A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine.

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens.

Comorbidities, Rather Than Older Age, Are Strongly Associated With Higher Utilization of Healthcare in Colorectal Cancer Survivors.

Background: Colorectal cancer (CRC) survivors generally have a higher healthcare utilization (HCU) than the general population due to cancer burden. However, it is unclear which factors are associated with this increased uptake. Our study aimed to (1) compare CRC-related and non-CRC visits to general practitioners (GPs) and medical specialists (MSs) by comorbidities, and (2) assess whether HCU differs by demographic, clinical, and psychological factors.

Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care.

The analysis of circulating tumor DNA (ctDNA) is at the threshold of implementation into standard care for colorectal cancer (CRC) patients. However, data about the clinical utility of liquid profiling (LP), its acceptance by clinicians, and its integration into clinical workflows in real-world settings remain limited. Here, LP tests requested as part of routine care since 2016 were retrospectively evaluated.

Advantages and Challenges of Using ctDNA NGS to Assess the Presence of Minimal Residual Disease (MRD) in Solid Tumors.

The ability to detect minimal residual disease (MRD) after a curative-intent surgery or treatment is of paramount importance, because it offers the possibility to help guide the clinical decisions related adjuvant therapy. Thus, the earlier MRD is detected, the earlier potentially beneficial treatment can be proposed to patients who might need it. Liquid biopsies, and in particular the next-generation sequencing of circulating tumor DNA (ctDNA) in the blood, have been the focus of an increasing amount of research in the past years.

Assessment of SARS-CoV-2 Infection among Healthcare Workers of a German COVID-19 Treatment Center.

To date, more than 160 million people have been infected with COVID-19 worldwide. In the present study, we investigated the history of SARS-CoV-2 infection among 3067 healthcare workers (HCW) in a German COVID-19 treatment center during the early phase of the pandemic (July 2020) based on the seroprevalence of SARS-CoV-2 antibodies and self-reported previous PCR results. The results demonstrate a low prevalence of SARS-CoV-2 infection ( = 107 [3.

Merging Genomics Public Datasets with Clinical Cancer Registry Data - Lessons Learned.

Publicly available datasets - for example via cBioPortal for Cancer Genomics - could be a valuable source for benchmarks and comparisons with local patient records. However, such an approach is only valid if patient cohorts are comparable to each other and if the documentation is complete and sufficient. In this paper, records from exocrine pancreatic cancer patients documented in a local cancer registry are compared with two public datasets to calculate overall survival.

Uptake Rates of Novel Therapies and Survival Among Privately Insured Versus Publicly Insured Patients With Colorectal Cancer in Germany.

Background: In the era of personalized medicine, cancer care is subject to major changes and innovations. It is unclear, however, to what extent implementation of such innovations and their impact on patient outcomes differ by health insurance type. This study compared provision of treatment and survival outcomes among patients with colorectal cancer (CRC) who had statutory health insurance (SHI) versus private health insurance (PHI) in Germany.

Magnitude of the Age-Advancement Effect of Comorbidities in Colorectal Cancer Prognosis.

Background: Comorbidities and old age independently compromise prognosis of patients with colorectal cancer (CRC). The impact of comorbidities could thus be considered as conveying worse prognosis already at younger ages, but evidence is lacking on how much worsening of prognosis with age is advanced to younger ages in comorbid versus noncomorbid patients. We aimed to quantify, for the first time, the impact of comorbidities on CRC prognosis in "age advancement" of worse prognosis.

Treatment selection bias for chemotherapy persists in colorectal cancer patient cohort studies even in comprehensive propensity score analyses.

Introduction: Propensity score methods are increasingly used to address confounding related to treatment selection in observational studies. Studies estimating the effect of chemotherapy in colon cancer (CC) patients, however, often lacked information on pertinent comorbidities and functional status (FS). We assessed to what extent comorbidities and FS impact treatment decisions in colorectal cancer patients and explain the benefit of chemotherapy in stage III CC patients.

Decreasing Use of Chemotherapy in Older Patients With Stage III Colon Cancer Irrespective of Comorbidities.

Background: Chemotherapy underuse in elderly patients (aged ≥75 years) with colon cancer has been reported in previous studies. However, these studies were mostly registry-based and limited in their potential to consider underlying reasons of such undertreatment. This study aimed to evaluate patient and hospital determinants of chemotherapeutic treatment in patients with stage III colon cancer, with a particular focus on age and underlying reasons for nontreatment of elderly patients.

Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.

Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours.

Methods: In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m epirubicin and 60 mg/m cisplatin on day 1 plus either 200 mg/m fluorouracil as continuous intravenous infusion or 1250 mg/m capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m docetaxel, 85 mg/m oxaliplatin, 200 mg/m leucovorin and 2600 mg/m fluorouracil as 24-h infusion on day 1 (FLOT; experimental group).

Olaparib.

