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Simple Summary: Inflammation-based prognostic markers have been recognized as useful in a range of oncologic conditions. Given the high mortality rate associated with pancreatic ductal adenocarcinoma (PDAC), the demand for accurate prognostic tools is significant. Nonetheless, the literature still shows conflicting results regarding the effectiveness of the various available scoring systems. Our data confirm that NLR and PNI are useful biomarkers regarding overall survival in PDAC. Especially in advanced disease stages, they seem to be of considerable benefit as easily accessible tools for prognosis prediction. Purpose: Prognostic inflammation-based parameters have been reported as useful tools in various oncologic diseases. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high mortality rate, making reliable prognostic markers highly desirable. However, there is still inconsistency in the literature regarding the efficacy of the different available scores. Methods: A total of 207 patients, who underwent primary resection of PDAC from January 2000 to December 2018 at the University Hospital of Erlangen, were included in this retrospective single-center study. Different biomarkers, including the preoperative neutrophil–lymphocyte ratio (NLR), the platelet–lymphocyte ratio (PLR), the c-reactive protein (CRP)–albumin ratio (CAR), the lymphocyte–CRP ratio (LCR), the prognostic nutritional index (PNI) and the modified Glasgow prognostic score (mGPS) were analyzed for their ability to predict overall survival (OS). Results: In our cohort, the median overall survival was 20.7 months. Among the investigated biomarkers, NLR and PNI were identified as independent prognostic markers (Hazard Ratio (HR) 1.6 (1.0–2.5), p = 0.048 and HR 0.6 (0.4–0.9), p = 0.018), whereas PLR, CAR, LCR and mGPS did not reach significance in the multivariate analysis. Subgroup analysis revealed that the prognostic value of NLR and PNI is particularly evident in locally advanced tumor stages (pT3/4 and pN+). Conclusions: The NLR and PNI could serve as valuable tools for estimating prognosis in patients with PDAC undergoing pancreatic resection in curative intention, especially in locally advanced tumor stages. However, conflicting results in the current literature highlight the need for further prospective studies to validate these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Relapse and treatment-related side effects pose significant challenges for older patients with high-risk blood cancers (myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)) undergoing hematopoietic stem cell transplants from HLA-haploidentical donors. We compared two preparative treatment regimens to identify the most tolerable and effective approach: one using fludarabine, cyclophosphamide, and melphalan, and the other using fludarabine, cyclophosphamide, and treosulfan. Our goal was to determine which treatment offers better survival rates and fewer side effects. We found that both regimens resulted in similar survival outcomes. However, the melphalan regimen was associated with fewer relapses but more treatment-related deaths, while the treosulfan regimen had fewer side effects but exhibited poorer disease control. These findings suggest that treosulfan may be safer, though higher doses might improve disease control, providing valuable insights for future treatments. Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated the feasibility of treosulfan-based conditioning, noting stable engraftment and low non-relapse mortality (NRM) in patients undergoing HLA-matched allo-HSCT. However, data on treosulfan-based conditioning in the HLA-haploidentical transplantation (HaploT) setting are limited. We retrospectively compared conditioning with fludarabine–cyclophosphamide (FC)–melphalan (110 mg/m2) and FC-treosulfan (30 g/m2) prior to HaploT using post-transplantation cyclophosphamide (PTCy) in patients with high-risk MDS/AML patients ≥ 50 years, transplanted from 2009–2021 at our institution (n = 80). After balancing patient characteristics by a matched-pair analysis, we identified twenty-one matched pairs. Two-year OS and LFS were similar among the groups (OS 66% and LFS 66%, p = 0.8 and p = 0.57). However, FC-melphalan was associated with a significantly lower probability of relapse compared to FC-treosulfan (0% vs. 24%, p = 0.006), counterbalanced by a higher NRM (33% vs. 10%, p = 0.05). Time to engraftment and incidences of acute and chronic graft-versus-host disease (GvHD) did not differ significantly. In conclusion, HaploT using FC-treosulfan in combination with PTCy in patients aged ≥50 years with MDS/AML appears safe and effective, particularly in advanced disease stages. We confirm the favorable extramedullary toxicity profile, allowing for potential dose intensification to enhance antileukemic activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant diseases represent a central challenge in modern medicine. Despite improved screening approaches and advanced diagnostics, malignant diseases such as HCC are still diagnosed at non-resectable/advanced stages. In these cases, minimally invasive treatment methods such as SIRT or other radioablation procedures are of particular importance as part of personalized oncological therapy. When choosing the right minimally invasive procedure, it would be useful to be able to use biomarkers as predictors of treatment response. With this background, the aim of this study is to evaluate the usefulness of CCL2 as a predictor of treatment response and survival. Purpose: Hepatocellular carcinoma (HCC) is the largest subgroup of primary liver tumors. Ablative therapies, such as selective internal radiation therapy (SIRT), are used in late stages for patients with unresectable liver metastases and no response to other therapies. CCL2 (C-C motif chemokine ligand 2) is a potent monocyte chemoattractant. It is associated with tumor progression and metastasis. The role of circulating CCL2 as a biomarker in HCC undergoing selective internal radiation therapy remains unclear. Methods: A total of 41 patients (8 female, 33 male) suffering from HCC and undergoing SIRT were enrolled. Pre- and post-therapy changes in circulating CCL2 levels were determined by bead-based immunoassay and compared with clinical laboratory parameters and patient data. Results: A total of 32 patients exhibited survival beyond 60 days. It was observed that levels of CCL2 correlated with scores indicating a higher likelihood of non-survival and with the severity of the disease. Moreover, a significant inverse correlation was discovered between CCL2 levels and the survival of patients over 60 days in relation to counts of leukocytes, granulocytes, monocytes, and C-reactive protein. Conclusions: CCL2 may serve as a potential marker for patient survival after SIRT. The prediction of which HCC patients are likely to benefit from SIRT may be helpful in guiding therapeutic management. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the use of intraoperative magnetic resonance imaging (iMRI) in the surgical resection of brain metastases (BMs). The research aims to determine how iMRI can improve the precision of tumor removal, thereby enhancing patient outcomes. By providing real-time, high-resolution images during surgery, iMRI assists surgeons in achieving more complete tumor resection, potentially reducing recurrence rates and improving survival chances. Integrating iMRI into surgical protocols helps preserve neurological functions, especially for patients with BM in critical brain areas. This study highlights the safety and effectiveness of iMRI in neurosurgery and suggests its broader adoption for the better management of BMs. Intraoperative magnetic resonance imaging (iMRI) has witnessed significant growth in the field of neurosurgery, particularly in glioma surgery, enhancing image-guided neuronavigation and optimizing the extent of resection (EOR). Despite its extensive use in the treatment of gliomas, its utility in brain metastases (BMs) remains unexplored. This study examined the effect of iMRI on BM resection. This retrospective study was conducted at the neurosurgical center of the University Hospital of the Technical University of Munich and involved 25 patients with BM who underwent resection using 3-Tesla iMRI between 2018 and 2022. Volumetric measurements of the resected contrast-enhancing metastases were performed using preoperative, intraoperative, and postoperative MRI images. The Karnofsky Performance Score (KPS) and neurological status of the patients were assessed pre- and postoperatively. Local recurrence and in-brain progression were reported in patients who underwent follow-up MRI at 3 and 6 months postoperatively. In this cohort (n = 25, mean age 63.6 years), non-small-cell lung cancer (NSCLC) was the most common origin (28%). The mean surgical duration was 219.9 min, and that of iMRI was 61.7 min. Indications for iMRI were primarily associated with preoperative imaging, suggesting an unclear entity that is often suspicious for glioma. Gross total resection (GTR) was achieved in 21 patients (84%). Continued resection was pursued after iMRI in six cases (24%), resulting in an improved EOR of 100% in five cases and 97.6% in one case. Neurological status postoperatively remained stable in 60%, improved in 24%, and worsened in 16% of patients. No wound healing or postoperative complications were observed. Among the thirteen patients who underwent follow-up MRI 3 months postoperatively, one patient showed local recurrence at the site of resection, and seven patients showed in-brain progression. Of the eight patients who underwent a 6-month follow-up MRI, two showed local recurrence, while three exhibited in-brain progression. The observed favorable profiles of GTR, coupled with the notable absence of wound-healing problems and acute postoperative complications, affirm the safety and feasibility of incorporating iMRI into the neurosurgical workflow for resecting BM with specific indications. The real-time imaging capabilities of iMRI offer unparalleled precision, aiding meticulous tumor delineation and informed decision-making, ultimately contributing to improved patient outcomes. Although our experience suggests the potential benefits of iMRI as a safe tool for enhancing EOR, we acknowledge the need for larger prospective clinical trials. Comprehensive investigations on a broader scale are imperative to further elucidate the specific indications for iMRI in the context of BMs and to study its impact on survival. Rigorous prospective studies will refine our understanding of the clinical scenarios in which iMRI can maximize its impact, guiding neurosurgeons toward more informed and tailored decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is a promising and recently approved treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to analyze which laboratory and PET imaging parameters are able to predict biochemical response and overall survival with this treatment. Two quantitative imaging biomarkers were identified that allow prediction of RLT outcome, further improving the pre-therapeutic characterization of mCRPC patients undergoing PSMA-RLT. The aim of this retrospective study was to identify pre-therapeutic predictive laboratory and molecular imaging biomarkers for response and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Pre-therapeutic laboratory and [68Ga]Ga-PSMA-11 PET/CT data of n = 102 mCRPC patients receiving [177Lu]Lu-PSMA-617 RLT within a prospective registry (REALITY Study, NCT04833517) were analyzed including laboratory parameters such as alkaline phosphatase (ALP), prostate-specific antigen (PSA), gamma glutamyl transferase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neuron specific enolase (NSE), hemoglobin (Hb), and imaging parameters such as maximum standardized uptake value of the tumor lesions (SUVmax), the mean standardized uptake value of all tumor lesions (SUVmean), the whole-body molecular tumor volume (MTV), and the whole-body total lesion PSMA (TLP). Mann–Whitney U test, univariate and multivariable Cox-regression were performed to test for association of the parameters with response and OS. The SUVmean of all lesions was significantly different between responders and non-responders (SUVmean responders 8.95 ± 2.83 vs. non-responders 7.88 ± 4.46, p = 0.003), whereas all other tested biochemical and imaging parameters did not reveal significant differences. Hb and the molecular imaging parameters MTV and TLP showed a significant association with OS (p = 0.013, p = 0.005; p = 0.009) in univariant Cox regression; however, only TLP remained significant in multivariable analysis (Hazard ratio 1.033, p = 0.009). This study demonstrates a statistically significant association between the quantitative PET/CT imaging parameter SUVmean and PSA response, as well as between the baseline TLP and OS of mCRPC patients undergoing RLT. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplant is an approach for the curative treatment of early stage hepatocellular carcinoma and the often underlying liver cirrhosis. However, a recurrence of the cancer is to be expected in 10 to 20% of cases after liver transplantation. The treatment of recurrent hepatocellular carcinoma remains difficult, as immunotherapy is usually not recommended for systemic treatment after transplantation. Therefore, it is often necessary to resort to tyrosine kinase inhibitors in advanced stage hepatocellular carcinoma. This multicenter trial aims at assessing the effect of tyrosine kinase inhibitors and immunosuppression on the outcome of patients with recurrent hepatocellular carcinoma after liver transplantation. Introduction: The tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib represent the first-line systemic therapy of choice for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Under sorafenib and lenvatinib, HCC patients have shown increasingly improved overall survival in clinical studies over the years. In contrast, data on overall survival for patients with HCC recurrence after LT under TKIs are scarce and limited to small retrospective series. In this retrospective, multicenter study, we investigated the efficacy of TKI therapy and the influence of immunosuppression in patients with HCC recurrence after LT. Methods: Retrospective data were collected from four transplant centers from Germany and Austria. We included patients with HCC recurrence after LT between 2007 and 2020 who were treated with a TKI. Results: In total, we analyzed data from 46 patients with HCC recurrence after LT. The most common underlying liver disease was hepatitis C, accounting for 52.2%. The median time to relapse was 11.8 months (range 0–117.7 months). The liver graft was affected in 21 patients (45.7%), and 36 patients (78.3%) had extrahepatic metastases at initial diagnosis of recurrence, with the lung being the most commonly affected (n = 25, 54.3%). Of the total, 54.3% (n = 25) of the patients were initially treated locally; 39 (85.8%) and 7 (15.2%) patients received sorafenib and lenvatinib, respectively, as first-line systemic therapy. Median overall survival of the whole cohort was 10.9 months (95% confidence interval (95% CI) 6.9–14.9 months) and median progression free survival was 5.7 months (95% CI 2.0–9.4 months) from treatment initiation. Conclusion: Since history of liver transplantation is considered a contraindication for immunotherapy, prognosis of patients with HCC recurrence after LT remains poor. [ABSTRACT FROM AUTHOR]

