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ObjectiveLong-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression.DesignWe crossed LSL-Kras +/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1β to generate KC-IL1β mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples.ResultsKC-IL1β mice developed PDAC with liver metastases. IL-1β treatment increased Kras+/G12D pancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1β pancreata. Adoptive transfer of B lymphocytes from KC-IL1β mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1β mice. B cells isolated from KC-IL1β mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+ T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1β pancreata, and depletion of IL-35 decreased the number of PD-L1+ B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival.ConclusionWe show here that IL-1β promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.

With the increasing use of genomic profiling for diagnosis and therapy guidance in many tumor types, precision oncology is rapidly reshaping cancer care. However, the current trajectory of drug development in oncology results in a paradox: if patients cannot access advanced diagnostics, we may be developing drugs that will reach few patients. In this Perspective, we outline the major challenges to the implementation of precision oncology and discuss critical steps toward resolving these, including facilitation of equal access to genomics tests, ensuring that clinical studies provide robust evidence for new drugs and technologies, enabling physicians to interpret genomics data, and empowering patients toward shared decision-making. A multi-stakeholder approach to evidence generation, value assessment, and healthcare delivery is necessary to translate advances in precision oncology into benefits for patients with cancer globally. Precision medicine is reshaping cancer care, but the benefits are not accessible to all patients. This Perspective outlines the major challenges to the implementation of precision oncology and discusses critical steps toward resolving these.

PurposeDespite promising achievements in precision cancer medicine (PCM), participating patients are still faced with manifold uncertainties, especially regarding a potential treatment benefit of molecular diagnostics (MD). Hence, MD poses considerable challenges for patient information and communication. To meet these challenges, healthcare professionals need to gain deeper insight into patients’ subjective experiences. Therefore, this qualitative study examined information aspects of MD programs in cancer patients.MethodsIn two German Comprehensive Cancer Centers, 30 cancer patients undergoing MD participated in semi-structured interviews on information transfer and information needs regarding MD. Additionally, patients provided sociodemographic and medical data and indicated their subjective level of information (visual analogue scale, VAS, 0–10).ResultsOn average patients had high levels of information (mean = 7, median = 8); nevertheless 20% (n = 6) showed an information level below 5 points. Qualitative analysis revealed that patients show limited understanding of the complex background of MD and have uncertainties regarding their personal benefit. Further, patients described unmet information needs. Existential threat in awaiting the results was experienced as burdensome. To withstand the strains of their situation, patients emphasized the importance of trusting their physician.ConclusionThe challenges in PCM consist in providing unambiguous information, especially concerning treatment benefit, and providing guidance and support. Therefore, psycho-oncology needs to develop guidelines for adequate patient communication in order to help healthcare providers and cancer patients to handle these challenges in the developing field of PCM.

ObjectivesTo evaluate whether template-based structured reports (SRs) add clinical value to primary CT staging in patients with diffuse large B-cell lymphoma (DLBCL) compared to free-text reports (FTRs).MethodsIn this two-centre study SRs and FTRs were acquired for 16 CT examinations. Thirty-two reports were independently scored by four haematologists using a questionnaire addressing completeness of information, structure, guidance for patient management and overall quality. The questionnaire included yes-no, 10-point Likert scale and 5-point scale questions. Altogether 128 completed questionnaires were evaluated. Non-parametric Wilcoxon signed-rank test and McNemar’s test were used for statistical analysis.ResultsSRs contained information on affected organs more often than FTRs (95 % vs. 66 %). More SRs commented on extranodal involvement (91 % vs. 62 %). Sufficient information for Ann-Arbor classification was included in more SRs (89 % vs. 64 %). Information extraction was quicker from SRs (median rating on 10-point Likert scale=9 vs. 6; 7–10 vs. 4–8 interquartile range). SRs had better comprehensibility (9 vs. 7; 8–10 vs. 5–8). Contribution of SRs to clinical decision-making was higher (9 vs. 6; 6–10 vs. 3–8). SRs were of higher quality (p < 0.001). All haematologists preferred SRs over FTRs.ConclusionsStructured reporting of CT examinations for primary staging in patients with DLBCL adds clinical value compared to FTRs by increasing completeness of reports, facilitating information extraction and improving patient management.Key Points• Structured reporting in CT helps clinicians to assess patients with lymphoma.• This two-centre study showed that structured reporting improves information content and extraction.• Patient management may be improved by structured reporting.• Clinicians preferred structured reports over free-text reports.

