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Simple Summary: This study focuses on Stage IIIA-N2 non-small cell lung cancer (NSCLC), which occurs when lung cancer has spread to lymph nodes in the centre of the chest but not to distant parts of the body. This type of cancer is difficult to treat, and survival rates remain low despite advances in therapy. The research is based on real-world data from Guy's Thoracic Cancer Database and aims to enhance our understanding of patient outcomes and identify important factors that impact survival and disease progression. By examining various treatment strategies, the study aims to offer insights that could help tailor treatment approaches to individual patients. The findings underscore the need for personalised care and the potential benefits of incorporating newer therapeutic options, ultimately leading to better survival outcomes for patients with this challenging form of lung cancer. Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive histologic subtype of urothelial carcinoma of the bladder (BC) with high rates of upstaging and metastases. The aim of our study was to characterize treatment patterns and outcomes using a large national database and our institutional experiences, combating the challenge posed by the rarity of this variant. We demonstrated that, despite an improved pT0 rate associated with NAC, there remains an inconclusive overall survival increase. Additionally, PUC demonstrated a high predilection for peritoneal metastasis, further highlighting the need for investigation into more effective and subtype-tailored treatment options. Background: Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC in the NCDB and our recent institutional experience. Methods: The NCDB was queried for localized PUC cases between 2004 and 2020. Patients with PUC from a single institution (Yale School of Medicine) were also incorporated from 2021 onwards to not double-count patients. The primary outcomes were overall survival and treatment trends. Results: A total of 146 patients were included, 123 from NCDB and 23 from Yale. The median overall survival (mOS) was 28 [IQR 7.5, 50.3] months, 23 [IQR 8.4, 46.3] months for the NCDB patients, and 36 [IQR 4.3, 68.1] for the Yale patients. The mOS for patients receiving neoadjuvant chemotherapy (NAC) was 60.0 [28.0, 91.9] vs. 14.8 months [0, 34.3] for patients without NAC, p = 0.038, though the benefit was not preserved in a Cox proportional hazard analysis incorporating the clinical stage, receipt of NAC, and age. The peritoneum was the most common site of metastasis (78.3%), followed by the liver and bones. Conclusion: Our findings underscore the formidable challenge posed by PUC, emphasizing its limited response to current therapies. Despite higher pT0 rates with NAC, the OS benefit remains inconclusive, highlighting the need for more effective treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer and the leading cause of cancer-related deaths among women globally, with over 2.26 million new cases in women in 2020. Male breast cancer, while rare (less than 1% of cases), is treated similarly to female breast cancer despite some clinical differences. Advances in treatment, such as using genomic and immunohistochemical markers, have significantly improved survival rates for women. Men with breast cancer are often older at diagnosis, and their prognosis may differ due to age and other factors. The survival analysis conducted on 2162 patients (19 males and 2143 females) suggests that male breast cancer may have a poorer prognosis compared to female breast cancer. Breast cancer is one of the most common cancers and the leading cause of cancer death in women. Less than 1% of breast cancer cases are male breast cancers. Although there has been significant progress made in the management of breast cancer, due to its rarity among men, the question of whether men and women with breast cancer have the same treatment response and survival rate still needs to be answered. The primary goal of this study is to compare survival outcomes between male and female breast cancer patients. Material and Method: This cohort study represents a retrospective and anonymized data analysis of 2162 breast cancer cases (19 males and 2143 females), registered over a period of 12 years, from 1 January 2010 to 31 December 2021, in the Clinic of Obstetrics and Gynecology, Diakoneo Diak Klinikum Schwäbisch Hall, Germany. Results: According to the Kaplan–Meier survival analysis, the estimated overall 3-year survival rate was 91.1% for women and 88.9% for men. The log-rank test of equality of survival distributions indicated a statistically significant difference in survival times between the two groups (p = 0.009). In the subsequent age-matched Kaplan–Meier analysis, the p-value was below the significance threshold (p = 0.068). Conclusions: Male breast cancer is a rare disease that may show some particularities in terms of survival compared to female breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to evaluate the role of adjuvant chemotherapy in patients who undergo pneumonectomy for pN1 NSCLC. We found no significant differences after 5 years between two cohorts (adjuvant CT and no adjuvant CT) in terms of the overall survival (p: 0.31), cancer-specific survival (p: 0.59), disease-free survival (p: 0.94), and relapse rate (p: 0.76). Patients with pN1 NSCLC that was completely resected through pneumonectomy and radical lymphadenectomy may represent a particular cohort, which could be strictly followed up without adjuvant chemotherapy. Introduction: We aimed to assess our 25-year experience in order to evaluate the role of adjuvant chemotherapy in patients who undergo pneumonectomy for pN1 NSCLC. Materials and Methods: We retrospectively reviewed the outcomes and medical records of patients undergoing pneumonectomy for NSCLC with pathological diagnosis of pN1, excluding all patients who underwent neoadjuvant treatment. We compared patients treated with adjuvant chemotherapy with patients who did not undergo neoadjuvant treatment during a follow-up soon after surgery. Gray's test was used to assess differences in the cumulative incidence of relapse or CSS between the different groups. Kaplan–Meier methods were used for drawing overall survival (OS) plots. In order to assess differences in survival between the groups, the log-rank test was used. The cumulative incidence of relapse, CSS, and OS were calculated at 1, 2, 3, 4, and 5 years of follow-up. Results: The 30-day and 90-day mortality rates of our cohort were 6% and 11,6%. Excluding the first three months after surgery (deaths linked to