: Consultancy; Jannsen: Consultancy; Servier: Consultancy; Abbvie: Consultancy; Seattle Genetics: Consultancy; Roche: Consultancy; Gilead: Consultancy. Park: Morphosys: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Gilead: Speakers Bureau; Takeda: Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Seattle Genetics: Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees. Berg: Takeda: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Gomez-Pinillos: Takeda: Current Employment. Martinez: Takeda: Current Employment. Chao: Takeda: Current Employment. Berger: Takeda Development Center Americas, Inc.: Current Employment. Gibbs: Takeda: Current Employment. Friedlander: Takeda: Current Employment. Ward: Takeda: Current Employment. Proscurshim: Takeda Pharmaceuticals: Current Employment, Current holder of individual stocks in a privately-held company. Caimi: TG Therapeutics: Consultancy; Kite: Consultancy; ADC Therapeutics: Consultancy; Verastem: Consultancy; Amgen: Consultancy; XaTek Inc.: Patents & Royalties; Celgene: Speakers Bureau.

Pyoderma gangrenosum (pg) is a rare neutrophilic dermatosis characterized by painful necrotic ulceration affecting preferentially the lower extremities. Diagnosis is challenging, and a thorough workup (including biopsy) is required. In this case report, we describe a 67-year-old patient with a diagnosis of myelodysplastic syndrome (mds) who developed fever and pg two days after the first cycle of subcutaneous azacitidine (Vidaza, Celgene Corporation, Summit, NJ, USA). On physical examination, the patient had four erythematous plaques at sites of subcutaneous injections of azacitidine on the arms, as well as three other plaques in proximity. A skin biopsy demonstrated a dense neutrophilic interstitial infiltrate in the dermis. After the diagnosis of pg, prednisone 1 mg/kg was started and the fever subsided rapidly. This was followed by the resolution of the cutaneous lesions. Changing the route of administration of azacitidine from subcutaneous to intravenous and adding a daily dose of prednisone during the treatment allowed the patient to receive a total of 10 cycles of azacitidine. This is the second case reported in the literature. Because azacitidine is frequently used in mds and acute myeloid leukemia, clinicians should be aware of this rare cutaneous adverse event. Our approach can be used to avoid the recurrence of pg when continuing azacitidine treatment.

Background: Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centers have undertaken efforts to care for patients with cancer in COVID-free zones. Nevertheless, nosocomial transmission of COVID-19 in patients with cancer likely occurs, but the frequency and relevance of these events remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify prognostic factors for COVID-19 severity in patients with cancer. Methods: Patients with cancer and a laboratory-confirmed or presumed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3rd and May 23rd, 2020, in the provinces of Quebec and British Columbia. Patients’ baseline characteristics including age, sex, comorbidities, cancer type, and type of anticancer treatment were collected. The primary outcome was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalization, supplemental oxygen, intensive-care unit (ICU) admission, and/or mechanical ventilation. Results: A total of 253 patients (N=250 adult and N=3 pediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N=236). Ninety patients (35.6%) received active anticancer treatment in the last 3 months prior to COVID-19 diagnosis. During a median follow-up of 23 days, 209 (82.6%) required hospitalization, 38 (15%) required admission to ICU, and 71 (28%) died. Forty-seven (19%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection, compared to a contemporary community-acquired population (27 days vs. 71 days, HR 2.2, 95% CI 1.2-4.0, p=0.002). Multivariate analysis demonstrated that hospital-acquired COVID-19, age, ECOG status, and advanced stage of cancer were independently associated with death. Conclusion: Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free zones. We also validated that age, poor ECOG, and advanced cancer were negative prognostic factors for COVID-19 in patients with cancer. Citation Format: Arielle Elkrief, Antoine Desilets, Neha Papneja, Lena Cvetkovic, Catherine Groleau, Yahia Abdelali Lakehal, Layla Shbat, Corentin Richard, Julie Malo, Wiam Belkaid, Erin Cook, Stephane Doucet, Thai Hoa Tran, Patrice Savard, Kevin Jao, Nathalie Daaboul, Eric Bhang, Jonathan Loree, Wilson Miller, Donald Vinh, Nathaniel Bouganim, Gerald Batist, Caroline Letendre, Bertrand Routy. High mortality among hospital-acquired COVID-19 infection in patients with cancer: An observational cohort study from Quebec and British Columbia [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S12-01.