Simple Summary: Sacrectomy represents a radical indication for bone sarcomas (e.g., osteosarcoma or chondrosarcoma) and chordomas, as well as selected carcinomas with invasion of the sacrum. Extralesional en bloc excision is surgically demanding and associated with resection-induced neurologic deficits and risks. Due to the low incidence of bone sarcomas, the rare localization in the sacrum and the complexity of the surgical procedure, studies reporting on the oncological outcome and corresponding complications in larger patient numbers are rare. The aim was to describe the oncosurgical management and the complication profile and to analyze our own treatment results after partial/total sacrectomy, with attention paid to a possible benefit by using intraoperative 3D navigation. There was a significant difference in progression-free and metastasis-free survival between sarcoma, chordoma and carcinoma patients. Complications were common, but no independently influencing causative factors could be identified. Although there was a subjective impression of improved intraoperative 3D orientation and easier identification of resection planes, the use of navigation did not significantly influence resection status or oncological patient outcome. Introduction: Bone sarcoma or direct pelvic carcinoma invasion of the sacrum represent indications for partial or total sacrectomy. The aim was to describe the oncosurgical management and complication profile and to analyze our own outcome results following sacrectomy. Methods: In a retrospective analysis, 27 patients (n = 8/10/9 sarcoma/chordoma/locally recurrent rectal cancer (LRRC)) were included. There was total sacrectomy in 9 (incl. combined L5 en bloc spondylectomy in 2), partial in 10 and hemisacrectomy in 8 patients. In 12 patients, resection was navigation-assisted. For reconstruction, an omentoplasty, VRAM-flap or spinopelvic fixation was performed in 20, 10 and 13 patients, respectively. Results: With a median follow-up (FU) of 15 months, the FU rate was 93%. R0-resection was seen in 81.5% (no significant difference using navigation), and 81.5% of patients suffered from one or more minor-to-moderate complications (especially wound-healing disorders/infection). The median overall survival was 70 months. Local recurrence occurred in 20%, while 44% developed metastases and five patients died of disease. Conclusions: Resection of sacral tumors is challenging and associated with a high complication profile. Interdisciplinary cooperation with visceral/vascular and plastic surgery is essential. In chordoma patients, systemic tumor control is favorable compared to LRRC and sarcomas. Navigation offers gain in intraoperative orientation, even if there currently seems to be no oncological benefit. Complete surgical resection offers long-term survival to patients undergoing sacrectomy for a variety of complex diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Adrenal metastases are frequent in solid malignancies such as lung cancer and melanoma. Recent studies support the use of ablative local therapies in oligometastatic or oligoprogressive patients. Online adaptive MR-guided radiotherapy improves tumor coverage and organ-at-risk sparing compared to non-adaptive radiotherapy. However, clinical data, especially the long-term results of this promising technique, are still limited. We here report the long-term outcomes of a large single-center cohort. (1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present study, the intraoperative fluorescence of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) is investigated in 80 cases. Brain metastases fluoresced in 57.5% of cases, with no significant correlation between fluorescence and primary tumor or histological subtype. Complete resection of brain metastases was detected in 82.5%, of which 56.1% were fluorescence positive, compared to 43.9% which were non-fluorescent. Thus, prior administration of 5-ALA tended to improve the resectability rate by 12.1%. Fluorescence-positive and -negative metastases showed significantly different overall survival in this study. Therefore, administration of 5-ALA as a surgical adjuvant may be beneficial in resecting brain metastases and may potentially optimize the surgical procedure. (1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: The evaluation of therapeutic approaches over a decade at a tertiary cancer center in Germany was undertaken due to the frequent and critical discussions surrounding the selection of chemotherapy regimens and the incorporation of prophylactic cranial irradiation (PCI) in the management of limited disease small cell lung cancer (LD-SCLC). We found significant differences in progression-free survival (PFS) and overall survival (OS) between patients treated with carboplatin and etoposide (CP) and those treated with cisplatin and etoposide (EP), with EP showing better outcomes. Concomitant chemotherapy was also associated with improved PFS and OS. Notably, PCI was found to significantly improve OS and showed a trend towards improved PFS. Female patients had better OS, and the type of chemotherapy and PCI remained independent predictors of survival. This research provides valuable insights into treatment patterns, outcomes, and survival predictors for LD-SCLC, emphasizing the importance of personalized treatment approaches and the potential benefits of PCI. However, the study's retrospective nature and sample-size limitations should be considered, highlighting the need for further prospective studies in this field. In this study, we investigated the outcomes and factors influencing treatment efficacy in 93 patients with limited disease small cell lung cancer (LD-SCLC), with a median age of 64 years. We focused on the impact of chemotherapy regimens, prophylactic cranial irradiation (PCI), and patient-related variables. The median follow-up for OS was 17.3 months. We observed a statistically significant difference in PFS between LD-SCLC patients treated with cisplatin and etoposide (EP) and those treated with carboplatin and etoposide (CP) (PFS: EP 13.63 months vs. CP 6.54 months, p < 0.01). Patients treated with EP had better overall survival (OS) than CP-treated patients (OS: EP 26.9 months vs. CP 16.16 months, p < 0.01). Concomitant chemotherapy was associated with improved PFS (p = 0.003) and OS (p = 0.002). Patients receiving PCI showed superior OS (p = 0.05) and a trend towards improved PFS (p = 0.057). Female gender was associated with better OS (p = 0.025). Most patients had an ECOG performance status of 0 (71%). This real-world study underscores the importance of multidisciplinary LD-SCLC management, emphasizing the roles of chemotherapy, radiotherapy, and PCI. These findings inform personalized treatment strategies and emphasize the need for prospective trials to validate these results and optimize LD-SCLC treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: HCC is the most common malignant primary hepatic tumor, which can be treated by various therapies including surgery, ablation, or transarterial methods such as cTACE. Each of these treatments has its own indications depending on the stage of the