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Simple Summary: Peritoneal metastases from gastric cancer are linked to a poor prognosis, with median survival ranging from 2 to 9 months. Standard treatments, including systemic chemotherapy and targeted therapies, have demonstrated only limited effectiveness. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an experimental approach under investigation for treating these metastases, but its widespread clinical use is hindered by insufficient evidence regarding its safety and efficacy. This retrospective study presents outcomes from the first PIPAC program in Lithuania, where 32 patients underwent 71 PIPAC procedures between 2015 and 2022. Intraoperative and postoperative complications occurred in 4.2% of cases. Although reductions in peritoneal carcinomatosis index (PCI) and ascites volume were noted, they were not statistically significant. The median overall survival after PM diagnosis was 12.5 months. These findings suggest that PIPAC is a safe and feasible treatment, but further research is needed to establish its efficacy. Background: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. Methods: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien–Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. Results: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10–17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4–10). Conclusions: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Older patients (≤75 years) with advanced colorectal cancer (CRC) may have worse survival than non-older patients. We hypothesized that, rather than age alone, concurrent factors may be more relevant for real-world survival. Methods: Patients diagnosed with CRC in a 5-year period (2014–2018) were analyzed to determine which factors influenced in overall survival (OS). Kaplan-Meier method was used to estimate OS. Univariate and multivariate analysis was conducted by Cox regression analysis. The study was approved by Ethics Committee. Results: Out of 477 patients diagnosed with CRC, 231 had advanced disease. Ninety-two patients (40%) were older than 75 years; median OS (mOS) was 17.1 m (95% CI: 14.3–23.3), p < 0.001. In non-older patients, mOS was 26.7 m (95% CI: 21.9–32.6), p < 0.001. We evaluated eighteen concurrent factors that included characteristics related to the patient (age, sex, comorbidities, polypharmacy, Eastern Cooperative Oncology Group (ECOG), and nutritional status), to the tumor (stage at diagnosis, tumor side, molecular profile, tumor burden, location, and number of metastasis), and to the treatment administered (systemic treatment for advanced disease, chemotherapy schedule and number of lines, severe adverse events and dose reductions, and surgery of liver metastasis). In the univariate analysis, age at diagnosis, ECOG, nutritional status, tumor side, molecular profile, tumor burden, systemic treatment for advanced disease, and surgery of liver metastases had significant impact on survival. However, multivariate analysis revealed that only four factors (tumor burden, nutritional status, systemic treatment for advanced disease, and surgery of liver metastases) were independently associated with OS but not older age at diagnosis. Conclusion: Older age is not an independent survival prognostic factor for advanced CRC. Tumor burden, nutritional status, systemic treatment for advanced disease, and surgery of liver metastasis were significant factors associated with OS. These findings suggest that older patients should not be excluded from cancer treatment based on age alone. Plain Language Summary: Older patients with advanced CRC constitute a heterogeneous population, including patients with excellent health status and others with multiple comorbidities, functional dependence, or limited life expectancy. Furthermore, the definition of an "elderly" or "older" patient is not widely accepted and may vary between studies, although 75 years may be an appropriate cut-off point, as confirmed in our study. At present, there are few prospective and randomized studies focused on the progression and treatment of advanced colorectal cancer in elderly patients, so understanding the factors that influence its clinical course is a difficult challenge. In this retrospective real-world study, we analyze the influence of advanced age on the survival of patients with advanced colorectal cancer. The analysis of eighteen characteristics that were grouped in three subcategories: characteristic related to the patient (age, sex, comorbidities, polypharmacy, ECOG, and nutritional status [albumin levels at diagnosis]), to the tumor (stage at diagnosis, tumor side, molecular profile, tumor burden [CEA levels at diagnosis], location and number of metastasis), and to the treatment administrated (systemic treatment for advanced disease, chemotherapy schedule and number of lines, severe adverse events and dose reductions, and surgery of liver metastasis) showed that older age at diagnosis is not an independent prognostic factor of overall survival in patients with metastatic colorectal cancer. However, tumor burden, nutritional status, systemic treatment of advanced disease, or surgery of liver metastases are independent predictors of survival. [ABSTRACT FROM AUTHOR]

Purpose: [18F]-FDG PET/CT and brain MRI are common approaches to detect metastasis in patients of lung cancer. Current guidelines for the use of PET/CT and MRI in clinical T1-category lung cancer lack risk-based stratification and require optimization. This study stratified patients based on metastatic risk in terms of the lesions' size and morphological characteristics. Methods: The detection rate of metastasis was measured in different sizes and morphological characteristics (solid and sub-solid) of tumors. To confirm the cut-off value for discriminating metastasis and overall survival (OS) prediction, the receiver operating characteristic (ROC) analysis was performed based on PET/CT metabolic parameters (SUVmax/SUVmean/SULpeak/MTV/TLG), followed by Kaplan–Meier analysis for survival in post-operation patients with and without PET/CT plus MRI. Results: 2,298 patients were included. No metastasis was observed in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm. The cut-off of PET/CT metabolic parameters on discriminating metastasis were 1.09 (SUVmax), 0.26 (SUVmean), 0.31 (SULpeak), 0.55 (MTV), and 0.81 (TLG), respectively. Patients undergoing PET/CT plus MRI exhibited longer OS compared to those who did not receive it in solid nodules ≥ 8.0 mm & sub-solid nodules ≥ 10.0 mm (HR, 0.44; p < 0.001); in solid nodules ≥ 8.0 mm (HR, 0.12; p<0.001) and in sub-solid nodules ≥ 10.0 mm (HR; 0.61; p=0.075), respectively. Compared to patients with metabolic parameters lower than cut-off values, patients with higher metabolic parameters displayed shorter OS: SUVmax (HR, 12.94; p < 0.001), SUVmean (HR, 11.33; p <0.001), SULpeak (HR, 9.65; p < 0.001), MTV (HR, 9.16; p = 0.031), and TLG (HR, 12.06; p < 0.001). Conclusion: The necessity of PET/CT and MRI should be cautiously evaluated in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm, however, these examinations remained essential and beneficial for patients with solid nodules ≥ 8.0 mm and sub-solid nodules ≥ 10.0 mm. [ABSTRACT FROM AUTHOR]

KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as well as interphase. This systematic review briefly describes the important structural elements of KIF2C, its regulation by multiple molecular mechanisms, and its broad cellular functions. Furthermore, it systematically summarizes its oncogenic potential in malignant progression and performs a meta-analysis of its prognostic value in cancer patients. KIF2C was shown to be involved in multiple crucial cellular processes including cell migration and invasion, DNA repair, senescence induction and immune modulation, which are all known to be critical during the development of malignant tumors. Indeed, an increasing number of publications indicate that KIF2C is aberrantly expressed in multiple cancer entities. Consequently, we have highlighted its involvement in at least five hallmarks of cancer, namely: genome instability, resisting cell death, activating invasion and metastasis, avoiding immune destruction and cellular senescence. This was followed by a systematic search of KIF2C/MCAK's expression in various malignant tumor entities and its correlation with clinicopathologic features. Available data were pooled into multiple weighted meta-analyses for the correlation between KIF2Chigh protein or gene expression and the overall survival in breast cancer, non-small cell lung cancer and hepatocellular carcinoma patients. Furthermore, high expression of KIF2C was correlated to disease-free survival of hepatocellular carcinoma. All meta-analyses showed poor prognosis for cancer patients with KIF2Chigh expression, associated with a decreased overall survival and reduced disease-free survival, indicating KIF2C's oncogenic potential in malignant progression and as a prognostic marker. This work delineated the promising research perspective of KIF2C with modern in vivo and in vitro technologies to further decipher the function of KIF2C in malignant tumor development and progression. This might help to establish KIF2C as a biomarker for the diagnosis or evaluation of at least three cancer entities. [ABSTRACT FROM AUTHOR]

