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Fungal infections in cancer patients can now be treated more successfully with less toxic novel compounds, therefore chemotherapy can be resumed following the treatment of an Invasive Fungal Infection (IFI). Secondary Prophylaxis (SP) is routinely instituted without prior systematic analysis of predictor variables for breakthrough IFI. Researchers are conducting a survey on SP regimens currently in use in 50 tertiary care centers in 10 countries. Several factors appear to have an impact on breakthrough IFI. Prospective studies on secondary prophylaxis and risk factors for breakthrough IFI are urgently warranted.

Background: Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/ tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/ tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches.Methods: FIRE-8 ( NCT05007132 ) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m2 body surface area (BSA), orally twice daily on days 1-5 and 8-12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled.Discussion: To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy.Trial Registration: EU Clinical Trials Register (EudraCT) 2019-004223-20 . Registered October 22, 2019, ClinicalTrials.gov NCT05007132 . Registered on August 12, 2021. [ABSTRACT FROM AUTHOR]

Background: NEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline-cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been developed. Patients and methods: This randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1-4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms. Results: A total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed. Conclusions: Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC. [ABSTRACT FROM AUTHOR]

Background: Mutations in rat sarcoma (RAS) genes may be a mechanism of secondary resistance in epidermal growth factor receptor inhibitor-treated patients. Tumor-tissue biopsy testing has been the standard for evaluating mutational status; however, plasma testing of cell-free DNA has been shown to be a more sensitive method for detecting clonal evolution. Materials and methods: Archival pre- and post-treatment tumor biopsy samples from a phase II study of panitumumab in combination with irinotecan in patients with metastatic colorectal cancer (mCRC) that also collected plasma samples before, during, and after treatment were analyzed for emergence of mutations during/post-treatment by next-generation sequencing and BEAMing. Results: The rate of emergence of tumor tissue RAS mutations was 9.5% by next-generation sequencing (n -- 21) and 6.3% by BEAMing (n -- 16). Plasma testing of cell-free DNA by BEAMing revealed a mutant RAS emergence rate of 36.7% (n -- 39). Exploratory outcomes analysis of plasma samples indicated that patients who had emergent RAS mutations at progression had similar median progression-free survival to those patients who remained wild-type at progression. Serial analysis of plasma samples showed that the first detected emergence of RAS mutations preceded progression by a median of 3.6 months (range, --0.3 to 7.5 months) and that there did not appear to be a mutant RAS allele frequency threshold that could predict near-term outcomes. Conclusions: This first prospective analysis in mCRC showed that serial plasma biopsies are more inclusive than tissue biopsies for evaluating global tumor heterogeneity; however, the clinical utility of plasma testing in mCRC remains to be further explored. [ABSTRACT FROM AUTHOR]

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

We found convincing evidence from numerous randomised controlled trials that G-CSF, biosimilar G-CSF and pegfilgrastim reduce the risk to develop febrile neutropenia and infections. As a rule of thumb, it seems the relative benefit is highest for patients with an intermediate risk of infections. Compared to other guidelines, we rated the evidence for growth factors during AML induction chemotherapy and pegfilgrastim use in haematological malignancies lower.Background Current evidence on myelopoietic growth factors is difficult to overview for the practicing haematologist/oncologist. International guidelines are sometimes conflicting, exclude certain patient groups, or cannot directly be applied to the German health system. This guideline by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO) gives evidence-based recommendations for the use of G-CSF, pegylated G-CSF, and biosimilars to prevent infectious complications in cancer patients undergoing chemotherapy, including those with haematological malignancies. Methods We systematically searched and evaluated current evidence. An expert panel discussed the results and recommendations. We then compared our recommendations to current international guidelines. Results We summarised the data from eligible studies in evidence tables, developed recommendations for different entities and risk groups. Conclusion Comprehensive literature search and expert panel consensus confirmed many key recommendations given by international guidelines. Evidence for growth factors during acute myeloid leukaemia induction chemotherapy and pegfilgrastim use in haematological malignancies was rated lower compared with other guidelines. [ABSTRACT FROM AUTHOR]

NEPA is an oral single, fixed-dose combination of netupitant, a new highly selective NK1 RA and palonosetron (PALO), a pharmacologically/clinically distinct 5-HT3 RA. It delivers antiemetic guideline-recommended prophylaxis by targeting two critical molecular pathways associated with chemotherapy-induced nausea/vomiting. This Phase III study demonstrated the superiority of NEPA compared with PALO.Background Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways. Patients and methods This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline–cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25–120 h) phase in cycle 1. Results The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0–120 h) (74.3% versus 66.6%; P = 0.001) and acute (0–24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO. Conclusions NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment. [ABSTRACT FROM AUTHOR]

We present evidence-based recommendations on diagnosis, management and prevention of central venous catheter-related infections (CRI) in cancer patients. Distinguishing between definite, probable and possible CR blood stream infections removal of the catheter is recommended if the patient's clinical state deteriorates or if S. aureus, Gram-negative bacilli or Candida spp. are isolated from blood cultures while the catheter may be preserved in selected cases.Background Cancer patients are at increased risk for central venous catheter-related infections (CRIs). Thus, a comprehensive, practical and evidence-based guideline on CRI in patients with malignancies is warranted. Patients and methods A panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) has developed a guideline on CRI in cancer patients. Literature searches of the PubMed, Medline and Cochrane databases were carried out and consensus discussions were held. Results Recommendations on diagnosis, management and prevention of CRI in cancer patients are made, and the strength of the recommendation and the level of evidence are presented. Conclusion This guideline is an evidence-based approach to the diagnosis, management and prevention of CRI in cancer patients. [ABSTRACT FROM PUBLISHER]

Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either ‘empirical’ or ‘preemptive’ antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders. [ABSTRACT FROM PUBLISHER]

Background: Anti-epidermal growth factor receptor treatment strategies, i.e. monoclonal antibodies such as cetuximab and panitumumab, or epidermal growth factor receptor (EGFR) small molecule tyrosine kinase inhibitors, such as erlotinib and gefitinib, have expanded the treatment options for different tumor types. Dermatologic toxic effects are the most common side-effects of EGFR inhibitor therapy. They can profoundly affect the patient's quality of life.Purpose: The aim of this study was to provide interdisciplinary expert recommendations on how to treat patients with skin reactions undergoing anti-EGFR treatment.Material and methods: An expert panel from Germany with expertise in medical oncology, dermatology or clinical pharmacology was convened to develop expert recommendations based on published peer-reviewed literature.Results: The expert recommendations for the state-of-the-art treatment of skin reactions induced by EGFR inhibitor therapy include recommendations for diagnostics and grading as well as grade-specific and stage-adapted treatment approaches and preventive measures. It was concluded that EGFR-inhibitor-related dermatologic reactions should always be treated combining basic care of the skin and a specific therapy adapted to stage and grade of skin reaction. For grade 2 and above, specific treatment recommendations for early- and later-stage skin reactions induced by EGFR-inhibitor therapy were proposed.Conclusion: This paper presents a German national expert opinion for the treatment of skin reactions in patients receiving EGFR inhibitor therapy. [ABSTRACT FROM PUBLISHER]

Antiseptic coating of intravascular catheters may be an effective means of decreasing catheter-related colonization and subsequent infection. The purpose of this study was to assess the efficacy of chlorhexidine and silver sulfadiazine (CH-SS)-impregnated central venous catheters (CVCs) to prevent catheter-related colonization and infection in patients with hematological malignancies who were subjected to intensive chemotherapy and suffered from severe and sustained neutropenia. Proven CVC-related bloodstream infection (BSI) was defined as the isolation of the same species from peripheral blood culture and CVC tip (Maki technique). This randomized, prospective clinical trial was carried out in 106 patients and compared catheter-related colonization and BSI using a CH-SS-impregnated CVC (n=51) to a control arm using a standard uncoated triple-lumen CVC (n=55). Patients were treated for acute leukemia (n=89), non-Hodgkin’s lymphoma (n=10), and multiple myeloma (n=7). Study groups were balanced regarding to age, sex, underlying diseases, insertion site, and duration of neutropenia. The CVCs were in situ a mean of 14.3±8.2 days (mean±SD) in the study group versus 16.6±9.7 days in the control arm. Catheter-related colonization was observed less frequently in the study group (five vs nine patients;p=0.035). CVC-related BSI were significantly less frequent in the study group (one vs eight patients;p=0.02). In summary, in patients with severe neutropenia, CH-SS-impregnated CVCs yield a significant antibacterial effect resulting in a significantly lower rate of catheter-related colonization as well as CVC-related BSI. [ABSTRACT FROM AUTHOR]

A case of disseminated infection with Fusarium oxysporum following chemotherapy of acute myelogenous leukemia is reported. Antifungal treatment was successful with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with amphotericin B deoxycholate 1.0–1.5 mg/kg qd and subsequently intravenous liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B deoxycholate 1.0–1.5 mg/kg qd had not stopped the progression of infection. The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders. [ABSTRACT FROM AUTHOR]

The article discusses testicular germ-cell tumors (GCT) in HIV-infected patients. It presents the case of a HIV seropositive 33-year-old man who underwent orchiectomy and adjuvant radiotherapy for stage I seminoma. The case showed that after completion of salvage high-dose chemotherapy (HDCT), the patient showed no residual GCT on positron emission tomography/computed tomography (PET/CT) scan. This result indicates that HDCT can benefit patients with HIV-related GCT.

