BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) Study is a prospective analysis of an international database and here we examine front-line treatments and quality-of-life in patients with newly diagnosed Mycosis Fungoides (MF). OBJECTIVES: a) differences in first-line approach according to the TNMB staging; b) parameters related to a first-line systemic approach; c) response rates and quality of life (QoL) measures. PATIENTS AND METHODS: 395 newly diagnosed patients with early-stage MF (IA-IIA) were recruited from 41 centers in 17 countries between 1/1/2015-31/12/2018 following central clinicopathological review. RESULTS: First-line therapy was skin directed therapy (SDT) (81.6%) whilst a smaller percentage (44 cases;11.1%) received systemic therapy. Expectant observation was 7.3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA: 6%; IB: 14%; IIA:20%; IA-IB vs IIA: p<0.0001), presence of plaques (T1a+T2a: 5%; T1b+T2b: 17%; p<0.001), higher mSWAT (10: 15%; <=10: 7%; p=0.01) and folliculotropic MF (FMF) (24% vs 12%; p=0.001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs T1a/T2a: OR: 3.07) and FMF (OR: 2.82). The overall response rate (ORR) to first-line SDT was 73% whilst the ORR to first-line systemic treatments was lower (57%) (p=0.027). Health related QoL improved significantly in both patients with responsive and stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices and that SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently

PURPOSE: To report outcomes of yttrium-90 ((90)Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with chi(2) tests. Survival after diagnosis and after treatment was assessed by Kaplan-Meier method. RESULTS: Grade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21-37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8-13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after (90)Y radioembolization (4%). CONCLUSIONS: This study provides observational data of treatment outcomes after (90)Y radioembolization in patients with unresectable ICC.

OBJECTIVE: As a fractionated course of radiotherapy proceeds tumour shrinkage leads to resolution of hypoxia and the initiation of accelerated proliferation of radioresistant cancer cells with better repair capacity. We hypothesise that, in tumours with significant hypoxia, improved tumour control could be achieved with biphasic fractionation schedules that either use acceleration after 3-4 weeks of conventional radiotherapy or deliver a higher proportional dose towards the end of a course of treatment. We conducted a modelling study based on the concept of biological effective dose (BED) comparing such novel regimens with conventional fractionation. METHODS: The comparator conventional fractionation schedule 70 Gy in 35 fractions delivered over 7 weeks was tested against the following novel regimens, both of which were designed to be isoeffective in terms of late normal tissue toxicity.40 Gy in 20 fractions over 4 weeks followed by 22.32 Gy in 6 consecutive daily fractions (delayed acceleration)30.4 Gy in 27 fractions over 4 weeks followed by 40 Gy in 15 fractions over 3 weeks (temporal dose redistribution)The delayed acceleration regimen is exactly identical to that of the comparator schedule over the first 28 days and the BED gains with the novel schedule are achieved during the second phase of treatment when reoxygenation is complete. For the temporal redistribution regimen, it was assumed that the reoxygenation fraction progressively increases during the first 4 weeks of treatment and an iterative approach was used to calculate the final tumour BED for varying hypoxic fractions. RESULTS: Novel fractionation with delayed acceleration or temporal fractionation results in tumour BED gains equivalent to 3.5-8 Gy when delivered in 2 Gy fractions. CONCLUSION: In hypoxic tumours, novel fractionation strategies result in significantly higher tumour BED in comparison to conventional fractionation. ADVANCES IN KNOWLEDGE: We demonstrate that novel biphasic fractionation regimens could overcome the effects of tumour hypoxia resulting in biological dose escalation.

The Christie NHS Foundation Trust is a leader in adapting patient care in response to treatment advances and new patient-centred care/efficiency initiatives. Due to extended waiting times in cancer clinics, The Christie developed an at-home treatment service to help reduce the pressure on clinics and improve patient experience. This article provides a detailed examination of the requirements necessary to successfully develop a home service for the delivery of systemic anticancer treatment. The authors discuss the criteria used to identify suitable at-home treatments, as well as necessary resources and equipment. The success of the Christie at Home service was examined using a patient survey to assess the standard of this care. Details are given regarding the challenges of implementing a homecare service and potential future challenges. As an example, systemic treatment with eribulin as a 'Christie at Home' therapy demonstrates the practicalities of introduction of new therapies in a homecare service.