Introduction Predictive markers of LV5FU2 maintenance benefit after first-line induction with FOLFIRINOX in patients with metastatic pancreatic cancer are necessary to select patients who will not be harmed by this strategy. Patients and Methods We focused on patients who received 12 cycles of FOLFIRINOX (arm A, N  = 88) or 8 cycles of FOLFIRINOX followed by LV5FU2 maintenance in controlled patients (arm B, N  = 91) from the PRODIGE-35 trial. Prognostic factors and predictors of efficiency were identified by using Cox regression. Median progression-free survival (PFS), overall survival (OS), and time to deterioration of quality of life (TTD-QoL) were evaluated. Results Poor independent prognostic factors were primary tumor in place, age <65 years and the presence of liver metastases for PFS, a baseline neutrophil/lymphocyte ratio (NLR) ≥5 and CA19.9 ≥500 UI/L for OS, independent of the treatment arm. Patients with one metastatic site had a longer PFS in arm A, whereas patients with ≥2 metastatic sites had a longer PFS in arm B. We also identified predictors of OS and TTD-QoL in arm B but these differences were not statistically significant. Conclusion Except for patients with one metastatic site who benefited more from 12 cycles of FOLFIRINOX, a maintenance strategy with LV5FU2 should be widely offered to mPC patients whose survival and QoL are preserved after 4 months of FOLFIRINOX. (ClinicalTrials.gov: NCT02352337). [ABSTRACT FROM AUTHOR]

Introduction: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. Methods: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60–80 mg/m2, every 3–4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. Results: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. Conclusion: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated one of the treatment options for advanced breast cancer patients after they completed standard therapy that combines hormone therapy and specific targeted agents called cyclin-dependent kinase 4/6 inhibitors. We wanted to understand why in real-world patients start chemotherapy after finishing standard initial treatment, how they respond to it, and what factors might affect their outcomes. We found that chemotherapy was often used when patients faced dissemination to internal organs with the risk of further progression, but it provided limited benefits. We suggest that modern drugs recommended by guidelines before chemotherapy should be better reimbursed in Poland. This research could help doctors make better treatment decisions and improve future clinical trials. The standard therapy for hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer includes the use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy. The optimal post-CDK4/6i treatment sequence is unclear. This cohort study evaluated the initiation, characteristics, and outcomes of chemotherapy following CDK4/6i-based treatment. Among the 227 patients who began CDK4/6i therapy, 114 completed it. Seventy-nine female patients received further treatment, including 55 receiving chemotherapy. The average age was 60.1 years. Post-CDK4/6i chemotherapy was typically (69.1%) first-line due to an impending visceral crisis. The median progression-free survival (mPFS) was 3.0 months (range 0.5–18.9), and the median overall survival (mOS) was 8.3 months (0.5–26.1). The median OS from the end of CDK4/6i treatment was 12.4 months (1.5–26.8). In univariate analysis, neither mPFS nor mOS was associated with age, tumor grade, receptor status, Ki67 status, time from diagnosis to CDK4/6i cessation, therapy line, or CDK4/6i type. Dose reduction occurred in 12 patients (21.8%), and chemotherapy was ceased due to adverse events in 8 patients (14.6%). Chemotherapy showed limited benefit regardless of the regimen. The role of chemotherapy may evolve with broader CDK4/6i use in adjuvant treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer continues to be the leading cause of cancer-related deaths worldwide. Many patients present advanced disease at the time of the diagnosis. Neoadjuvant therapy aims to reduce the tumor stage and improve the operability of patients, and simultaneously leads to tumor regression. The tumor regression grade reflects the degree of pathological response to therapy. Thus, we conducted this study to identify the predictors for pathologic response after neoadjuvant treatment followed by surgery. The second goal of our research was to find the relationship between survival and tumor regression. Our study revealed that the histology of the primary tumor, lymph node size in the preoperative CT scan (>1.7 cm), and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict the effectiveness of tumor regression. Age > 70 years, extended resection > one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into a lung adenocarcinoma group (LUAD) and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small-cell lung cancer were included in the study. A total of 58 (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Additionally, 9 (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III, respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7 cm), and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR [95% confidence interval, p-value] of 6.88 [2.40–19.77, p < 0.0001], 3.13 [1.11–8.83, p = 0.0310], and 3.76 [1.20–11.81, p = 0.0233], respectively). Age > 70 years, extended resection > one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care. [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: Tertiary lymphoid structures (TLS) arise in non-lymphoid tissues due to inflammation or cancer and play a key role in adaptive immune responses. In this study, we analyzed the TLS maturity in 78 patients with pathological T4 colorectal cancer (CRC). Mature TLS, identified by organized T (CD3+) and B (CD20+) lymphocytes with Ki-67-positive B cells, have been linked to microsatellite instability and improved cancer-specific and post-recurrence survival. High tumor Ki-67 expression correlated with poorer outcomes. The absence of mature TLS independently predicted poor survival. Tumors with mature TLS showed a higher infiltration of CD3+ T cells, FOXP3+ T cells, and CD86+ immune cells, including M1-like macrophages. Focusing on the Ki-67 expression pattern, the simultaneous evaluation of TLS maturity and tumor proliferation potency is suggested to be a potential prognostic indicator in CRC. Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with locally advanced or metastatic urothelial carcinoma have a poor prognosis. Enfortumab vedotin, administered after cisplatin-based chemotherapy and followed by immune checkpoint inhibitors, is widely known to prolong overall survival (OS). However, the predictive factors of enfortumab vedotin treatment that prolong OS remain unclear. In this study, patients who received enfortumab vedotin with shrinking tumors showed a significant increase in OS compared to those who received chemotherapy other than enfortumab vedotin or those who did not receive any treatment. Multivariate analysis identified neutrophil-to-lymphocyte ratio and dysgeusia as potential predictors of OS. Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, enfortumab vedotin therapy is effective for patients with locally advanced or metastatic urothelial carcinoma. Randomized phase III trial results have demonstrated enfortumab vedotin (EV), an antibody–drug conjugate (ADC) consisting of an anti-Nectin-4 human IgG1 monoclonal antibody and monomethyl auristatin E, is a useful treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that progressed after immune checkpoint inhibitor (ICI) therapies. This multicenter retrospective cohort study aimed to identify predictive factors for the efficacy of EV therapy and prolonged overall survival (OS) of patients in clinical practice. This study included patients with la/mUC who received ICI treatment. Patients who subsequently received EV treatment, those who received non-EV chemotherapy, and those who received no treatment were defined as EV, non-EV, and best supportive care (BSC) groups, respectively. The median OS was 20, 15, and 7 months in the EV, non-EV, and BSC groups, respectively (p < 0.001). Patients with la/mUC who had a complete or partial response after EV treatment had a significantly prolonged OS compared with those with stable or progressive disease. Univariate analysis showed age, neutrophil-to-lymphocyte ratio (NLR), dysgeusia, and rash as independent predictors of OS improvement. NLR and dysgeusia were independent predictors of OS after EV in multivariate analysis. Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, EV therapy is an effective treatment for patients with la/mUC after ICI treatment. [ABSTRACT FROM AUTHOR]