The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. This study was accompanied by a prospective translational project analyzing cell-free circulating tumor DNA (ctDNA) in plasma to test whether ctDNA analysis may help to guide clinical treatment decision making. FIRE-4.5 included mCRC patients with BRAF V600E mutation detected by tissue-based analyses. Liquid biopsies (LBs) were collected at baseline (pre-treatment) and during therapy. Digital droplet PCR (ddPCR) technology was applied for determination of BRAF mutations and the in vitro diagnostics (IVD)-certified ONCOBEAM RAS procedure for analysis of RAS mutations. The BRAF V600E variants in ctDNA were analyzable in 66 patients at start of the therapy, at baseline. No BRAF V600E mutations were detected in 26% (17/66) of patients and was associated with a significantly longer progression-free survival (PFS: 13.2 vs 6.5 months; HR 0.47; P = 0.014) and overall survival (OS: 36.8 vs 13.2 months; HR 0.35; P = 0.02) as compared to ctDNA mutant patients. Patients with detectable BRAF mutations showed a clear superiority of FOLFOXIRI plus bevacizumab with regard to PFS (10.4 vs 5.7 months; HR 0.4; P = 0.009) and OS (16.6 vs 11.6 months; HR 0.5; P = 0.15), while this was not the case for BRAF wild-type patients. Follow-up LBs were obtained from 51 patients. Patients converting from BRAF V600E mutant to a BRAF V600 wild-type status (36%, N = 18) had a superior PFS (8.6 vs 2.3 months; P = 0.0002) and OS (17.4 vs 5.1 months; P < 0.0001) compared to patients with stable or increased mutational allele frequency (12%, N = 6). Those patients also achieved a significantly greater disease control rate (89% vs 20%; P = 0.008). In conclusion, LB evaluating ctDNA is informative and may help to guide treatment in patients with BRAF V600E-mutated mCRC., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Introduction: The phase 2 RAMONA study demonstrated that second-line nivolumab ± ipilimumab immunotherapy was feasible and effective in older patients with advanced esophageal squamous cell cancer (ESCC). Here, we presented results from functional status (FS) and quality-of-life (QoL) analyses., Materials and Methods: Patients aged ≥65 years with advanced ESCC and disease progression following first-line therapy were enrolled for study treatment with nivolumab ± ipilimumab. Geriatric assessments (GA) consisting of G8 and GoGo/SlowGo evaluation, and quality of life (QoL) assessments with EORTC QLQ-C30 questionnaires were conducted at baseline and during the treatment. A post hoc analysis was performed to compare therapy efficacy, toxicity, and QoL between age groups (≥70 years vs. <70 years) and functionality groups (G8 > 14 vs. ≤14 and GoGo vs. SlowGo)., Results: In 66 treated patients with a median age of 70.5 years, older patients had non-inferior overall survival and tumor response compared to younger patients, with no increased treatment-related adverse events. Fitter patients (G8 > 14, GoGo) had a clinically, yet not statistically significant, survival advantage than less fit patients (G8 ≤ 14, SlowGo) patients. Moreover, FS by G8 and GoGo/SlowGo significantly correlated with QoL. Overall, QoL was impaired at baseline but remained stable in all scales over the course of immunotherapy., Discussion: The administration of nivolumab ± ipilimumab second-line immunotherapy in older patients with ESCC did not show age-dependent effects and maintained QoL. GA could identify functional deficits and limitations of QoL and should be implemented in the context of immunotherapy., Clinicaltrials: gov: NCT03416244., Competing Interests: Declaration of Competing Interest NMB reports research funding and receipt of equipment from Deutsche Forschungsgemeinschaft. RDH reports advisory for Amgen, Astra Zeneca, Bristol Myers Squibb, Boehringer, Daichi, Lilly, Merck, MSD, Pierre Fabre, Roche, and Servier; honoraria for lectures and presentations from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer, Daichi, Lilly, medac, Merck, MSD, Pierre Fabre, Roche, Saladax, Sanofi, and Servier; and consulting fees from Amgen, Astra Zeneca, Bayer, BMS, Boehringer, Daichi, Lilly, medac, Merck, MSD, Pierre Fabre, Roche, Saladax, Sanofi, and Servier. AV reports consultancy and advisory role for AstraZeneca, Amgen, BeiGene, Böhringer Mannheim, BMS, BTG, Daichi-Sankyo, EISAI, Incyte, Ipsen, MSD, PierreFabre, Roche, Servier, Sirtex, Tahio and Terumo. MdW reports research funding from Pfizer, Abbvie, Novartis, Astellas, Bristol Myers Squibb, AstraZeneca and MorphoSys; speaker's honoraria from AstraZeneca and Janssen; travel or accommodation expenses from Astellas and Janssen. RJ reports consulting fees from Roche and Bayer; payments for lectures and presentations from Dr. Falk Pharma and Bristol Myers Squibb; for writing of manuscripts from Boston Scientific and Springer Nature; advisory for Heidelberg University Hospital; and leading the Endoscopy section of the German Society of Gastroenterology. GS reports consulting fees from Servier, Pharmacosmos, Bristol Myers Squibb, Amgen and travel support from Daichi-Sankyo. PTP reports consulting fees from Bristol Myers Squibb, AstraZeneca, and MSD. TL is Scientific Head at CROLLL GmbH. HB is an employee of a commercial provider of clinical statistics and programming services (Staburo GmbH, Munich). MPE reports funding for conducting the trial from AIO-Studien-gGmbH which is the regulatory sponsor of the trial, and advisory for Bristol Myers Squibb. NH reports advisory for Bristol Myers Squibb. All remaining authors declare no conflicts of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: In the pivotal phase III RECOURSE trial, trifluridine/tipiracil (FTD/TPI) improved progression-free and overall survival (PFS, OS) of patients with pre-treated metastatic colorectal cancer (mCRC). Subsequently, the TALLISUR trial provided post-authorisation efficacy and safety data and patient-reported outcomes on quality of life (QoL) in a German patient cohort. The present analysis reports the final data on efficacy, safety and QoL and investigates the impact of baseline characteristics and associated prognostic subgroups on outcome., Methods: In this prospective, multi-centre, Germany-wide, phase IV study, patients with pre-treated mCRC were given the choice to receive either FTD/TPI or best supportive care (BSC). To assess the primary endpoint, QoL, EORTC QLQ-C30 questionnaires were employed. Secondary endpoints included QoL assessed through EQ-5D-5L questionnaires, OS, PFS and safety. Additionally, 3 subgroups were defined according to a post-hoc analysis of the RECOURSE trial: best, good and poor prognostic characteristics (BPC, GPC, PPC). Patients with < 3 metastatic sites at inclusion and/or ≥ 18 months from diagnosis to inclusion were considered to have GPC. GPC patients without liver metastasis at inclusion were considered to have BPC. All remaining patients were considered to have PPC., Results: Of 195 patients, 186 decided to receive FTD/TPI and 9 to receive BSC. The low number of patients in the BSC-arm did not allow statistically meaningful analyses. Treatment with FTD/TPI was associated with maintained QoL. For all patients, median OS was 6.9 months (95% CI 6.1 - 8.3) and for the defined subgroups (BPC n = 20 vs GPC n = 65 vs PPC n = 121) 12.2, 7.9 and 6.8 months (95% CI 6.0 - 18.2, 6.2 - 13.3, 5.4 - 8.1). The most frequent TEAEs were neutropenia (29.6%), anaemia (24.7%) and nausea (23.7%). Febrile neutropenia occurred in 1.1%., Conclusions: Treatment of patients suffering from pre-treated mCRC with FTD/TPI was associated not only with prolonged survival and delayed progression, but also with maintained QoL. Independent of other baseline characteristics such as ECOG performance status and age, low metastatic burden and indolent disease were factors associated with favourable outcome., Clinical Trial Registration: EudraCT-Number 2017-000292-83, first registration 19/06/2017., (© 2024. The Author(s).)

