Background: Systemic cancer therapy may trigger anxiety/depressive symptoms and toxicity. Relaxation techniques can help alleviate toxicities but their implementation in clinical practice is challenging. We hypothesize that virtual reality (VR) systems which project a relaxing nature environment may help to reduce psychological stress and toxicities of cancer therapies. This trial aims to evaluate the feasibility of a supportive VR intervention in patients receiving cancer therapies in an outpatient setting. Patients and methods: OncoVR is a randomized, open-label, cross-over trial to investigate the feasibility and impact of VR support during cancer therapy to improve anxiety, depressive symptoms, and toxicity in patients with gastrointestinal cancers. In total, 54 participants will be assigned to receive systemic therapy with VR support, followed by a subsequent course without VR support (arm A). Patients in arm B will first receive therapy without VR support, followed by a subsequent course with VR support. Primary endpoints are the feasibility of VR support (80% of the patients can tolerate its use for a minimum duration of 20 min), and changes in anxiety/depressive symptoms using the Hospital Anxiety and Depression Scale (HADS-D) and Positive and Negative Affect Schedule (PANAS) questionnaires. Secondary endpoints include the incidence and severity of therapy-associated toxicities per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) and Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) grading, and patient experience using the Player Experience Inventory (PXI) questionnaire.

BACKGROUND:Despite the prognostic relevance of cachexia in pancreatic cancer, individual body composition has not been routinely integrated into treatment planning. In this multicenter study, we investigated the prognostic value of sarcopenia and myosteatosis automatically extracted from routine computed tomography (CT) scans of patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS:We retrospectively analyzed clinical imaging data of 601 patients from three German cancer centers. We applied a deep learning approach to assess sarcopenia by the abdominal muscle-to-bone ratio (MBR) and myosteatosis by the ratio of abdominal inter- and intramuscular fat to muscle volume. In the pooled cohort, univariable and multivariable analyses were carried out to analyze the association between body composition markers and overall survival (OS). We analyzed the relationship between body composition markers and laboratory values during the first year of therapy in a subgroup using linear regression analysis adjusted for age, sex, and American Joint Committee on Cancer (AJCC) stage. RESULTS:Deep learning-derived MBR [hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.47-0.77, P < 0.005] and myosteatosis (HR 3.73, 95% CI 1.66-8.39, P < 0.005) were significantly associated with OS in univariable analysis. In multivariable analysis, MBR (P = 0.019) and myosteatosis (P = 0.02) were associated with OS independent of age, sex, and AJCC stage. In a subgroup, MBR and myosteatosis were associated with albumin and C-reactive protein levels after initiation of therapy. Additionally, MBR was also associated with hemoglobin and total protein levels. CONCLUSIONS:Our work demonstrates that deep learning can be applied across cancer centers to automatically assess sarcopenia and myosteatosis from routine CT scans. We highlight the prognostic role of our proposed markers and show a strong relationship with protein levels, inflammation, and anemia. In clinical practice, automated body composition analysis holds the potential to further personalize cancer treatment.

Purpose: Patients with BRAF V600E mutant metastatic colorectal cancer (mCRC) have a dismal prognosis. The best strategies in these patients remain elusive. Against this background, we report the clinical course of patients with BRAF V600E mutant mCRC to retrieve the best treatment strategy. Patients and Methods: Clinico-pathological data were extracted from the electronic health records. Kaplan-Meier method was used to estimate overall (OS) and progression-free survival (PFS). Objective response rate (ORR) was assessed according to RECIST 1.1. Results: In total, 51 patients were enrolled. FOLFOXIRI was administered to 12 patients, 29 patients received FOLFOX or FOLFIRI as first-line treatment. Median OS was 17.6 months. Median PFS with FOLFOXIRI (13.0 months) was significantly prolonged (HR 0.325) as compared to FOLFOX/FOLFIRI (4.3 months). However, this failed to translate into an OS benefit (p=0.433). Interestingly, addition of a monoclonal antibody to chemotherapy associated with superior OS (HR 0.523). A total of 64.7% patients received further-line therapy, which included a BRAF inhibitor in 17 patients. Targeted therapy associated with very favourable OS (25.1 months). Conclusion: Patients with BRAF V600E -mutated mCRC benefit from the addition of an antibody to first-line chemotherapy. Further line treatment including a BRAF inhibitor has a dramatic impact on survival.