Introduction: We previously conducted a phase I/Ib study (NCT03712943) with regorafenib and nivolumab in patients with refractory metastatic mismatch repair proficient (pMMR) colorectal cancer (CRC). This study aimed to investigate the role of Xerna™ TME Panel in predicting the treatment response. Methods: Twenty-two archival pretreatment tumor samples were subjected to the Xerna™ TME Panel, a machine learning-based RNA-sequencing biomarker assay. The Xerna tumor microenvironment (TME) subtypes were evaluated for correlation with overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and other biomarkers including KRAS, PD-L1, CD8 expression, and Treg cells in TME. Results: Based on Xerna™ TME Panel, 4 patients with immune-active (IA) subtype and 6 patients with immune-suppressed subtype were classified as biomarker-positive, and five with angiogenic (A) subtype and seven with immune desert subtype were biomarker-negative. While not reaching statistical significance, Xerna TME biomarker-positive patients seemed to have longer median PFS (7.9 vs. 4.1 months, p = 0.254), median OS (15.75 vs. 11.9 months, p = 0.378), and higher DCR (70% vs. 58%, p = 0.675). The IA subtype in our cohort had higher levels of CD4+ FOXP3+ Treg cells, whereas the A subtype showed lower levels of Treg cells. Conclusion: Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab might be of value for predictive clinical benefit. Further studies are needed to evaluate the predictive role of Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces. METHODS: This retrospective cohort study analyzed patient outcomes according to Ra-223 placement using administrative databases of four Canadian provinces, encompassing 4301 patients with mCRPC who received at least two lines of life-prolonging therapy (LPT) for mCRPC. Outcomes included OS, event-free survival (EFS), and healthcare resource utilization. Each province was analyzed separately. RESULTS: OS, measured from the start of second-line LPT, differed between provinces: those in Ontario receiving second-line Ra-223 had a longer OS vs. those receiving it in third-line or later (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95). There was no difference between lines of therapy in patients in British Columbia (HR 1.165, 95% CI, 0.894-1.518, p=0.2576), and OS was numerically worse but not statistically significant in patients receiving Ra-223 in second-line in Quebec (HR 1.44, 95% CI, 0.93-2.24). Other outcomes also varied across provinces, with second-line use of Ra-223 being associated with longer EFS and reduced healthcare utilization vs. third-line use in Ontario but not in Quebec. CONCLUSIONS: Significant heterogeneity exists in the management and outcomes of mCRPC between provinces, particularly regarding the placement of Ra-223 in the treatment sequence. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to assess the prognostic value of muscle invasion (MI), a key histopathological feature of tumor aggressiveness, and construct a superior prognostic prediction model combining the current TNM staging system. Materials and Methods: MI was analyzed in the whole‐slide images from a total of 301 patients with primary buccal mucosa squamous cell carcinoma (BMSCC). Survival times of patients with/without MI were evaluated by Kaplan–Meier analysis. MI was further combined with the TNM staging system to explore its predictive value for prognosis. Moreover, 204 cases of head and neck carcinoma from the TCGA database were included. Results: MI positive rate reached to 76% (229/301) in patients with BMSCC. MI was associated with poor overall survival (p = 0.012) and disease‐free survival (p = 0.022). The novel system (TNM staging combined with MI) revealed strong predictive performance, with the largest area under the curve (OS: p < 0.001, DFS: p < 0.004). MI and the established classification system were also had good predictive ability in the TCGA cohort. Conclusions: MI is an independent predictor of poor prognosis of BMSCC. The inclusion of MI in prediction system can augment the risk stratification of patients with oral squamous cell carcinoma and may assist in the clinical decision‐making process. [ABSTRACT FROM AUTHOR]

Simple Summary: Advancements in immune, targeted, and regional therapies have emerged in the past fifteen years in the management of high-risk, advanced, and metastatic melanomas. Rare melanoma variants include acral, mucosal, uveal, and desmoplastic melanoma. Though underrepresented in larger landmark trials for modern therapeutic options, results from these trials have been extrapolated and applied in the management of these rarer subtypes of melanoma. This article aims to review the current treatment recommendations for acral, mucosal, uveal, and desmoplastic melanomas. Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to analyze patterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India. Methods: From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan–Meir curves compared outcome variables based on ROC analysis-classified tumor volume. Results: During a median follow up of 25.4 months (17.3–39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024). Conclusions: For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC. [ABSTRACT FROM AUTHOR]

Sarcomas constitute a group of rare malignant neoplasms, commonly subcategorized into soft tissue sarcomas (STS) and bone sarcomas. This study aims to describe the treatment modalities and outcome of head and neck sarcoma (HNS) patients in western Denmark and to identify prognostic factors for overall survival and recurrence in HNS patients. The Aarhus sarcoma registry, The National Danish Sarcoma Database, and the Danish National Pathology Registry were used to identify HNS adult patients diagnosed between 1979 and 2022. Altogether, 291 patients were included in this study. The prevalent histological subtypes were undifferentiated pleomorphic sarcoma (16%; 48/291) and leiomyosarcoma (15%; 44/291) for STS patients (n = 230) and chondrosarcoma (10%; 28/291) and osteosarcoma (7%; 19/291) for bone sarcoma patients (n = 61). Surgery with curative intent was performed in 71% (164/230) and 70% (43/61) of STS and bone sarcoma patients, respectively. Clear resection was achieved in 59% (97/164) of STS patients and 44% (19/43) of bone sarcoma patients. Eighty-nine patients relapsed (STS n = 66, bone sarcoma n = 23) after a median time of 2.7/5.5 years for STS/bone sarcoma patients. The five-year overall survival rates were 45% for STS patients and 66% for bone sarcoma patients. The following factors were significantly, negatively associated with overall survival in STS patients: Age (hazard ratio (HR)) = 1.02, p < 0.001), tumour size ≥5 cm (HR = 1.75, p = 0.003), metastatic disease (HR = 3.17, p < 0.001), high grade tumour (HR = 2.24, p = 0.004), previous cancer (HR = 2.84, p < 0.001), and high Aarhus composite biomarker score (ACBS) (HR = 4.56, p = 0.001). For relapse in STS patients, higher tumour grade (HR = 3.19, p = 0.014), intralesional margins (HR = 2.84, p < 0.001), ≥2 previous cancers (HR = 3.00, p = 0.004), and high ACBS (HR = 3.29, p = 0.047), were negatively associated. For bone sarcomas only higher age (HR = 1.02, p = 0.049) and intralesional margins (HR = 2.91, p = 0.042) were significant negative factors for overall survival. Multiple prognostic factors for overall survival and relapse were identified, especially for STS patients. • 5-year survival was 45% for soft tissue sarcoma patients and 66% for bone sarcoma patients. • The Aarhus composite biomarker score is a prognostic factor for soft tissue sarcoma. • A previous cancer diagnosis is negatively associated with overall survival in soft tissue sarcoma patients. [ABSTRACT FROM AUTHOR]