disease. cTACE is mostly performed in patients with intermediate stage HCC. This large retrospective single-center study shows the long-term results including survival and prognostic factors of patients with HCC treated by TACE in different treatment settings over 20 years. The aim of this study was to retrospectively evaluate the effects of conventional transarterial chemoembolization (cTACE) for the treatment of hepatocellular carcinoma over 20 years regarding overall survival (OS) and prognostic factors for OS. During the period from 1996 to 2016, 836 patients with HCC were treated with cTACE. Data evaluation was performed on the basis of pre- and postinterventional MRI and CT scans. Survival analysis was performed by Kaplan–Meier estimator; prognostic factors were determined by the use of Cox regression analysis. Overall, 4084 (mean 4.89 TACE sessions/patient) procedures were assessed. Median OS was 700 days (99% CI, 632.8–767.2). Depending on the indication, patients treated with a neoadjuvant intention showed the best OS (1229 days, 99% CI 983.8–1474.2) followed by curative intention (787 days, 99% CI 696.3–877.7), and then palliative intention (360 days, 99% CI 328.4–391.6). Portal vein thrombosis (HR 2.19, CI 1.63–2.96, and p < 0.01) and Child–Pugh class B or worse (HR 1.44, CI 1.11–1.86, and p < 0.001) were significantly associated with shorter OS. Patients with HCC benefit from TACE after careful patient selection. Portal vein thrombosis and Child–Pugh class B or worse are significantly unfavorable prognostic factors for patients' survival. [ABSTRACT FROM AUTHOR]

Simple Summary: This research analyzed health data from 27,869 female breast cancer patients and 55,738 controls in Germany to develop a breast cancer disease model, focusing on stages and tumor subtypes from 2010 to 2020. It found that the majority of patients had HR+ tumors, with HR+/HER2− being the most common subtype. The study revealed significant survival differences across stages and subtypes, with stages B and C showing much lower survival rates than early-stage or control groups. It also noted worse outcomes for the HR−/HER2− subtype. This is the first study of its kind to utilize German claims data to model breast cancer, offering crucial insights into the disease's real-world epidemiology and treatment outcomes. Breast cancer is the leading cause of cancer-related mortality among women in Germany and worldwide. This retrospective claims data analysis utilizing data from AOK Baden-Wuerttemberg, a major statutory German health insurance provider, aimed to construct and assess a real-world data breast cancer disease model. The study included 27,869 female breast cancer patients and 55,738 age-matched controls, analyzing data from 2010 to 2020. Three distinct breast cancer stages were analyzed: Stage A (early breast cancer without lymph node involvement), Stage B (early breast cancer with lymph node involvement), and Stage C (primary distant metastatic breast cancer). Tumor subtypes were estimated based on the prescription of antihormonal or HER2-targeted therapy. The study established that 77.9% of patients had HR+ breast cancer and 9.8% HER2+; HR+/HER2− was the most common subtype (70.9%). Overall survival (OS) analysis demonstrated significantly lower survival rates for stages B and C than for controls, with 5-year OS rates ranging from 79.3% for stage B to 35.4% for stage C. OS rates were further stratified by tumor subtype and stage, revealing varying prognoses. Distant recurrence-free survival (DRFS) analysis showed higher recurrence rates in stage B than in stage A, with HR−/HER2− displaying the worst DRFS. This study, the first to model breast cancer subtypes, stages, and outcomes using German claims data, provides valuable insights into real-world breast cancer epidemiology and demonstrates that this breast cancer disease model has the potential to be representative of treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer patients whose tumor has already developed metastases are now living longer and longer in studies. These results are encouraging but must be viewed with caution because study participants are in most cases very special, i.e., they are younger or have fewer concomitant diseases than the average patient. For this reason, we analyzed all patients who were diagnosed with metastases between 1995 and 2022. The analysis showed that survival has also improved continuously in this real-world patient group. In a comparison of the periods 2018–2022 vs. 1995–2000, patients live about 1.5 years longer, a total of approximately 48 months. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of synthetic patient data can help address patient privacy concerns and the general availability of clinical data. It can overcome the challenges associated with obtaining real patient data for use in medical research, healthcare analytics, and clinical decision support. We propose an approach to provide synthetic patient data for laryngeal cancer, a relatively rare but complex disease. We adapted an existing synthesis technology to produce realistic prevalence and age distributions in the generated patient datasets. We verified the methodology and validated the results using real patient data from a German cancer registry. Background: Obtaining large amounts of real patient data involves great efforts and expenses, and processing this data is fraught with data protection concerns. Consequently, data sharing might not always be possible, particularly when large, open science datasets are needed, as for AI development. For such purposes, the generation of realistic synthetic data may be the solution. Our project aimed to generate realistic cancer data with the use case of laryngeal cancer. Methods: We used the open-source software Synthea and programmed an additional module for development, treatment and follow-up for laryngeal cancer by using external, real-world (RW) evidence from guidelines and cancer registries from Germany. To generate an incidence-based cohort view, we randomly drew laryngeal cancer cases from the simulated population and deceased persons, stratified by the real-world age and sex distributions at diagnosis. Results: A module with age- and stage-specific treatment and prognosis for laryngeal cancer was successfully implemented. The synthesized population reflects RW prevalence well, extracting a cohort of 50,000 laryngeal cancer patients. Descriptive data on stage-specific and 5-year overall survival were in accordance with published data. Conclusions: We developed a large cohort of realistic synthetic laryngeal cancer cases with Synthea. Such data can be shared and published open source without data protection issues. [ABSTRACT FROM AUTHOR]

Simple Summary: Older patients ≥ 55 years represent more than 50% of all sarcoma patients and have a worse prognosis compared to younger patients. Age alone should not be a reason to deprive patients of standard treatment with chemotherapy and surgery, provided they are functionally fit enough and willing to take the risk of adverse events. The E-TRAB study evaluated the feasibility and prognostic value of a comprehensive geriatric assessment representing different domains such as activities of daily living, co-morbidities and Patient-Reported Outcomes (PROs) for quality of life (QoL) and treatment tolerability. The study included 69 patients with soft tissue sarcoma (STS) between 55 and 88 years who were unsuited for treatment with anthracyclines and ifosfamide and received trabectedin as first-line therapy. Results show evidence that specific geriatric screening instruments could help predict or limit adverse treatment effects and, thereby, optimize treatment strategies in older STS patients. E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3. [ABSTRACT FROM AUTHOR]

