The impact of the high emergency lung transplantation program in cystic fibrosis in France: insight from a comparison with Canada

IntroductionFrance implemented a high emergency lung transplantation (HELT) program nationally in 2007. A similar program does not exist in Canada. The objectives of our study were to compare health outcomes within France as well as between Canada and France before and after the HELT program in a population with Cystic Fibrosis (CF).MethodsThis population-based cohort study utilised data from the French and Canadian CF registries. A cumulative incidence curve assessed time to transplant with death without transplant as competing risks. The Kaplan-Meier method was used to estimate post-transplant survival.ResultsBetween 2002 and 2016, there were 1075 (13.0%) people with CF in France and 555 (10.2%) people with CF in Canada who underwent lung transplantation. The proportion of lung transplant increased in France after the HELT program was initiated (4.5% versus 10.1%) whereas deaths pre-transplant decreased from 85.3% in the pre-HELT to 57.1% in the post-HELT period. Between 2008–2016, people in France were significantly more likely to receive a transplant (Hazard Ratio (HR) 1.56, 95% CI 1.37–1.77, p<0.001) than die (HR 0.55, 95% CI 0.46–0.66, p<0.001) compared to Canada. Post-transplant survival was similar between the countries and there was no difference in survival when comparing pre- and post-HELT period in France.ConclusionFollowing the implementation of the HELT program, people living with CF in France were more likely to receive a transplant than die. Post-transplant survival in the post-HELT period in France did not change compared to the pre-HELT period, despite potentially sicker patients being transplanted, and is comparable to Canada.

Testosterone recovery after androgen deprivation therapy in prostate cancer: building a predictive model

Purpose: To analyze variability, associated factors, and the design of nomograms for individualized testosterone recovery after androgen deprivation therapy (ADT) withdrawal.Methods: A longitudinal study was performed on 208 patients in 2003-2019 period. The castrate and normogonadic levels were defined as testosterone, 0.50 and 3.50 ng/ml respectively. Cumulative incidence curve describes testosterone recovery. A univariate and multivariate analysis was performed to predict testosterone recovery with the candidate prognostic factors: PSA at diagnosis, Clinical stage, biopsy Gleason score, age at cessation of ADT, duration of ADT, primary therapy for patients, and LHRH agonist. Results: The median follow­up of the study was 80 months, interquartile range (49,99). The 25% and 81% of patients did not recover the castrate and normogonadic level, respectively. Months of ADT and age at ADT withdrawal were significant predictors for testosterone recovery. We built two nomograms of testosterone estimation recovery at 12, 24, 36 and 60 months. The castration recovery model shows good calibration. The c-index was 0.677, with areas under the ROC­curve (AUC) of 0.74, 0.78, 0.78 and 0.78, at 12, 24, 36 and 60 months, respectively. The normogonadic recovery model had an overestimation of high probabilities. The c­index was 0.683, with AUC values of 0.81, 0.71, 0.71 and 0.70 at 12, 24, 36 and 60 months, respectively.Conclusion: Depending on the age of patients and time of treatment, clinicians can discontinue ADT to maintain castrate levels without treatment with enough confidence, or even recover testosterone to normogonadic levels in short courses of treatment with high probabilities.

Safety of Influenza Vaccine in Patients With Cancer Receiving Pembrolizumab

PURPOSE: There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population. PATIENTS AND METHODS: We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison. RESULTS: Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older ( P = .002) and received more cycles of pembrolizumab ( P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037). CONCLUSION: Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.

Surveillance strategy based on the incidence and patterns of recurrence after curative endoscopic submucosal dissection for early gastric cancer.

87 Background: To suggest an appropriate surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancers, based on incidence and patterns of local, metachronous, and extragastric recurrence. Methods: Between 2003 and 2011, 1497 consecutive patients with 1539 differentiated-type early gastric cancers meeting absolute or expanded indication criteria underwent curative ESD. They were followed up with esophagogastroduodenoscopy (EGD) and abdominal computed tomography (CT) under a standardized surveillance protocol. Long-term outcomes were analyzed for 1306 patients with at least 1 year’s follow-up. Results: Incidences of residual and synchronous lesions detected within 1 year were 0.13 % and 0.87 %, respectively. During median 47 months of follow-up, there was 1 local recurrence (0.08 %; early gastric cancer) and 47 cases of metachronous recurrence (3.6 %; 44 early gastric cancers, 3 pT2 advanced gastric cancers); all were curatively treated. During a 5-year surveillance, the cumulative incidence curve of metachronous recurrence increased linearly. Median time from ESD to metachronous recurrence was 30 months. There were 2 extragastric recurrences (0.15 %) in lymph nodes, at 5 and 4 years, respectively, after curative ESD for absolute and expanded indications. The patient with the expanded indications underwent a palliative operation and died of gastric cancer progression. Conclusions: There was a constant incidence rate of metachronous recurrence during a 5-year surveillance period and there was extragastric recurrence at least 4 years after ESD of early gastric cancer even for absolute indications. Therefore, annual or biannual surveillance EGD and abdominal CT might be necessary for at least 5 years after curative ESD for early gastric cancers, with absolute as well as expanded indications.