Background and objective Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC), which is featured by low incidence, high malignancy rate, robust aggressive behavior and inferior prognosis. To date, there is no standardized treatment. The aim of this study is to better understand and accumulate more clinical experience of the disease by summarizing the clinicopathological features, diagnosis methods, therapeutic regimen and prognostic factors of PSC. Methods A total of 39 patients with PSC who diagnosed and received treatment in Beijing Chest Hospital from December 2013 to December 2023 were retrospectively recruited, and information including demographic characteristics, clinicopathological features, tumor-node-metastasis (TNM) stage, diagnosis method and therapeutic regimen were carefully collected. Meanwhile, follow-up was conducted. Kaplan-Meier method was used to analyze the prognostic factors of the disease. Results The PSC patients in this study ranged in age from 45 to 76 years old, including 35 males and 4 females. There were no specific clinical manifestations of PSC at initial diagnosis. Among the 39 patients, 20 underwent surgical resection and 19 received palliative chemoradiation or symptomatic supportive treatment. The 1-year and 5-year survival rates were 61.90% and 35.20% respectively. Univariate analysis indicated that family history of carcinoma, primary tumor site, TNM stage, lymph node metastasis, distant metastasis, whether or not received surgical resection, surgical method, treatment regimens, tumor tissue programmed cell death ligand 1 (PD-L1) expression ≥1% and mesenchymal-epithelial transition factor (MET) pathway abnormalities were correlated with the overall survival (OS) of patients (P<0.05). In the subsequent multivariate analysis, lymph node metastasis emerged as the only independent prognosticator in predicting inferior OS (P=0.037). Conclusion PSC is rarely seen in clinical practice and commonly occurs in elder men with smoking history. Tumor tissue PD-L1 expression ≥1% and MET abnormalities may predict inferior prognosis of PSC and lymph node metastasis was determined as the independent prognosticator of PSC. Surgical resection along with adjuvant medical treatment is the cornerstone for early and locally advanced patients, and the clinical utility of molecular targeting therapy and immunotherapy in PSC needs to be further investigated. [ABSTRACT FROM AUTHOR]

Recent studies have explored the prognostic role of the C-reactive protein to albumin ratio (CAR) in patients with bile duct cancer (BTC), but the results have been inconsistent. This study aimed to provide insight into the prognostic significance of the CAR in BTC prior to treatment using a meta-analysis. Summarized hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for prognosis and clinicopathological features using fixed or random effects models. Fourteen studies with a total of 1,543 subjects were included in this meta-analysis. Elevated CAR was significantly associated with poor overall survival (HR = 2.17, 95% CI = 1.81–2.60, P < 0.001) and decreased disease-free survival or recurrence-free survival (HR = 2.53, 95% CI = 1.98–3.25, P < 0.001) in BTC. In addition, high CAR was significantly associated with the presence of lymph node metastasis (OR = 1.54, 95% CI = 1.12– 2.13, P = 0.008), bile duct invasion (OR = 2.64, 95% CI = 1.54–4.54, P < 0.001), and tumor stages III–IV (OR = 3.11, 95% CI = 1.05–9.20, P = 0.040). However, there was no significant association between CAR and sex, microvascular invasion, or resection. An elevated CAR was significantly related to worse long-term and short-term survival and advanced clinicopathological features of BTC. CAR could serve as a valuable, noninvasive prognostic marker in patients with BTC. [ABSTRACT FROM AUTHOR]

Purpose: Anatomical structures and organ preservation concepts of the head and neck are important for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Neoadjuvant chemotherapy has been applied to improve organ preservation; however, pathological complete remission is still unsatisfactory. The purpose of this study was to explore the pathological complete response (pCR) rate and safety of immune checkpoint blockade combined with neoadjuvant chemotherapy (NAC) in patients with LA HNSCC. Methods: Fifty-one patients participated in this retrospective study, and of these, 25 received NAC only (cisplatin+5-fluorouracil+nab-paclitaxel), and 26 received NAC (cisplatin+5-fluorouracil) plus pembrolizumab. Pathological complete remission, the objective response rate (ORR), delayed surgery and toxicity were compared between the two groups. Results: A significant difference was observed in the pCR rate and ORR between the NAC+ICB group and the NAC group. Delaying surgery and Grade 3 or 4 AEs occurred more frequently in the NAC group. In the NAC-only group, during a median follow-up period of 31.80 months, the recurrence-free survival (RFS) rate was 80.0%, the disease-free survival (DFS) rate was 80.0% and the overall survival (OS) rate was 88.0%. In the NAC+ICB group, during the median follow-up period of 22.99 months, the RFS rate was 96.2%, the DFS rate was 96.2% and the OS rate was 100%. Conclusion: The combination of pembrolizumab with NAC could improve the pathological response without increasing the risk of toxicity, which provides pathological evidence for the treatment of LA HNSCC patients with NAC+ICB. [ABSTRACT FROM AUTHOR]

Objective: The treatment with 177Lutetium PSMA (177Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC) has recently been approved by the FDA and EMA. Since treatment success is highly variable between patients, the prediction of treatment response and identification of short- and long-term survivors after treatment could help tailor mCRPC diagnosis and treatment accordingly. The aim of this study is to investigate the value of radiomic parameters extracted from pretreatment 68Ga-PSMA PET images for the prediction of treatment response. Methods: A total of 45 mCRPC patients treated with 177Lu-PSMA-617 from two university hospital centers were retrospectively reviewed for this study. Radiomic features were extracted from the volumetric segmentations of metastases in the bone. A random forest model was trained and validated to predict treatment response based on age and conventionally used PET parameters, radiomic features and combinations thereof. Further, overall survival was predicted by using the identified radiomic signature and compared to a Cox regression model based on age and PET parameters. Results: The machine learning model based on a combined radiomic signature of three features and patient age achieved an AUC of 0.82 in 5-fold cross-validation and outperformed models based on age and PET parameters or radiomic features (AUC, 0.75 and 0.76, respectively). A Cox regression model based on this radiomic signature showed the best performance to predict overall survival (C-index, 0.67). Conclusion: Our results demonstrate that a machine learning model to predict response to 177Lu-PSMA treatment based on a combination of radiomics and patient age outperforms a model based on age and PET parameters. Moreover, the identified radiomic signature based on pretreatment 68Ga-PSMA PET images might be able to identify patients with an improved outcome and serve as a supportive tool in clinical decision making. [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]

Background: Pancreatic cancer (PC) first‐line therapy often consists of polychemotherapy regimens, but choosing a second‐line therapy after disease progression, especially following first‐line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab‐paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods: The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results: AG was well‐tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second‐line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first‐line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first‐line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second‐line OS and PFS. Conclusions: This study represents the largest real‐world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first‐line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first‐line therapy. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101–0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169–8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071–0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28–80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic liver resection (LLR) has proved effective in the treatment of oligometastatic disease (1 or 2 colorectal liver metastases CRLM) with similar long-term outcomes and improved short-term results compared to open liver resection (OLR). Feasibility of parenchymal sparing LLR for high tumour burden diseases is largely unknown. Aim of the study was to compare short and long-term results of LLR and OLR in patients with ≥ 3 CRLM. Methods: Patients who underwent first LR of at least two different segments for ≥ 3 CRLM between 01/2012 and 12/2021 were analysed. Propensity score nearest-neighbour 1:1 matching was based on relevant prognostic factors. Results: 277 out of 673 patients fulfilled inclusion criteria (47 LLR and 230 OLR). After match two balanced groups of 47 patients with a similar mean number of CRLM (5 in LLR vs 6.5 in OLR, p = 0.170) were analysed. The rate of major hepatectomy was similar between the two group (10.6% OLR vs. 12.8% LLR). Mortality (2.1% OLR vs 0 LLR) and overall morbidity rates (34% OLR vs 23.4% LLR) were comparable. Length of stay (LOS) was shorter in the LLR group (5 vs 9 days, p = 0.001). No differences were observed in median overall (41.1 months OLR vs median not reached LLR) and disease-free survival (18.3 OLR vs 27.9 months LLR). Conclusion: Laparoscopic approach should be considered in selected patients scheduled to parenchymal sparing LR for high tumour burden disease as associated to shorter LOS and similar postoperative and long-term outcomes compared to the open approach. [ABSTRACT FROM AUTHOR]

