Common Tumor Entity Research Articles

New tumor markers for testicular cancer - in the here and now and in the future

Germ cell tumors of the testis are the most common tumor entities in young men. Since the introduction of platinum-based chemotherapy in the 1970s, most patients can be cured despite the aggressiveness of germ cell tumors. Optimal serum tumor markers are required for diagnostics, therapy monitoring and aftercare, and these are subject to high requirements. The conventional testicular tumor markers human chorionic gonadotropin (hCG), alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) only meet these requirements with insufficient sensitivity (30-70%). The markers investigated in recent decades, such as PLAP, CEA and NSE, have not become established. Currently, miRNA-371 is being researched in particular. Reliable findings are available for initial staging with significantly better specificities of miRNA-371 compared to conventional tumor markers. Further prospective studies are being conducted for other possible clinical applications, such as follow-up care, therapy monitoring or residual tumors, in order to investigate the revolutionary potential of miRNA-371 in these areas as well. Research is also currently being conducted on circulating tumor cells (CTCs) and cell-free DNA (cfNA) in various areas of application. With regard to germ cell tumors of the testis, however, these analyses are still in their infancy, but it is hoped that this will provide a further sufficient opportunity to use serum tumor markers.

Cutaneous metastases: From epidemiology to therapy.

Cutaneous metastases are seen in up to 10% of all oncology patients and can occur in different locations depending on the entity. Cutaneous metastases are often associated with a high psychological burden and, especially in the case of exulceration, with shame and social withdrawal. This review discusses the diagnostic and therapeutic options. The most common tumor entities in which cutaneous metastases are observed are discussed, and local and systemic treatment options are presented according to the current state of research.

Safety and efficacy of Holmium-166 selective internal radiotherapy of primary and secondary liver cancer confirmed by real-world data.

Holmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry. Retrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients' health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma. A total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries. This study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.

Deep learning based histological classification of adnex tumors

BackgroundCutaneous adnexal tumors are a diverse group of tumors arising from structures of the hair appendages. Although often benign, malignant entities occur which can metastasize and lead to patients´ death. Correct diagnosis is critical to ensure optimal treatment and best possible patient outcome. Artificial intelligence (AI) in the form of deep neural networks has recently shown enormous potential in the field of medicine including pathology, where we and others have found common cutaneous tumors can be detected with high sensitivity and specificity. To become a widely applied tool, AI approaches will also need to reliably detect and distinguish less common tumor entities including the diverse group of cutaneous adnexal tumors. MethodsTo assess the potential of AI to recognize cutaneous adnexal tumors, we selected a diverse set of these entities from five German centers. The algorithm was trained with samples from four centers and then tested on slides from the fifth center. ResultsThe neural network was able to differentiate 14 different cutaneous adnexal tumors and distinguish them from more common cutaneous tumors (i.e. basal cell carcinoma and seborrheic keratosis). The total accuracy on the test set for classifying 248 samples into these 16 diagnoses was 89.92 %. Our findings support AI can distinguish rare tumors, for morphologically distinct entities even with very limited case numbers (< 50) for training. ConclusionThis study further underlines the enormous potential of AI in pathology which could become a standard tool to aid pathologists in routine diagnostics in the foreseeable future. The final diagnostic responsibility will remain with the pathologist.

CTNI-13. CONCURRENT INTRATHECAL CHEMOTHERAPY AND INVOLVED-FIELD RADIOTHERAPY FOR LEPTOMENINGEAL METASTASIS FROM SOLID TUMORS: A PHASE II STUDY (NCT03082144)

