Cancers

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21 pages, 5573 KiB

Open AccessArticle

Overlapping Stromal Alterations in Myeloid and Lymphoid Neoplasms

by Lucienne Bogun, Annemarie Koch, Bo Scherer, Ulrich Germing, Roland Fenk, Uwe Maus, Felix Bormann, Karl Köhrer, Patrick Petzsch, Thorsten Wachtmeister, Guido Kobbe, Sascha Dietrich, Rainer Haas, Thomas Schroeder, Stefanie Geyh and Paul Jäger

Cancers 2024, 16(11), 2071; https://doi.org/10.3390/cancers16112071 - 30 May 2024

Viewed by 1074

Abstract

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow [...] Read more.

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms. We aimed to identify overlapping mechanisms in MSCs derived from myeloid and lymphoid neoplasms contributing to disease progression and suppression of HSPCs to develop interventions that target these mechanisms. MSCs derived from healthy donors (n = 44) and patients diagnosed with myeloproliferative neoplasia (n = 11), myelodysplastic syndromes (n = 16), or acute myeloid leukemia (n = 25) and B-Non-Hodgkin lymphoma (n = 9) with BM infiltration and acute lymphoblastic leukemia (n = 9) were analyzed for their functionality and by RNA sequencing. A reduced growth and differentiation capacity of MSCs was found in all entities. RNA sequencing distinguished both groups but clearly showed overlapping differentially expressed genes, including major players in the BMP/TGF and WNT-signaling pathway which are crucial for growth, osteogenesis, and hematopoiesis. Functional alterations in healthy MSCs were inducible by exposure to supernatants from malignant cells, implicating the involvement of these factors in disease progression. Overall, we were able to identify overlapping factors that pose potential future therapeutic targets. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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11 pages, 1189 KiB

Open AccessEditor’s ChoiceArticle

Early Serum Markers for Immune Checkpoint Inhibitor Induced Hypophysitis in Melanoma Patients

by Fouad Mitri, Devayani Machiraju, Christina Naoum and Jessica C. Hassel

Cancers 2024, 16(7), 1340; https://doi.org/10.3390/cancers16071340 - 29 Mar 2024

Cited by 1 | Viewed by 1523

Abstract

Background: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activities and are widely used for the treatment of advanced cancers. However, they may lead to immune-related adverse events (irAEs) and some of them, such as hypophysitis, can be life-threatening. Here, early diagnosis is [...] Read more.

Background: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activities and are widely used for the treatment of advanced cancers. However, they may lead to immune-related adverse events (irAEs) and some of them, such as hypophysitis, can be life-threatening. Here, early diagnosis is critical. Methods: We retrospectively analyzed 40 melanoma patients who developed hypophysitis during ICI treatment with either ipilimumab and/or anti-PD1 therapy and compared them to 40 control patients who did not develop hypophysitis during the ICI treatment, matched for age, gender, type of immunotherapy, and stage. Clinical data and blood values such as LDH, CRP, TSH, T3, T4, and absolute immune cell counts were retrieved from the medical records. Patient characteristics, laboratory values, progression-free survival, and overall survival were compared between the two groups. Results: Patients with ir-hypophysitis had a median age of 59 years, and most of them were male. Clinically, frequent symptoms were fatigue, headache, dizziness, and gastrointestinal symptoms such as nausea or abdominal pain. The onset of ir-hypophysitis differed much between ipilimumab- (median 8 weeks) and anti-PD1 (median 40 weeks)-induced hypophysitis (p < 0.001). At baseline, besides a slightly increased CRP level (p = 0.06), no differences were observed in patients who later developed hypophysitis compared to the control. After treatment started, hypophysitis patients showed a constant and significant decline in T4 levels from the start of therapy until diagnosis (p < 0.05), independent of the ICI treatment regime. However, a decline in T3 and TSH was only noted in patients with ipilimumab-induced ir-hypophysitis. Furthermore, serum sodium levels declined rapidly at the diagnosis of hypophysitis (p < 0.001). In addition, there was a constant increase in the absolute counts of eosinophils and lymphocytes from baseline in hypophysitis patients (p < 0.05). Conclusion: Ir-hypophysitis reveals different clinical pictures and onset times depending on the ICI regime used. Whereas a drop in T4 levels was indicative of developing hypophysitis independent of the ICI regime, TSH levels only declined in patients under ipilimumab-based ICI regimes. To best monitor our patients, it is important to recognize these differences. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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12 pages, 1304 KiB