Simple Summary: The optimal radiotherapy (RT) dose for tracheobronchial adenoid cystic carcinoma (ACC) remains unclear due to its scarcity. This retrospective study evaluated the efficacy of dose-escalated RT for primary tracheobronchial ACC by dividing patients into groups of either low (<70.0 Gy EQD2) or high (≥70.0 Gy EQD2) RT doses. In the definitive RT group, the high-dose group showed better local control and survival rates compared to the low-dose group. The treatment related toxicities were the trachea or main bronchus stenosis. Dose-escalated RT may be effective for the definitive treatment of tracheobronchial ACC. Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. Patients classified into the low- and high-dose groups received RT doses <70.0 and ≥70.0 Gy in EQD2, respectively. The primary endpoint was freedom from local progression (FFLP) and overall survival (OS). Throughout the follow-up period, seven patients (14.6%) experienced local progression, while 31 (64.6%) exhibited distant metastasis, most commonly in the lungs. In total, the 5-year FFLP and OS rates were 85.7 and 84.7%, respectively. Multivariate analysis revealed that regional lymph node metastasis at diagnosis and receipt of definitive RT were associated with poorer OS. In the subgroup analysis, the definitive RT group had a 5-year FFLP rate of 33.3 and 78.2% in the low- and high-dose groups (p = 0.065), whereas 5-year OS rates were 66.7 and 79.0%, respectively (p = 0.022). Four patients (8.3%) experienced Grade 3 toxicity with tracheal or main bronchus stenosis. Dose-escalated RT with conventional fractionation may be effective in patients with tracheobronchial ACC, especially for a definitive aim. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the last decade, early-onset colorectal cancer incidence has continued to increase. The disparities in outcomes and overall survival (OS) between early-onset colorectal cancer and average-onset colorectal cancer remain controversial. The aim of our study was to compare survival rates and identify potential influential factors affecting outcomes between these two groups. Our results show better overall survival and cancer specific survival in patients with early-onset colorectal cancer which could be contributed to better general health, fewer comorbidities and higher likelihood of receiving aggressive cancer treatments. Background: Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before the age of 50 years, and its incidence has been increasing over the last decade, now accounting for 10% of all new CRC diagnoses. Average-onset colorectal cancer (AO-CRC) has shown a steady decline in its incidence and related mortality over the past 20 years. The disparities in outcomes and overall survival (OS) between EO-CRC and AO-CRC are controversial. Our study compared OS and cause-specific survival (CSS) between metastatic EO-CRC (mEO-CRC) and metastatic AO-CRC (mAO-CRC) and identified the associated factors. Methods: Data on patient characteristics, tumor characteristics, incidence, and mortality were obtained from the SEER database from 2010 to 2020. We identified 23,278 individuals aged > 18 years with a confirmed diagnosis of all histological subtypes of metastatic CRC (M1 on TNM stage) using ICD-O-3 site codes. mEO-CRC and mAO-CRC were compared. OS distributions and CCS were analyzed using the Kaplan–Meier method and log-rank test to assess differences. A Cox regression model was used to assess the associations between variables. Results: mEO-CRC constituted 17.79% of the cases, whereas 82.21% had mAO-CRC. Most patients with mEO-CRC were 45–49 years old (47.66%), male (52.16%) and White (72.57%) and had adenocarcinoma histology (87.30%). Left colon tumors were most prevalent in both groups (40.26%) but were more prevalent in mEO-CRC patients than in mAO-CRC patients (49.63% vs. 38.23%, p < 0.001). Patients with mEO-CRC had higher OS (p < 0.001) and CSS (p < 0.001) than those with mAO-CRC. Patients with mEO-CRC also had significantly better median overall survival (30 months vs. 18 months, p < 0.001). The factors associated with worse OS included mAO-CRC (p < 0.001), mucinous adenocarcinoma (p < 0.001), male sex (p = 0.003), and a lack of surgical intervention (p < 0.001). Conclusions: Most patients with mEO-CRC fall within the range of 45 to 49 years of age. Patients with mEO-CRC were more likely to receive cancer-directed therapy (including chemotherapy and radiotherapy) and had better OS and CSS than those with mAO-CRC. This is likely attributable to the better performance status, fewer comorbidities, and better tolerance to cancer-directed therapy in mEO-CRC patients. The factors associated with worse OS and CSS were age > 50 years, mucinous adenocarcinoma, male sex, and no surgical treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine carcinomas (NECs) of the tubular gastrointestinal tract are rare and associated with worse clinical outcomes. Data from 10,387 patients were collected from the SEER database with a median age of 63 years. The most common primary tumor site was the small intestine. women had a superior 5-year survival rate. Age > 65 years, descending colon and anorectal sites were associated with worse prognosis. Surgical intervention and tumors located in the small intestine and appendix showed a better prognosis. Background: Neuroendocrine carcinomas (NECs) of the tubular gastrointestinal tract (GI-NECs) are rare and associated with worse clinical outcomes. This population-based study aims to highlight key demographics, clinicopathological factors, and survival outcomes in the US population. Methods: Data from 10,387 patients with GI-NECs were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2000 to 2020. Results: Most patients were >40 years old at the time of presentation with a median age of 63 years old, with almost equal ethnic distribution per US population data. The most common primary tumor site was the small intestine (33.6%). The metastatic spread was localized in 34.8%, regional in 27.8%, and distant in 37.3% of cases, and the liver was the most common site of metastasis (19.9%) in known cases of metastases. Most NEC patients underwent surgery, presenting the highest 5-year overall survival of 73.2% with a 95% confidence interval (CI) (95% CI 72.0–74.4%), while chemotherapy alone had the lowest 5-year survival of 8.0% (95% CI 6.4–10.0%). Compared to men, women had a superior 5-year survival rate of 59.0% (95% CI 57.6–60.5%). On multivariate analysis, age > 65 (HR 2.49, 95% CI 2.36–2.54%, p ≤ 0.001), distant metastasis (HR 2.57, 95% CI 2.52–2.62%, p ≤ 0.001), tumor size > 4 mm (HR 1.98, 95%, CI 1.70–2.31%, p ≤ 0.001), esophageal (HR 1.49, 95% CI 0.86–2.58%, p ≤ 0.001), transverse colon (HR 1.95, 95% CI 1.15–3.33%, p ≤ 0.01), descending colon (HR 2.12, 95% CI 1.12, 3.97%, p = 0.02) anorectal sites, and liver or lung metastases were associated with worse survival. Surgical intervention and tumors located in the small intestine or appendix showed a better prognosis. Conclusion: GI-NECs are a group of rare malignancies associated with a poor prognosis. Therefore, epidemiological studies analyzing national databases may be the best alternative to have a more comprehensive understanding of this condition, assess the impact of current practices, and generate prognosis tools. [ABSTRACT FROM AUTHOR]

Simple Summary: The VELOUR randomized phase III trial established aflibercept (an anti-angiogenic targeting VEGF-A, VEGF-B, and placenta growth factor) combined with FOLFIRI as an effective treatment in patients with metastatic colorectal cancer (mCRC) failing a prior oxaliplatin-based regimen. This real-world study mandated by Polish Health Authorities aimed at assessing the benefits/risks of aflibercept plus FOLFIRI prescribed to Polish patients with mCRC according to reimbursement criteria. The activity of aflibercept plus FOLFIRI in such patients was confirmed, and no new safety signal was reported. Background: This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland. Methods: Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every 2 weeks until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); overall survival (OS) and safety were the secondary endpoints. Results: A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9–9.9] and 27.0 months [95% CI, 23.9–30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS. Main grade ≥ 3 adverse events were neutropenia (16%), hypertension (8%), diarrhea (4%), and stomatitis (4%). Conclusions: The benefits/risks of Aflibercept plus FOLFIRI administered per the Polish reimbursement criteria in second-line treatment of mCRC after failure of a prior oxaliplatin-based regimen is confirmed. [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]