CD11b + Gr-1 + myeloid-derived suppressor cells (MDSCs) expand in the spleen during cancer and promote progression through suppression of cytotoxic T cells. An anti-inflammatory reflex arc involving the vagus nerve and memory T cells is necessary for resolution of acute inflammation. Failure of this neural circuit could promote procarcinogenic inflammation and altered tumour immunity. Here we show that splenic TFF2, a secreted anti-inflammatory peptide, is released by vagally modulated memory T cells to suppress the expansion of MDSCs through CXCR4. Splenic denervation interrupts the anti-inflammatory neural arc, resulting in the expansion of MDSCs and colorectal cancer. Deletion of Tff2 recapitulates splenic denervation to promote carcinogenesis. Colorectal carcinogenesis could be suppressed through transgenic overexpression of TFF2, adenoviral transfer of TFF2 or transplantation of TFF2-expressing bone marrow. TFF2 is important to the anti-inflammatory reflex arc and plays an essential role in arresting MDSC proliferation. TFF2 offers a potential approach to prevent and to treat cancer. During colorectal inflammation and cancer, myeloid cells accumulate in the spleen and suppress the host immunity response. In this study, the authors use a mouse model of colitis to demonstrate that upon vagus stimulation splenic memory T cells release TFF2, which suppresses the expansion of myeloid cells and cancer progression.

Background Precision medicine (PM) is a form of personalized medicine that recognizes that individuals with the same condition may have different underlying factors and uses molecular information to provide tailored treatments. This approach can improve treatment outcomes and transform lives through favorable risk/benefit ratios, avoidance of ineffective interventions, and possible cost savings, as evidenced in the field of lung cancer and other oncology/therapeutic settings, including cardiac disease, diabetes, and rare diseases. However, the potential benefits of PM have yet to be fully realized. Discussion There are many barriers to the implementation of PM in clinical practice, including fragmentation of the PM landscape, siloed approaches to address shared challenges, unwarranted variation in availability and access to PM, lack of standardization, and limited understanding of patients' experience and needs throughout the PM pathway. We believe that a diverse, intersectoral multistakeholder collaboration, with three main pillars of activity: generation of data to demonstrate the benefit of PM, education to support informed decision‐making, and addressing barriers across the patient pathway, is necessary to reach the shared goal of making PM an accessible and sustainable reality. Besides healthcare providers, researchers, policymakers/regulators/payers, and industry representatives, patients in particular must be equal partners and should be central to the PM approach―from early research through to clinical trials and approval of new treatments―to ensure it represents their entire experience and identifies barriers, solutions, and opportunities at the point of delivery. Conclusion We propose a practical and iterative roadmap to advance PM and call for all stakeholders across the healthcare system to employ a collaborative, cocreated, patient‐centered methodology to close gaps and fully realize the potential of PM. Key points The potential of precision medicine (PM) approaches to transform patients' lives has been demonstrated in the cancer setting, but also has benefits in therapeutic areas beyond oncology. Barriers to PM implementation include fragmentation of the PM landscape, siloed approaches, variation in availability and access to PM, lack of standardization, and limited understanding of the patient experience and needs throughout the PM pathway. Collaboration between different PM stakeholders, including patient communities, is essential to realize the potential of PM and make it an accessible reality for all those who could benefit.

Purpose In 2016, the University of Munich Molecular Tumor Board (MTB) was implemented to initiate a precision oncology program. This review of cases was conducted to assess clinical implications and functionality of the program, to identify current limitations and to inform future directions of these efforts. Methods Charts, molecular profiles, and tumor board decisions of the first 1000 consecutive cases (01/2016–03/2020) were reviewed. Descriptive statistics were applied to describe relevant findings. Results Of the first 1000 patients presented to the MTB; 914 patients received comprehensive genomic profiling. Median age of patients was 56 years and 58% were female. The most prevalent diagnoses were breast (16%) and colorectal cancer (10%). Different types of targeted or genome-wide sequencing assays were used; most of them offered by the local department of pathology. Testing was technically successful in 88%. In 41% of cases, a genomic alteration triggered a therapeutic recommendation. The fraction of patients receiving a tumor board recommendation differed significantly between malignancies ranging from over 50% in breast or biliary tract to less than 30% in pancreatic cancers. Based on a retrospective chart review, 17% of patients with an MTB recommendation received appropriate treatment. Conclusion Based on these retrospective analyses, patients with certain malignancies (breast and biliary tract cancer) tend to be more likely to have actionable variants. The low rate of therapeutic implementation (17% of patients receiving a tumor board recommendation) underscores the importance of meticulous follow-up for these patients and ensuring broad access to innovative therapies for patients receiving molecular tumor profiling.