Open AccessArticle

Metastatic Breast Cancer: Prolonging Life in Routine Oncology Care

by Rudolf Weide, Stefan Feiten, Christina Waßmann, Bernhard Rendenbach, Ute Braun, Oswald Burkhard, Peter Ehscheidt and Marcus Schmidt

Cancers 2024, 16(7), 1255; https://doi.org/10.3390/cancers16071255 - 22 Mar 2024

Viewed by 1608

Abstract

Overall survival (OS) of patients with metastatic breast cancer (MBC) has improved within controlled clinical trials. Whether these advances translate into improved OS in routine care is controversial. We therefore analyzed retrospectively unselected female patients from five oncology group practices and one university [...] Read more.

Overall survival (OS) of patients with metastatic breast cancer (MBC) has improved within controlled clinical trials. Whether these advances translate into improved OS in routine care is controversial. We therefore analyzed retrospectively unselected female patients from five oncology group practices and one university outpatient clinic, whose initial diagnosis of MBC was between 1995 and 2022. A total of 1610 patients with a median age of 63 years (23–100) were evaluated. In all, 82.9% had hormone-receptor-positive disease, and 23.8% were HER2-positive. Evaluation in time cohorts by initial MBC diagnosis date showed a continuous prolongation of median OS from 31.6 months (0.5–237.3+) (1995–2000) to 48.4 months (0.4–61.1+) (2018–2022) (p = 0.003). Univariable analyses showed a significant dependence on the time cohort of diagnosis, metastatic status at initial diagnosis, age at metastasis, hormone and HER2 status, general condition, metastasis localization, and the number of affected organs. A multivariable analysis revealed a significant dependence of survival probability on receptor status, general condition, and number of metastatic sites, as well as the time between initial breast cancer diagnosis and the diagnosis date of MBC in months. In sum, OS of patients with MBC has improved continuously and significantly in routine care over the last 27 years. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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17 pages, 2492 KiB

Open AccessArticle

Pelvic Exenteration for Recurrent Vulvar Cancer: A Retrospective Study

by Sabrina Classen-von Spee, Saher Baransi, Nando Fix, Friederike Rawert, Verónica Luengas-Würzinger, Ruth Lippert, Michelle Bonin-Hennig, Peter Mallmann and Björn Lampe

Cancers 2024, 16(2), 276; https://doi.org/10.3390/cancers16020276 - 8 Jan 2024

Cited by 1 | Viewed by 4148

Abstract

Pelvic exenteration (PE) is one of the most radical surgical approaches. In earlier times, PE was associated with high morbidity and mortality. Nowadays, due to improved selection of suitable patients, perioperative settings, and postoperative care, patients’ outcomes have been optimized. To investigate patients’ [...] Read more.

Pelvic exenteration (PE) is one of the most radical surgical approaches. In earlier times, PE was associated with high morbidity and mortality. Nowadays, due to improved selection of suitable patients, perioperative settings, and postoperative care, patients’ outcomes have been optimized. To investigate patients’ outcomes and identify possible influencing clinical and histopathological factors, we analysed 17 patients with recurrent vulvar cancer who underwent PE in our department between 2007 and 2022. The median age was 64.9 years, with a difference of 40 years between the youngest and the oldest patient (41 vs. 81 years). The mean overall survival time was 55.7 months; the longest survival time reached up to 164 months. The achievement of complete cytoreduction (p = 0.02), the indication for surgery (curative vs. palliative), and the presence of distant metastases (both p = 0.01) showed a significant impact on overall survival. The presence of lymphatic metastases (p = 0.11) seems to have an influence on overall survival (OS) time. Major complications appeared in 35% of the patients. Our results support the existing data for PE in cases of recurrent vulvar cancer; for a group of selected patients, PE is a treatment option with good overall survival times and acceptable morbidity. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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17 pages, 782 KiB