Simple Summary: This longitudinal cohort study investigates the role of soluble Tumor Necrosis Factor Receptor 1 (sTNF-R1) in non-small-cell lung cancer (NSCLC) patients. Serum sTNF-R1 levels were measured in 134 NSCLC patients before, during, and after treatment at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019. This study reveals that baseline sTNF-R1 levels were higher in NSCLC patients compared to the general population, and they exhibited a linear increase over time. Importantly, individual changes in sTNF-R1 levels during and after treatment were found to be strongly associated with the risk of mortality, highlighting the potential of the sTNF-R1 trajectory as a valuable prognostic marker in NSCLC. Background: Tumor necrosis factor (TNF) is a multipotent cytokine involved in inflammation and anti-tumor activity. TNF- α exerts its function upon binding to TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2). This study investigates the relationship of soluble (s) TNF-R1 levels in non-small-cell lung cancer (NSCLC) patients with treatment and overall survival. Methods: In total, 134 NSCLC patients treated at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019 were included in this study. Serum levels of sTNF-R1 were measured via ELISA at baseline and during and after treatment. A linear mixed-effects model was used to assess sTNF-R1 changes over time. Linear regression was applied to investigate the association between clinical characteristics and changes in sTNF-R1. Cox regression models were used to estimate associations with overall mortality. Results: The estimated average sTNFR-1 at baseline was 2091.71 pg/mL, with a change of 6.19 pg/mL per day. Cox models revealed that the individual change in sTNF-R1 was more strongly associated with mortality than its baseline value, especially after adjusting for covariates. Conclusions: This study provides evidence that the individual change in sTNF-R1 levels during and after treatment were associated with the risk of mortality, suggesting the use of the sTNF-R1 trajectory as a prognostic marker. [ABSTRACT FROM AUTHOR]

Simple Summary: Infiltration of the aerodigestive tract determines the prognosis in advanced thyroid carcinoma, ultimately leading to suffocation. To avoid this fatal outcome, surgical treatment strategies—within the framework of multidisciplinary patient care—are required. There are no established guidelines to rely on, and an individualized surgical treatment approach is required. The aim of this study was to present and critically analyze the stepwise escalatory surgical treatment strategy, which was applied over a 16-year time period at the University Medical Center Mainz, in respect to the resulting recurrence-free survival. The feasibility of stage-adapted tracheal resections is illustrated by the present study. Despite the risk of potentially life-threatening complications from the operations, prolonged recurrence-free and overall survival were observed in the institutional cohort of patients suffering from high-stage thyroid carcinoma. (1) Background: Infiltration of the aerodigestive tract in advanced thyroid carcinoma determines the prognosis and quality of life. Different stages of tracheal tumor invasion require customization of the surgical concept. (2) Methods: In the period from January 2007 to January 2023, patients who underwent surgery for advanced thyroid carcinomas with trachea resections were included in a retrospective observational study. The surgical resection concepts and operation-associated complications were documented. The overall survival and post-resection survival were analyzed. (3) Results: From 2007 to 2023, at the single-center UMC Mainz, 33 patients (15 female and 18 male) underwent neck surgery with trachea resections for locally advanced thyroid carcinomas. Of these, 14 were treated with non-transmural (trachea shaving) and 19 transmural trachea resections (9 "window" resections, 6 near-circular resections, 3 sleeve resections and 1 total laryngectomy with extramucosal esophageal resection). The two-year postoperative survival rate was 82.0 percent. The two-year recurrence-free survival rate was 75.0 percent (mean follow-up period: 29.2 months). (4) Conclusions: Tracheal resections for locally advanced tumor infiltration are feasible as an element of highly individualized treatment concepts. [ABSTRACT FROM AUTHOR]

Simple Summary: Here, we report real-world treatment patterns and the overall survival of 104 patients with relapsing/refractory (R/R) MF who had received first-line therapy between 1984 and 2016. Our study found that second- and third-line therapies for R/RMF were heterogeneous, including systemic therapies, radiotherapy and topical therapies. More than two-thirds of patients at second- and third-line treatment received chemotherapy, and we observed that the median overall survival was longer with non-chemotherapy (not reached) vs. chemotherapy (6.5 years) treatment, suggesting that non-chemotherapy options may be more beneficial to patients. (1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lymphoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analyzed patient records (1984–2016) from 27 clinical sites in Europe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS) and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. The median (range) times from the start of first-line therapy to the first R/R MF and from the first to the second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radiotherapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). The median (95% confidence interval [CI]) OS from the diagnosis of the first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); the estimated median PFS (95% CI) from the time of the first R/R MF was 1.3 (1.0–2.1) years. (4) Conclusions: High rates of R/R disease were observed after second- and third-line treatments in this real-world cohort, with longer median OS in patients receiving non-chemotherapy treatment versus chemotherapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of the relation of human papillomavirus (HPV) infection and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. All patients with OPSCC (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). HPV+ patients had significantly better OS than HPV-negative (−) patients. In multivariable analysis, HPV− patients had an increased 4.5-fold higher hazard of death, but the smoking status had no independent influence on risk of death. In binary logistic regression analysis, smokers showed a 4.5 increased odds ratio (OR) of being tested HPV− than for nonsmokers. HPV− smokers formed the majority in Thuringia. Optimizing OPSCC therapeutic strategies due to the dominance of HPV− is more important than discussing de-escalation strategies for HPV+ patients. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor cells can evade recognition and killing via immune cells by expressing co-inhibitory membrane molecules, which suppress the activity of tumor-specific T cells. Immune checkpoint inhibitor (ICI) therapies act by blocking these inhibitory pathways via monoclonal antibodies. Due to the limited efficacy of ICI therapy, biomarkers have to be detected, a process that can identify patients who benefit from this long-term treatment. In this pilot study, immune monitoring of four blood cell markers was performed over time in advanced non-small cell lung cancer (NSCLC) patients undergoing combined immune/chemotherapy and surviving ≥12 months. We demonstrate that a low neutrophil/lymphocyte ratio (NLR), a low percentage of suppressive HLA-DRlow monocytes, and/or clearly detectable numbers of slan+ non-classical monocytes and of dendritic cells can be predictive markers for therapy responses and treatment outcomes. These markers might have an impact on the treatment decisions for NSCLC patients, but need to be validated in larger cohorts. An important challenge remains in identifying the baseline characteristics of cancer patients who will mostly benefit from immune checkpoint inhibitor (ICI) therapies. Furthermore, biomarkers could help in the choice of an optimal therapy duration after a primary therapy response. In this pilot study, the time courses of four different immune cell parameters were followed in 12 patients with advanced non-small-cell lung cancer (NSCLC) undergoing ICI therapy combined with chemotherapy and surviving at least 12 months. Blood was collected at the time point of the first and third antibody administration, as well as after 12 months of patients' survival. Using multi-color flow cytometry, two suppressive markers (neutrophil/lymphocyte ratio (NLR) and the frequency of circulating HLA-DRlow monocytes), as well as two markers of an ongoing immune response (6-Sulfo LacNAc (slan)+ non-classical monocytes and dendritic cell (DC) subtypes), were determined. In most of those who survived > 12 months, a low NLR and a low number of HLA-DRlow monocytes combined with clearly detectable numbers of slan+ non-classical monocytes and of DC subtypes were seen. Two of the patients had an increase in the suppressive markers paired with a decrease in slan+ non-classical monocytes and in DC subtypes, which, in at least one patient, was the correlate of an ongoing clinical progression. Our results implicate that the NLR, specific subtypes of monocytes, and the number of blood DCs might be useful predictive biomarkers for cancer patients during long-term treatment with ICI/chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Sufficient prognostic parameters are still lacking in penile cancer. In this study, we sought to evaluate the current TNM classification in terms of its ability to estimate prognosis and to identify additional independent prognostic parameters. We found that lymph node metastasis—as well as lymphovascular invasion in node-negative patients—had the strongest impact on prognosis, whereas HPV did not show an influence on outcome. Furthermore, the pT1b stage seems questionable, and a revision of the current TNM classification is advised. Background: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent TNM classification is questionable; in line with previous studies, we found that it has not improved prognosis estimation. Methods: We evaluated 297 patients from Germany, Russia, and Portugal. Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16, and histopathological parameters were evaluated for all patients. Results: Advanced lymph node metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS), cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS and OS did not significantly differ between T categories. In patients without lymph node metastasis at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome in basaloid carcinomas, but without statistical significance. HPV status was not associated with prognosis, either in the total cohort or in the usual type alone. Conclusion: Lymphatic involvement has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is therefore required. [ABSTRACT FROM AUTHOR]

Simple Summary: Certification in oncology aims to establish structural and procedural standards according to evidence-based guidelines. The WiZen study is the largest study so far to analyze the effect of the certification of designated cancer centers on survival in Germany. Based on clinical cancer registry data of 47.440 colorectal cancer patients treated between 2009 and 2017, the present study shows that treatment at colorectal cancer centers has been associated with significantly better outcomes. Patients treated at certified facilities had an eleven percent (colon)/nine percent (rectum) lower risk of dying within the first five years after diagnosis. These findings support the shift towards a more structured cancer care system. (1) Background: The WiZen study is the largest study so far to analyze the effect of the certification of designated cancer centers on survival in Germany. This certification program is provided by the German Cancer Society (GCS) and represents one of the largest oncologic certification programs worldwide. Currently, about 50% of colorectal cancer patients in Germany are treated in certified centers. (2) Methods: All analyses are based on population-based clinical cancer registry data of 47.440 colorectal cancer (ICD-10-GM C18/C20) patients treated between 2009 and 2017. The primary outcome was 5-year overall survival (OAS) after treatment at certified cancer centers compared to treatment at other hospitals; the secondary endpoint was recurrence-free survival. Statistical methods included Kaplan–Meier analysis and multivariable Cox regression. (3) Results: Treatment at certified hospitals was associated with significant advantages concerning 5-year overall survival (HR 0.92, 95% CI 0.89, 0.96, adjusted for a broad range of confounders) for colon cancer patients. Concentrating on UICC stage I–III patients, for whom curative treatment is possible, the survival benefit was even larger (colon cancer: HR 0.89, 95% CI 0.84, 0.94; rectum cancer: HR 0.91, 95% CI 0.84, 0.97). (4) Conclusions: These results encourage future efforts for further implementation of the certification program. Patients with colorectal cancer should preferably be directed to certified centers. [ABSTRACT FROM AUTHOR]

Simple Summary: The outcome of patients with advanced melanoma has profoundly improved over the last 15 years. Novel medications blocking BRAF, a protein involved in stimulating cell division, or inhibiting immune checkpoints associated with T-cell activation significantly improved overall survival. Mutations of the BRAF protein kinase cause cells to make an abnormal protein that promotes tumor growth. In patients with BRAF V600 mutations, dabrafenib and trametinib blocking BRAF V600 and MEK, respectively, have demonstrated improved efficacy in two large clinical trials (COMBI-d, COMBI-v) compared to blocking BRAF signaling with single agents. This led to the approval of dabrafenib plus trametinib for the treatment of patients with advanced melanoma. The study (COMBI-r) presented here investigated the use of dabrafenib plus trametinib in everyday clinical practice. COMBI-r confirms the data from COMBI-d and COMBI-v and provides additional data in patients with brain metastases or previous treatments who had been excluded from the pivotal trials. Combined BRAF/MEK-inhibition constitutes a relevant treatment option for BRAF-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators' upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine neoplasms (NENs) of unknown primary (NEN-UPs) encompass a small group within all diagnosed NENs. As a result, diagnostic work-up and the therapy algorithm are not standardized. In this study we consecutively analyzed a cohort of 113 patients, initially diagnosed as NEN-UPs. After extensive diagnostic work-up, in 11.5% (13 patients) a primary tumor site could be identified. Our study revealed that an