Precision medicine has revolutionised cancer treatments; however, actionable biomarkers remain scarce. To address this, we develop the Oncology Biomarker Discovery (OncoBird) framework for analysing the molecular and biomarker landscape of randomised controlled clinical trials. OncoBird identifies biomarkers based on single genes or mutually exclusive genetic alterations in isolation or in the context of tumour subtypes, and finally, assesses predictive components by their treatment interactions. Here, we utilise the open-label, randomised phase III trial (FIRE-3, AIO KRK-0306) in metastatic colorectal carcinoma patients, who received either cetuximab or bevacizumab in combination with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI). We systematically identify five biomarkers with predictive components, e.g., patients with tumours that carry chr20q amplifications or lack mutually exclusive ERK signalling mutations benefited from cetuximab compared to bevacizumab. In summary, OncoBird characterises the molecular landscape and outlines actionable biomarkers, which generalises to any molecularly characterised randomised controlled trial. Identifying actionable biomarkers remains a challenge. Here, the authors develop a framework Oncology Biomarker Discovery (OncoBird), apply it to a phase III trial and investigate the molecular and biomarker landscape of metastatic colorectal carcinoma patients.

Background Cancer requires interdisciplinary intersectoral care. The Care Coordination Instrument (CCI) captures patients’ perspectives on cancer care coordination. We aimed to translate, adapt, and validate the CCI for Germany (CCI German version). Methods The original English version contains 29 items in three domains, measured on a 4-point Likert scale (strongly disagree to strongly agree). Validation was conducted in three phases (mixed methods): (I) translation; (II) adaptation: pilot testing and revision in an iterative process using semi-structured, cognitive interviews with patients and professionals (physicians specializing in cancer), with interviews transcribed and qualitatively analyzed by inductive coding; and (III) validation: quantitative validation performed online (LimeSurvey), of at least 80 German patients, each with common cancer (breast, prostate) and rare cancer (different entities), with examination of factor structure (factor analysis) and determination of internal consistency (Cronbach's α) as well as potential influencing factors such as gender, education, or migration background (multivariable regression). Results Six patients and six professionals tested the translated instrument for comprehensibility, readability, and acceptability. Two items were consistently problematic for interviewees. A 31-item version (29 items + 2 alternative items) was validated in 192 patients. The alternative items had a higher variance in response behavior and were better understood; therefore, they replaced the two problematic items. However, the three original domains could not be confirmed statistically. Exploratively, a two-factorial structure (with cross-loadings) emerged, which can be interpreted as “communication/information” (16 items) and “need-based navigation” (17 items). Overall, the instrument had a high internal consistency (total score α = 0.931, M  = 47.16, SD  = 14.25; communication/information α = 0.924, M  = 30.14, SD  = 8.93; need-based navigation α = 0.868, M  = 23.99, SD  = 8.37). Significant factors on the care coordination score are treatment location (hospital vs. private practice oncologist M  = -9.83 score points, p  = 0.011) and gender (women vs. men M = 8.92 score points, p  = 0.002). Conclusion The CCI German version is a valid instrument for measuring patients’ perceptions of cancer care coordination. Both domains reflect important aspects of care. The sensitivity of the CCI should be examined in future studies involving different cancer entities.

Prediction of response to checkpoint inhibition (ICI) and immune related adverse events (irAEs) remain a challenge in the immunotherapy of solid tumors. To better understand the real-world clinical courses under ICI and identify possible predictive markers for response and irAEs, we retrospectively collected and analysed data from our interdisciplinary CCCMunichLMU outpatient clinic. We analysed the clinical course, standard laboratory parameters and staging results of 342 patients who received ICI therapy in the interdisciplinary outpatient clinic of the CCCMunichLMU between January 2015 and November 2020. Initial response to ICI was defined as complete response, partial response, stable disease or mixed response with treatment continuation in the second radiologic staging after start of therapy. Median age of the included patients was 67 years (25–89). More male patients received ICI on our outpatient ward than female patients (67.8% vs. 32.2%). The most common entities were urothelial carcinoma (21.3%) and bronchial carcinoma (19.6%), followed by renal cell carcinoma (18.7%), and head and neck tumors (10.8%). 24.6% of patients were initial responders. Patients who did not respond to ICI therapy had lower leukocyte, lymphocyte, monocyte, and neutrophil counts before treatment start compared to initial responders. The consolidation of these laboratory parameters into a score could not accurately predict initial response or progression-free survival (PFS). IrAEs occurred in approximately one-third of all included patients. The main side effects in patients expierencing irAEs were thyroiditis (20.5%), pneumonitis (16.4%), hepatitis (15.8%), and dermatological side effects (11.0%). Patients experiencing irAEs had a significantly longer PFS than patients without irAEs. Side effects were more frequent and severe in patients treated with combined ICI. Autoimmune disorders were not associated with more frequent occurrence of irAEs. This retrospective analysis illustrates the real-world use of ICI in clinical practice. With only 24.6% of patients responding to ICI, the clinical need for predictive markers is obvious and standard laboratory parameters such as white blood cell counts may become part of a comprehensive score to predict response and adverse events.