Olaparib (Lynparza [AstraZeneca, Cambridge, UK], formerly referred to as AZD2281 or KU0059436) is an oral poly(ADP-ribose) polymerase (PARP) inhibitor. It is rationally designed to act as a competitive inhibitor of NAD at the catalytic site of PARP1 and PARP2, both members of the PARP family of enzymes that are central to the repair of DNA single-strand breaks (SSBs) mediated via the base excision repair (BER) pathway. Inhibition of the BER pathway by olaparib leads to the accumulation of unrepaired SSBs, which leads to the formation of deleterious double-strand breaks (DSBs).

Larotrectinib (LOXO-101).

One of the most challenging issues in oncology research and treatment is identifying oncogenic drivers within an individual patient's tumor which can be directly targeted by a clinically available therapeutic drug. In this context, gene fusions as one important example of genetic aberrations leading to carcinogenesis follow the widely accepted concept that cell growth and proliferation are driven by the accomplished fusion (usually involving former proto-oncogenes) and may therefore be successfully inhibited by substances directed against the fusion. This concept has already been established with oncogenic gene fusions like BCR-ABL in chronic myelogenous leukemia (CML) or anaplastic lymphoma kinase (ALK) in lung cancer, including special tyrosine kinase inhibitors (TKIs) which are able to block the activation of the depending downstream proliferation pathways and, consequently, tumor growth.

Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer.

Background: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer.

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m, days 1, 15, 29), high-dose methotrexate (3 g/m days 2, 16, 30), procarbazine (60 mg/m days 2-11) and lomustine (110 mg/m, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol.

Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial.

Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection.

Methods: In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres.

Clinical Cancer Registries - Are They Up for Health Services Research?

Clinical cancer registries are a valuable data source for health services research (HSR). HSR is in need of high quality routine care data for its evaluations. However, the secondary use of routine data - such as documented cancer cases in a disease registry - poses new challenges in terms of data quality, IT-management, documentation processes and data privacy.

Pretransplant NPM1 MRD levels predict outcome after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia.

The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-eight of the 67 patients had a FLT3-ITD (42%). Median age at transplantation was 54.

Electrochemical Effects after Transarterial Chemoembolization in Combination with Percutaneous Irreversible Electroporation: Observations in an Acute Porcine Liver Model.

Purpose: To evaluate the effects of combined use of transarterial chemoembolization and irreversible electroporation (IRE) for focal tissue ablation in an acute porcine liver model.

Materials And Methods: Two established interventional techniques were combined: IRE with zones of irreversible and reversible electroporation and chemoembolization with microspheres, iodized oil, and doxorubicin. IRE was performed before chemoembolization in two pigs (pigs 1 and 2; IRE/chemoembolization group), chemoembolization was performed before IRE in two pigs (pigs 3 and 4; chemoembolization/IRE group), and only IRE was performed in two pigs (pigs 5 and 6).

Transition probabilities of HER2-positive and HER2-negative breast cancer patients treated with Trastuzumab obtained from a clinical cancer registry dataset.

Records of female breast cancer patients were selected from a clinical cancer registry and separated into three cohorts according to HER2-status (human epidermal growth factor receptor 2) and treatment with or without Trastuzumab (a humanized monoclonal antibody). Propensity score matching was used to balance the cohorts. Afterwards, documented information about disease events (recurrence of cancer, metastases, remission of local/regional recurrences, remission of metastases and death) found in the dataset was leveraged to calculate the annual transition probabilities for every cohort.

A method for using real world data in breast cancer modeling.

Objectives: Today, hospitals and other health care-related institutions are accumulating a growing bulk of real world clinical data. Such data offer new possibilities for the generation of disease models for the health economic evaluation. In this article, we propose a new approach to leverage cancer registry data for the development of Markov models.

Prediction of 5-Year Survival with Data Mining Algorithms.

Survival time prediction at the time of diagnosis is of great importance to make decisions about treatment and long-term follow-up care. However, predicting the outcome of cancer on the basis of clinical information is a challenging task. We now examined the ability of ten different data mining algorithms (Perceptron, Rule Induction, Support Vector Machine, Linear Regression, Naïve Bayes, Decision Tree, k-nearest Neighbor, Logistic Regression, Neural Network, Random Forest) to predict the dichotomous attribute "5-year-survival" based on seven attributes (sex, UICC-stage, etc.

Personalized treatment for colorectal cancer: novel developments and putative therapeutic strategies.

Background: Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and continues to be a major healthcare concern. Molecular heterogeneity of CRC is believed to be one of the main factors responsible for the considerable variability in treatment response. With the recent development of powerful genomic technologies, novel insights in tumor biology of CRC have now been provided, facilitating the recognition of new molecular subtypes with prognostic and predictive implications.

Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial.

Background: Integrins are involved in tumour progression and metastasis, and differentially expressed on colorectal cancer (CRC) cells. Abituzumab (EMD 525797), a humanised monoclonal antibody targeting integrin αν heterodimers, has demonstrated preclinical activity. This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part).