Management of Febrile Neutropenia - a German Prospective Hospital Cost Analysis in Lymphoproliferative Disorders, Non-Small Cell Lung Cancer, and Primary Breast Cancer

Background: Febrile neutropenia/leukopenia (FN/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. Patients and Methods: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast cancer (PBC) patients. Costs are presented from a hospital perspective. Results: A total of 325 consecutive patients (47% LPD, 37% NSCLC, 16% PBC; 46% women; 38% age >= 65 years) with 68 FN/FL episodes were evaluated. FN/FL occurred in 22% of the LPD patients, 8% of the NSCLC patients, and 27% of the PBC patients. 55 FN/FL episodes were associated with at least 1 hospital stay (LPD n = 34, NSCLC n = 10, PBC n = 11). Mean (median) cost per FN/FL episode requiring hospital care amounted to (sic) 3,950 ((sic) 2,355) and varied between (sic) 4,808 ((sic) 3,056) for LPD, (sic) 3,627 ((sic) 2,255) for NSCLC, and (sic) 1,827 ((sic) 1,969) for PBC patients. 12 FN/FL episodes (LPD n = 9, NSCLC n = 3) accounted for 60% of the total expenses. Main cost drivers were hospitalization and drugs (60 and 19% of the total costs). Conclusions: FN/FL treatment has economic relevance for hospitals. Costs vary between tumour types, being significantly higher for LPD compared to PBC patients. The impact of clinical characteristics on asymmetrically distributed costs needs further evaluation

Case Report: A severe case of immunosuppressant-refractory immune checkpoint inhibitor-mediated colitis rescued by tofacitinib

Immune checkpoint inhibitor therapy for cancer treatment can give rise to a variety of adverse events. Here we report a male patient with metastatic melanoma who experienced life-threatening colitis and duodenitis following treatment with ipilimumab and nivolumab. The patient did not respond to the first three lines of immunosuppressive therapy (corticosteroids, infliximab, and vedolizumab), but recovered well after administration of tofacitinib, a JAK inhibitor. Cellular and transcriptional data on colon and duodenum biopsies shows significant inflammation in the tissue, characterized by a large number of CD8 T cells and high expression of PD-L1. While cellular numbers do decrease during three lines of immunosuppressive therapy, CD8 T cells remain relatively high in the epithelium, along with PD-L1 expression in the involved tissue and expression of colitis-associated genes, indicating an ongoing colitis at that moment. Despite all immunosuppressive treatments, the patient has an ongoing tumor response with no evidence of disease. Tofacitinib might be a good candidate to consider more often for ipilimumab/nivolumab-induced colitis

Trends in overall survival and treatment patterns in two large population-based cohorts of patients with breast and colorectal cancer

Previous studies showed substantial improvement of survival rates in patients with cancer in the last two decades. However, lower survival rates have been reported for older patients compared to younger patients. In this population-based study, we analyzed treatment patterns and the survival of patients with breast cancer (BC) and colorectal cancer (CRC). Patients with stages I- III BC and CRC and diagnosed between 2003 and 2012 were selected from the Netherlands Cancer Registry (NCR). Trends in treatment modalities were evaluated with the Cochran-Armitage trend test. Trends in five-year overall survival were calculated with the Cox hazard regression model. The Ederer II method was used to calculate the five-year relative survival. The relative excess risk of death (RER) was estimated using a multivariate generalized linear model. During the study period, 98% of BC patients aged <75 years underwent surgery, whereas for patients ≥75 years, rates were 79.3% in 2003 and 66.7% in 2012 (p < 0.001). Most CRC patients underwent surgery irrespective of age or time period, although patients with rectal cancer aged ≥75 years received less surgery or radiotherapy over the entire study period than younger patients. The administration of adjuvant chemotherapy increased over time for CRC and BC patients, except for BC patients aged ≥75 years. The five-year relative survival improved only in younger BC patients (adjusted RER 0.95-0.96 per year), and was lower for older BC patients (adjusted RER 1.00, 95% Confidence Interval (CI) 0.98- 1.02, and RER 1.00; 95% CI 0.98-1.01 per year for 65-74 years and ≤75 years, respectively). For CRC patients, the five-year relative survival improved over time for all ages (adjusted RER on average was 0.95 per year). In conclusion, th

Comparison of the fracture resistance of endodontically treated teeth restored with prefabricated posts and composite resin cores with different post lenghts

OBJECTIVE: This study evaluated the fracture strengths of endodontically treated teeth restored with prefabricated posts with different post lengths. MATERIAL AND METHODS: Thirty freshly extracted canines were endodontically treated. They were randomly divided into groups of 10 teeth and prepared according to 3 experimental protocols, as follows; Group 1/3 PP: teeth restored with prefabricated post and composite resin core (Z250) with post length of 5.0mm; Group 1/2 PP and Group 2/3 PP: teeth restored with prefabricated post and composite resin core (Z250) with different combinations of post length of 7.5mm and 10mm, respectively. All teeth were restored with full metal crowns. The fracture resistance (N) was measured in a universal testing machine (crosshead speed 0.5mm/min) at 45 degrees to the tooth long axis until failure. Data were analyzed by one-way analysis of variance (alpha=.05). RESULTS: The one-way analysis of variance demonstrated no significant difference among the different post lengths (P>;.05) (Groups 1/3 PP = 405.4 N, 1/2 PP = 395.6 N, 2/3 PP = 393.8 N). Failures occurred mainly due to core fracture. CONCLUSIONS: The results of this study showed that an increased post length in teeth restored with prefabricated posts did not significantly increase the fracture resistance of endodontically treated teeth