Background Guidelines diverge about the need for systematic HBV screening for all patients starting chemotherapy. At the Centre hospitalier de l’Universite de Montreal (CHUM), systematic HBV screening is requested on pre-printed chemotherapy order (PPCO) at high risk of HBVr with follow-up by a pharmacist. For all other PPCO, doctors can request HBV screening and follow-up. A decision algorithm is available for all clinicians. The aim of this study is to assess whether patients undergoing routine HBV screening could reduce the incidence of HBVr. Methods This is a retrospective observational study including patients who received an IV chemotherapy for cancer between July 2017 and June 2018 at the CHUM. We compared the incidence and complications of HBVr in patients with HBV screening as requested on PPCO (group 1) or on demand from the medical team (group 2) to patients who were not screened (group 3). Results On a total of 1374 patients, 179 of 206 (13%) patients were screened as requested on PPCO (group 1) and 421 (30%) by the medical team (group 2). Patient characteristics, duration of treatment and follow-up for all groups are listed in the table. No difference was seen on the incidence of HBVr between screened and unscreened patients (0% vs 0.1%; p = 0.36) probably because of a lack of follow-up after chemotherapy. Optimal follow-up for HBVr based on the decisional algorithm appears to be better in group 1 than group 2 (50% vs 25%; p = 0.13). For patients on anti-CD20 therapy in group 1, HBV screening was done for 92% of patients which is a higher rate compare to previously reported data. In group 3, 89 patients had ALT elevation (>100U/L and x3 baseline value) during chemotherapy but only 17 patients (19%) were tested for the possibility of HBVr. Table . 1837P Group 1 n = 206 (%) Group 2 n = 421 (%) Group 3 n = 747 (%) Screening before chemotherapy 179 (86.9) 421 (100) 0 (0) Nb of pts who had finished chemotherapy treatment at the time of analysis 174 (84.5) 402 (95.5) 699 (93.6) Median duration (months) of chemotherapy (IQR) 10.5 (6.4-14.4) 4 (1.4-9.1) 3.6 (1.6-5.6) HBsAg + Anti-HBc + HBV-DNA + 0 (0) 17 (8.3) 1 (0.5) 2 (0.5) 36 (8.6) 2 (0.5) - Incomplete screening 5 (2.8) 31 (7.4) - Antiviral prophylaxis required Antiviral prophylaxis initiated 8 (3.9) 7 (3.4) 3 (0.7) 3 (0.7) - Follow-up required Follow-up Optimal follow-up 18 (8.7) 10 (4.9) 9 (4.4) 36 (8.6) 13 (3.1) 9 (2.1) - Number of patients who had a follow-up after chemotherapy 3 (1.5) 5 (1.2) HBV reactivation 0 (0) 0 (0) 1 (0.1) Conclusions Systematic HBV detection requested on PPCO is an effective way to increase HBV screening and prevent HBVr in patients receiving chemotherapy. However, this method does not guarantee optimal follow-up and requires improvements. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure D. Martel: Honoraria (self): Abbvie Canada; Honoraria (self): Gilead Sciences Canada; Honoraria (self): Merck Canada. V. Martel-Laferriere: Research grant / Funding (self), Clinical Research Scholars - Junior 1: Fonds de la recherche en sante du Quebec. S. Doucet: Honoraria (self), Advisory / Consultancy: AbbVie Canada; Honoraria (self), Advisory / Consultancy: Gilead Sciences Canada; Honoraria (self): Merck Canada; Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self): Seattle Genetics. J. Adam: Honoraria (self): Amgen Canada; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: AbbVie; Advisory / Consultancy: Lundbeck. All other authors have declared no conflicts of interest.