Background: The key endpoints for the assessment of the effect of maintenance therapy for metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed to compare dermatology-related quality of life (DRQOL) in patients with RAS wild-type (wt) mCRC treated with fluorouracil and folinic acid (FU/FA) + panitumumab (Pmab) versus FU/FA alone as maintenance therapy after folinic acid, fluorouracil and oxaliplatin + Pmab induction., Patients and Methods: The phase II randomized PanaMa (AIO KRK 0212; NCT01991873) trial included 387 patients at 70 community/academic sites in Germany. For this prespecified secondary analysis, DRQOL outcomes were assessed using the Functional Assessment of Cancer Therapy-epidermal growth factor receptor inhibitor (FACT-EGFRI), Dermatology Life Quality Index (DLQI), and Skindex-16 questionnaires at every second cycle of therapy until disease progression/death., Results: At least one DRQOL questionnaire was completed by a total of 310/377 (82%) patients who received induction therapy, and by 216/248 (87%) patients who were randomized and received maintenance therapy. Patients who experienced skin toxicity according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) during induction therapy had significantly worse DRQOL according to all three measures, compared to those who did not [i.e. Skindex-16, mean difference at cycle 2 -12.87; 95% confidence interval (CI) -20.01 to -5.73; P < 0.001]. During maintenance therapy, significantly improved recovery was observed in all DRQOL measures for patients receiving FU/FA, compared to those receiving additional Pmab (i.e. Skindex-16, mean difference at cycle 6 -16.53; 95% CI -22.68 to -10.38; P < 0.001)., Conclusions: In this secondary analysis of a phase II randomized clinical trial, patient-reported DRQOL outcomes correlated with skin toxicity according to NCI-CTCAE during induction therapy. Maintenance therapy with FU/FA + Pmab was associated with deteriorated DRQOL versus FU/FA alone in patients with RAS wt mCRC., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: We evaluated additional mutations in RAS wild-type (WT) metastatic colorectal cancer (mCRC) as prognostic and predictive biomarkers for the efficacy of added panitumumab to a 5-fluorouracil plus folinic acid (FU/FA) maintenance as pre-specified analysis of the randomized PanaMa trial., Patients and Methods: Mutations (MUT) were identified using targeted next-generation sequencing (NGS; Illumina Cancer Hotspot Panel v2) and IHC. RAS/BRAF V600E/PIK3CA/AKT1/ALK1/ERBB2/PTEN MUT and HER2/neu overexpressions were negatively hyperselected and correlated with median progression-free survival (PFS) and overall survival (OS) since start of maintenance treatment, and objective response rates (ORR). Univariate/multivariate Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI)., Results: 202 of 248 patients (81.5%) of the full analysis set (FAS) had available NGS data: hyperselection WT, 162 (80.2%); MUT, 40 (19.8%). From start of maintenance therapy, hyperselection WT tumors were associated with longer median PFS as compared with hyperselection MUT mCRC (7.5 vs. 5.4 months; HR, 0.75; 95% CI, 0.52-1.07; P = 0.11), OS (28.7 vs. 22.2 months; HR, 0.53; 95% CI, 0.36-0.77; P = 0.001), and higher ORR (35.8% vs. 25.0%, P = 0.26). The addition of panitumumab to maintenance was associated with significant benefit in hyperselection WT tumors for PFS (9.2 vs. 6.0 months; HR, 0.66; 95% CI, 0.47-0.93; P = 0.02) and numerically also for OS (36.9 vs. 24.9 months; HR, 0.91; 95% CI, 0.61-1.36; P = 0.50), but not in hyperselection MUT tumors. Hyperselection status interacted with maintenance treatment arms in terms of PFS (P = 0.06) and OS (P = 0.009)., Conclusions: Extended molecular profiling beyond RAS may have the potential to improve the patient selection for anti-EGFR containing maintenance regimens., (©2024 American Association for Cancer Research.)