Abstract BACKGROUND The role of involved-field radiation therapy (IFRT) and intrathecal chemotherapy (IC) in leptomeningeal metastasis (LM) from solid tumors was gradually underestimated in the era of targeted therapy. This study was aimed to investigate the safety and effectiveness of concurrent IFRT and intrathecal methotrexate (MTX)/cytarabine (Ara-C) for LM, particularly for those who developed LM while receiving targeted therapy. METHODS Enrolled patients were randomly assigned to two subgroups (IFRT&amp;IC-MTX and IFRT&amp;IC-Ara-C), and first treated with induction IC (MTX or Ara-C) twice per week, up to 4 times. Then patients were given concurrent treatment, which consisted of IFRT (40 Gy total; 2 Gy/f) and IC (MTX 15 mg or Ara-C 50 mg, once per week). The involved field consisted of symptomatic or painful sites and disease observed on magnetic resonance imaging (MRI), including the whole brain and basis crania and/or segment of spinal canal. Primary endpoint was clinical response rate (RR). Secondary endpoints were safety and overall survival (OS). RESULTS Fifty-three patients received induction intrathecal MTX (n = 27) or Ara-C (n = 26). Forty-two patients completed concurrent therapy. Total RR was 34% (18/53). The improvement rate of neurological symptoms and KPS scores were 72% (38/53) and 66% (35/53) respectively. Adverse events (AEs) rate was 28% (15/53). Eight patients (15%, 8/53) showed grade 3-4 AEs, including myelosuppression (n = 4) and radiculitis (n = 5). Median OS was 6.5 months (95% CI, 5.3-7.7 months). Median survival for 18 patients who had clinical response was 7.9 months (95% CI, 4.4-11.4 months), and 0.8 months (95% CI, 0.08-1.5 months) for 6 patients who had LM progression. The median survival in 22 patients who received prior targeted therapy was 6.3 months (95% CI, 4.5-8.1 months). CONCLUSION Concurrent IFRT and intrathecal MTX or Ara-C was proved to be a feasible treatment option with an acceptable safety profile for LM from a common tumor entity.

OS02.4.A IMPACT OF SURGERY ON SURVIVAL IN PATIENTS WITH MULTIPLE BRAIN METASTASES

Abstract BACKGROUND Surgical resection of brain metastases (BM) alleviates symptoms and can improve patients’ survival. However, the benefit of resection in multiple BM is controversial due to patients’ limited life expectancy. Therefore, we investigated the impact of resection of multiple BM on patients’ survival. MATERIAL AND METHODS We reviewed clinical data from 544 patients (216 female, 328 male) who underwent surgery for BM in our hospital between 2010 and 2022. Overall survival (OS) was estimated using the Kaplan-Meier estimator. In addition, follow-up data, adjuvant treatment and tumor recurrence data were collected. RESULTS We identified 280 patients (51.5%) with one and 264 patients (48.5%) with two or more BM. Bronchial carcinoma represented the most common primary tumor entity (n= 185, 88 one and 97 multiple BM), followed by melanoma (n= 109, 44 one and 65 multiple BM), breast cancer (n= 54, 31 one and 23 multiple BM), gastro-intestinal tumor (n= 64, 39 one and 25 multiple BM) and lastly cancer of unknown primary (CUP) (n= 29, 11 one and 18 multiple BM). We then compared the survival between patients with a single with those with multiple BM. The median OS of all patients with one BM was with 11.6 months significantly longer than those with two or more BM (7.3 months, p&amp;lt; 0.001, 95% CI one vs. multiple BM: 8.6-14.5 vs. 6.2-8.4 months, respectively). Notably, 29.3% of patients with one BM and 16.5% with multiple BM lived longer than 24 months after resection (long-term survivor, p= 0.001). Regarding primary tumor histology, patients with breast cancer with a single BM had a significant longer OS with 19.7 compared to patients with multiple BM (5.0 months, p= 0.031). Remarkably, 33.3% of all long-term survivors with breast cancer had multiple BM. Patients with a single BM originating from other cancers showed a superior but yet not significant OS in comparison with their counterparts with multiple BM after resection. This included: gastro-intestinal cancer 12.2 vs. 6.5 months (p= 0.160), melanoma 11.6 vs. 7.3 months (p= 0.236) and CUP 3.0 vs. 2.7 months (p= 0.258). The long-term survivor rate of patients with resected multiple BM varied between 20.6% in melanoma and 7.4% in patients with CUP. CONCLUSION Despite limited prognosis in patients with multiple BM, surgical resection should be considered as an effective treatment option. Our study shows that a substantial subset of patients with multiple BM who underwent resection survive longer than 24 months after resection.

