Introduction/Background SHAPE was an international Phase III trial comparing radical hysterectomy to simple hysterectomy for early-stage cervical cancer. Simple hysterectomy was non-inferior to radical hysterectomy with respect to pelvic recurrence rate at 3 years, but superior in terms of postoperative complications, quality of life, and sexual health. Our objective was to conduct a cost-effectiveness analysis comparing the two treatment strategies. Methodology A Markov model compared the costs in 2023 Canadian dollars and benefits of simple hysterectomy versus radical hysterectomy (both with lymph node assessment). The model was informed by empirical data from SHAPE, and costs from national and provincial sources. Health utilities were derived from EQ-5D-5L surveys conducted in Canada, United Kingdom, France, and Ireland. Effectiveness was measured in quality-adjusted life years (QALYs). Sensitivity analyses accounted for uncertainty around various parameters. Time horizon was 5 years. Monte Carlo simulation estimated the number of patients in various scenarios experiencing different complications. Results Simple hysterectomy was more effective and less costly than radical hysterectomy. Average lifetime costs were $20,044 and $21,714, and average gains were 3.55 and 3.53 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. These scores exceeded baseline for simple hysterectomy (0.82) but never recovered to baseline by year 3 for radical hysterectomy (0.82). Assuming 800 patients with early cervical cancer in Canada annually, we estimated 3 versus 82 patients with urinary retention, and 49 versus 88 patients with urinary incontinence persisting 4 weeks after simple versus radical hysterectomy, respectively. Results were most sensitive to variability in health utilities associated with surgery, but stable through wide ranges of costs and recurrence estimates. Conclusion Simple hysterectomy with lymph node assessment is less costly and more effective in terms of quality adjusted life expectancy compared to radical hysterectomy for early-stage cervical cancer. Disclosures None.

Concrete is the common extensively utilized man-made material in the world. Concrete plays an important role in our Infrastructure development that shows our status worldwide among the other nations. One of the difficulties that have arisen since the introduction of concrete structures in the building business is how to increase concrete strength while still being efficient and cost-effective. The use of novel materials in concrete will boost the strength of the concrete in a more significant way; one such development is High Strength Concrete.

Advancements in genomic and precision medicine have changed the way oncology clinical trials are designed. Compared to the traditional single tumour-based trial, master protocols, which are often classified as basket, umbrella, or platform trials, conduct studies on multiple subgroups under a single overarching protocol. This paper presents the perspectives of patients, clinicians, public payers, private payers, and industry, which were discussed during the third webinar. The discussion section of this paper summarizes the major points raised by the presenters, as well as questions from the audience and answers from the presenters.

Introduction: For patients with symptomatic advanced stage indolent lymphoma, rituximab (R) was traditionally used alongside cyclophosphamide, vincristine, prednisone (CVP), or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Bendamustine plus rituximab (BR) has been found to increase progression-free survival compared to R-CHOP/CVP, although controversy exists around its toxicity profile. Since 2013, bendamustine has been approved for universal public reimbursement for this indication in Ontario, Canada, and become the preferred regimen. We examined survival and toxicity of patients with indolent lymphoma treated with BR compared with RCVP/CHOP in Ontario. Methods: We conducted a retrospective cohort population-based study using administrative healthcare databases from Ontario, Canada. Patients with a diagnosis of indolent lymphoma, excluding mantle cell lymphoma, who were treated with R-CVP/CHOP from 2005 to 2012 or with BR from 2013-2018 were included. The two treatment groups were propensity score matched based on lymphoma subtype, age, sex, prior cancer diagnosis, time since diagnosis and rural/urban residence. The primary outcome of the study is overall survival (OS) from time of first treatment to date of death or end of study period. Secondary outcomes include toxicities, such as infections and secondary malignancies, associated resource use, and outcomes of patients treated with rituximab maintenance therapy. Results: A propensity-matched cohort of 2029 patients treated with BR and 2029 patients treated with R-CVP/CHOP were included. The median age of patients was 64 years and 48% were female in the cohort. A majority of patients had a diagnosis of follicular lymphoma (59.3% of patients treated with BR, 59.7% of patients treated with R-CVP/CHOP, p = 0.88). Median follow-up time was 41 and 87 months for patients treated with BR and R-CVP/CHOP, respectively. In this well-matched cohort, BR was associated with a significant improvement in survival compared to R-CVP/CHOP (HR 0.76, 95% CI 0.67-0.88, p < 0.01). Five-year OS was 80% and 75% for patients treated with BR and R-CVP/CHOP, respectively (Figure 1). A total of 974 patients died during the follow-up period (331 treated with BR, 643 treated with R-CVP/CHOP), of which 875 had causes of death available. A majority of patients in both groups died from lymphoma (63.2% treated with BR, 66.4% treated with R-CVP/CHOP). Death from secondary malignancies was less common (11.8% treated with BR, 12.8% treated with R-CVP/CHOP). Few patients died from infection (6.2% treated with BR, 3.2% treated with R-CVP/CHOP). Conclusions: Our study demonstrates improved OS with BR compared to R-CVP/CHOP for patients with previously untreated indolent lymphoma. Cause of death in both cohorts was most frequently attributable to lymphoma. This supports BR as the standard of care for treatment of symptomatic indolent lymphoma. Kaplan-Meier plot of overall survival of the treatment groups from time of treatment initiation The research was funded by: This project was in part supported by the American Society of Hematology HONORS (Hematology Opportunities for the Next Generation of Research Scientists) Award granted to Adam Suleman. Keywords: Indolent non-Hodgkin lymphoma, Combination Therapies No conflicts of interest pertinent to the abstract.