Despite molecular selection, patients (pts) with RAS wildtype mCRC represent a heterogeneous population including diversity in metastatic spread. We investigated metastatic patterns for their prognostic and predictive impact on maintenance therapy with 5-fluorouracil/folinic acid ± panitumumab. The study population was stratified according to (1) number of involved metastatic sites (single vs multiple organ metastasis), liver-limited disease vs (2) liver metastasis plus one additional site, and (3) vs liver metastasis plus ≥two additional sites. Kaplan-Meier method and Cox regressions were used to correlate efficacy endpoints. Single organ metastasis was observed in 133 pts (53.6%) with 102 pts (41.1%) presenting with liver-limited disease, while multiple organ metastases were reported in 114 pts (46.0). Multiple compared to single organ metastases were associated with less favorable PFS (HR 1.48, 95% CI 1.13-1.93; P = .004) and OS (HR 1.37, 95% CI 0.98-1.93; P = .068) of maintenance therapy. While metastatic spread involving one additional extrahepatic site was not associated with clearly impaired survival compared to liver-limited disease, pts with liver metastasis plus ≥two additional sites demonstrated less favorable PFS (HR 1.92, 95% CI 1.30-2.83; P < .001), and OS (HR 2.38, 95% CI 1.51-3.76; P < .001) of maintenance therapy. Pmab-containing maintenance therapy appeared active in both pts with multiple (HR 0.58; 95% CI, 0.39-0.86; P = .006) as well as to a lesser numerical extent in pts with single organ metastasis (HR 0.83; 95% CI, 0.57-1.21; P = .332; Interaction P = .183). These data may support clinical decisions when EGFR-based maintenance therapy is considered., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Most patients with metastatic colorectal cancer (mCRC) have limited treatment options following standard-of-care therapy. VEGFR-tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity in mCRC in combination with immune checkpoint inhibitors (ICIs), particularly in patients without liver metastases. The TKI zanzalintinib (XL092) targets VEGFR, MET and TAM kinases, proteins that are involved in tumor growth, angiogenesis, metastasis and immunosuppression. Zanzalintinib has immunomodulatory properties that may enhance response to ICIs. Presented is the design of STELLAR-303, a global, phase III, open-label, randomized study evaluating zanzalintinib plus atezolizumab versus regorafenib in patients with non-MSI-H mCRC who progressed during/after or are refractory/intolerant to standard-of-care therapy. The primary end point is overall survival in patients without liver metastases. Clinical Trial Registration: NCT05425940 (ClinicalTrials.gov).

Accurately evaluating cognitive load during work-related tasks in complex real-world environments is challenging, leading researchers to investigate the use of eye blinking as a fundamental pacing mechanism for segmenting EEG data and understanding the neural mechanisms associated with cognitive workload. Yet, little is known about the temporal dynamics of eye blinks and related visual processing in relation to the representation of task-specific information. Therefore, we analyzed EEG responses from two experiments involving simulated driving (re-active and pro-active) with three levels of task load for each, as well as operating a steam engine (active vs. passive), to decode the temporal dynamics of eye blink activity and the subsequent neural activity that follows blinking. As a result, we successfully decoded the binary representation of difficulty levels for pro-active driving using multivariate pattern analysis. However, the decoding level varied for different re-active driving conditions, which could be attributed to the required level of alertness. Furthermore, our study revealed that it was possible to decode both driving types as well as steam engine operating conditions, with the most significant decoding activity observed approximately 200 ms after a blink. Additionally, our findings suggest that eye blinks have considerable potential for decoding various cognitive states that may not be discernible through neural activity, particularly near the peak of the blink. The findings demonstrate the potential of blink-related measures alongside EEG data to decode cognitive states during complex tasks, with implications for improving evaluations of cognitive and behavioral states during tasks, such as driving and operating machinery.

Assessing drivers' cognitive load is crucial for driving safety in challenging situations. This research employed the occurrence of drivers' natural eye blinks as cues in continuously recorded EEG data to assess the cognitive workload while reactive or proactive driving. Twenty-eight participants performed either a lane-keeping task with varying levels of crosswind (reactive) or curve road (proactive). The blink event-related potentials (bERPs) and spectral perturbations (bERSPs) were analyzed to assess cognitive load variations. The study found that task load during reactive driving did not significantly impact bERPs or bERSPs, possibly due to enduring alertness for vehicle control. The proactive driving revealed significant differences in the occipital N1 component with task load, indicating the necessity to adapt the attentional resources allocation based on road demands. Also, increased steering complexity led to decreased frontal N2, parietal P3, occipital P2 amplitudes, and alpha power, requiring more cognitive resources for processing relevant information. Interestingly, the proactive and reactive driving scenarios demonstrated a significant interaction at the parietal P2 and occipital N1 for three difficulty levels. The study reveals that EEG measures related to natural eye blink behavior provide insights into the effect of cognitive load on different driving tasks, with implications for driver safety., (© 2023. The Author(s).)