The development of an online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making: a usability and pilot study

An online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making was developed. A two-phase usability test was conducted among 12 couples (N = 22; 2 persons participated without their partner) at risk for hereditary cancer and 15 health care providers. Couples and health care providers expressed similar suggestions for improvements, and evaluated the modified decision aid as acceptable, easy to use, and comprehensible. The final decision aid was pilot tested (N = 16) with paired sample t tests comparing main outcomes (decisional conflict, knowledge, realistic expectations regarding the reproductive options and decision self-efficacy) before (T0), immediately (T1) and 2 weeks after (T2) use of the decision aid. Pilot testing indicated decreased decisional conflict scores, increased knowledge, and improved realistic expectations regarding the reproductive options, at T1 and T2. No effect was found for couples’ decision self-efficacy. The positive findings during usability testing were thus reflected in the pilot study. The decision aid will be further evaluated in a nationwide pretest–posttest study to facilitate implementation in the onco-genetic counselling setting. Ultimately, it is expected that the decision aid will enable end-users to make an informed decision

Crowding by Invisible Flankers

BACKGROUND: Human object recognition degrades sharply as the target object moves from central vision into peripheral vision. In particular, one's ability to recognize a peripheral target is severely impaired by the presence of flanking objects, a phenomenon known as visual crowding. Recent studies on how visual awareness of flanker existence influences crowding had shown mixed results. More importantly, it is not known whether conscious awareness of the existence of both the target and flankers are necessary for crowding to occur. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that crowding persists even when people are completely unaware of the flankers, which are rendered invisible through the continuous flash suppression technique. Contrast threshold for identifying the orientation of a grating pattern was elevated in the flanked condition, even when the subjects reported that they were unaware of the perceptually suppressed flankers. Moreover, we find that orientation-specific adaptation is attenuated by flankers even when both the target and flankers are invisible. CONCLUSIONS: These findings complement the suggested correlation between crowding and visual awareness. What's more, our results demonstrate that conscious awareness and attention are not prerequisite for crowding

High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes 20-Year Follow-up of a Phase 3 Randomized Clinical Trial:20-Year Follow-up of a Phase 3 Randomized Clinical Trial

Importance: Trials of adjuvant high-dose chemotherapy (HDCT) have failed to show a survival benefit in unselected patients with breast cancer, but long-term follow-up is lacking. Objective: To determine 20-year efficacy and safety outcomes of a large trial of adjuvant HDCT vs conventional-dose chemotherapy (CDCT) for patients with stage III breast cancer. Design, Setting, and Participants: This secondary analysis used data from a randomized phase 3 multicenter clinical trial of 885 women younger than 56 years with breast cancer and 4 or more involved axillary lymph nodes conducted from August 1, 1993, to July 31, 1999. Additional follow-up data were collected between June 1, 2016, and December 31, 2017, from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from February 1, 2018, to October 14, 2019. Interventions: Participants were randomized 1:1 to receive 5 cycles of CDCT consisting of fluorouracil, 500 mg/m 2, epirubicin, 90 mg/m 2, and cyclophosphamide, 500 mg/m 2, or HDCT in which the first 4 cycles were identical to CDCT and the fifth cycle was replaced by cyclophosphamide, 6000 mg/m 2, thiotepa, 480 mg/m 2, and carboplatin, 1600 mg/m 2, followed by hematopoietic stem cell transplant. Main Outcomes and Measures: Main end points were overall survival and safety and cumulative incidence risk of a second malignant neoplasm or cardiovascular events. Results: Of the 885 women in the study (mean [SD] age, 44.5 [6.6] years), 442 were randomized to receive HDCT, and 443 were randomized to receive CDCT. With 20.4 years median follow-up (interquartile range, 19.2-22.0 years), the 20-year overall survival was 45.3% with HDCT and 41.5% with CDCT (hazard ratio, 0.89; 95% CI, 0.75-1.06). The absolute improvement in 20-year overall survival was 14.6% (hazard ratio, 0.72; 95% CI, 0.54-0.95) for patients with 10 or more invoved axillary lymph nodes and 15.4% (hazard ratio, 0.67; 95% CI, 0.42-1.05) for patients with triple-negative breast cancer. The cumulative incidence risk of a second malignant neoplasm at 20 years or major cardiovascular events was similar in both treatment groups (20-year cumulative incidence risk for second malignant neoplasm was 12.1% in the HDCT group vs 16.2% in the CDCT group, P =.10), although patients in the HDCT group more often had hypertension (21.7% vs 14.3%, P =.02), hypercholesterolemia (15.7% vs 10.6%, P =.04), and dysrhythmias (8.6% vs 4.6%, P =.005). Conclusions and Relevance: High-dose chemotherapy provided no long-term survival benefit in unselected patients with stage III breast cancer but did provide improved overall survival in very high-risk patients (ie, with ≥10 involved axillary lymph nodes). High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT03087409