Introduction: Rituximab in combination with cytotoxic chemotherapy followed by autologous stem cell transplantation (ASCT) and maintenance rituximab (MR) is a standard treatment strategy in young and fit patients with mantle cell lymphoma (MCL). Various chemotherapy regimens can be used as part of induction therapy, but there is no single standard of care. Frontline therapy can be improved by adding novel agents such as Bruton tyrosine kinase inhibitors (BTKi) which are active in relapsed/refractory MCL and can be safely combined with immunochemotherapy. In the European Triangle study (NCT02858258) ibrutinib is given for 3 weeks with R-CHOP, but not with R-DHAP, which means patients receive intermittent BTKi exposure before ASCT. Continuous, uninterrupted BTKi could maximize the benefit of front-line therapy given that responses are known to develop over time. Acalabrutinib achieves BTK inhibition at lower doses than ibrutinib and also has less off-target BTK inhibition. We hypothesize that combining continuous acalabrutinib with R-CHOP may result in a tolerable, outpatient, highly active regimen allowing a high proportion of patients to proceed with ASCT and/or achieve MRD negativity. Methods: NCT04566887 is a phase II, non-randomized, open-label, single-arm study conducted across 7 academic centres in Canada. Patients ≥18 years of age with previously untreated MCL, performance status 0-2, adequate organ function and considered fit for ASCT will be included. Patients receive 6 cycles of R-CHOP at standard doses plus acalabrutinib 100 mg twice per day orally (Figure 1). Responding patients proceed with ASCT and subsequently receive MR and acalabrutinib for a total of 2 years. Patients who do not proceed to ASCT for reasons other than progressive disease also receive MR and acalabrutinib. The primary endpoint is the complete response rate after 6 cycles of induction with centrally reviewed PET/CT using the Lugano Classification for Malignant Lymphoma. Secondary endpoints include frequency of adverse events, response rates according to the International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017), rate of minimal residual disease (MRD) negativity prior to ASCT and at any time during study treatment, event-free survival, and overall survival. MRD testing will be performed on serial peripheral blood and bone marrow aspirates using a panel that covers commonly mutated MCL genes, including the CCND1 breakpoint region. Serial peripheral blood samples will also be used for other correlative studies including analyses of circulating tumor DNA and microRNA. Diagnostic tumor tissue will be centrally analyzed using the MCL35 assay. Patient reported outcomes will be assessed using the FACT-Lym and EORTC QLQ-C30 questionnaires. Keywords: Molecular Targeted Therapies, Indolent non-Hodgkin lymphoma, Ongoing Trials Conflicts of interests pertinent to the abstract D. Villa Consultant or advisory role: Janssen, Nanostring Research funding: AstraZeneca (research funding to the institution) J. Kuruvilla Research funding: AstraZeneca (research funding to the institution)

Background:In Ontario, no clearly defined standard of care for the management of mantle cell lymphoma (mcl) has been developed, and substantial variability from centre to centre is evident. This guidance document was prompted by the need to harmonize practice in Ontario with respect to first-line, conditioning, and post-transplantation maintenance therapy for patients newly diagnosed with transplantation-eligible mcl. Methods:The medline and embase databases were systematically searched from January 2013 to January 2020 for evidence, and the best available evidence was used to draft recommendations relevant to first-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of transplantation-eligible newly diagnosed mcl. Final approval of this guidance document was obtained from the Stem Cell Transplant Advisory Committee. Recommendations:These recommendations apply to all cases of transplantation-eligible newly diagnosed mcl:■ Alternating cycles of r-chop (rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisolone) and r-dhap [rituximab plus dexamethasone-high-dose cytarabine-cisplatin] is the recommended first-line treatment for symptomatic patients newly diagnosed with mcl before autologous stem-cell transplantation (asct).■ Rituximab plus hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone (r-hypercvad), alternating with methotrexate and cytarabine, is not recommended for the treatment of patients with newly diagnosed mcl.■ beam (carmustine-etoposide-cytarabine-melphalan), beac (carmustine-etoposide-cytarabine-cyclophosphamide), and total-body irradiation-based regimens are reasonable conditioning options for patients with mcl who have responded to first-line therapy and who are undergoing asct.■ Maintenance therapy with rituximab is recommended for patients with newly diagnosed mcl who have undergone asct.

