Nordic Lymphoma Group

The Australian Journal of General Practice (AJGP) aims to provide relevant, evidence-based, clearly articulated information to Australian general practitioners (GPs) to assist them in providing the highest quality patient care

We wanted to investigate the association between circulating tumor DNA (ctDNA) detection at baseline, during and after neoadjuvant treatment, after surgery, and recurrence, in patients with nonmetastatic cancer. In this systematic review and meta-analysis, we included studies that investigated patients undergoing neoadjuvant treatment for nonmetastatic cancer and provided recurrence indices stratified for ctDNA status at the following timepoints: baseline, during treatment, posttreatment, and postsurgery. Study quality was reported with the Newcastle-Ottawa scale, REMARK checklist, and GRADE approach. PubMed, Embase, Cochrane Library, and Web of Science were our data sources (inception to 3 June 2021). The main outcome was risk of recurrence. We identified ten studies including 727 patients with rectal, breast, gastric, and bladder cancer. All studies reported posttreatment ctDNA analysis, while seven, four, and six reported baseline, during treatment, and postsurgery ctDNA analysis, respectively. ctDNA detection was associated to recurrence across all timepoints [baseline: risk ratio (RR) 2.86, 95% confidence interval (CI) 1.33-6.14, during treatment: RR 3.81, 95% CI 2.09-6.92, posttreatment: RR 4.29, 95% CI 2.79-6.60, postsurgery: RR 8.03, 95% CI 3.16-20.43]. Heterogeneity was low to moderate. This meta-analysis of observational studies found that ctDNA detection in patients undergoing neoadjuvant treatment for nonmetastatic cancer was associated with recurrence. A stronger association was evident in posttreatment and postsurgery timepoints. However, some studies reported low negative predictive value (NPV) of pathological complete response, showing that ctDNA-detection-guided escalation and de-escalation studies following neoadjuvant treatment regimens are needed before its role as a treatment guidance can be affirmed.

Background There is increasing evidence that the inactivated influenza vaccine contains immunostimulatory properties that favor cytotoxicity and benefit survival in large population-based studies. This study aimed to determine whether an influenza vaccine was associated with risk of recurrence, overall mortality, and disease-free survival in patients undergoing curative surgery for colorectal cancer. Material and methods We performed a register-based study based in Denmark in the period 2009–2015. The primary outcome was a risk of recurrence, while the secondary outcomes were overall mortality and disease-free survival. Results A total of 9869 patients were included, with 5146 patients receiving an influenza vaccine between one year before and six months after surgery. In a multivariate Cox regression model, there was no association with risk of recurrence (HR 0.94, 95% CI 0.85–1.05), overall mortality (HR 0.95, 95% CI 0.87–1.03), and disease-free survival (HR 1.01, 95% CI 0.94–1.09). In patients receiving the vaccine between six and twelve months before surgery, we found an association to decreased risk of recurrence (HR 0.78, 95% CI 0.67–0.91) but no association with overall mortality (HR 1.04, 95% CI 0.93–1.17) or disease-free survival (HR 0.97, 95% CI 0.88–1.07). Subgroup analysis of patients revealed contradictory results. Conclusion We believe that this study's findings support the need for further clinical studies to investigate the causal effects of the influenza vaccine on oncological outcomes.

The WKFlatNSCS benchmark was convened to evaluate the appropriateness of data and methodsto determine stock status for four sole stocks; North Sea (Sol.27.4), eastern English Channel(Sol.27.7d), Bristol Channel, Celtic Sea (Sol.27.7fg) and southwest of Ireland (Sol.27.7h–k); andone turbot stock, Skagerrak and Kattegat (tur.27.3a).For sole in the North Sea a new index of stock abundance was derived, combining data fromBelgium, Germany and The Netherlands (two survey series using different vessels). An updatedcategory 1 assessment was agreed, continuing to use the Aarts and Poos model previously employed.Reference points were calculated using Eqsim and the forecast settings agreed.For sole in the eastern English Channel, the main objective of the benchmark was to resolve anissue with the plus group in the French landings and commercial landings per unit of effort data.The catch data were revised several times between the data evaluation workshop and the benchmarkmeeting, and at the benchmark meeting, it became clear that there were issues that couldnot be addressed at that time concerning:1. whether the methodology used to estimate ages for length classes where no samples forageing had been taken was appropriate; and,2. whether the calculations of effort being used to raise the sampled discards was beingcalculated appropriately and consistently between the sampled fleet and the total fleet.As a result it was not possible to evaluate whether the catch-at-age data were appropriate for theassessment, or to evaluate the performance of an assessment. A further process following thebenchmark meeting will be set up to complete this work.For Sole in Bristol Channel, Celtic Sea, maturity assumptions and average stock weights-at-agewere revised. An updated category 1 assessment was developed, reducing the reliance on commercialtuning series, and moving to a statistical catch-at-age model (SAM). Reference pointswere calculated using Eqsim and the forecast settings agreed.For Sole in the southwest of Ireland, no appropriate method for evaluating the stock status andtrends was found, due to the sampling only covering a small part of the total fishery, which isnot considered to be representative of the whole area. The Workshop agreed to use category 5 toprovide advice for this stock.For Turbot in Skagerrak and Kattegat, a synthesis of work on stock boundaries within Division3a was presented, indicating that turbot in this area may be part of two stocks, the North Sea andBaltic Sea. A combined index from five surveys (BTS, BITS, IBTS and two Danish national surveys)was used as a tuning index for a SPiCT biomass dynamics model to determine stock status.The Workshop identified the need for future work:• to provide a basis for catch advice for sole in 7d this year;• to collect more sample data from 7h and to identify whether sole in 7h are connected tothose in 7e or 7fg by genetics and movement for a future benchmark;• to investigate whether the management boundaries for turbot in 3a are appropriate basedon current understanding of stock boundaries for a future benchmark.