BACKGROUND:Existing risk scores appear insufficient to assess the individual survival risk of patients with advanced pancreatic ductal adenocarcinoma (PDAC) and do not take advantage of the variety of parameters that are collected during clinical care.METHODS:In this retrospective study, we built a random survival forest model from clinical data of 203 patients with advanced PDAC. The parameters were assessed before initiation of systemic treatment and included age, CA19-9, C-reactive protein, metastatic status, neutrophil-to-lymphocyte ratio and total serum protein level. Separate models including imaging and molecular parameters were built for subgroups.RESULTS:Over the entire cohort, a model based on clinical parameters achieved a c-index of 0.71. Our approach outperformed the American Joint Committee on Cancer (AJCC) staging system and the modified Glasgow Prognostic Score (mGPS) in the identification of high- and low-risk subgroups. Inclusion of the KRAS p.G12D mutational status could further improve the prediction, whereas radiomics data of the primary tumor only showed little benefit. In an external validation cohort of PDAC patients with liver metastases, our model achieved a c-index of 0.67 (mGPS: 0.59).CONCLUSIONS:The combination of multimodal data and machine-learning algorithms holds potential for personalized prognostication in advanced PDAC already at diagnosis.

Systemic-inflammatory response parameters (SIR) are known prognostic markers in different tumour entities, but have not been evaluated in patients with iCCA treated with systemic chemotherapy. Therefore, we evaluated the impact of different SIR markers on the clinical course of patients with advanced iCCA treated at our center. SIR markers were retrospectively evaluated in 219 patients with iCCA at the West-German-Cancer-Center Essen from 2014 to 2019. Markers included neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), CRP, and the modified Glasgow-Prognostic-Score (mGPS), which were correlated with clinico-pathological findings, response to chemotherapy (ORR), progression-free (PFS) and overall survival (OS) using Kaplan–Meier analyses, and Cox proportional models. Median overall survival (OS) of the entire cohort was 14.8 months (95

Abstract Purpose: We report efficacy and safety of 90Y-labeled FAPI-46 (90Y-FAPI-46-RLT) in patients with advanced sarcoma, pancreatic cancer, and other cancer entities. Experimental Design: Up to four cycles of radioligand therapy (RLT) were offered to patients with (i) progressive metastatic malignancy, (ii) exhaustion of approved therapies, and (iii) high fibroblast activation protein (FAP) expression, defined as SUVmax ≥ 10 in more than 50% of tumor. Primary endpoint was RECIST response after RLT. Secondary endpoints included PET response (PERCIST), overall survival (OS), dosimetry, and safety of FAP-RLT. Results: Among 119 screened patients, 21 (18%) were found eligible [n = 16/3/1/1 sarcoma/pancreatic cancer/prostate/gastric cancer; 38% Eastern Cooperative Oncology Group (ECOG) ≥ 2] and received 47 90Y-FAPI-46-RLT cycles; 16 of 21 (76%) patients underwent repeat RLT. By RECIST, disease control was confirmed in 8 of 21 patients [38%; 8/16 (50%) of evaluable patients). There was one partial response (PR) and seven stable diseases after RLT. Disease control was associated with prolonged OS (P = 0.013). PERCIST response was noted in 8 of 21 patients [38%; 8/15 (53%) of evaluable patients]. Dosimetry was acquired in 19 (90%) patients. Mean absorbed dose was 0.53 Gy/GBq in kidney, 0.04 Gy/GBq in bone marrow, and <0.14 Gy/GBq in liver and lung. Treatment-related grade 3 or 4 adverse events were observed in 8 (38%) patients with thrombocytopenia (n = 6) and anemia (n = 6) being most prevalent. Conclusions: 90Y-FAPI-46-RLT was safe and led to RECIST PR in one case as well as stable disease in about one third of patients with initially progressive sarcomas, pancreatic cancer, and other cancers. Discontinuation after the first cycle and a low rate of PR requires future improvement of FAP-RLT.

Ziel/Aim Initial reports on fibroblast activation protein (FAP) targeted radioligand therapy, such as Y-90-FAPI46, has shown a favorable safety profile with low rates of adverse events and acceptable toxicity. Nonetheless efficacy of this novel treatment has not been properly evaluated before. Here we report radiographic and metabolic response to Y-90-FAPI46 radioligand therapy in extensively pretreated patients with various solid tumors.