Background: There remains clinical equipoise over the best initial treatment strategy for advanced-stage Hodgkin lymphoma. Recent PET-adapted trials (RATHL, HD18, AHL2011) have tried to balance the trade-off that occurs with an inferior progression-free survival in the ABVD strategy, but higher rates of hematologic toxicity, infertility, and second malignancy in the BEACOPP strategy. The overall lifetime cost of each strategy remains unknown, especially costs which incorporate therapies for relapsed disease including brentuximab consolidation after autologous stem cell transplant and palliative therapy with nivolumab, and associated health state utilities. Methods: We developed a Markov decision analytic model to compare the life expectancy, quality-adjusted life expectancy (QALYs), and direct costs with varying upfront treatment regimens for a hypothetical cohort of transplant-eligible patients with newly-diagnosed advanced-stage Hodgkin lymphoma. A 20-year time horizon was used. Baseline probability estimates and utilities were derived from a systematic review of published studies (i.e. HD2000, Viviani, EORTC, HD15, HD18, RATHL, AHL2011, Echelon-1). A Canadian public health payer's perspective was considered and costs are presented in 2018 Canadian dollars. All costs and benefits were discounted by 1.5%. Sensitivity analyses were performed for key variables. Results: See Table 1 for results of the 20-year model. In the base-case analysis, the AHL2011 protocol was associated with both cost-savings and improved quality-adjusted outcomes over all other treatment strategies (Figure 1A). Sensitivity analyses demonstrated that the model was robust to key variables including probability of treatment-related mortality, probability of death from secondary malignancy, and probability of infertility secondary to BEACOPP. The threshold utility of infertility was found to be 0.71 (Figure 1B). Probabilistic sensitivity analyses (10,000 simulations) were performed (Figure 1C). For the WTP threshold of $100,000, AHL2011 was the dominant strategy 73% of the time (Figure 1D). Conclusions: The preferred treatment strategy for patients with newly diagnosed advanced-stage Hodgkin lymphoma is the AHL2011 PET-adapted regimen. This strategy maximizes life expectancy, quality-adjusted life years, and is the most cost-effective strategy, accounting for increased rates of hematologic toxicity, secondary malignancy, and infertility caused by exposure to at least 2 cycles of BEACOPP. Keywords: ABVD; BEACOPP; Hodgkin lymphoma (HL).

WHO classification. Follicular helper T cells (TFH) appear as the cell counterpart of a major proportion of PTCL worldwide, including angio-immunoblastic T-cell lymphoma and other nodal lymphomas with a TFH phenotype; the later disclose a rather homogeneous mutational landscape which recapitulates a multi-step oncogenic process associating epigenetic deregulation (TET2 +/DNMT3Amutations, often at early stages), and second hit mutations affecting the T-cell receptor signaling pathway (RHOA,..). This oncogenic model has been confirmed in mouse models and opens the field for using emerging epigeneticor signalingmodulating therapies. Among anaplastic large cell lymphoma (ALCL), those with ALK rearrangement constitute the best-delineated entity. ALK-negative ALCLs appear genetically heterogeneous with translocation-associated subsets (DUSP22, TP63,...) found in both systemic and cutaneous types. DUSP22-rearranged ALK-negative ALCL likely constitutes a unique category with a distinct signature and a good outcome. Except for DUSP22-rearranged ALCL, a constitutive activation of STAT3 is shared by ALK-positive and ALK-negative ALCLs, including the newly described usually indolent breast implantassociated ALCL. Lymphomas derived from cells of the innate immune system affect preferentially extranodal sites, which are continuously exposed to various antigens. Chronic immunosuppression and genetic background may also play a role. There is evidence of plasticity in terms of cellular derivation (NK, Tγδ,Tαβ) within a single entity. Most of these tumors also harbor a combination of mutations affecting different classes of epigenetic modifyers, and mutation-induced activation of the JAK-STAT pathway which may serve as potential therapeutic targets. While most of these proliferations are highly malignant, some more indolent forms have been identified, arising in the skin or the GI tract. Despite significant progress in the understanding of PTCLs, 20-30% of PTCL patients remain “unspecified”, a basket category which may contain emerging (GATA3 or T-bet) subtypes. Most PTCL probably harbor distinct therapeutic vulnerabilities supporting the need for biologically-oriented therapeutic strategies to improve patient’s outcome.