Photochemical Internalization with Fimaporfin: Enhanced Bleomycin Treatment for Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) still represents the world's sixth most common tumor entity, with increasing incidence. The reachability of light makes HNSCC suitable for light-based therapies such as Photochemical Internalization (PCI). The drug Bleomycin is cytotoxic and used as an anti-tumor medication. Since Bleomycin is endocytosed as a relatively large molecule, part of it is degraded in lysosomes before reaching its intracellular target. The goal of our study was to improve the intracellular availability of Bleomycin with PCI. We investigate the intracellular delivery of Bleomycin after PCI with the photosensitizer Fimaporfin. A systematic variation of Bleomycin and Fimaporfin concentrations and light irradiation led to the pronounced cell death of HNSCC cells. After optimization, the same level of tumor cell death of 75% was reached with a 20-fold lower Bleomycin concentration. This would allow treatment of HNSCC with high local tumor cell death and reduce the side effects of Bleomycin, e.g., lung fibrosis, at the same time. This demonstrates the increased efficacy of the anti-tumor medication Bleomycin in combination with PCI.

A phase II study of concurrent involved-field radiotherapy and intrathecal chemotherapy for leptomeningeal metastasis from solid tumors

BackgroundThe role of involved-field radiation therapy (IFRT) and intrathecal chemotherapy (IC) in leptomeningeal metastasis (LM) from solid tumors was gradually underestimated in the era of targeted therapy. This study was aimed to investigate the safety and effectiveness of concurrent IFRT and intrathecal methotrexate (MTX)/cytarabine (Ara-C) for LM, particularly for those who developed LM while receiving targeted therapy. Materials and MethodsEnrolled patients were given induction IC first and then concurrent treatment, which consisted of IFRT (40 Gy total; 2 Gy/f) and IC (MTX 15 mg or Ara-C 50 mg, once per week). Primary endpoint was clinical response rate (RR). Secondary endpoints were safety and overall survival (OS). ResultsFifty-three patients received induction intrathecal MTX (n = 27) or Ara-C (n = 26). Forty-two patients completed concurrent therapy. Total RR was 34% (18/53). The improvement rate of neurological symptoms and KPS scores were 72% (38/53) and 66% (35/53) respectively. Adverse events (AEs) rate was 28% (15/53). Eight patients (15%, 8/53) showed grade 3–4 AEs, including myelosuppression (n = 4) and radiculitis (n = 5). Median OS was 6.5 months (95% CI, 5.3–7.7 months). Median survival for 18 patients who had clinical response was 7.9 months (95% CI, 4.4–11.4 months), and 0.8 months (95% CI, 0.08–1.5 months) for 6 patients who had LM progression. The median survival in 22 patients who received prior targeted therapy was 6.3 months (95% CI, 4.5–8.1 months). ConclusionConcurrent IFRT and intrathecal MTX or Ara-C was proved to be a feasible treatment option with an acceptable safety profile for LM from a common tumor entity.

Molecular In-Depth Characterization of Chondrosarcoma for Current and Future Targeted Therapies.