Background: The PanaMa trial demonstrated significant benefit in progression-free survival with the addition of panitumumab (Pmab) to fluorouracil and folinic acid (FU/FA) as maintenance therapy following first-line induction therapy with FOLFOX/Pmab in patients with RAS wild-type metastatic colorectal cancer. Here, we report health-related quality of life (HRQOL) analyses from the PanaMa trial., Methods: HRQOL outcomes were evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at every cycle of therapy until disease progression/death. HRQOL outcomes were mean and individual changes in EORTC QLQ-C30 from baselines (before induction therapy and before maintenance therapy) to each cycle of treatment. Comparative analyses were performed by randomisation status and treatment arm for induction- and maintenance-therapy, respectively. The trial is registered with clinicaltrials.gov (NCT01991873)., Results: At least one HRQOL questionnaire was completed by a total of 349/377 (93%) patients who received induction therapy, and by 237/248 (96%) patients who were randomised and received maintenance therapy. During induction therapy, most HRQOL dimensions remained stable or showed improvement, while appetite loss and diarrhoea significantly deteriorated. During maintenance therapy, HRQOL dimensions remained stable, while those that deteriorated during induction therapy showed significant improvement, without significant differences between the treatment arms., Conclusion: Maintenance therapy improves HRQOL dimensions that initially deteriorated during induction therapy while stabilising HRQOL in other dimensions. The addition of Pmab to FU/FA as maintenance therapy in patients with RAS wild-type metastatic colorectal cancer prolongs progression-free survival without negative impact on HRQOL., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexej Ballhausen: Stock and other ownership interests: BioNTech SE. Honoraria: Amgen. Research funding: Amgen (Inst). Travel, Accommodations, Expenses: Amgen. Meinolf Karthaus: Consulting or advisory role: Amgen. Travel, Accommodations, Expenses: Amgen. Ullrich Graeven: Stock and other ownership interests: BioNTech SE. Honoraria: Boehringer Ingelheim, Amgen, AstraZeneca, Bristol Myers Squibb, MSD Oncology, Sanofi Aventis GmbH, Fujifilm, Novartis, Celltrion. Consulting or advisory role: Amgen, MSD Oncology. Research funding: Ipsen (Inst), MacroGenics (Inst). Travel, Accommodations, Expenses: Boehringer Ingelheim, GlaxoSmithKline. Lothar Müller: Travel, Accommodations, Expenses: Octapharma, Pierre Fabre. Ludwig Fischer von Weikersthal: Honoraria: Pierre Fabre, Lilly. Annabel Helga Sophie Alig: Honoraria: MSD. Travel, Accommodations, Expenses: Merck, BMS GmbH and Co. KG. Eray Goekkurt: Consulting or advisory role: MSD, Bristol Myers Squibb, AstraZeneca/Daiichi Sankyo, Pfizer. Annika Kurreck: Honoraria: Taiho Pharmaceutical, Amgen, Servier. Travel, Accommodations, Expenses: medac, Amgen, Servier. Arndt Stahler: Honoraria: Roche, Servier, Taiho Pharmaceutical. Consulting or advisory role: Bristol Myers Squibb/Pfizer, Novocure. Travel, Accommodations, Expenses: Amgen, Roche, Lilly, Pfizer. Stefan Kasper: Employment: University Hospital Essen. Honoraria: Bristol Myers Squibb, MSD Oncology, AstraZeneca, Merck Serono, Amgen, Roche, Servier, Amgen, Lilly, Sanofi/Aventis, Novartis, Pierre Fabre. Consulting or Advisory Role: Roche, Merck Serono, Amgen, MSD Oncology, Sanofi, Bristol Myers Squibb, Lilly, Servier, AstraZeneca, Janssen-Cilag, Novartis, Pierre Fabre, Incyte. Research funding: Merck Serono, Bristol Myers Squibb, Celgene, Lilly, Servier, Roche/Genentech. Travel, Accommodations, Expenses: Merck Serono, Lilly, Amgen, Sanofi, Roche, Pierre Fabre, BMS. Other relationship: Sanofi, Amgen, Merck Serono, Bristol Myers Squibb, Roche, Lilly. Volker Heinemann: Honoraria: Roche, Amgen, Sanofi, Merck, Servier, Pfizer, Pierre Fabre, AstraZeneca, MSD, Seagen. Consulting or advisory role: Merck, Amgen, Roche, MSD, Bristol Myers Squibb, MSD Oncology, Novartis, Pierre Fabre, TERUMO, GlaxoSmithKline, Servier/Pfizer, AstraZeneca, OncoSil, Nordic Bioscience. Research funding: Merck (Inst), Amgen (Inst), Roche (Inst). Travel, Accommodations, Expenses: Merck. Sebastian Stintzing: Honoraria: Merck KGaA, Roche, Amgen, Servier, MSD, Pfizer, Pierre Fabre, Bristol Myers Squibb GmbH, Nordic Bioscience, AstraZeneca. Consulting or advisory role: Merck Kgaa, Roche, Amgen, Pierre Fabre, Msd, Astrazeneca, Servier, Glaxosmithkline, Terumo, Nordic Bioscience, Seagen. Research Funding: Pierre Fabre (Inst), Roche Molecular Diagnostics (Inst), Merck Serono (Inst), Amgen (Inst). Travel, Accommodations, Expenses: Merck KGaA, Roche, Sanofi, Bayer, Sirtex Medical, Amgen, Lilly, Takeda, Pierre Fabre, AstraZeneca. Tanja Trarbach: Research funding: Amgen. Travel, Accommodations, Expenses: Ipsen, Takeda, OMT, AbbVie, Novartis, MSD, Sanofi/Aventis, Amgen, Johnson and Johnson/Janssen. Dominik Paul Modest: Honoraria: Merck Serono, Amgen, Servier, Bristol Myers Squibb, Taiho Pharmaceutical, Merck Sharp and Dohme, Pierre Fabre, Onkowissen, Sanofi, Lilly, AstraZeneca/MedImmune, Incyte, Takeda. Consulting or advisory role: Merck Serono, Amgen, Merck Sharp and Dohme, Roche, Servier, Incyte, Bristol Myers Squibb, Pierre Fabre, Lilly, Cor2Ed, IQVIA, Onkowissen. Research funding: Amgen (Inst), Servier (Inst). Travel, Accommodations, Expenses: Amgen, Merck Serono, Servier. No other potential conflicts of interest were reported., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: BRAF V600E mutation is associated with a poor outcome in metastatic colorectal cancer (mCRC). This clinical trial investigated the efficacy of triplet chemotherapy (fluorouracil, folinic acid, oxaliplatin, and irinotecan) combined with either cetuximab or bevacizumab in patients with previously untreated BRAF V600E -mutant mCRC., Patients and Methods: In this controlled, randomized, open-label phase II trial, 109 patients were randomly assigned, 107 of whom were included into the full analysis set (FAS). Patients were randomly assigned in a 2:1 ratio to receive either FOLFOXIRI plus cetuximab in the experimental arm (n = 72) or FOLFOXIRI plus bevacizumab in the control arm (n = 35). The primary end point was objective response rate (ORR) according to RECIST 1.1., evaluated in patients treated according to protocol (ATP population). Progression-free survival (PFS), overall survival (OS), toxicity, and feasibility were analyzed as secondary end points., Results: Eighteen patients discontinued study treatment before the first tumor assessment, thus resulting in the ATP population of 89 patients. In these patients, ORR was 51% (30/59) in the cetuximab-based experimental arm and 67% (20/30) in the bevacizumab-based control arm (odds ratio, 1.93; 80% CI, 1.06 to 3.52; P = .92 [one-sided]). In the full analysis set, median PFS was significantly inferior in the experimental arm (6.7 months v 10.7 months; hazard ratio [HR], 1.89; P = .006). Median OS analyzed at an event rate of 64.5% showed a trend toward shorter survival in cetuximab-treated patients (12.9 months v 17.1 months; HR, 1.4; P = .20)., Conclusion: To our knowledge, FIRE-4.5 is the first prospective and randomized study investigating first-line treatment of BRAF V600E -mutant mCRC. FOLFOXIRI plus cetuximab does not induce a higher ORR when compared with FOLFOXIRI plus bevacizumab in first-line treatment of BRAF V600E -mutant mCRC. Bevacizumab-based chemotherapy remains the preferable first-line treatment of patients with BRAF V600E -mutant mCRC.