Double Umbilical Cord Blood Transplantation Offers Stable Donor Engraftment and The Prospect Of Cure In Adult Patients With High-Risk Hematologic Malignancies

Allogeneic stem cell transplantation (allo-SCT) remains the main therapeutic option for patients with high-risk hematologic malignancies, albeit with the requirement of a properly matched and timely available donor. Dual-unit umbilical cord blood transplantation (dUCBT) has become an alternative modality, which offers immediate access to allo-SCT for most adult patients who lack an appropriate volunteer donor. We retrospectively analyzed the outcomes of consecutive dUCBT procedures that were undertaken by our center over a seven-year period, with focus on factors affecting engraftment and survival. Between 2006 and 2013, 40 patients underwent dUCBT at a median age of 37 years (range, 16-60) for various hematologic malignancies (acute myeloid leukemia: 22, myelodysplastic syndrome: 5, chronic myelogenous leukemia: 2, acute lymphoblastic leukemia: 6, mixed-phenotype acute leukemia: 2, plasmacytoid dendritic cell neoplasm: 1, hepatosplenic T cell lymphoma: 1, chronic lymphocytic leukemia: 1). The majority of patients (73.7%) had advanced or intermediate-phase disease at the time of transplantation, with a median time from diagnosis to transplant of 17.7 months (range:3.1-92.3). Recipient body weight ranged from 48 to 110 kg (median, 73). The conditioning regimen was myeloablative in 33 (82.5%) patients (busulfan-based in 22, and total body irradiation-based in 11 cases). Antithymocyte globulin was not administered during conditioning, with the exception of one case. Most units (55/80, 68.75%) were 4/6 antigen matched to recipient at HLA-A, -B, and -DRB1 loci, and the remaining were 5/6 matched. By retrospective high-resolution typing for class I HLA alleles, histocompatibility was demoted in 62.3% of units. By additional allele-level typing at HLA-C and -DQB1 loci, the degree of compatibility varied from 8/10 to 3/10, with 80.5% of the units being ≤6/10 matched to the patient. The median dose of cryopreserved total nucleated cells (TNC) per unit was 2.53 x 107/kg (range, 1.09-5.66). At infusion, patients received in total a median of 4.55 x 107 TNC/kg (range, 2.65-9.3) and 1.7 x 105 CD34+ cells/kg (range, 0.54-5.14) from both units. The cumulative incidence (CI) of neutrophil engraftment was 92.5% (37/40 patients), with achievement of an absolute neutrophil count (ANC) greater than 500/uL at a median of 20 days (range, 12-52) (Figure 1). Platelet recovery (>50x109/L) occurred at a CI of 63.2%, and a median time of 84 days (range, 32-363). No influence of cell dose (TNC or CD34+) or of the degree of HLA match on the incidence and kinetics of engraftment could be detected. Acute graft-versus-host disease (aGVHD) of grades II-IV and III-IV developed in 85% and 12.65% of patients, respectively. The CI of chronic GVHD was 31% (extensive in 54.5% of cases). There was a statistical trend for increased incidence of cGVHD with <6/10 HLA match at the allele level (p=0.068; HR, 3.35; 95% confidence interval [ci], 0.92-12.24). Non-relapse mortality (NRM) reached 43.1% (95% ci, 27.0-58.2) at 10.3 months, but no case of NRM was noted thereafter (Figure 2). Major causes of NRM were infection/sepsis (n=11), GVHD (n=3), and engraftment failure (n=3). The CI of relapse was 22.7% (95% ci, 10.7-37.5). Relapse was the cause of death of 6 patients. With a median follow-up of 30 months (range, 2-84), overall (OS) and disease-free survival (DFS) rates at 2 years were 36.5% (95% ci, 21-52) and 34.2% (95% ci, 19.3-49.6), respectively (Figure 3). Sixteen of 40 patients are alive and disease-free for a median time of 30 months from transplant. Age ≤37 years, recipient CMV seronegativity, and early disease phase at transplant were associated with improved OS in univariate analysis. Age remained as the only independent risk factor for OS in multivariate analysis of OS (p=0.022). Age ≤37 years was also found to be associated with reduced NRM (p=0.055), and favorable DFS (p=0.04).Figure 1Cumulative Incidence curve of neutrophil (ANC>500/uL) engraftment.Figure 1. Cumulative Incidence curve of neutrophil (ANC>500/uL) engraftment.Figure 2Cumulative Incidence curve of non-relapse mortality.Figure 2. Cumulative Incidence curve of non-relapse mortality.Figure 3Overall Survival (Kaplan-Meier curve).Figure 3. Overall Survival (Kaplan-Meier curve). In conclusion, dUCBT can lead to stable donor engraftment even across multiple HLA disparities and can overcome the barrier of cell dose. Despite considerable early mortality, dUCBT offers the possibility of long-term survival in about one third of adult patients with poor-prognosis hematologic malignancies, for whom allo-SCT would not be otherwise feasible. Disclosures: No relevant conflicts of interest to declare.

Incidence of Intraoperative Hypotension as a Function of the Chosen Definition

Background Intraoperative hypotension (IOH) is a common side effect of general anesthesia and has been reported to be associated with adverse perioperative outcomes. These associations were found using different definitions for IOH. It is unknown whether the incidences of IOH found with those different definitions are comparable. The authors aimed to describe the relation between the chosen definition and incidence of IOH. Methods First, a systematic literature search was performed to identify recent definitions of IOH that have been used in the anesthesia literature. Subsequently, these definitions were applied to a cohort of 15,509 consecutive adult patients undergoing noncardiac surgery during general anesthesia. The incidence of IOH according to the different threshold values was calculated, and the effect of a defined minimal duration of a hypotensive episode was studied. Results Many different definitions of IOH were found. When applied to a cohort of patients, these different definitions resulted in different IOH incidences. Any episode of systolic blood pressure below 80 mmHg was found in 41% of the patients, whereas 93% of the patients had at least one episode of systolic blood pressure more than 20% below baseline. Both definitions are frequently used in the literature. The relation between threshold values from the literature and IOH incidence shows an S-shaped cumulative incidence curve, with occurrence frequencies of IOH varying from 5% to 99%. Conclusions There is no widely accepted definition of IOH. With varying definitions, many different incidences can be reproduced. This might have implications for previously described associations between IOH and adverse outcomes.