extensive diagnostic work-up, in particular somatostatin receptor (SSTR)-PET, is associated with a better clinical outcome. Our study proposes that a detailed diagnostic investigation and the identification of a primary tumor site can provide the rationale for a tumor-specific therapy, contributing to a prolonged survival in NEN-UPs. Neuroendocrine neoplasms (NENs) represent a rare and heterogenous group of tumors with predominantly gastroenteropancreatic or pulmonary origin. Despite numerous diagnostic efforts, the primary tumor site remains unknown in up to 20% of the patients diagnosed with NEN. In this subgroup of NEN patients, a standard diagnostic algorithm has not yet been integrated into clinical routine. Of note, an undetermined primary tumor site in NENs is associated with an impaired clinical outcome by at least "formally" limiting treatment options exclusively approved for NENs of a certain histological origin. In this retrospective study, a patient cohort of 113 patients initially diagnosed with NEN of unknown primary (NEN-UP) was analyzed. In 13 patients (11.5%) a primary tumor site could be identified subsequently, amongst others, by performing somatostatin receptor (SSTR)-PET-based imaging, which was irrespective of the initial clinical or demographic features. Diagnostic work-up and therapeutic regimens did not differ significantly between patients with an identified or unidentified primary tumor site; only a detailed immunohistochemical assessment providing additional information on the tumor origin proved to be significantly associated with the detection of a primary tumor site. Our study revealed that a profound diagnostic work-up, particularly including SSTR-PET-based imaging, leads to additional treatment options, finally resulting in significantly improved clinical outcomes for patients with NEN-UPs. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis of intrahepatic cholangiocarcinoma in a cirrhotic liver is considered a contradiction for transplantation in Germany, as well as many other international transplantation programs. The aim of our retrospective study was to evaluate the long-term outcomes of patients with incidental combined hepatocellular- and cholangiocarcinoma and sole intrahepatic cholangiocarcinomas after liver transplantation. Between January 2010 and December 2022, iCCA was found in eight patients post-transplant. We confirmed high overall survival and low recurrence rates after liver transplantation. It can be stated that liver transplantation in the case of combined hepatocellular carcinoma and sole intrahepatic cholangiocarcinoma presents a possible curative therapy option. Background: Data about liver transplantation for mixed tumors from hepatocellular carcinoma to cholangiocarcinoma are limited. Furthermore, the diagnosis of intrahepatic cholangiocarcinoma or combined tumors in a cirrhotic liver is considered a contraindication for transplantation. Our aim was to evaluate the long-term outcomes of patients with incidental cholangiocarcinoma or combined tumors after liver transplantation. Methods: In our descriptive analysis, data were evaluated from all patients since 2010 who received a liver transplant due to an assumed hepatocellular carcinoma at Jena University Hospital. Survival rates were determined using the Kaplan–Meier method. Results: Between January 2010 and December 2022, an incidental intrahepatic cholangiocarcinoma was found in eight patients post-transplant. Four combined hepatocellular and cholangiocarcinoma and four sole intrahepatic cholangiocarcinomas were found. A recurrence through distant metastases from combined hepatocellular- and cholangiocarcinoma was found in one patient at one year after transplantation. Another patient developed a pulmonary primary tumor independently one year post-transplant. The recurrence rate was at 14.3%. While two patients died, the 1- and 5-year overall survival rates post-transplant were 87.5% and 75%, respectively. Conclusion: Patients with intrahepatic cholangiocarcinoma or combined hepatocellular- and cholangiocarcinoma could profit from liver transplantation. [ABSTRACT FROM AUTHOR]

Simple Summary: Locally advanced rectal cancer (LARC) is a heterogeneous disease showing a limited response to neoadjuvant therapies that may be associated with a worse prognosis; therefore, the prediction of long-term outcomes by surrogate endpoints could help with patient stratification from the diagnosis. While the pathologic complete response (pCR) is widely adopted as the primary endpoint in trials, there is little use of 2-year disease-free survival (2yDFS) in this context, although there is some evidence that it can be a strong predictor for overall survival (OS). We conducted a pooled analysis on a large cohort of LARC patients coming from 11 trials, aiming to assess the strength of the combination of pCR and 2yDFS as surrogate endpoints for OS. The results could contribute to understanding the prognostic role of the two single and combined endpoints to identify early on the high-risk patients and consequently tailor therapies. LARC is managed by multimodal treatments whose intensity can be highly modulated. In this context, we need surrogate endpoints to help predict long-term outcomes and better personalize treatments. A previous study identified 2yDFS as a stronger predictor of OS than pCR in LARC patients undergoing neoadjuvant RT. The aim of this pooled analysis was to assess the role of pCR and 2yDFS as surrogate endpoints for OS in a larger cohort. The pooled and subgroup analyses were performed on large rectal cancer randomized trial cohorts who received long-course RT. Our analysis focused on the evaluation of OS in relation to the pCR and 2-year disease status. A total of 4600 patients were analyzed. Four groups were identified according to intermediate outcomes: 12% had both pCR and 2yDFS (the better); 67% achieved 2yDFS but not pCR (the good); 1% had pCR but not 2yDFS; and 20% had neither pCR nor 2yDFS (the bad). The pCR and 2yDFS were favorably associated with OS in the univariate analysis, and 2yDFS maintained a statistically significant association in the multivariate analysis independently of the pCR status. The combination of the pCR and 2yDFS results in a strong predictor of OS, whereas failure to achieve 2yDFS carries a poor prognosis regardless of the pCR status. This new stratification of LARC patients could help design predictive models where the combination of 2yDFS and pCR should be employed as the primary outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: It is known that socioeconomically disadvantaged people more often develop esophageal cancer. Therefore, we assumed that those patients more often have advanced tumor stages and comorbidities at the time of surgery and, thus, are more likely to suffer from postoperative complications and poorer survival. To clarify this, we used the purchasing power of the respective postal codes to estimate the socioeconomic status (SES) of 310 patients who had undergone surgery for esophageal cancer in our institution. Fortunately, it turns out that SES was not associated with tumor stage or comorbidities at the time of surgery. Moreover, SES was neither related to postoperative complications nor overall survival. In conclusion, socioeconomic inequalities of patients treated at a high-volume center do not affect treatment results. In Germany, socioeconomically deprived citizens more often develop esophageal carcinoma, since typical risk factors follow the social gradient. Therefore, we hypothesized that socioeconomic