Open AccessArticle

Symptomatic Patients with Hyperleukocytic FLT3-ITD Mutated Acute Myeloid Leukemia Might Benefit from Leukapheresis

by Kiavasch Mohammad Nejad Farid, Tim Sauer, Michael Schmitt, Carsten Müller-Tidow and Anita Schmitt

Cancers 2024, 16(1), 58; https://doi.org/10.3390/cancers16010058 - 21 Dec 2023

Cited by 3 | Viewed by 1386

Abstract

Purpose: We aimed to identify subsets of patients who benefit from emergency LA and to establish a therapeutic algorithm for AML patients with hyperleukocytosis. Methods: In this single-center retrospective cohort study, a total of 20 consecutive patients underwent LA because of their clinical [...] Read more.

Purpose: We aimed to identify subsets of patients who benefit from emergency LA and to establish a therapeutic algorithm for AML patients with hyperleukocytosis. Methods: In this single-center retrospective cohort study, a total of 20 consecutive patients underwent LA because of their clinical symptoms. Overall survival (OS) analysis was conducted using the Kaplan–Meier plot method. Univariate and multivariate analyses (using multiple logistic regression) were performed. At the time of diagnosis, all patients received a standard diagnostic workup for AML including FLT3-ITD mutational analysis. Results: FLT3-ITD mut AML patients receiving LA had a median OS of 437 days (range 5–2379 days) with a corresponding 14-day survival of 92.3%, while FLT3 wt AML patients displayed a significantly lower median OS of only 5 days (range 1–203 days) with a corresponding 14-day survival of 14.3% (p = 0.0001). Conclusions: Among patients with clinical symptoms of leukostasis, the subset of FLT3-ITD mut AML patients showed a better outcome with lower early mortality after emergency LA. Based on these observations, we established a therapeutic algorithm for AML patients with hyperleukocytosis. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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10 pages, 919 KiB

Open AccessArticle

Oncologic Outcome of Robotic-Assisted and Laparoscopic Sentinel Node Biopsy in Endometrial Cancer

by Atanas Ignatov, József Mészáros, Stylianos Ivros, Paolo Gennari and Tanja Ignatov

Cancers 2023, 15(24), 5894; https://doi.org/10.3390/cancers15245894 - 18 Dec 2023

Cited by 1 | Viewed by 1265

Abstract

Background: Recently, sentinel lymph node biopsy (SLNB) has been introduced in the surgical staging of endometrial cancer as an alternative to systematic lymph node dissection (LND). However, the survival impact of SLNB is not yet well characterised. Methods: We performed a retrospective study [...] Read more.

Background: Recently, sentinel lymph node biopsy (SLNB) has been introduced in the surgical staging of endometrial cancer as an alternative to systematic lymph node dissection (LND). However, the survival impact of SLNB is not yet well characterised. Methods: We performed a retrospective study of 419 patients with endometrial cancer treated with SLNB alone or with pelvic and para-aortic LND. For SLNB mapping, indocyanine green was used. Results: Median follow-up was 66 months. After exclusions, 337 patients were eligible for analysis. Of them, 150 underwent SLNB and 187 LND. During the follow-up time, 27 (24.7%) of the 150 who underwent SLNB and 54 (28.9%) of the 187 who underwent LND were diagnosed with recurrent disease (p = 0.459). The estimated 5-year disease-free survival (DFS) rate was 76.7% and 72.2% for patients in the SLNB and LND group, respectively (p = 0.419). The 5-year overall survival (OS) rates were 80.7% and 77.0% in the SLNB and LND group, respectively (p = 0.895). Survival rates were similar in both groups independent of lymph node status. Multivariable analysis confirmed that the staging approach was not associated with oncological outcome. For patients without lymph node metastases, patient outcome was worsened by advanced tumour stage and non-endometrioid tumour histology. In the group of patients with confirmed lymph node metastases, advanced tumour stage and inadequate adjuvant treatment significantly reduced DFS and OS. Conclusion: Our data suggested that SLNB did not compromise the oncological outcome of patients with endometrial cancer compared to LND. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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11 pages, 2407 KiB

Open AccessArticle

Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy

by Christoph Wetz, Tristan Ruhwedel, Imke Schatka, Jane Grabowski, Henning Jann, Giulia Metzger, Markus Galler, Holger Amthauer and Julian M. M. Rogasch

Cancers 2023, 15(24), 5717; https://doi.org/10.3390/cancers15245717 - 6 Dec 2023

Cited by 1 | Viewed by 1169

Abstract

Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in [...] Read more.

Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. Methods: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. Results: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan–Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7–27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2–15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6–21.8 months) with stable ALP values (Δ ± 10%). Conclusions: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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16 pages, 1756 KiB

Open AccessArticle

Functional Outcome and Overall Survival in Patients with Primary or Secondary CNS Lymphoma after Surgical Resection vs. Biopsy

by Franziska Staub-Bartelt, Jos Rittenauer, Michael Sabel and Marion Rapp

Cancers 2023, 15(21), 5266; https://doi.org/10.3390/cancers15215266 - 2 Nov 2023

Cited by 2 | Viewed by 1424

Abstract

Background: Central nervous system lymphoma (CNSL) is rare form of brain tumour. It manifests either as primary CNS lymphoma (pCNSL) originating within the central nervous system or as secondary CNS lymphoma (sCNSL), arising as cerebral metastases of systemic lymphoma. For a significant period, [...] Read more.

Background: Central nervous system lymphoma (CNSL) is rare form of brain tumour. It manifests either as primary CNS lymphoma (pCNSL) originating within the central nervous system or as secondary CNS lymphoma (sCNSL), arising as cerebral metastases of systemic lymphoma. For a significant period, surgical resection was considered obsolete due to the favourable response to chemotherapy and the associated risk of postoperative deficits. The objective of the present study was to demonstrate the benefits of resection in CNSL patients, including extended survival and improved postoperative function. Methods: A retrospective study involving patients diagnosed with either PCNSL or SCNSL that were surgically approached at our neurosurgical department between 2010 and 2022 was conducted. Patients were categorised into three subgroups based on their neurosurgical approach: (1) stereotactical biopsy, (2) open biopsy, (3) resection. We then performed statistical analyses to assess overall survival (OS) and progression-free survival (PFS). Additionally, we examined various secondary factors such as functional outcome via Karnofsky Performance Index (KPS) and prognosis scoring. Results: 157 patients diagnosed with PCNSL or SCNSL were enclosed in the study. Of these, 101 underwent stereotactic biopsy, 21 had open biopsy, and 35 underwent resection. Mean age of the cohort was 64.94 years, with majority of patients being female (54.1%). The resection group showed longest OS at 44 months (open biopsy = 13 months, stereotactic biopsy = 9 months). Calculated median follow-up was 34.5 months. In the Cox regression model, postoperative KPS 70% (p < 0.001) and resection vs. stereotactic biopsy (p = 0.040) were identified as protective factors, whereas older age at diagnosis was identified as a risk factor (p < 0.001). In the one-way analysis of variance, differences in postoperative KPS were found among all groups (p = 0.021), while there was no difference in preoperative KPS among the groups. Conclusions: Our data show a favourable outcome when resection is compared to either stereotactic or open biopsy. Additionally, the marginally improved postoperative functional status observed in patients who underwent resection, as opposed to in those who underwent biopsy, provides further evidence in favour of the advantages of surgical resection for enhancing neurological deficits. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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17 pages, 1402 KiB

Open AccessArticle

Impact of Human Papillomavirus-Negative Dominance in Oropharyngeal Cancer on Overall Survival: A Population-Based Analysis in Germany from 2018 to 2020

by Mussab Kouka, Laura Gerlach, Jens Büntzel, Holger Kaftan, Daniel Böger, Andreas H. Müller, Thomas Ernst and Orlando Guntinas-Lichius

Cancers 2023, 15(21), 5259; https://doi.org/10.3390/cancers15215259 - 2 Nov 2023

Cited by 1 | Viewed by 1195

Abstract

The impact of the relation of human papillomavirus (HPV) and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. A total of 498 patients with OPSCC (76.9% men; mean age [...] Read more.