Chondrosarcoma (CHS) are heterogenous, but as a whole, represent the second most common primary malignant bone tumor entity. Although knowledge on tumor biology has grown exponentially during the past few decades, surgical resection remains the gold standard for the treatment of these tumors, while radiation and differentiated chemotherapy do not result in sufficient cancer control. An in-depth molecular characterization of CHS reveals significant differences compared to tumors of epithelial origin. Genetically, CHS are heterogenous, but there is no characteristic mutation defining CHS, and yet, IDH1 and IDH2 mutations are frequent. Hypovascularization, extracellular matrix composition of collagen, proteoglycans, and hyaluronan create a mechanical barrier for tumor suppressive immune cells. Comparatively low proliferation rates, MDR-1 expression and an acidic tumor microenvironment further limit therapeutic options in CHS. Future advances in CHS therapy depend on the further characterization of CHS, especially the tumor immune microenvironment, for improved and better targeted therapies.

Drug monitoring detects under- and overdosing in patients receiving 5-fluorouracil-containing chemotherapy—results of a prospective, multicenter German observational study

Body surface area (BSA)-based dosing of 5-fluorouracil (5-FU) results in marked inter-individual variability in drug levels, whereas determination of plasma 5-FU concentration and area under the curve (AUC) is a more precise dosing method but has not been integrated into clinical routine. We conducted a multicenter, prospective study to study 5-FU AUC distributions and assess clinical factors predicting therapeutic dosing in patients receiving BSA-dosed 5-FU. Between June 2017 and January 2018, a total of 434 patients receiving continuous, infusional BSA-dosed 5-FU from 37 sites in Germany were included. Plasma 5-FU concentration and AUC were measured in venous blood samples at steady state. The primary objective was to determine 5-FU AUC distributions in relation to the target range, which is defined as 20-30 mg× h/l. The second objective was to explore clinical parameters that correlate with achievement of 5-FU AUC target range. The primary tumor was mainly located in the gastrointestinal tract (96.3%), with colorectal cancer being the most common (71.2%) tumor entity. 5-FU was administered as monotherapy (8.1%) or as part of FOLFOX (33.2%), FOLFIRI (26.3%), or other regimens (12.4%). Treatment setting was adjuvant (31.3%) or metastatic (64.5%). The median AUC was 16 mg× h/l. Only 20.3% of patients received 5-FU treatment within the target range, whereas the majority of patients (60.6%) were underdosed and 19.1% of patients were overdosed. In the univariate logistic regression, treatment setting was the only clinical parameter that significantly correlated with achievement of the target range. Patients treated in the metastatic setting had a 2.1 (95% confidence interval 1.186-3.776, P= 0.011) higher odds to reach the target range compared with patients treated in the adjuvant setting. The majority of patients received suboptimal doses of 5-FU using BSA dosing. Therapeutic drug monitoring of 5-FU is an option for optimized individualized cancer therapy and should be integrated into the clinical practice.

Survival after resection of brain metastasis: impact of synchronous versus metachronous metastatic disease

PurposePatients with brain metastasis (BM) from solid tumors are in an advanced stage of cancer. BM may occur during a known oncological disease (metachronous BM) or be the primary manifestation of previously unknown cancer (synchronous BM). The time of diagnosis might decisively impact patient prognosis and further treatment stratification. In the present study, we analyzed the prognostic impact of synchronous versus (vs.) metachronous BM occurrence following resection of BM.MethodsBetween 2013 and 2018, 353 patients had undergone surgical therapy for BM at the authors’ neuro-oncological center. Survival stratification calculated from the day of neurosurgical resection was performed for synchronous vs. metachronous BM diagnosis.ResultsNon-small-cell lung carcinoma (NSCLC) was the most common tumor entity of primary site (43%) followed by gastrointestinal cancer (14%) and breast cancer (13%). Synchronous BM occurrence was present in 116 of 353 patients (33%), metachronous BM occurrence was present in 237 of 353 patients (67%). NSCLC was significantly more often diagnosed via resection of the BM (56% synchronous vs. 44% metachronous situation, p = 0.0001). The median overall survival for patients with synchronous BM diagnosis was 12 months (95% confidence interval (CI) 7.5–16.5) compared to 13 months (95% CI 9.6–16.4) for patients with metachronous BM diagnosis (p = 0.97).ConclusionsThe present study indicates that time of BM diagnosis (synchronous vs. metachronous) does not significantly impact patient survival following surgical therapy of BM. These results suggest that the indication for neurosurgical BM resection should be made regardless of a synchronous or a metachronous time of BM occurrence.

