The socioeconomic impact of cancer on patients and their relatives: Organisation of European Cancer Institutes task force consensus recommendations on conceptual framework, taxonomy, and research directions.

Loss of income and out-of-pocket expenditures are important causes of financial hardship in many patients with cancer, even in high-income countries. The far-reaching consequences extend beyond the patients themselves to their relatives, including caregivers and dependents. European research to date has been limited and is hampered by the absence of a coherent theoretical framework and by heterogeneous methods and terminology. To address these shortages, a task force initiated by the Organisation of European Cancer Institutes (OECI) produced 25 recommendations, including a comprehensive definition of socioeconomic impact from the perspective of patients and their relatives, a conceptual framework, and a consistent taxonomy linked to the framework. The OECI task force consensus statement highlights directions for future research with a view towards policy relevance. Beyond descriptive studies into the dimension of the problem, individual severity and predictors of vulnerability should be explored. It is anticipated that the consensus recommendations will facilitate and enhance future research efforts into the socioeconomic impact of cancer and cancer care, providing a crucial reference point for the development and validation of patient-reported outcome instruments aimed at measuring its broader effects.

Real-World Impact of Adjuvant Anti-HER2 Treatment on Characteristics and Outcomes of Women With HER2-Positive Metastatic Breast Cancer in the ESME Program.

BACKGROUND: Although adjuvant cancer treatments increase cure rates, they may induce clonal selection and tumor resistance. Information still lacks as whether (neo)adjuvant anti-HER2 treatments impact the patterns of recurrence and outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC). We aimed to assess this in the large multicenter ESME real-world database. PATIENTS AND METHODS: We examined the characteristics and outcomes (overall survival (OS) and progression-free survival under first-line treatment (PFS1)) of HER2+ patients with MBC from the French ESME program with recurrent disease, as a function of the previous receipt of adjuvant trastuzumab. Multivariable analyses used Cox models adjusted for baseline demographic, prognostic factors, adjuvant treatment received, and disease-free interval. RESULTS: Two thousand one hundred and forty-three patients who entered the ESME cohort between 2008 and 2017 had a recurrent HER2+ MBC. Among them, 56% had received (neo)adjuvant trastuzumab and 2.5% another anti-HER2 in this setting. Patients pre-exposed to trastuzumab were younger, had a lower disease-free interval, more HR-negative disease and more metastatic sites. While the crude median OS appeared inferior in patients exposed to adjuvant trastuzumab, as compared to those who did not (37.2 (95%CI 34.4-40.3) versus 53.5 months (95% CI: 47.6-60.1)), this difference disappeared in the multivariable model (HR = 1.05, 95%CI 0.91-1.22). The same figures were observed for PFS1. CONCLUSIONS: Among patients with relapsed HER2+ MBC, the receipt of adjuvant trastuzumab did not independently predict for worse outcomes when adjusted to other prognostic factors.

Retrospective analysis of the safety of peripherally inserted catheters versus implanted port catheters during first-line treatment for patients with diffuse large B-cell lymphoma.

OBJECTIVES: Both peripherally inserted central catheters (PICCs) and implanted port catheters (PORTs) are commonly used for the delivery of immunochemotherapy. We compared the safety of the two types of devices in a homogeneous and monocentric population of diffuse large B-cell lymphoma (DLBCL) patients who were treated with first-line immunochemotherapy by evaluating the numbers of catheter-related venous thromboses (VTs) and infections that occurred in the six months after implantation according to the type of device. METHODS: Using a propensity score, the adjusted relative risk (ARR) between the type of catheter and the occurrence of catheter-related complications (infection and/or VT) of interest was retrospectively determined. RESULTS: 479 patients were enrolled (266 PORTs/213 PICCs), and 26 VTs (5.4%) and 30 infections (6.3%) were identified in the period following PICC/PORT implantation. The adjusted relative risk (ARR) of catheter-related complications (infection and/or VT) according to the type of device was 2.6 (95% CI =1.3-5.9, p = .0075). This risk increase associated with the PICC device was significant for both infections (ARR = 3.2; 95% CI = 1.3-10.9) and thrombosis (ARR = 4; 95% CI = 1.5-11.6). CONCLUSION: Our study supports the preferential use of PORTs for the first line of treatment for DLBCL patients.

Are patients living far from hospital at higher risk of late adjuvant chemotherapy for colon cancer?