Demographic change is leading to an increasing proportion of older employees in the labor market. At the same time, work activities are becoming more and more complex and require a high degree of flexibility, adaptability, and cognitive performance. Cognitive control mechanism, which is subject to age-related changes and is important in numerous everyday and work activities, plays a special role. Executive functions with its core functions updating, shifting, and inhibition comprises cognitive control mechanisms that serve to plan, coordinate, and achieve higher-level goals especially in inexperienced and conflicting actions. In this review, influences of age-related changes in cognitive control are demonstrated with reference to work and real-life activities, in which the selection of an information or response in the presence of competing but task-irrelevant stimuli or responses is particularly required. These activities comprise the understanding of spoken language under difficult listening conditions, dual-task walking, car driving in critical traffic situations, and coping with work interruptions. Mechanisms for compensating age-related limitations in cognitive control and their neurophysiological correlates are discussed with a focus on EEG measures. The examples illustrate how to access influences of age and cognitive control on and in everyday and work activities, focusing on its functional role for the work ability and well-being of older people., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Getzmann, Reiser, Gajewski, Schneider, Karthaus and Wascher.)

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespective of sex. Sex-associated differences relating to safety and efficacy in the treatment of mCRC, however, are gaining interest., Methods: PanaMa investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type mCRC. In this post hoc analysis, the study population was stratified for sex. Evaluated efficacy endpoints during maintenance treatment were progression-free survival (PFS, primary endpoint of the trial), overall survival (OS) and objective response rate during maintenance therapy. Safety endpoints were rates of any grade and grade 3/4 adverse events during maintenance therapy., Results: In total, 165 male and 83 female patients were randomized and treated. Male and female patients showed numerically better objective response rates with Pmab, without reaching statistical significance. Male patients derived a significant benefit from the addition of Pmab to maintenance treatment with regard to PFS [hazard ratio (HR) 0.63; 95% confidence interval (CI) 0.45-0.88; P = 0.006] that was not observed in female patients (HR 0.85; 95% CI 0.53-1.35; P = 0.491). The better PFS for male patients treated with Pmab did not translate into improved OS (HR 0.85; 95% CI 0.55-1.30; P = 0.452). Female patients showed numerically improved OS when treated with Pmab. There was no difference in the total of grade ≥3 adverse events during maintenance regarding sex (P = 0.791). Female patients, however, had a higher rate of any grade nausea, diarrhea and stomatitis., Conclusions: In the PanaMa trial, the addition of Pmab to maintenance treatment of RAS wild-type mCRC with FU/FA improved the outcome in terms of the primary endpoint (PFS) particularly in male patients. Female patients did not show the same benefit while experiencing higher rates of adverse events. Our results support the development of sex-specific protocols., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Driving safety strongly depends on the driver's mental states and attention to the driving situation. Previous studies demonstrate a clear relationship between EEG measures and mental states, such as alertness and drowsiness, but often only map their mental state for a longer period of time. In this driving simulation study, we exploit the high temporal resolution of the EEG to capture fine-grained modulations in cognitive processes occurring before and after eye activity in the form of saccades, fixations, and eye blinks. A total of 15 subjects drove through an approximately 50-km course consisting of highway, country road, and urban passages. Based on the ratio of brain oscillatory alpha and theta activity, the total distance was classified into 10-m-long sections with low, medium, and high task loads. Blink-evoked and fixation-evoked event-related potentials, spectral perturbations, and lateralizations were analyzed as neuro-cognitive correlates of cognition and attention. Depending on EEG-based estimation of task load, these measures showed distinct patterns associated with driving behavior parameters such as speed and steering acceleration and represent a temporally highly resolved image of specific cognitive processes during driving. In future applications, combinations of these EEG measures could form the basis for driver warning systems which increase overall driving safety by considering rapid fluctuations in driver's attention and mental states., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Chemotherapy-induced nausea and the subsequent vomiting (CINV) are adverse effects of cancer treatment associated with considerable burden for the patient. CINV has a significant negative impact on quality of life. The consequent loss of fluids and electrolytes can lead to impaired renal function or weight loss, which may lead to hospitalization. If CINV later results in anticipatory vomiting, this complicates both CINV prophylaxis and further chemotherapy, which can endanger the continuation of cancer treatment. The introduction of high-dose dexamethasone as well as 5‑HT3 and NK1 receptor antagonists has led to a significant improvement of CINV prophylaxis since the 1990s. Recommendations on CINV prophylaxis are in available in guidelines. Adherence to these guidelines results in better outcomes., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Consensus molecular subtypes (CMSs) were evaluated as prognostic and predictive biomarkers of patients with RAS wild-type metastatic colorectal cancer (mCRC) receiving fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab) after Pmab + mFOLFOX6 induction within the randomized phase II PanaMa trial., Methods: CMSs were determined in the safety set (ie, patients that received induction) and full analysis set (FAS; ie, randomly assigned patients who received maintenance) and correlated with median progression-free survival (PFS) and overall survival (OS) since the start of induction or maintenance treatment and objective response rates (ORRs). Hazard ratios (HRs) and 95% CI were calculated by univariate/multivariate Cox regression analyses., Results: Of 377 patients of the safety set, 296 (78.5%) had available CMS data: CMS1/2/3/4: 29 (9.8%)/122 (41.2%)/33 (11.2%)/112 (37.8%) and unclassifiable: 17 (5.7%). The CMSs were prognostic biomarkers in terms of PFS ( P < .0001), OS ( P < .0001), and ORR ( P = .02) since the start of induction treatment. In FAS patients (n = 196), with CMS2/4 tumors, the addition of Pmab to FU/FA maintenance therapy was associated with longer PFS (CMS2: HR, 0.58 [95% CI, 0.36 to 0.95], P = .03; CMS4: HR, 0.63 [95% CI, 0.38 to 1.03], P = .07) and OS (CMS2: HR, 0.88 [95% CI, 0.52 to 1.52], P = .66; CMS4: HR, 0.54 [95% CI, 0.30 to 0.96], P = .04). The CMS interacted significantly with treatment in terms of PFS (CMS2 v CMS1/3: P = .02; CMS4 v CMS1/3: P = .03) and OS (CMS2 v CMS1/3: P = .03; CMS4 v CMS1/3: P < .001)., Conclusion: The CMS had a prognostic impact on PFS, OS, and ORR in RAS wild-type mCRC. In PanaMa, Pmab + FU/FA maintenance was associated with beneficial outcomes in CMS2/4, whereas no benefit was observed in CMS1/3 tumors.