The impact of the relation of human papillomavirus (HPV) and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. A total of 498 patients with OPSCC (76.9% men; mean age 62.5 years) from 2018 to 2020 were included. OPSCC cases were 37.3% HPV-positive (+) (31.2% smokers; mean incidence: 2.91/100,000 population) and 57.8% HPV-negative (63.5% smokers; mean incidence: 4.50/100,000 population). Median follow-up was 20 months. HPV+ patients had significantly better OS than HPV-negative (−) patients (HPV+: 2-year OS: 90.9%; HPV−: 2-year OS: 73.6%; p < 0.001). In multivariable analysis, HPV− patients (hazard ratio (HR) = 4.5; 95% confidence interval (CI): 2.4–8.6), patients with higher N classification (N2: HR = 3.3; 95% CI: 1.71–6.20; N3: HR = 3.6; 95% CI: 1.75–7.31) and with a higher cancer staging (III: HR = 5.7; 95% CI: 1.8–17.6; IV: HR = 19.3; 95% CI: 6.3–57.3) had an increased hazard of death. HPV− smokers formed the majority in Thuringia. Nicotine and alcohol habits had no impact on OS. Optimizing OPSCC therapeutic strategies due to the dominance of HPV− is more important than discussing de-escalation strategies for HPV+ patients. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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18 pages, 34483 KiB

Open AccessArticle

Leveraging Attention-Based Convolutional Neural Networks for Meningioma Classification in Computational Histopathology

by Jannik Sehring, Hildegard Dohmen, Carmen Selignow, Kai Schmid, Stefan Grau, Marco Stein, Eberhard Uhl, Anirban Mukhopadhyay, Attila Németh, Daniel Amsel and Till Acker

Cancers 2023, 15(21), 5190; https://doi.org/10.3390/cancers15215190 - 28 Oct 2023

Cited by 4 | Viewed by 2100

Abstract

Convolutional neural networks (CNNs) are becoming increasingly valuable tools for advanced computational histopathology, promoting precision medicine through exceptional visual decoding abilities. Meningiomas, the most prevalent primary intracranial tumors, necessitate accurate grading and classification for informed clinical decision-making. Recently, DNA methylation-based molecular classification of [...] Read more.

Convolutional neural networks (CNNs) are becoming increasingly valuable tools for advanced computational histopathology, promoting precision medicine through exceptional visual decoding abilities. Meningiomas, the most prevalent primary intracranial tumors, necessitate accurate grading and classification for informed clinical decision-making. Recently, DNA methylation-based molecular classification of meningiomas has proven to be more effective in predicting tumor recurrence than traditional histopathological methods. However, DNA methylation profiling is expensive, labor-intensive, and not widely accessible. Consequently, a digital histology-based prediction of DNA methylation classes would be advantageous, complementing molecular classification. In this study, we developed and rigorously assessed an attention-based multiple-instance deep neural network for predicting meningioma methylation classes using tumor methylome data from 142 (+51) patients and corresponding hematoxylin-eosin-stained histological sections. Pairwise analysis of sample cohorts from three meningioma methylation classes demonstrated high accuracy in two combinations. The performance of our approach was validated using an independent set of 51 meningioma patient samples. Importantly, attention map visualization revealed that the algorithm primarily focuses on tumor regions deemed significant by neuropathologists, offering insights into the decision-making process of the CNN. Our findings highlight the capacity of CNNs to effectively harness phenotypic information from histological sections through computerized images for precision medicine. Notably, this study is the first demonstration of predicting clinically relevant DNA methylome information using computer vision applied to standard histopathology. The introduced AI framework holds great potential in supporting, augmenting, and expediting meningioma classification in the future. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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15 pages, 733 KiB

Open AccessArticle

Laparoscopic Fertility-Sparing Surgery for Early Ovarian Malignancies

by Julia S. M. Zimmermann, Pauline Ramisch, Marc P. Radosa, Christoph G. Radosa, Askin C. Kaya, Sara Y. Brucker, Florin A. Taran, Uwe A. Ulrich, Andreas Hackethal, Martin Deeken, Marc Sütterlin, Benjamin Tuschy, Erich-Franz Solomayer and Julia C. Radosa

Cancers 2023, 15(20), 5099; https://doi.org/10.3390/cancers15205099 - 22 Oct 2023

Cited by 3 | Viewed by 1612

Abstract

The demand for fertility-sparing surgery (FSS) has increased in the last decade due to increased maternal age, increased incidence of ovarian malignancies in younger patients, and technical advances in surgery. Data on oncological safety and fertility outcomes of patients with ovarian cancer after [...] Read more.