AIMS: Late adjuvant chemotherapy (aCT) administration after colectomy (>56 d) is known to be associated with impaired prognosis. We aim to identify risk factors associated with late aCT, especially the travel time between patients' home and hospital. METHODS: We performed a retrospective monocentre cohort study. Patients included had a colectomy for a stage III or high risk stage II colon cancer between 2009 and 2015 performed at a French university hospital. Risk factors for late aCT were identified using a fractional polynomial logistic regression. RESULTS: Ninety-four patients were included. The risk of late aCT was associated with travel time length, emergent colectomy, the need for scheduled care before aCT, and length of time between colectomy and postoperative multidisciplinary meeting advising aCT. CONCLUSION: Our study suggests that, in patients with colon cancer, factors unrelated to disease severity and complexity could be associated with a higher risk of late aCT.

Deprived social status is associated with decreased use of oral chemotherapy in patients with metastatic colorectal cancer: A retrospective cohort study on administrative databases in a French University Hospital.

Factors associated with the choice of oral versus intravenous CT are not clearly established. Our purpose was to evaluate the influence of social status and home distance to hospital on the use of oral CT in patients with metastatic colorectal cancer (mCRC). This retrospective single-center study included mCRC patients between 2011 and 2017. Patient social status was assessed by European Deprivation Index (EDI) and home distance to the hospital was calculated. Univariable and multivariable logistic regression analyses were performed. One hundred and seventy-five mCRC patients were included, with 71 receiving oral CT. Most deprived patients received less oral CT (OR 0.5 [0.26, 0.96], p = .039). No association was found for road distance. Previous use of adjuvant oral CT was associated with oral CT in mCRC (OR 2.65 [1.06, 6.66], p = .038). Our results suggest that deprived social status is a factor associated with decreased use of oral CT in patients with mCRC. Clinical trial registration: no registration.

Real-world Evaluation of Oral Vinorelbine in the Treatment of Metastatic Breast Cancer: An ESME-MBC Study.

BACKGROUND/AIM: Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. PATIENTS AND METHODS: Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. RESULTS: A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. CONCLUSION: Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.

Impact of age at diagnosis of metastatic breast cancer on overall survival in the real-life ESME metastatic breast cancer cohort.

BACKGROUND: Young age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups (<40, 40 to 60 and > 60 years(y)). METHODS: ESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014. RESULTS: Among 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were <40, 40-60 and > 60 y respectively. Pts <40 had significantly more aggressive presentations than other age groups: more frequent HER2+ (25.7 vs 15.3% in >60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts <40, 40-60 and > 60y, respectively (p < 0.0001). Compared to pts <40y, older pts had a statistically significant higher risk of death (all causes of death included), although of limited clinical value (HR = 1.1, IC 95%:1.01-1.20). There was a significant trend for better OS in pts <40y with HER2+ and luminal diseases. A possible explanation is a greater use of anti-Her2 therapies as first-line treatments: 86.6, 81.9 and 74.9% for pts <40, 40-60 and > 60y, respectively (p < 0.0001). CONCLUSION: Although young age seems associated with more aggressive presentations at diagnosis of MBC, it has no deleterious effect on OS in this large series.

Patients' perception and attitude to totally implantable venous access for urologic or digestive cancer: A cross-sectional study.

INTRODUCTION: Totally implanted venous access (TIVA) improves the safety and welfare of patients treated with cancer chemotherapy (CCT). We aimed to evaluate patients' perception of TIVA placement, TIVA use, and information on TIVA, and to assess the association between patients' perception and their attitude regarding a potential TIVA re-implantation. METHODS: We conducted a single center cross-sectional survey in a university hospital in Northern France. Patients included were consecutive urologic or digestive cancer inpatients admitted for a CCT cycle via TIVA between April 9th and May 9th 2014. We analyzed patients' satisfaction, experience, and attitude, especially when requiring potential TIVA re-implantation under local anesthesia (LA), using a standardized questionnaire and medical records. We analyzed risk factors for refusing potential TIVA re-implantation under LA using multivariate logistic regression. RESULTS: Eighty-one patients were interviewed (no refusals), including 57 with a TIVA device placed under LA in our university hospital. Among them, 52/57 (91%) reported satisfactory TIVA placement, but respectively 21/57 (37%) and 18/57 (32%) complained of painful or uncomfortable TIVA placement; 51/57 (89%) were satisfied with care provided during CCT cycles. Risk factors for refusing potential re-implantation under LA were: TIVA placement considered painful (P=0.012) or uncomfortable (P=0.038) and dissatisfaction with care provided during CCT cycles (P=0.028). DISCUSSION: We show that despite good overall satisfaction regarding TIVA, some aspects were less positive and warrant improvement actions. It suggests that these actions could not only improve patients' experience of TIVA use but could also facilitate continuation of treatment in the long term.