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We demonstrate and discuss the use of mobile electroencephalogram (EEG) for neuroergonomics. Both technical state of the art as well as measures and cognitive concepts are systematically addressed., Background: Modern work is increasingly characterized by information processing. Therefore, the examination of mental states, mental load, or cognitive processing during work is becoming increasingly important for ergonomics., Results: Mobile EEG allows to measure mental states and processes under real live conditions. It can be used for various research questions in cognitive neuroergonomics. Besides measures in the frequency domain that have a long tradition in the investigation of mental fatigue, task load, and task engagement, new approaches-like blink-evoked potentials-render event-related analyses of the EEG possible also during unrestricted behavior., Conclusion: Mobile EEG has become a valuable tool for evaluating mental states and mental processes on a highly objective level during work. The main advantage of this technique is that working environments don't have to be changed while systematically measuring brain functions at work. Moreover, the workflow is unaffected by such neuroergonomic approaches.

Background: In patients with RAS wild-type metastatic colorectal cancer, depth of response (DpR) has gained importance as a novel end-point in clinical trials. We investigated the overall DpR, as well as the prognostic and predictive impact of DpR to induction therapy (six cycles of 5-fluorouracil, leucovorin [FU/FA], oxaliplatin [FOLFOX] and panitumumab [Pmab]) on consecutive maintenance therapy (FU/FA plus Pmab or FU/FA alone) in patients treated within the PanaMa trial., Methods: Central radiological assessment was performed according to RECIST 1.1. DpR was defined as percentage change in tumour diameter within defined time intervals (induction therapy, maintenance therapy, total course of therapy). For prognostic and predictive analyses, median DpR (

Introduction: In further-line mCRC treatment, median progression-free survival (PFS) is rather short, and many patients do not benefit from any antitumor treatment and should therefore be treated according to best-supportive care. A risk score based on standard laboratory values using markers of tumor inflammation aims to define a patient cohort with high treatment benefit and might offer insights into tumor biology. As regorafenib has been dropped off the German market due to an unfavorable risk-benefit ratio, patient selection is key for any further-line treatment option., Methods: We used Cox regression analysis to determine laboratory markers that are independent prognostic factors of OS and PFS outcome. The influence of these variables was weighted using an estimator, which was calculated using Cox regression analysis. The estimators were implemented as multiplication factors, resulting in a risk score. A cut-off value for the resulting risk values was then determined via Cox regression analysis resulting in a low- and high-risk subgroup., Results: Using data of 82 patients, a risk score identifying long-term survival in patients with last-line mCRC treatment could be calculated. The following parameters were associated with significantly longer survival in multivariate analysis: NLR ≤5 (p = &lt;0.001), AP ≤200 U/L (p = 0.001), CRP ≤3.2 mg/dL (p = &lt;0.001). The following estimator values were used to calculate a risk score: NLR: 0.132 (p = 0.046), AP: 0.004 (p = 0.014), and CRP: 0.032 (p = 0.039). Implementing the estimators as multiplication factors yielded the following risk score: 0.132*NLR + 0.004*AP + 0.032*CRP = Risk value. Cox regression resulted in low- and high-risk subgroups with risk values below and above 1.4, respectively. In the group with a low-risk score (&lt;1.4), patients had a median OS of 10.5 months after initiating regorafenib. Patients with a high-risk score (&gt;1.4) survived only 3.3 months after starting therapy with regorafenib (n = 43, p &lt; 0.001, HR = 3.76)., Conclusions: The presented composite risk score stratifies patients into two prognostic subgroups characterized by standard laboratory values. Patients with signs of systemic inflammation characterized by elevated NLR, AP, and CRP have a high composite risk score and a significant shorter overall survival. Although this score needs to be prospectively validated in larger cohorts, it may be used to stratify patients suitable for further-line treatment studies., (© 2023 The Author(s). Published by S. Karger AG, Basel.)