The demand for fertility-sparing surgery (FSS) has increased in the last decade due to increased maternal age, increased incidence of ovarian malignancies in younger patients, and technical advances in surgery. Data on oncological safety and fertility outcomes of patients with ovarian cancer after laparoscopic FSS are sparse, but some retrospective studies have shown that open FSS may be offered to selected patients. We assessed the role of minimally invasive FSS in comparison with radical surgery (RS) in terms of oncological safety and reproductive outcomes after FSS in this multicenter study. Eighty patients with FIGO stage I/II ovarian cancer treated with laparoscopic FSS or RS between 01/2000 and 10/2018 at the participating centers (comprehensive gynecological cancer centers with minimally invasive surgical expertise) were included in this retrospective analysis of prospectively kept data. Case–control (n = 40 each) matching according to the FIGO stage was performed. Progression-free survival [150 (3–150) and 150 (5–150) months; p = 0.61] and overall survival [36 (3–150) and 50 (1–275) months; p = 0.65] did not differ between the FSS and RS groups. Eight (25.8%) women became pregnant after FSS, resulting in seven (22.5%) deliveries; three (37.5%) patients conceived after in vitro fertilization, and five (62.5%) conceived spontaneously. Laparoscopic FSS seems to be applicable and oncologically safe for patients with early-stage ovarian cancer, with adequate fertility outcomes. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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15 pages, 982 KiB

Open AccessArticle

Effects of an Integrative Day Care Clinic Program with a Focus on Nature Therapy in a Hospital Park Setting on Quality of Life in Oncological Patients—A Non-Randomized Controlled Study

by Lisa Kuballa, Christian S. Kessler, Farid I. Kandil, Christel von Scheidt, Meline Meinköhn, Barbara Koch, Manfred Wischnewsky, Andreas Michalsen and Michael Jeitler

Cancers 2023, 15(18), 4595; https://doi.org/10.3390/cancers15184595 - 16 Sep 2023

Viewed by 1543

Abstract

Cancer often causes long-term physical and psychological impairments. Lifestyle modification and nature-based interventions (NBIs) can have a positive impact on patients’ quality of life (QOL). This participants-blinded, non-randomized controlled study assessed parameters at weeks 0, 12, and 24, including, as a primary endpoint, [...] Read more.

Cancer often causes long-term physical and psychological impairments. Lifestyle modification and nature-based interventions (NBIs) can have a positive impact on patients’ quality of life (QOL). This participants-blinded, non-randomized controlled study assessed parameters at weeks 0, 12, and 24, including, as a primary endpoint, QOL in cancer patients on the Functional Assessment of Cancer Therapy—General (FACT-G) at week 12. QOL in breast cancer patients, fatigue, well-being, stress, anxiety/depression, socio-psychological well-being, benefits of nature interaction, insomnia, self-efficacy, mindfulness, and self-compassion were assessed as secondary endpoints. N = 107 cancer patients (96.3% women; 52.5 ± 9.3 years, 80.4% breast cancer) were assigned to either a 12-week nature-based (NDC; n = 56) or conventional (DC; n = 51) oncology day care clinic program, whereby the assignment group was not known to the participants. There was no significant group difference for the primary endpoint. At week 24, QOL, fatigue, mindfulness and self-compassion scores were significantly higher, and at weeks 12 and 24, the insomnia score was significantly lower in NDC compared to DC. In conclusion, this study indicates positive and clinically relevant effects of the program on QOL, fatigue, and psychological parameters. NBIs seem to have a more pronounced effect. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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10 pages, 1045 KiB