Introduction In the CASSINI study, rivaroxaban thromboprophylaxis significantly reduced primary venous thromboembolism (VTE) endpoints during the intervention period, but several thromboembolic events designated as secondary efficacy endpoints were not included in the primary analysis. This study was aimed to evaluate the full impact of rivaroxaban thromboprophylaxis on all prespecified thromboembolic endpoints occurring on study. Methods CASSINI was a double-blind, randomized, placebo-controlled study in adult ambulatory patients with cancer at risk for VTE (Khorana score /=2). Patients were screened at baseline for deep-vein thrombosis (DVT) and randomized if none was found. The primary efficacy endpoint was a composite of lower extremity proximal DVT

BACKGROUND: Inclusion of all patients with advanced biliary tract cancer (aBTC), irrespective of anatomic location, in prospective trials, is debated. Survival rates from landmark analysis offer more relevant information once patients have survived for some time. AIM: assess survival impact of BTC anatomic site origin and landmark survival (LS). PATIENTS AND METHODS: Patients enrolled into prospective first-line aBTC clinical trials were included. OS was analysed using Cox-proportional-hazard-regression; LS and 95% confidence intervals (CIs) were calculated. RESULTS: Overall: 1333 patients included (Jan 97-Dec 15); median age 63-years (range 23-85); 46%-male; 84%-ECOG-PS0/1; 25%-locally-advanced (LA), 72%-metastatic, 3%-not reported (NR); gallbladder-(GBC): 385 (29%), cholangiocarcinoma not-specified-(CCA-NS): 363 (27%), extrahepatic-(EHC): 247 (19%), intrahepatic-(IHC): 209 (16%), ampulla: 53 (4%), 76 (6%) NR. Treatment was mono-chemotherapy: 310-(23%), cisplatin/gemcitabine: 482-(36%), other combination: 520-(39%), NR: 21-(2%). Median OS: 10.2-months (95%-CI 9.6-10.9). All sites (treatment-adjusted) had decreased risk of death vs GBC: EHC-(P<.001), IHC-(P<.002), CCA-NS-(P<.003), ampulla-(P=.003). This reduced risk vs GBC was maintained in those receiving cisplatin/gemcitabine in EHC-(P<.001) and IHC-(P<.001), but not in CCA-NS-(P=.82) or ampulla-(P=.96). Probabilities of surviving an additional year given survival to 1, 2, 3, and 4 years post-trial registration were 37%, 45%, 61%, and 63% respectively. For patients who survived 1 year; those receiving combination therapy vs mono (P=.008) (acknowledging potential selection bias), and those with IHC and CCA-NS vs GBC had better LS (both P<.05). Metastatic stage vs LA was associated with shorter LS (P=.002). ECOG-PS and gender had no evidence of effect on LS (P.05

We compared the International Prognostic Index (IPI), Revised (R)-IPI and age-adjusted (aa)-IPI as prognostic indices for patients with diffuse large B-cell lymphoma (DLBCL) in the UK National Cancer Research Institute (NCRI) R-CHOP 14 versus 21 trial (N = 1080). The R-IPI and aa-IPI showed no marked improvement compared to the IPI for overall and progression-free survival, in terms of model fit or discrimination. Similar results were observed in exploratory analyses incorporating the Grupo Espanol de Linfomas/Transplante de Medula Osea (GELTAMO)-IPI, where baseline beta2-microglobulin data were available (N = 655). Although our findings support current use of the IPI, a novel prognostic tool to better delineate a high-risk DLBCL group in the rituximab era is needed.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857. FINDINGS: Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6.9 months (IQR 2.8-10.9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2.7 months [95% CI 1.6-4.2] vs 1.4 months [1.4-1.6]; hazard ratio 0.37; 95% CI 0.25-0.54; one-sided p<0.0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths. INTERPRETATION: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. FUNDING: Agios Pharmaceuticals.

Gemcitabine/cisplatin is standard of care for first-line treatment of patients with advanced biliary tract cancer (aBTC); new treatments are needed. NUC-1031 is designed to overcome key cancer resistance mechanisms associated with gemcitabine. The tolerability/efficacy signal of NUC-1031/cisplatin in the Phase Ib ABC-08 study suggested that this combination may represent a more efficacious therapy than gemcitabine/cisplatin for patients with aBTC, leading to initiation of the global NuTide:121 study which will include 828 patients /=18 years with untreated histologically/cytologically-confirmed aBTC (including cholangiocarcinoma