Primary central nervous system lymphoma (PCNSL) comprises approximately 5 % of all primary brain tumors. During the past two decades the incidence of PCNSL has increased, and as a result clinical research to determine the optimal treatment for PCNSL patients also has increased. Diagnosis is based on histopathologic findings traditionally established by biopsy only. More recent data raise controversy and challenges this biopsy-only paradigm, showing a potential advantage for surgical resection with progression-free survival (PFS) and overall survival (OS). Using high-dose intravenous (IV) methotrexate-based chemotherapy alone or as part of a regimen can lead to disease cure. The role of whole brain radiotherapy (WBRT) remains controversial and more frequently is omitted to avoid potential delayed neurocognitive effects, especially in patients older than age 60 years. Newer data from Memorial Sloan Kettering Cancer Center (MSKCC) using five cycles of Rituximab, Methotrexate, Vincristine, and Procarbazine (R-MVP) followed by low-dose WBRT (2,340 cgy), and then two cycles of Ara-C had excellent disease control with low neuro-toxicity and is now the basis of an ongoing RTOG (Radiation Treatment Oncology Group) trial comparing early versus delayed WBRT. Other chemotherapeutics and novel treatments, such as autologous stem cell transplantation, are being studied for potential use in PCNSL. Unlike many other primary brain tumors seen in adults, PCNSL is potentially curable; therefore, balancing treatment decisions with long-term neurocognitive effects and toxicities is crucial.

A new study has shown that rituximab and bendamustine provide better outcomes and less toxicity than rituximab plus CHOP chemotherapy in patients with indolent lymphomas. However, whether this represents a practice-changing development is unclear and we should not rush to judgement without answering some key questions.

Cancer patients receiving chemotherapy often need central venous catheters (CVC). There is no laboratory marker to identify patients at high risk of thrombosis who may benefit from thromboprophylaxis. D-Dimer dosing is a well studied test that may correlate with thrombosis risk. The aim of this study is to determine if d-dimer levels are a predictor of CVC thrombosis. Adult cancer patients needing a new CVC for more than 1 month and without an ongoing indication for anticoagulation were included. D-dimer dosing was done before (0–3 days), 24–48h after and 7 days after insertion of CVC. Duplex ultrasonography (US) was performed approximately 30 days after installation. We planned to look at quantitative d-dimer variation in patients to establish its prognostic value in relationship with eventual thrombosis occurrence. Thirty five patients are included in this analysis. There were 63% males and 37% females and the median age was 57. Eighty nine percent had solid tumors (64% gastrointestinal, 23% head and neck, 13% breast) and 11% had an hematologic malignancy. Fifty one percent received concomitant radiotherapy. Seventy nine percent had continuous infusion chemotherapy. Twenty two patients underwent US and 27 patients had at least 2 out of three planned d-dimer values. The incidence of venous thrombosis in the whole cohort was 31% (5 symptomatic, 6 asymptomatic) whereas 24 patients were considered free of thrombosis (11 confirmed by duplex, 13 clinically asymptomatic). In patients with available US results, baseline d-dimer level was similar for those with or without thrombosis (924 and 902). For these patients, the absolute increase of d-dimer was not significantly different in the two groups (194 vs 115 at day 1–2; 421 vs 63 at day 7) as well as relative increase (51% vs 31% at day 1–2; 145% vs 40% at day 7). Baseline d-dimer level was similar for the five patients with symptomatic thrombosis compared to the other 30 patients (1038 and 859), but higher at day 7 (1616 vs 905 p=0,048). Different strategies were analysed to try to define a high and a low risk group and two were selected. First, the population with a cutoff value of d-dimer levels at day 7 of > 1100 had a 40% risk of symptomatic thrombosis vs 0% for those below 1100. Second, an absolute increase in d-dimer values at day 1–2 of more than 500 was associated with a 66,7% risk of symptomatic thrombosis vs 0% for the others. Although numbers are small, patients with symptomatic thrombosis were more frequently receiving G-CSF, red cell transfusions, platelets transfusions and were less likely to be receiving continuous infusion chemotherapy. Our pilot study suggests that d-dimer testing after CVC insertion might permit risk stratification for thrombotic complications. If confirmed by larger trials, this strategy might be useful to plan more effective prophylaxis studies in these populations.