Little is known about resource use in the care of neuroendocrine tumors (NETs). This study defined patterns of costs in NET management and compared them with those of a more common malignancy, colon cancer (CC).

OBJECTIVE:This evidence summary set out to assess the available evidence about the follow-up of asymptomatic survivors of lymphoma who have received curative-intent treatment.METHODS:The medline and embase databases and the Cochrane Database of Systematic Reviews were searched for evidence published between 2000 and August 2015 relating to lymphoma survivorship follow-up. The evidence summary was developed by a Working Group at the request of the Cancer Care Ontario Survivorship and Cancer Imaging programs because of the absence of evidence-based practice documents in Ontario for the follow-up and surveillance of asymptomatic patients with lymphoma in complete remission.RESULTS:Eleven retrospective studies met the inclusion criteria. The proportion of relapses initially detected by clinical manifestations ranged from 13% to 78%; for relapses initially detected by imaging, the proportion ranged from 8% to 46%. Median time for relapse detection ranged from 8.6 to 19 months for patients initially suspected because of imaging and from 8.6 to 33 months for those initially suspected because of clinical manifestations. Only one study reported significantly earlier relapse detection for patients initially suspected because of clinical manifestations (mean: 4.5 months vs. 6.0 months, p = 0.042). No benefit in terms of overall survival was observed for patients depending on whether their relapse was initially detected because of clinical manifestations or surveillance imaging.SUMMARY:Findings in the present study support the importance of improving awareness on the part of survivors and clinicians about the symptoms that might be associated with recurrence. The evidence does not support routine imaging for improving outcomes in this patient population.

BACKGROUNDPromising new drugs such as lenalidomide, an immunomodulatory agent, are available for the treatment of multiple myeloma. We describe the process of creating a provincial guideline for the use of lenalidomide, alone or in combination with other drugs, in relapsed, refractory, or newly diagnosed disease (including smoldering and symptomatic patients, and candidates and non-candidates for transplant) and in maintenance treatment (after transplant or non-transplant therapy); and for strategies to manage lenalidomide-related toxicities.METHODSOutcomes of interest included overall survival, event-free survival, progression-free survival, time to progression, time to next treatment, response rate, and incidence of serious toxicity. The medline, embase, and Cochrane Library databases, as well as meeting abstracts and the Web sites of relevant organizations, were systematically searched for relevant literature.RESULTSRecommendations were developed using the evidence from published studies and the clinical expertise of the working group and of the Cancer Care Ontario Hematology Disease Site Group.CONCLUSIONSLenalidomide in combination with dexamethasone can be recommended for both previously untreated and treated patients with multiple myeloma. Guidelines for the management of cytopenias, venous thromboembolism, and second primary malignancies are discussed.

ABSTRACT Background RADIANT-3 was a phase III study investigating the effect of the mammalian target of rapamycin inhibitor everolimus on progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET; Yao et al, NEJM, 2011). Everolimus significantly improved PFS compared with placebo (11 vs 4.6 months, P  Methods Baseline plasma levels of VEGF-A, PlGF, sVEGFR1, and sVEGFR2 were determined by ELISA using multiplexed MSD platform. The optimal cutoffs for these markers were explored using the “survival tree analysis” method. Interaction of treatment and baseline marker status ( Results PFS was significantly improved to a similar extent in patients receiving everolimus compared with patients who received placebo, regardless of baseline levels of markers (P  Conclusions These exploratory analyses demonstrated consistent everolimus efficacy in all patients with advanced pNET irrespective of their baseline VEGF pathway biomarker levels. However, levels of VEGF-A, PlGP, and sVEGFR1 are potential prognostic factors for pNET. Marker Cutoff (pg/mL) Median PFS Prognostic effect HR [95% CI]; P value Treatment effect P value VEGF-A 246.1 8.3 vs 5.5 1.50 [1.17-1.92]; PlGF 32.06 8.0 vs 4.2 1.52 [1.14-2.02]; .004 SVEGFR1 226.2 8.3 vs 5.5 1.62 [1.27-2.07]; SVEGFR2 24503.1 10.8 vs 5.7 1.30 [0.96-1.76]; .090 Disclosure J.C. Yao: Consultant/advisory role for Novartis, Ipsen, Pfizer, Endo; Honoraria from Novartis; Research funding from Novartis, Genentech. M. Shah: Honoraria for presentations and participation in Advisory Board Meetings: Novartis, Ipsen, Pfizer Research grant: Novartis. A. Panneerselvam: Novartis employee. S. Stergiopoulos: Novartis employee. D. Chen: Novartis employee. M. Pavel: Honoraria for presentations and participation in Advisory Board Meetings: Novartis, Ipsen, Pfizer Research grant: Novartis. All other authors have declared no conflicts of interest.