Colorectal cancer

Being one of the most common tumor entities worldwide, the colorectal carcinoma accounts for approximately 10% of all tumor-related deaths. With screening programs such as preventive colonoscopy, adecreasing incidence and mortality rate can be seen in the last decades. Many risk factors, which favor or prevent the development of colorectal carcinoma, can be traced back to lifestyle choices. Many patients with localized disease can be cured through tumor resection and adjuvant chemotherapy, in systemic disease, targeted therapy and immunotherapy have improved survival in the last years. This article aims to provide an overview on the basic epidemiologic, diagnostic and therapeutic principles of colorectal carcinoma, as well as ashort excerpt of the newest therapeutic developments.

Differentiation of Intracerebral Tumor Entities with Quantitative Contrast Attenuation and Iodine Mapping in Dual-Layer Computed Tomography.

Purpose: To investigate if quantitative contrast enhancement and iodine mapping of common brain tumor (BT) entities may correctly differentiate between tumor etiologies in standardized stereotactic CT protocols. Material and Methods: A retrospective monocentric study of 139 consecutive standardized dual-layer dual-energy CT (dlDECT) scans conducted prior to the stereotactic needle biopsy of untreated primary brain tumor lesions. Attenuation of contrast-enhancing BT was derived from polyenergetic images as well as spectral iodine density maps (IDM) and their contrast-to-noise-ratios (CNR) were determined using ROI measures in contrast-enhancing BT and healthy contralateral white matter. The measures were correlated to histopathology regarding tumor entity, isocitrate dehydrogenase (IDH) and MGMT mutation status. Results: The cohort included 52 female and 76 male patients, mean age of 59.4 (±17.1) years. Brain lymphomas showed the highest attenuation (IDM CNR 3.28 ± 1,23), significantly higher than glioblastoma (2.37 ± 1.55, p < 0.005) and metastases (1.95 ± 1.14, p < 0.02), while the differences between glioblastomas and metastases were not significant. These strongly enhancing lesions differed from oligodendroglioma and astrocytoma (Grade II and III) that showed IDM CNR in the range of 1.22–1.27 (±0.45–0.82). Conventional attenuation measurements in DLCT data performed equally or slightly superior to iodine density measurements. Conclusion: Quantitative attenuation and iodine density measurements of contrast-enhancing brain tumors are feasible imaging biomarkers for the discrimination of cerebral tumor lesions but not specifically for single tumor entities. CNR based on simple HU measurements performed equally or slightly superior to iodine quantification.

P15.08.B Intraoperative confocal laser endomicroscopy of brain tumors - potential and challenges from a neuropathological perspective

Abstract Background Intraoperative consultation, usually in the form of a frozen section, is an integral part of current neuropathology practice. Typical indications include determination of specimen adequacy, intraoperative diagnosis and distinction between tumoral and non-tumoral tissue in diffusely infiltrating gliomas in tumor periphery. The latter is currently limited by the fact that typically not all potential regions of interest can be sampled for frozen sections and the turnaround times of frozen sections usually do not permit multiple repetitive assessments. The commercial availability of a clinical-grade in vivo laser endomicroscope for neurosurgical applications may have the potential to change this and to permit a microscopic analysis in near-real time, which in turn may have a significant impact on resection strategies for brain tumors. In this work, we investigate the potential role of CLE in neurosurgery and the transferability of histological criteria to confocal imaging. Material and Methods The potential role of CLE in neurosurgery in comparison to other techniques for intraoperative tumor assessment was determined by analyzing common intraoperative neuropathological workflows and identifying unaddressed opportunities. The transferability of the histological criteria from standard histology to confocal imaging was achieved by analyzing matched image pairs (standard histology and CLE) from several common tumor entities. Results We identified the time gap between specimen resection and the availability of the frozen section results as an important application for intraoperative CLE imaging in neurosurgery. Importantly, neuropathologists could assess tissue in near real time in an unlimited number of digital biopsies prior to resection, which adds a potent new tool to the neurosurgical armamentarium. CLE images revealed features similar to already known tissue architecture/morphology seen in standard histology, which correlated well in matched histological images. Unique aspects of individual cells and other surrounding tumor tissue elements were observed in vivo while the CLE probe acquired images throughout its focal-depth range. Conclusion Widespread application of CLE may have a major impact on neuropathologists' role in intraoperative diagnosis and bring along both opportunities and challenges. For broad clinical adoption, strategies for histological criteria validation as well as for determination of diagnostic accuracy need to be developed.