Transarterial chemoembolisation with irinotecan-loaded drug-eluting beads (DEBIRI TACE) can be considered in patients with unresectable colorectal cancer liver metastases (CRLM) who progress after all approved standard therapies or in patients unsuitable for systemic therapy. Between September 2010 and March 2020, thirty patients (22 men and 8 women; mean age 66.8 ± 13.2) were included in this retrospective study. DEBIRI TACE was conducted in 43% of patients unsuitable for systemic therapy as a first-line treatment and 57% as salvage therapy after the progression of systemic therapy. All the patients had liver-limited disease. In the case of unilobar disease, two treatments were performed at four-week intervals, and in the case of bilobar disease, four treatments were performed at two-week intervals. All patients were premedicated and monitored after the procedure. Adverse events were graded according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system for complications. The median overall survival (OS) from the beginning of DEBIRI TACE in the salvage group was 17.4 months; in the group without prior systemic therapy, it was 21.6 months. The median overall survival of all patients was 17.4 months (95% confidence interval [CI]: 10.0–24.7 months), and progression-free survival (PFS) was 4.2 months (95% CI: 0.9–7.4 months). The one-year survival rate after the procedure was 61%, and the two-year rate was 25%. Univariate analysis showed better survival of patients with four or fewer liver metastases (p = 0.002). There were no treatment-related deaths or grade 4 and 5 adverse events. Nonserious adverse events (Grades 1 and 2) were present in 53% of patients, and Grade 3 adverse events were present in 6% of the patients. DEBIRI TACE is a well-tolerated treatment option for patients with liver metastases of colorectal cancer. Patients with four or fewer liver metastases correlated with better survival. [ABSTRACT FROM AUTHOR]

This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET). This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months. Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 vs. 10%, p = 0.01) and increased hepatic burden (20% vs. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (−23%) and liver-adjusted ADCmean/ADCmean liver (−16%), compared to R's increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of < 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver < 6.9 (p = 0.024) and ∆ Size NELM > 0% + ∆ ADCmin < −2.9% (p = 0.021). Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs. [ABSTRACT FROM AUTHOR]

Background: Distant metastases of ovarian cancer are rarely detected alone. The effectiveness of surgical intervention for pulmonary metastases from ovarian cancer remains uncertain. This study aimed to investigate the clinicopathologic characteristics and outcomes of patients undergoing resection for pulmonary metastasis from ovarian cancer. Case presentation: The clinicopathologic characteristics and outcomes of radical surgery for pulmonary metastasis from ovarian cancer were investigated. Out of 537 patients who underwent pulmonary metastasis resection at two affiliated hospitals between 2010 and 2021, four (0.74%) patients who underwent radical surgery for pulmonary metastasis from ovarian cancer were included. The patients were aged 67, 47, 21, and 59 years; the intervals from primary surgery to detection of pulmonary metastasis from ovarian cancer were 94, 21, 36, and 50 months; and the overall survival times after pulmonary metastasectomy were 53, 50, 94, and 34 months, respectively. Three of the four patients experienced recurrence after pulmonary metastasectomy. Further, preoperative carbohydrate antigen (CA) 125 levels were normal in two surviving patients and elevated in the two deceased patients. Conclusion: In this study, three of the four patients experienced recurrence after pulmonary metastasectomy, but all patients survived for > 30 months after surgery. Patients with ovarian cancer and elevated CA125 levels may not be optimal candidates for pulmonary metastasectomy. To establish appropriate criteria for pulmonary metastasectomy in patients with ovarian cancer, further research on a larger patient cohort is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation-associated sarcomas pose a significant clinical challenge due to their complexity, aggressiveness, and poor prognosis. Our retrospective study is one of the largest descriptions of radiation-associated sarcomas, aiming to shed light on their clinicopathologic characteristics and highlight treatment approaches. Our research found a significant association between high radiation-associated sarcoma histologic grade and inferior clinical outcomes. We also found that localized radiation-associated sarcoma patients who underwent margin-negative resections lived significantly longer than their counterparts. Our analysis thus confirms the paramount role of tumor grade and the central importance of margin-negative oncologic resection in determining clinical outcomes for radiation-associated sarcomas. Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic triple-negative breast cancer is an aggressive cancer with an average survival of 8 to 13 months. However, survival varies significantly among patients. We studied a large group of women in the National Cancer Database to better understand these survival differences. We found that the key factors influencing survival were comorbidity score (overall health status), histology (cancer subtype), number of metastatic sites (extent of cancer spread), and whether or not they received chemotherapy or immunotherapy. Our study's findings can help better predict survival based on an individual's specific factors and guide treatment strategies. Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with poor median overall survival (OS) ranging from 8 to 13 months. There exists considerable heterogeneity in survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival, utilizing a large patient sample from the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinicopathological, and treatment data and overall survival (OS) outcomes were collected. Kaplan–Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: In this sample, 2273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help individualize prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: This study assessed the outcomes of extremity soft-tissue sarcomas (ESTS) in 169 patients treated with radiotherapy (RT) and surgery between 2007 and 2020 in Strasbourg. Predominantly grade 2–3 tumors were found, mainly deep-seated in the lower limbs. Outcomes were promising, with 5- and 10-year LC, DC, and OS rates of 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. Factors influencing the outcomes included radiation dose, grade, histologic subtype, depth and treatment technique. Introduction: The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies. Methods: We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. We assessed local control (LC), distant control (DC), overall survival (OS), and complications. Results: A total of 169 patients diagnosed with localized ESTS were included. The median age was 64 years (range 21–94 years). ESTS primarily occurred proximally (74.6%) and in the lower limbs (71%). Most tumors were grade 2–3 (71.1%), deep-seated (86.4%), and had R0 margins (63.9%). Most patients were treated with helical tomotherapy (79.3%). The median biologically effective dose (BED) prescribed was 75 BEDGy4 (range 45.0–109.9). The median follow-up was 5.5 years. The 5- and 10-year LC, DC, and OS rates were 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. According to the univariate analysis, LC was worse for patients who received less than 75 BEDGy4 (p = 0.015). Deep tumors were associated with worse OS (p < 0.05), and grade 2–3 and undifferentiated pleomorphic sarcoma (UPS) were linked to both shorter DC and shorter OS (p < 0.05). IMRT was associated with longer LC than 3DRT (p = 0.018). Multivariate analysis revealed that patients with liposarcoma had better OS (p < 0.05) and that patients with distant relapse had shorter OS (p < 0.0001). Conclusion: RT associated with surgical resection was well tolerated and was associated with excellent long-term rates of LC, DC, and OS. Compared with 3DRT, IMRT improved local control. Liposarcoma was a favorable prognostic factor for OS. Intermediate- and high-grade tumors and deep tumors were associated with lower DC and OS. [ABSTRACT FROM AUTHOR]