The impact of a patient's social status on the cost of vaginal deliveries: an observational study in a French university hospital.

INTRODUCTION: We aimed to assess the association between a patient's social status and the cost of stay for a single uncomplicated vaginal delivery. Currently, few data have been reported. MATERIAL AND METHODS: We conducted an observational study with data retrieved from the medical and administrative databases of a university hospital in North-West France. We included all patients admitted in 2014 and classified in either Diagnosis-Related Group (DRG) « Single uncomplicated vaginal deliveries in a primiparous patient ¼ or DRG « Single uncomplicated vaginal deliveries in a multiparous patient ¼. Criteria defining poor social status were: a specific healthcare benefit in relation to low income or for foreign undocumented patients, and/or a consultation with a social worker during the hospital stay except if no social problem was diagnosed. We compared the cost of stay between patients with poor social status and patients with good social status using a multivariate median regression stratified on parity, and adjusted for age, gestational age and neonatal hospitalization. RESULTS: Among 686 primiparous patients, 21% had poor social status, which was associated with an increase in the median cost of stay (+€475; 95% CI [+334 to +616]), mostly explained by a 1-day increase in the median length of stay.Among 899 multiparous patients, 29% had poor social status, which was not associated with the cost of stay. DISCUSSION: Social status had an impact on the cost of vaginal deliveries in primiparous patients. Our findings suggest a need to redefine the DRG classification according to patients' social status.

Totally implanted venous access-associated adverse events in oncology: Results from a prospective 1-year surveillance programme.

INTRODUCTION: During the last decade, most studies on totally implanted venous access-associated adverse events (TIVA-AE) were conducted retrospectively and/or were based on a limited sample size. The aim of our survey was two-fold: to estimate the incidence of TIVA-AE and to identify risk factors in patients with cancer. METHODS: Data from our routine surveillance of TIVA-AE were collected prospectively between October 2009 and January 2011 in two oncology referral centers in Northern France. The open cohort under surveillance during the same time period was reconstituted retrospectively using data from the hospital information systems. Incidences of first TIVA-AE per 1000 TIVA-days were calculated. Risk factors were identified using multivariate logistic regressions. RESULTS: We included 2286 cancer patients, corresponding to 582,347 TIVA-days. Among the 133 first TIVA-AE observed (incidence 0.23 per 1000 TIVA-days [0.19-0.27]), there were 50 infectious AE (incidence 0.09 [0.06-0.11]) and 83 non-infectious AE (incidence 0.14 [0.11-0.17]). Compared to non-metastatic solid cancers, metastatic cancers (aOR=2.3 [0.9-6.0]), and hematologic malignancies (aOR=3.2 [1.1-8.8]) tended to be associated with a higher risk of infectious TIVA-AE (P=0.087). Solid cancer type was associated with non-infectious TIVA-AE (P=0.030), especially digestive cancers. DISCUSSION: We report accurate estimations of TIVA-AE incidences in one of the largest populations among previously published studies. As in previous studies, metastatic cancers and hematologic malignancies tended to be associated with a higher risk of infectious TIVA-AE. Further studies are warranted to confirm the effect of digestive cancers.

Predictive value of 18F-FDG PET/CT in adults with T-cell lymphoblastic lymphoma: post hoc analysis of results from the GRAALL-LYSA LLO3 trial.