deprivation might also be associated with advanced tumor stages and comorbidities at the time of surgery. As a consequence, socioeconomic deprivation may be related to postoperative complications and reduced overall survival. Therefore, 310 patients who had undergone esophagectomy for cancer in curative intent between 2012 and 2020 at the University Medical Center Hamburg-Eppendorf (UKE) were included in this study. Socioeconomic status (SES) was estimated using the purchasing power of patients' postal codes as a surrogate parameter. No association was found between SES and tumor stage or comorbidities at the time of surgery. Moreover, SES was neither associated with postoperative complications nor overall survival. In conclusion, socioeconomic inequalities of patients treated at a high-volume center do not affect treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: About 0.5% of pancreatic malignancies are adenosquamous carcinomas. The pathophysiology of these carcinomas is poorly understood and clinical data is sparse. We compared characteristics and prognostic factors of adenosquamous carcinoma and ductal adenocarcinoma, which represent the most common type of pancreatic cancer based on data from the German cancer registry group. Adenosquamous carcinoma showed poorer differentiation and higher frequency of blood vessel invasion indicative of a more aggressive tumor biology. Adenosquamous tumor differentiation was a strong negative prognostic factor. Survival of patients with adenosquamous carcinoma was shorter compared to patients with a ductal adenocarcinoma after surgical tumor resection. This study suggests that distinct multimodal treatment protocols should be considered for adenosquamous carcinomas of the pancreas. Background: Adenosquamous carcinoma of the pancreas (ASCP) is a rare malignancy and its pathophysiology is poorly understood. Sparse clinical data suggest that clinical outcome and overall survival is worse in comparison to common pancreatic ductal adenocarcinoma (PDAC). Methods: We evaluated clinical outcome and prognostic factors for overall survival of patients with ASCP in comparison to patients with PDAC recorded between 2000 and 2019 in 17 population-based clinical cancer registries at certified cancer centers within the Association of German Tumor Centers (ADT). Results: We identified 278 (0.5%) patients with ASCP in the entire cohort of 52,518 patients with pancreatic cancer. Significantly, more patients underwent surgical resection in the cohort of ASCP patients in comparison to patients with PDAC (p < 0.001). In the cohort of 142 surgically resected patients with ASCP, the majority of patients was treated by pancreatoduodenectomy (44.4%). However, compared to the cohort of PDAC patients, significantly more patients underwent distal pancreatectomy (p < 0.001), suggesting that a significantly higher proportion of ASCP tumors was located in the pancreatic body/tail. ASCPs were significantly more often poorly differentiated (G3) (p < 0.001) and blood vessel invasion (V1) was detected more frequently (p = 0.01) in comparison with PDAC. Median overall survival was 6.13 months (95% CI 5.20–7.06) for ASCP and 8.10 months (95% CI 7.93–8.22) for PDAC patients, respectively (p = 0.094). However, when comparing only those patients who underwent surgical resection, overall survival of ASCP patients was significantly shorter (11.80; 95% CI 8.20–15.40 months) compared to PDAC patients (16.17; 95% CI 15.78–16.55 months) (p = 0.007). ASCP was a highly significant prognostic factor for overall survival in univariable regression analysis (p = 0.007) as well as in multivariable Cox regression analysis (HR 1.303; 95% CI 1.013–1.677; p = 0.039). Conclusions: In conclusion, ASCP showed poorer differentiation and higher frequency of blood vessel invasion indicative of a more aggressive tumor biology. ASCP was a significant prognostic factor for overall survival in a multivariable analysis. Overall survival of resected ASCP patients was significantly shorter compared to resected PDAC patients. However, surgical resection still improved survival significantly. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is frequently seen in elderly patients. The aim of our retrospective study was to evaluate the impact of age on postoperative short-term and long-term outcomes in patients undergoing curative pancreatic resection for PDAC. Our data confirm that pancreatic resections can be performed with equal short-term outcomes even in older age. However, patient age significantly influenced the overall and disease-free survival of patients with PDAC undergoing primary resection in curative intent. Therefore, the choice of the optimal therapy concept for each patient should be individualized taking into account the patient's age. (1) Purpose: to evaluate the impact of age on postoperative short-term and long-term outcomes in patients undergoing curative pancreatic resection for PDAC. (2) Methods: This retrospective single-center study comprised 213 patients who had undergone primary resection of PDAC from January 2000 to December 2018 at the University Hospital of Erlangen, Germany. Patients were stratified according the age into two groups: younger (≤70 years) and older (>70 years) patients. Postoperative outcome and long-term survival were compared between the groups. (3) Results: There were no significant differences regarding inhospital morbidity (58% vs. 67%, p = 0.255) or inhospital mortality (2% vs. 7%, p = 0.073) between the two groups. The median overall survival (OS) and disease-free survival (DFS) were significantly shorter in elderly patients (OS: 29.2 vs. 17.1 months, p < 0.001, respectively; DFS: 14.9 vs. 10.4 months, p = 0.034). Multivariate analysis revealed that age was a significant independent prognostic predictor for OS and DFS (HR 2.23, 95% CI 1.58–3.15; p < 0.001 for OS and HR 1.62, 95% CI 1.17–2.24; p = 0.004 for DFS). (4) Conclusion: patient age significantly influenced overall and disease-free survival in patients with PDAC undergoing primary resection in curative intent. [ABSTRACT FROM AUTHOR]

There is conflicting evidence regarding the efficacy of neoadjuvant/perioperative chemotherapy (NCT) for gastro-esophageal cancer (GEC) on overall survival. This study aimed to analyze the outcomes of multimodal treatments in a large single center cohort. We performed a retrospective analysis of patients treated with NCT, followed by intended curative oncological surgery for locally advanced gastric cancer. Uni- and multivariate regression analysis were performed to identify the predictors of overall survival. From over 3000 patients, 702 eligible patients were analyzed. In the univariate analysis clinical stage, application of preoperative PLF, requirement of surgical extension, UICC-stage, grading, R-status, Lauren histotype, and HPR were the prognostic survival factors. In multivariate analysis PLF regimen, UICC-stages, R-status, Lauren histotype, and histopathologic regression (HPR) were significant predictors of overall survival. Overall HPR-rate was 26.9%. HPR was highest in the cT2cN0 stage (55.9%), and lowest in the cT3/4 cN+ stage (21.6%). FLOT demonstrated the highest HPR (37.5%). Independent predictors for HPR were the clinical stage and grading. Kaplan Meier analyses demonstrated significant survival benefits for the responding patients (p < 0.0001). HPR after NCT was an important prognostic factor to predict overall survival for locally advanced GEC. FLOT should be the preferred regimen in patients undergoing NCT ahead of surgery. [ABSTRACT FROM AUTHOR]