The multicenter, single-arm, phase II trial (Simon's two stage design) evaluated the efficacy of mFOLFOX6 + cetuximab (500 mg/m2) q2w as 1st line therapy in KRAS wt mCRC. Final extended molecular and subgroup analyses are presented. Primary endpoint was response rate (ORR) per RECIST 1.0. In stage 1 and 2, 13 and 25 responders were needed in 37 and 53 pts, respectively, to further evaluate this therapy (H1 p > 0.55). Secondary endpoints were PFS, OS, safety, metastasectomy and quality of life (QoL). Extended molecular profiling was performed using NGS-based panel sequencing including NRAS, KRAS, BRAF, PIK3CA and TP53. Clinical parameters included: tumor location (left-sided LCRC), early tumor-shrinkage (ETS), depth of response (DPR), metastasectomy and inflammation markers (neutrophil/lymphocyte ratio-NLR). Differences in ORR, PFS and OS were calculated using chi-square and log rank tests. Hazard ratios were calculated by Cox regression analysis. The primary endpoint was met with 57 pts enrolled (ITT) and 53 pts evaluable for response. There were 26 responders in stage 1 (70%) and 38 responders in the ITT (ORR of 67%). Median PFS and OS were 9.6 (7.4-11.7) and 29.4 (19.3-39.5) months, respectively. Secondary metastasectomy was achieved in 31.7%. Grade 3/4 AEs occurred in 52%, including leukocytopenia, rash and GI-toxicity. Molecular profiling could be performed in 44 pts (77%). Additional RAS or BRAF mutations were detected in 17.8% and 10.6%, respectively, with a negative impact on outcomes. TP53 mutations were detected in 62.5% without impact on outcomes. Pts with LCRC, ETS or metastasectomy had significantly prolonged OS, whereas pts with high NLR (>5) had inferior OS (all p-values <0.05). Median DPR was 45.9%, and correlated with PFS and OS (p < 0.01) and RAS/BRAF mutational status (p < 0.01). This study supports the efficacy and safety of q2w cetuximab given in combination with mFOLFOX6. Extended mutational analyses of key oncogenes and routinely assessed clinical parameters may help to identify patients with maximum likelihood of benefit from cetuximab-based chemotherapy.

Objectives: Pulmonary adenocarcinomas (ADC) can be sub-grouped based on dominant oncogenic drivers. EGFR mutations define an entity of metastatic ADC with favorable prognosis and high susceptibility to EGFR tyrosine kinase inhibition. In contrast, the clinical impact of additional ERBB family members in ADC is less defined. To this end we prospectively studied HER2 expression, gene amplification, and mutation in relation to outcome of patients with advanced or metastatic ADC.Materials and methods: Diagnostic tumor biopsies from 193 sequential patients with stage III/IV ADC were prospectively studied for HER2 expression by immunohistochemistry (IHC). Cases with IHC scores 2+ or 3+ were analyzed by HER2 chromogenic in situ hybridization (CISH), and sequencing of HER2 exons 20 and 23. Additional prospectively determined biomarkers included PTEN, cMET, pAKT, and pERK expression, KRAS, EGFR, BRAF and PIK3CA mutations, and ALK fluorescence ISH (FISH).Results and conclusion: HER2-IHC was feasible in 176 (91.2%) cases. Of 53 (30%) cases with IHC scores 2+13+, 45 (85%) could be studied by CISH and 34 (64%) by sequencing. The lower number of HER2-mutational analyses resulted from exhaustion of tumor tissue and DNA following mutational analysis of KRAS, EGFR, BRAF and PIK3CA. HER2 amplification was detected in 4 cases (2.3%), while no mutation was found. HER2 expression correlated with expression of pAKT and cMET. Expression of HER2 and pAKT was associated with favorable overall survival in stage IV disease. HER2-expressing ADC more frequently harbored KRAS mutations, while HER2 expression was absent in all 4 cases with BRAF mutation.HER2-IHC was not predictive of HER2 gene amplification, or mutation, which both were rare events in prospectively studied patients with advanced or metastatic ADC. Expression of HER2 and pAKT define a population of patients with stage IV ADC with a distinct disease course, who could benefit from specifically tailored pharmacotherapies. (c) 2015 Elsevier Ireland Ltd. All rights reserved.