PURPOSE: We examined whether FDG PET can be used to predict outcome in patients with lymphoblastic lymphoma (LL). METHODS: This was a retrospective post hoc analysis of data from the GRAAL-LYSA LL03 trial, in which the treatment of LL using an adapted paediatric-like acute lymphoblastic leukaemia protocol was evaluated. PET data acquired at baseline and after induction were analysed. Maximum standardized uptake values (SUVmax), total metabolic tumour volume and total lesion glycolysis were measured at baseline. The relative changes in SUVmax from baseline (ΔSUVmax) and the Deauville score were determined after induction. RESULTS: The population analysed comprised 36 patients with T-type LL. SUVmax using a cut-off value of ≤8.76 vs. >8.76 was predictive of 3-year event-free survival (31.6% vs. 80.4%; p = 0.013) and overall survival (35.0% vs. 83.7%; p = 0.028). ΔSUVmax using a cut-off value of ≤80% vs. >80% tended also to be predictive of 3-year event-free survival (40.0% vs. 76.0%; p = 0.054) and overall survival (49.2% vs. 85.6%; p = 0.085). Total metabolic tumour volume, baseline total lesion glycolysis and response according to the Deauville score were not predictive of outcome. CONCLUSIONS: A low initial SUVmax was predictive of worse outcomes in our series of patients with T-type LL. Although relatively few patients were included, the study also suggested that ΔSUVmax may be useful for predicting therapeutic efficacy.

First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.

BACKGROUND: High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids. METHODS: We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1:1) to receive either oral prednisone alone, 1·0 or 1·5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0·5 or 1·0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589. FINDINGS: Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38·4-71·7; p<0·0001. This difference corresponded to a relative risk of success of 2·61 (95% CI 1·71-3·99, p<0·0001), corresponding to 1·82 patients (95% CI 1·39-2·60) who would need to be treated with rituximab plus prednisone (rather than prednisone alone) for one additional success. No patient died during the study. More severe adverse events of grade 3-4 were reported in the prednisone-alone group (53 events in 29 patients; mean 1·20 [SD 1·25]) than in the rituximab plus prednisone group (27 events in 16 patients; mean 0·59 [1·15]; p=0·0021). The most common of these events in both groups were diabetes and endocrine disorder (11 [21%] with prednisone alone vs six [22%] with rituximab plus prednisone), myopathy (ten [19%] vs three [11%]), and bone disorders (five [9%] vs five [19%]). INTERPRETATION: Data from our trial suggest that first-line use of rituximab plus short-term prednisone for patients with pemphigus is more effective than using prednisone alone, with fewer adverse events. FUNDING: French Ministry of Health, French Society of Dermatology, Roche.

Copy number variations in DCC/18q and ERBB2/17q are associated with disease-free survival in microsatellite stable colon cancer.

We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4-year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5-4.1) and 3.1 (95% CI, 1.2-8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II-III MSS colon cancer.

Is the Risk of Wound Infection Related to Bilateral Internal Thoracic Artery Graft Potentiated by Age?

BACKGROUND: Older age and the use of bilateral internal thoracic artery (ITA) grafting are both considered risk factors for surgical wound infection (SWI) after coronary artery bypass grafting (CABG). The 2014 European Guidelines recommend that bilateral ITA grafting should be considered in patients aged younger than 70 years. Our aim was to investigate interaction between age and the number of ITA grafts. METHODS: All patients aged 18 years and older who had undergone CABG with at least 1 ITA at Rouen University Hospital between 2001 and 2012 were selected. Data regarding surgical procedure (single/bilateral ITA grafting) were extracted from the medical information system. SWI was identified from prospective surveillance of patients according to Centers for Disease Control and Prevention criteria. Independent factors associated with SWI were assessed by logistic regression, and an interaction test between age (≤69 or ≥70 years) and the number of ITA grafts was performed. RESULTS: SWI occurred in 71 of 2,726 patients (2.6%). Bilateral ITA grafting was associated with SWI (adjusted odds ratio [aOR], 2.55; 95% confidence interval, 1.51 to 4.30). After fitting an interaction term between age and number of ITA grafts, the aORs for SWI after bilateral ITA grafting substantially differed between patients aged 69 years and younger (aOR, 1.88; 95% confidence interval, 0.94 to 3.75) and 70 years and older (aOR, 3.52; 95% confidence interval, 1.69 to 7.33). However, this interaction failed to reach statistical significance (p = 0.2213), possibly because of insufficient statistical power (23.5%) despite the large sample size. CONCLUSIONS: Age 70 years and older compared with age 69 years and younger was associated with higher occurrence of SWI after bilateral ITA grafting, but this interaction was not statistically significant. Larger studies are needed to test this interaction.

Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study.

PURPOSE: This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). PATIENTS AND METHODS: This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. RESULTS: The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. CONCLUSION: In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.