Introduction: Resection of colorectal liver metastasis has emerged as the standard treatment. Our study compares oncological outcomes of patients with resected synchronous bilobar versus unilobar colorectal liver metastasis. Methods: This retrospective study presents long-term follow-up data of 105 consecutive patients with primary colorectal cancer and synchronous liver metastasis. All patients underwent primary tumor and metastasis resections between 2007 and 2019. Results: Fifty-five patients with bilobar and 50 patients with unilobar colorectal liver metastases were included. No significant difference in overall, tumor-specific, or recurrence-free survival was observed between patients with bilobar and unilobar metastases. After case-control matching, the results were confirmed in patients with similar tumor burdens. In the multivariate analysis, chemotherapy following liver metastasis resection was a significant prognostic factor associated with improved overall survival (hazard ratio 0.518, 95% confidence interval: 0.302–0.888, p = 0.017). Conclusion: Overall survival, as well as tumor-specific and recurrence-free survival, did not differ between patients with unilobar and bilobar liver metastasis. These findings contribute to the understanding that primary tumor and metastasis resection in eligible patients improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach. Methods: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks. Results: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99–7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11–0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82–0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03–0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not. Conclusions: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease. [ABSTRACT FROM AUTHOR]

With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. BRAF-targeted therapy is a standard of care in resected stage III–IV melanoma, while anti-programmed death-1 (PD1) immunotherapy is now a standard of care option in resected stage IIB through IV disease. With both modalities, recurrence-free survival and distant-metastasis-free survival are improved by a relative 35–50%, yet no improvement in overall survival has been demonstrated. Neoadjuvant anti-PD1 therapy improves event-free survival by approximately an absolute 23%, although improvements in overall survival have yet to be demonstrated. Understanding which patients are most likely to recur and which are most likely to benefit from treatment is now the highest priority question in the field. Biomarker analyses, such as gene expression profiling of the primary lesion and circulating DNA, are preliminarily exciting as potential biomarkers, though each has drawbacks. As in the setting of metastatic disease, markers that inform positive outcomes include interferon-γ gene expression, PD-L1, and high tumor mutational burden, while negative predictors of outcome include circulating factors such as lactate dehydrogenase, interleukin-8, and C-reactive protein. Integrating and validating these markers into clinically relevant models is thus a high priority. Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known regarding the significance of tumor burden in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Patients were stratified into high tumor burden (HTB) and low tumor burden (LTB) groups according to their tumor burden score. Our study showed tumor burden was significantly correlated with survival in R/M HNSCC patients, independent of PD-L1 status. HTB patients receiving EPF had better survival than those receiving PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival on PPF than EPF. For LTB PD-L1 negative patients, survival was similar between PPF and EPF. Hence, PD-L1 and TBS should be considered by the multi-disciplinary team for the treatment of R/M HNSCC. Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. Patients and Methods: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan–Meier curves were plotted for outcomes estimation. Results: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. Conclusions: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases from Hepatopancreaticobiliary (HPB) cancers are extremely rare and indicate a very poor prognosis. Patients with HPB cancers often have several months of life expectancy from the diagnosis of the brain metastases. Due to the rarity, there is no established protocol on how to treat brain metastases from HPB malignancies. Stereotactic radiosurgery provides the advantage of out-patient noninvasive management of brain metastases. We aim to retrospectively review the post-SRS outcomes of HPB patients with brain metastases in search for the optimal radiation delivery dose for HPB brain metastases. Our study showed that SRS could achieve a 94.7% local tumor control rate per tumor and newly developed brain metastases could be treated with repeat SRS. The favorable outcome of the present study indicates that SRS is effective in controlling HPB brain metastases and is instrumental in preserving patients' quality of life. Background: The role of stereotactic radiosurgery (SRS) for patients with brain metastases from hepatopancreaticobiliary (HPB) cancers has yet to be established. The authors present a single-institution experience of patients with HPB cancers who underwent SRS when their cancer spread to the brain. Methods: We surveyed our Gamma Knife SRS data base of 18,000 patients for the years 1987–2022. In total, 19 metastatic HPB cancer patients (13 male) with 76 brain metastases were identified. The median age at SRS was 61 years (range: 48–83). The primary cancer sites were hepatocellular carcinoma (HCC, 11 patients), cholangiocarcinoma (CCC, 2 patients), and pancreatic carcinoma (PCC, 6 patients). The median Karnofsky Performance Score (KPS) was 80 (range: 50–90). Two patients underwent pre-SRS whole-brain fractionated radiation therapy (WBRT) and eight patients underwent pre-SRS surgical resection. All SRS was delivered in single session. The median margin dose was 18 Gy (range: 15–20). The median cumulative tumor volume was 8.1 cc (range: 1.0–44.2). Results: The median patient overall survival (OS) after SRS was 7 months (range 1–79 months). Four patients had documented local tumor progression after SRS at a median time of 8.5 months (range: 2–15) between SRS and progression. Out of 76 treated tumors, 72 tumors exhibited local control. The local tumor control rate per patient was 78.9%. The local tumor control per tumor was 94.7%. Four patients developed new brain metastases at a median of 6.5 months (range: 2–17) after SRS. No patient experienced adverse radiation effects (AREs). At the last follow-up, 18 patients had died, all from systemic disease progression. Conclusions: Metastatic spread to the brain from HPB cancers occurs late in the course of the primary disease. In this study, all deceased patients ultimately died from primary disease progression. SRS is a non-invasive strategy that maximally preserves quality of life, and our results reported favorable outcomes compared to the existing literature. SRS should be considered as one of the primary management strategies for patients with brain metastatic spread from HPB cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is one of the most lethal bone tumors worldwide. Immune checkpoint blockades have achieved significant success in solid tumors; however, their role in osteosarcoma remains obscure. Therefore, we aim to explore the clinical significance of soluble immune checkpoint-related proteins in osteosarcoma in this study. We identified four soluble immune checkpoint-related proteins as predictors of progress-free survival and lung metastasis-free survival of osteosarcoma patients. Our findings indicated that soluble immune checkpoint-related proteins could be promising biomarkers for the outcomes and immunotherapy of osteosarcoma. Background: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. Methods: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. Results: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10−2, 1.7 × 10−2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10−4, 9.5 × 10−4, respectively). Conclusion: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. Methods: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. Results: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than −15% had significantly longer OS. Conclusion: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: In cancer, including head and neck cancer (HNC), certain key players in the body's inflammatory process, such as the interleukin (IL)-6 and IL-1 systems, are associated with outcomes. We studied some of these key players in a subgroup of HNC patients. From one blood sample measured at diagnosis, we determined high levels of molecules from members of the IL-6 and IL-1 families with their associated soluble cytokine receptors. High values indicated a lower survival rate. This prediction was to some extent better than the standard clinical predictors used. The results highlight potential new targets for immune treatment development. Additionally, these findings could contribute to the refinement of cancer treatment strategies, particularly in the context of emerging immune therapies. Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (−) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(−) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Regional lymph node recurrence after radical surgery for non‐small cell lung cancer (NSCLC) is an oligo‐recurrent disease; however, no treatment strategy has been established. In the present study we aimed to determine the clinical outcomes of postoperative regional lymph node recurrence and identify prognostic predictors in the era of molecular‐targeted therapy. Methods: We retrospectively analyzed data on clinical characteristics and outcomes of patients with regional lymph node recurrence after surgery who underwent treatment for NSCLC between 2002 and 2022. Results: A total of 53 patients were included in this study. The median time between surgery and detection of recurrence was 1.21 years. Radiotherapy (RT) alone and chemoradiotherapy (CRT) were performed in 38 and six patients, respectively. Driver gene alterations were detected in eight patients (EGFR: 6, ROS1:1, and BRAF: 1) and programmed death‐ligand 1 (PD‐L1) expression was examined in 22 patients after 2016. Median progression‐free survival (PFS) and overall survival (OS) after lymph node recurrences were 1.32 and 4.34 years, respectively. Multiple lymph node recurrence was an independent prognostic factor for PFS, whereas driver gene alteration was the only prognostic factor for OS. There was no significant difference in the OS between patients stratified according to the initial treatment modality for lymph node recurrence. Conclusion: Our results suggest that the number of tumor recurrences may correlate with PFS, while detection of driver gene alterations could guide decision‐making for the appropriate molecular‐targeted therapy to achieve longer OS. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic gastric cancer (mGC) have poor prognosis. This real-world study aimed to describe treatment regimens and survival of mGC patients. Methods: A retrospective analysis was conducted using anonymized German claims data (AOK PLUS) covering a period from 2010 to 2021. The study population included newly diagnosed mGC cases identified from 2011 to 2020. The index date was defined as the first diagnosis of metastasis on or after gastric cancer diagnosis. Therapy regimens were identified based on inpatient and outpatient data, and subsequently stratified by line of treatment. Survival analyses were conducted using the Kaplan–Meier method. Results: The cohort consisted of 5,278 mGC incident cases (mean age: 72.7 years; male: 61.9%). Nearly half of the incident cases received mGC-related treatment (49.8%). Treated patients were more often male, younger, and had fewer comorbidities compared to untreated patients. Of the 2,629 mGC patients who started the first line of treatment (1LOT), 32.8% switched to 2LOT, and 10.2% reached 3LOT. Longer survival time was observed among disease-specific treated cases compared with untreated cases (median real-world overall survival (rwOS): 12.7 months [95%CI 12.1 – 13.3 months] vs. 3.7 months [95%CI 3.4 – 4.0 months]). Conclusion: Systemic therapy was not received in almost half of the mGC patients. In those patients, a very short median rwOS was observed. Treatment patterns were generally in line with the guideline recommendations, however, therapy switching rates and poor prognosis indicate high unmet needs also in the treated population. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis, a critical aspect of oncologic diseases, is intricately governed by genetic factors. This article delves into the role of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation, investigating its implications in human cervical cancer. We analyzed five RRP1B polymorphisms in 172 cervical cancer patients to understand their associations with disease characteristics and survival. Certain variations were linked to decreased tumor size, reduced metastasis risk, and improved overall survival, suggesting their potential as markers for predicting prognosis in cervical cancer. Metastasis is a key determinant of cancer progression, influenced significantly by genetic mechanisms. RRP1B, primarily a nucleolar protein, emerges as a suppressor of metastasis, forming alliances with various cellular components and modulating gene expression. This study investigates the involvement of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation in cervical cancer. Through a comprehensive analysis of 172 cervical cancer patients, we evaluated five RRP1B single nucleotide polymorphisms (SNPs) (rs2838342, rs7276633, rs2051407, rs9306160, and rs762400) for their associations with clinicopathological features and survival outcomes. Significant associations were observed between specific genetic variants and clinicopathological parameters. Notably, the A allele of rs2838342 was associated with reduced odds of advanced tumor size, worse prognosis, and, preliminarily, distant metastasis, while the T allele of rs7276633 correlated with a decreased risk of higher tumor size and worse prognosis. Additionally, the C allele of rs2051407 demonstrated protective effects against larger tumors, metastasis, and adverse prognosis. The rs9306160 C allele exhibited a protective effect against metastasis. The rs762400 G allele was significant for reduced tumor size and metastasis risk. Furthermore, the rs2838342 A allele, rs7276633 T allele, rs2051407 C allele, and rs762400 G allele were associated with improved overall survival, demonstrating their potential significance in predicting prognoses in cervical cancer. Linkage disequilibrium and haplotypes analysis enabled us to evaluate the collective effect of the analyzed SNPs, which was in line with the results of allelic models. Our findings underscore the clinical relevance of RRP1B SNPs as prognostic markers in cervical cancer, shedding light on the intricate interplay between genetic factors and disease-progression dynamics. This research provides critical insights for future investigations and underscores the importance of incorporating RRP1B SNP detection into prognostic-assessment tools for accurate prediction of disease outcomes in cervical cancer. [ABSTRACT FROM AUTHOR]