Clinical application of advanced multi-omics tumor profiling: Shaping precision oncology of the future.

Next-generation DNA sequencing technology has dramatically advanced clinical oncology through the identification of therapeutic targets and molecular biomarkers, leading to the personalization of cancer treatment with significantly improved outcomes for many common and rare tumor entities. More recent developments in advanced tumor profiling now enable dissection of tumor molecular architecture and the functional phenotype at cellular and subcellular resolution. Clinical translation of high-resolution tumor profiling and integration of multi-omics data into precision treatment, however, pose significant challenges at the level of prospective validation and clinical implementation. In this review, we summarize the latest advances in multi-omics tumor profiling, focusing on spatial genomics and chromatin organization, spatial transcriptomics and proteomics, liquid biopsy, and exvivo modeling of drug response. We analyze the current stages of translational validation of these technologies and discuss future perspectives for their integration into precision treatment.

Incidence and clinical outcome of primary carcinomas of the major salivary glands: 10-year data from a population-based state cancer registry in Germany

PurposeThe aim of this project was to provide an overview of the epidemiology of primary salivary gland carcinomas (SGC) in terms of incidence, distribution of clinicopathological features and survival in one of the largest cancer registries in Europe.MethodsData were collected from patients with SGC of the major salivary glands registered in the population-based state cancer registry (Landeskrebsregister LKR) in North Rhine-Westphalia (NRW), Germany from 01/01/2009 to 12/31/2018. Age standardization of incidence was performed and relative survival estimates were computed by sex, histological group, age group and T-, N-, and M-stage.ResultsA total of 1680 patients were included in this analysis. The most frequent tumor localization was the parotid gland (78%). Adenocarcinoma (not otherwise specified) was the most common tumor entity (18.5%). Most tumors were found in stages T1–T3 (29% T1; 29% T2; 28% T3). The age-standardized incidence rate (ASR) for SGC was 0.65/100,000 and remained stable during the observation period. There was an age-dependent incidence increasing especially from the age 70 years and onwards. The overall 5-year relative survival (RS) for all patients with SGC was 69.2%. RS was 80–95.6% for T1–2 stage tumors, 60.3% for T3, 47.3% for T4 stage, 87.4% for N0 and 51.2% for N1–2, 74.4% for M0 and 44.9% for M1.ConclusionAge-standardized incidence for SGC has been stable for the observed 10-year period. Smaller tumors and those without lymph node or distant metastases had a better RS than more advanced tumors.

Radiophysiomics: Brain Tumors Classification by Machine Learning and Physiological MRI Data.