Open AccessArticle

Long-Term Clinical Results of MR-Guided Stereotactic Body Radiotherapy of Liver Metastases

by Fabian Weykamp, Philipp Hoegen, Sebastian Regnery, Efthimios Katsigiannopulos, C. Katharina Renkamp, Kristin Lang, Laila König, Elisabetta Sandrini, Eva Meixner, Carolin Rippke, Carolin Buchele, Jakob Liermann, Jürgen Debus, Sebastian Klüter and Juliane Hörner-Rieber

Cancers 2023, 15(10), 2786; https://doi.org/10.3390/cancers15102786 - 17 May 2023

Cited by 6 | Viewed by 1838

Abstract

(1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of [...] Read more.

(1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of an ongoing prospective observational registry. Local hepatic control (LHC), distant hepatic control (DHC), progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan–Meier method. Toxicity was documented according to CTCAE (v.5.0). (3) Results: Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation). Median prescribed dose was 50 Gy in five fractions equal to a biologically effective dose (BED) (alpha/beta = 10 Gy) of 100 Gy. At 1 and 2 years, LHC was 98% and 75%, DHC was 34% and 15%, PFS was 21% and 5% and OS was 83% and 57%. Two-year LHC was higher in case of BED > 100 Gy (100% vs. 57%; log-rank p = 0.04). Acute grade 1 and 2 toxicity (mostly nausea) occurred in 26% and 7% of the patients, with no grade ≥ 3 event. (4) Conclusions: To our knowledge, this is the largest cohort of MR-guided liver SBRT. Long-term local control was promising and underscores the aim of achieving >100 Gy BED. Nonetheless, distant tumor control remains challenging. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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10 pages, 1187 KiB

Open AccessFeature PaperArticle

Radiomics-Based Prediction of Future Portal Vein Tumor Infiltration in Patients with HCC—A Proof-of-Concept Study

by Fabian Stoehr, Roman Kloeckner, Daniel Pinto dos Santos, Mira Schnier, Lukas Müller, Aline Mähringer-Kunz, Thomas Dratsch, Sebastian Schotten, Arndt Weinmann, Peter Robert Galle, Jens Mittler, Christoph Düber and Felix Hahn

Cancers 2022, 14(24), 6036; https://doi.org/10.3390/cancers14246036 - 8 Dec 2022

Cited by 3 | Viewed by 2132

Abstract

Portal vein infiltration (PVI) is a typical complication of HCC. Once diagnosed, it leads to classification as BCLC C with an enormous impact on patient management, as systemic therapies are henceforth recommended. Our aim was to investigate whether radiomics analysis using imaging at [...] Read more.

Portal vein infiltration (PVI) is a typical complication of HCC. Once diagnosed, it leads to classification as BCLC C with an enormous impact on patient management, as systemic therapies are henceforth recommended. Our aim was to investigate whether radiomics analysis using imaging at initial diagnosis can predict the occurrence of PVI in the course of disease. Between 2008 and 2018, we retrospectively identified 44 patients with HCC and an in-house, multiphase CT scan at initial diagnosis who presented without CT-detectable PVI but developed it in the course of disease. Accounting for size and number of lesions, growth type, arterial enhancement pattern, Child–Pugh stage, AFP levels, and subsequent therapy, we matched 44 patients with HCC who did not develop PVI to those developing PVI in the course of disease (follow-up ended December 2021). After segmentation of the tumor at initial diagnosis and texture analysis, we used LASSO regression to find radiomics features suitable for PVI detection in this matched set. Using an 80:20 split between training and holdout validation dataset, 17 radiomics features remained in the fitted model. Applying the model to the holdout validation dataset, sensitivity to detect occurrence of PVI was 0.78 and specificity was 0.78. Radiomics feature extraction had the ability to detect aggressive HCC morphology likely to result in future PVI. An additional radiomics evaluation at initial diagnosis might be a useful tool to identify patients with HCC at risk for PVI during follow-up benefiting from a closer surveillance. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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23 pages, 4548 KiB

Open AccessArticle

Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma

by Jennifer Menegatti, Jacqueline Nakel, Youli K. Stepanov, Karolina M. Caban, Nicole Ludwig, Ruth Nord, Thomas Pfitzner, Maryam Yazdani, Monika Vilimova, Tim Kehl, Hans-Peter Lenhof, Stephan E. Philipp, Eckart Meese, Thomas Fröhlich, Friedrich A. Grässer and Martin Hart

Cancers 2022, 14(20), 5031; https://doi.org/10.3390/cancers14205031 - 14 Oct 2022

Cited by 4 | Viewed by 2816

Abstract

Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein expression of DLBCL cell [...] Read more.

Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein expression of DLBCL cell lines. Methods: miR-142 was deleted by CRISPR/Cas9 knockout in cell lines from DLBCL. Results: By proteome analyses, miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in GC-DLBCL lines BJAB and SUDHL4. Various mitochondrial ribosomal proteins were up-regulated in line with their pro-tumorigenic properties, while proteins necessary for MHC-I presentation were down-regulated in accordance with the finding that miR-142 knockout mice have a defective immune response. CFL2, CLIC4, STAU1, and TWF1 are known targets of miR-142, and we could additionally confirm AKT1S1, CCNB1, LIMA1, and TFRC as new targets of miR-142-3p or -5p. Conclusions: Seed-sequence mutants of miR-142 confirmed potential targets and novel targets of miRNAs can be identified in miRNA knockout cell lines. Due to the complex contribution of miRNAs within cellular regulatory networks, in particular when miRNAs highly present in RISC complexes are replaced by other miRNAs, primary effects on gene expression may be covered by secondary layers of regulation. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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Review

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13 pages, 3442 KiB

Open AccessReview

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

by Sebastian Gottfried Walter, Peter Knöll, Peer Eysel, Alexander Quaas, Christopher Gaisendrees, Robert Nißler and Lena Hieggelke

Cancers 2023, 15(9), 2556; https://doi.org/10.3390/cancers15092556 - 29 Apr 2023

Cited by 5 | Viewed by 2731

Abstract

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, [...] Read more.

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. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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Other

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12 pages, 959 KiB

Open AccessSystematic Review

Potential of Fecal Carcinoembryonic Antigen for Noninvasive Detection of Colorectal Cancer: A Systematic Review

by Xianzhe Li, Lara Stassen, Petra Schrotz-King, Zitong Zhao, Rafael Cardoso, Janhavi R. Raut, Megha Bhardwaj and Hermann Brenner

Cancers 2023, 15(23), 5656; https://doi.org/10.3390/cancers15235656 - 30 Nov 2023

Viewed by 1532

Abstract

Carcinoembryonic antigen (CEA) is more abundant in feces than in serum; however, evidence for the role of fecal CEA (FCEA) in the detection of colorectal cancer (CRC) is limited. We conducted a systematic review of studies that evaluated FCEA for the noninvasive detection [...] Read more.

Carcinoembryonic antigen (CEA) is more abundant in feces than in serum; however, evidence for the role of fecal CEA (FCEA) in the detection of colorectal cancer (CRC) is limited. We conducted a systematic review of studies that evaluated FCEA for the noninvasive detection and diagnosis of CRC. PubMed and Web of Science were searched for relevant studies published until 18 January 2023. Information on publication year, study design, country, study population characteristics, FCEA and serum CEA (SCEA) concentrations, and diagnostic performance was summarized. Two authors independently extracted data and assessed the risk of bias and applicability of each included study. Seven studies published between 1979 and 2021, all conducted in clinical settings and together involving 399 CRC patients and 889 controls, were identified. Significant differences in FCEA concentrations were observed between CRC and control groups in all studies. Methods for detecting FCEA varied, with the electronic chemiluminescence immunoassay (ECLIA) being used in the most recent studies. Reported sensitivities, specificities, and area under the curves of FCEA ranged from 50.0% to 85.7%, 73.0% to 100.0%, and 0.704 to 0.831, respectively. In direct comparisons, the diagnostic performance of FCEA was better than that of SCEA. The potential role of FCEA as a novel, noninvasive, easily measurable biomarker for the diagnosis of CRC requires further evaluation in screening settings. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)

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