Background Primary therapy of localized myxofibrosarcoma (MFS) remains controversial. Primary resection is complicated by a high rate of local recurrence, and the refractoriness to non-surgical treatment results in a higher risk of metastasis. The aim of the present study was to contribute the findings of a single sarcoma-specialized center and encourage investigating new treatment options. Patients and Methods We analyzed 134 patients treated with localized MFS in our center regarding prognostic factors defining overall survival, local recurrence, and metastasis. We focused on multimodal treatment of localized MFS: surgery, radiation, chemotherapy, hyperthermia, and isolated limb perfusion. Results The 5-year OS was 74.9%. From a total of 134 patients: 74 (55.2%) stayed disease free, 48 (35.8%) had a local recurrence (LR), and 23 (17.2%) developed a distant metastasis (DM). The 5-year LR-free survival (LRFS) and DM-free survival (DMFS) were 66.1% and 80.8%, respectively. Older age, tumor size (cT) cT ≥ 2, non-extremity localization, and distant metastasis were adverse predictive factors for OS. Performing an incision biopsy, surgery in a sarcoma-center, wide local excision or compartment-oriented excision, negative margins, and radiotherapy were positive predictive factors for LR. Tumor size cT ≥ 3 was a negative predictive factor for DM. Grading was a negative predictive factor for LR (G ≥ 2) and for DM (G3) in the multivariable analysis. Conclusion Adjuvant radiation had a positive impact on LRFS in all localized tumor stages, even in cT1 tumors. Chemotherapy did not have a significant impact on DMFS, regardless of tumor stage. Our findings indicate that myxofibrosarcoma may be a chemotherapy-resistant entity and a much closer monitoring is required, in case of neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Background: Brain metastases (BMs) are common in small cell lung cancer (SCLC), and the efficacy of immune checkpoint inhibitors (ICIs) in these patients is uncertain. In this study we aimed to develop and validate a radiomics nomogram based on magnetic resonance imaging (MRI) for intracranial efficacy prediction of ICIs in patients with BMs from SCLC. Methods: The training and validation cohorts consisted of 101 patients from two centers. The interclass correlation coefficient (ICC), logistic univariate regression analysis, and random forest were applied to select the radiomic features, generating the radiomics score (Rad‐score) through the formula. Using multivariable logistic regression analysis, a nomogram was created by the combined model. The discrimination, calibration, and clinical utility were used to assess the performance of the nomogram. Kaplan–Meier curves were plotted based on the nomogram scores. Results: Ten radiomic features were selected for calculating the Rad‐score as they could differentiate the intracranial efficacy in the training (area under the curve [AUC], 0.759) and the validation cohort (AUC, 0.667). A nomogram was created by combining Rad‐score, treatment lines, and neutrophil‐to‐lymphocyte ratio (NLR). The training cohort obtained an AUC of 0.878 for the combined model, verified in the validation cohort (AUC = 0.875). Kaplan–Meier analyses showed the nomogram was associated with progression‐free survival (PFS) (p = 0.0152) and intracranial progression‐free survival (iPFS) (p = 0.0052) but not overall survival (OS) (p = 0.4894). Conclusion: A radiomics nomogram model for predicting the intracranial efficacy of ICIs in SCLC patients with BMs can provide suggestions for exploring individual‐based treatments for patients. [ABSTRACT FROM AUTHOR]