Simple SummaryThe pretreatment diagnosis of contrast-enhancing brain tumors is still challenging in clinical neuro-oncology due to their very similar appearance on conventional MRI. A precise initial characterization, however, is essential to initiate appropriate treatment management, which can substantially differ between brain tumor entities. To overcome the disadvantage of the low specificity of conventional MRI, several new neuroimaging methods have been developed and validated over the past decades. This increasing amount of diagnostic information makes a timely evaluation without computational support impossible in a clinical setting. Artificial intelligence methods such as machine learning offer new options to support clinicians. In this study, we combined nine common machine learning algorithms with a physiological MRI technique (we named this approach “radiophysiomics”) to investigate the effectiveness of the multiclass classification of contrast-enhancing brain tumors in a clinical setting. We were able to demonstrate that radiophysiomics could be helpful in the routine diagnostics of contrast-enhancing brain tumors, but further automation using deep neural networks is required.The precise initial characterization of contrast-enhancing brain tumors has significant consequences for clinical outcomes. Various novel neuroimaging methods have been developed to increase the specificity of conventional magnetic resonance imaging (cMRI) but also the increased complexity of data analysis. Artificial intelligence offers new options to manage this challenge in clinical settings. Here, we investigated whether multiclass machine learning (ML) algorithms applied to a high-dimensional panel of radiomic features from advanced MRI (advMRI) and physiological MRI (phyMRI; thus, radiophysiomics) could reliably classify contrast-enhancing brain tumors. The recently developed phyMRI technique enables the quantitative assessment of microvascular architecture, neovascularization, oxygen metabolism, and tissue hypoxia. A training cohort of 167 patients suffering from one of the five most common brain tumor entities (glioblastoma, anaplastic glioma, meningioma, primary CNS lymphoma, or brain metastasis), combined with nine common ML algorithms, was used to develop overall 135 classifiers. Multiclass classification performance was investigated using tenfold cross-validation and an independent test cohort. Adaptive boosting and random forest in combination with advMRI and phyMRI data were superior to human reading in accuracy (0.875 vs. 0.850), precision (0.862 vs. 0.798), F-score (0.774 vs. 0.740), AUROC (0.886 vs. 0.813), and classification error (5 vs. 6). The radiologists, however, showed a higher sensitivity (0.767 vs. 0.750) and specificity (0.925 vs. 0.902). We demonstrated that ML-based radiophysiomics could be helpful in the clinical routine diagnosis of contrast-enhancing brain tumors; however, a high expenditure of time and work for data preprocessing requires the inclusion of deep neural networks.

Incidences and characteristics of primary lung malignancies in childhood in Germany: An analysis of population-based data from German cancer registries.

Primary lung malignancies are a heterogeneous group of cancers that occur very rarely in childhood. Due to limited knowledge of their epidemiologic and clinical features, these tumors present a challenge to the treating physicians. This study aimed to increase the knowledge about the occurrence of primary lung malignancies in childhood in Germany. Pseudonymized data of cases recorded at the German Center for Cancer Registry Data (ZfKD) between 1990 and 2017 were retrieved. Primary lung malignancies were identified using the ICD- and ICD-O classification. Numbers were compared to those reported to the German Childhood Cancer Registry (GCCR). Crude incidence rates were calculated using the ZfKD database. A total of 168 patients diagnosed with primary lung malignancies in the age below 19 years were identified from the ZfKD. The median age at diagnosis was 13 years. The most common tumor entities were lung carcinoids (n=49), lung carcinoma (n=36), and pleuropulmonary blastoma (n=14). An unexpected accumulation of lung cancer cases was noted in the first year of life without a clearly specified histopathological diagnosis. A substantial discrepancy in the numbers of primary lung malignancies between ZfKD and GCCR was found. We present population-based data on the occurrence of primary childhood lung malignancies in Germany, which were more frequent than previously anticipated but likely remained underreported. For better understanding and optimal treatment of these entities, cancer registration needs to be improved through mandatory reporting to the GCCR and regular data sharing between GCCR, population-based and clinical cancer registries.

