Summary 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.
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)).
ESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014.
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).
Although young age seems associated with more aggressive presentations at diagnosis of MBC, it has no deleterious effect on OS in this large series.
•Young age is a poor prognosis factor in early stage breast cancer.•Young age is associated with an aggressive presentation in metastatic breast cancer.•Young age had no impact on overall survivall in metastatic breast cancer.•Oppositely, older women (>60y) had a stightly poorer prognosis at the metastatic stage.
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.
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.
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.
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.
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.
Purpose
Readmission indicators are used around the world to assess the quality of hospital care. We aimed to assess the relevance of this type of indicator in oncology, especially for socially ...deprived patients. Our objectives were (1) to assess the proportion of unplanned hospitalizations (UHs) in cancer patients, (2) to assess the proportion of UHs that were avoidable, i.e., related to poor care quality, and (3) to analyze cancer patients the effect of patients’ deprivation level on the type of UH (avoidable UHs vs. unavoidable UHs).
Methods
In a French university hospital, we selected all hospitalizations over a year for a random sample of cancer patients. Based on medical records, we identified those among UHs due to avoidable health problems. We assessed the association between social deprivation, home-to-hospital distance, or home-to-general practitioner with the type of UH (avoidable vs. unavoidable) via a multivariate binary logit estimation.
Results
Among 2349 hospitalizations (355 patients), there were 383 UHs (16 %), among which 38% were avoidable. Among UHs, the European Deprivation Index was significantly associated with the risk of avoidable UHs, with a lower risk of avoidable UH for patients with medium or high social deprivation.
Conclusion
Our results suggest that the use of UHs rate as a quality indicator is questionable in oncology. Indeed, the majority of UHs were not avoidable. Furthermore, within UHs, those involving patients with medium or high social deprivation are more often unavoidable in comparison with other patients.
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.
Abstract
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.
There is limited real-world information on the impact of adjuvant and neoadjuvant anti-HER2-targeted treatments on patterns of recurrence and outcomes of patients with HER2+ metastatic breast cancer. This article reports on how anti-HER2 targeted treatment in the early setting impacts overall and progression-free survival under first-line treatment of patients with metastatic HER2+ breast cancer.
This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL).
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.
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.
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.
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.
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 (SUV
max
), total metabolic tumour volume and total lesion glycolysis were measured at baseline. The relative changes in SUV
max
from baseline (ΔSUV
max
) and the Deauville score were determined after induction.
Results
The population analysed comprised 36 patients with T-type LL. SUV
max
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). ΔSUV
max
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 SUV
max
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 ΔSUV
max
may be useful for predicting therapeutic efficacy.
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