The prognosis of diffuse large B-cell lymphoma (DLBCL) having MYC rearrangement (MYC-R), including double hit lymphoma (DHL), is poor by standard immunochemotherapy. To evaluate the significance of hematopoietic stem cell transplantation (SCT) for DLBCL with MYC-R, we retrospectively analyzed Japanese SCT registry data. In total, 54 patients with DLBCL with MYC-R were identified from 4336 registered adult DLBCL patients. Detailed clinical and cytogenetic information was obtained for 48 patients. The median age at diagnosis of the 48 patients was 54.5 (range 21-67) years. Twenty-six (54%) patients had MYC-R only (single hit), and 22 (46%) had MYC-R and BCL2, and/or BCL6 rearrangement (double/triple hit). In 12 patients who received auto-SCT during the first complete response (CR), both the 2-year overall survival (OS) and progression-free survival (PFS) rates were 75.0% (95% confidence interval [CI], 40.8%-91.2%). In 20 patients who received auto-SCT after relapsed or refractory state, the 2-year OS and PFS rates were 68.2% (95% CI, 41.9%-84.5%) and 59.6% (95% CI, 35.1%-77.4%), respectively. In 17 patients who received allo-SCT, only 4 patients underwent SCT in CR. The 2-year OS and PFS rates were 29.4% (95% CI, 10.7%-51.1%) and 17.6% (95% CI, 4.3%-38.3%), respectively. The rate of non-relapse mortality at 1 year was 41.2% (95% CI, 17.1%-64.0%) in this group. The outcomes of single hit and double or triple hit were not different. These findings suggest that auto-SCT may be effective for MYC-R DLBCL, including DHL patients of chemosensitive relapsed or refractory state. Since most patients received allo-SCT not in CR, the outcome of allo-SCT was unsatisfactory due to high non-relapse mortality and early relapse. To clarify the role of allo-SCT for MYC-R DLBCL, further accumulation of patients is necessary.

Abstract The purpose of the phase II study is to determine safety, tolerability, MTD and efficacy of SCO-101 in combination with FOLFIRI in patients with FOLFIRI resistant metastatic colorectal cancer. SCO-101 is a low molecular weight molecule (Acidic di-aryl urea). Preclinical studies have shown that it inhibits the SRPK1 kinase which phosphorylates and thereby activates proteins involved in the regulation of alternative splicing. It also degrades the ABCG2 drug efflux pump to which irinotecan (SN38) is a substrate. SCO-101 has successfully passed 4 clinical phase I studies in healthy volunteers and demonstrated to be a safe oral drug with very limited toxicity and good PK parameters. It reverses irinotecan- and several other types of anti-cancer drug resistance in in vitro and in vivo preclinical cancer models. The clinical phase II study: An open-label, non-randomized, prospective study, enrolling patients with acquired FOLFIRI resistant metastatic colorectal cancer. The study consists of two parts: -Part 1 is a dose escalation part based on a traditional 3+3 design. Increasing doses of SCO-101 are investigated in combination with a fixed, patient specific, dose of FOLFIRI. The primary objectives of part 1, is to determine the safety- and toxicity profile and the MTD of SCO-101. The MTD will be the recommended dose of SCO-101 for part 2 (RDP2); -Part 2 is the efficacy part, where up to 25 patients (Simons Two Stage Design) receive the SCO-101 RDP2 in combination with FOLFIRI. Primary objectives are to determine the safety- and toxicity profile and assess objective response rates. A number of potential biomarkers for SCO-101 efficacy will be evaluated. Approval for the study has been obtained and the study will start recruiting patients primo 2020. SCO-101 has two unique mechanisms of action. No other drugs have been presented that inhibits the SRPK1 kinase. Several published preclinical studies have associated high SRPK1 activity with progression of cancer including development of cancer drug resistance. SCO-101 is also the first drug described that degrades the ABCG2 drug efflux pump. If a positive signal is obtained in the clinical study, we will continue with a randomized clinical design allowing for time-dependent end-points, e.g. PFS and OS. Citation Format: Peter Michael Vestlev, Nicklas L. Roest, Jakob HV Schou, Jan Stenvang, Nils Brünner. Clinical phase II study of SCO-101 - an inhibitor of SRPK1 and ABCG2 - restoring sensitivity to FOLFIRI in metastatic FOLFIRI resistant colorectal cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT264.