Distribution of gastrointestinal neuroendocrine tumors in Europe: results from a retrospective cross-sectional study

BackgroundGastrointestinal (non-pancreatic) neuroendocrine tumors (GI-NETs) represent a rare but increasingly common tumor entity. Prognosis and biological behavior of these tumors is extremely heterogenous and largely dependent on the specific tumor site, stage and differentiation. However, systematic data on the epidemiology of GI-NET, especially in terms of geographic distributions are missing.MethodsWe used the Oncology Dynamics database (IQVIA) to identify a total of 1354 patients with GI-NET from four European countries (Germany, France, Spain, UK) and compared them with regard to major patient and tumor related characteristics including patients’ age, sex, tumor stage, tumor grading and differentiation.ResultsOut of the analyzed 1354 NET patients, 535 were found in the UK (39.5%), 289 in Germany (21.3%), 283 in Spain (20.9%) and 247 in France (18.2%). More patients were male than female (53.8% vs. 46.2%) with no significant differences between the analyzed countries. In contrast, the age distribution varied between the different countries, with the highest number of patients identified in the age groups of 61–70 years (31.0%) and 71–80 years (30.7%). The vast majority of patients showed a tumor origin in the small intestine, in German patients NET of the large intestine were slightly overrepresented and NET of the stomach underrepresented compared to all other countries. More than 80% of patients had stage IV disease at the time of diagnosis. Regarding tumor histology, most tumors showed a G2 tumor; interestingly, a G3 grading was found in 40.9% of patients in Germany (Ki-67 > 20%).ConclusionThe distribution of important patient- and tumor-specific characteristics of neuroendocrine tumors shows regional differences in four major European countries. These data may help to better understand the specific epidemiology of GI-NET in Europe.

The Role of Conventional TACE (cTACE) and DEBIRI-TACE in Colorectal Cancer Liver Metastases.

Simple SummaryLiver metastases of colorectal cancer have an enormous clinical impact and prevalence. As colorectal cancer is one of the most common cancers, such patients are routinely encountered in day-to-day practice. Still, surgery and systemic chemotherapy constitute the first-line therapies depending on clinical setting. However, if patients present with non-resectable liver-only or liver-dominant metastases and/or do not respond to systemic chemotherapy, local therapies based on a vascular approach can be offered by interventional radiologists to achieve local tumor control or to downstage tumor burden. These therapies are generally called transarterial chemoembolization (TACE). Such treatments can also be combined with systemic or other local therapies. Depending on local practice and expertise, TACE can be offered with a combination of chemotherapeutic agents and embolizing agents or drug-eluting beads which embolize the metastases and its feeding vascular supply and release a chemotherapeutic agent over time. In the following review we compare these different approaches in the local therapy of liver metastases of colorectal cancer by presenting representative study results.Colorectal cancer (CRC) is one of the most common tumor entities worldwide and a common cause of cancer-associated death. Colorectal cancer liver metastases (CRLM) thereby constitute a severe life-limiting factor. The therapy of CRLM presents a major challenge and surgical resection as well as systemic chemotherapy remain the first-line treatment options. Over the years several locoregional, vascular- and image-based treatments offered by interventional radiologists have emerged when conventional therapies fail, or metastases recurrence occurs. Among such options is the conventional/traditional transarterial chemoembolization (cTACE) by local injection of a combination of chemotherapeutic- and embolic-agents. A similar treatment is the more recent irinotecan-loaded drug-eluting beads TACE (DEBIRI-TACE), which are administered using the same approach. Numerous studies have shown that these different types of chemoembolization can be applied in different clinical settings safely. Furthermore, such treatments can also be combined with other local or systemic therapies. Unfortunately, due to the incoherent patient populations of studies investigating TACE in CRLM, critics state that the definite evidence supporting positive patient outcomes is still lacking. In the following article we review studies on conventional and DEBIRI-TACE. Although highly dependent on the clinical setting, prior therapies and generally the study population, cTACE and DEBIRI-TACE show comparable results. We present the most representative studies on the different chemoembolization procedures and compare the results. Although there is compelling evidence for both approaches, further studies are necessary to determine which patients profit most from these therapies. In conclusion, we determine TACE to be a viable option in CRLM in different clinical settings. Nevertheless, a multidisciplinary approach is desired to offer patients the best possible care.