postoperative comorbidity), after 5 years we found no significant differences between the two cohorts (adjuvant CT and no adjuvant CT) in terms of the overall survival (OS) (p: 0.31), cancer-specific survival (CSS) (p: 0.59), disease-free survival (DFS) (p: 0.94), and relapse rate (p: 0.76). Conclusions: Patients with pN1 NSCLC that was completely resected through pneumonectomy and radical lymphadenectomy may represent a particular cohort, which could be strictly followed up without adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcopenia refers to a progressive and systemic reduction in skeletal muscle mass and strength and is a primary component of cancer cachexia. This retrospective study examined the impact of the rate of muscle loss between two time points during the pretreatment period with concurrent chemoradiotherapy on the clinical outcomes during subsequent durvalumab maintenance treatment. As the results showed, patients who experienced psoas muscle loss during chemoradiotherapy had a shorter progression-free survival and experienced reduced effectiveness of durvalumab treatment. This study highlights the importance of monitoring psoas muscle changes during chemoradiotherapy to predict the success of subsequent durvalumab therapy better in non-small cell lung cancer patients. Sarcopenia assessed at a single time point is associated with the efficacy of immunotherapy, and we hypothesized that longitudinal changes in muscle mass may also be important. This retrospective study included patients with non-small cell lung cancer (NSCLC) who received durvalumab treatment after concurrent chemoradiotherapy (CCRT) between January 2017 and April 2023. Muscle loss and sarcopenia were assessed based on the lumbar skeletal muscle area. Patients with a decrease in muscle area of 10% or more during CCRT were categorized into the muscle loss group, while those with a decrease of less than 10% were categorized into the muscle maintenance group. We evaluated the relationship between muscle changes during CCRT and the efficacy of durvalumab treatment. Among the 98 patients, the muscle maintenance group had a significantly longer PFS of durvalumab treatment compared to the muscle loss group (29.2 months [95% confidence interval (CI): 17.2—not reached] versus 11.3 months [95% CI: 7.6–22.3]; p = 0.008). The multivariable analysis confirmed that muscle change was a significant predictor of a superior PFS (HR: 0.47 [95% CI: 0.25–0.90]; the p-value was less than 0.05). In contrast, the OS between the groups did not differ significantly (not reached [95% CI: 21.8 months—not reached] and 36.6 months [95% CI: 26.9—not reached]; p = 0.49). Longitudinal muscle changes during CCRT are a predictor of durvalumab's efficacy in patients with NSCLC after CCRT. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases from systemic cancer are the most common tumors of the central nervous system. For prostate metastases to the brain, the clinical progression is poorly understood. This retrospective study aims to elucidate clinical risk factors associated with overall survival (OS; months post-diagnosis) in prostate metastases to the brain, and then develop a nomogram to aid in clinical decision making for this vulnerable population. We identified several factors associated with survival, including race, tumor size, and the presence of additional metastases. This study should serve as a clinical framework for prognostication in metastatic prostate cancer to the brain. Brain metastases are an uncommon yet life-limiting manifestation of prostate cancer. However, there is limited insight into the natural progression, therapeutics, and patient outcomes for prostate cancer once metastasized to the brain. This is a retrospective study of 461 patients with metastatic prostate cancer to the brain with a primary outcome of median overall survival (OS). The Surveillance, Epidemiology, and End Results (SEER) database was examined using Cox regression univariate and multivariable analyses, and a corresponding nomogram was developed. The median overall survival was 15 months. In the multivariable analysis, Hispanic patients had significantly increased OS (median OS 17 months, p = 0.005). Patients with tumor sizes greater than three centimeters exhibited significantly reduced OS (median OS 19 months, p = 0.014). Patients with additional metastases to the liver exhibited significantly reduced OS (median OS 3.5 months, p < 0.001). Increased survival was demonstrated in patients treated with chemotherapy or systemic treatment (median OS 19 months, p = 0.039), in addition to radiation and chemotherapy (median OS 25 months, p = 0.002). The nomogram had a C-index of 0.641. For patients with prostate metastases to the brain, median OS is influenced by race, tumor size, presence of additional metastases, and treatment. The lack of an association between traditional prostate cancer prognosis metrics, including Gleason and ISUP grading, and mortality highlights the need for individualized, metastasis-specific prognosis metrics. This prognostic nomogram for prostate metastases to the brain can be used to guide the management of affected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study of 61 patients with diffuse gliomas, APT-weighted imaging in the solid tumor component provided quantitative metrics associated with WHO grade and survival. Mean APT values of the necrotic component showed high variability between subjects, warranting further investigation. These results highlight the importance of assessing the different tumor components with APT-weighted imaging, to provide useful diagnostic and prognostic information for the management of patients with gliomas. Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2–3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Single small primary liver cancers are curable with treatments such as surgical resection, ablation, and liver transplant; however, many patients initially receive trans-arterial chemo-embolisation (TACE), which is generally not considered a curative treatment in itself, and often go on to receive further follow-up treatments. Little is known regarding the outcomes of such patients compared to those who receive upfront ablation. Our real-world multi-centre study demonstrates that key survival outcomes are similar between those initially undergoing TACE and those receiving ablation after controlling for other key clinical variables and allowing for subsequent individualised treatment selection. Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC. [ABSTRACT FROM AUTHOR]

Simple Summary: The survival of glioblastoma (GBM) patients remains at just 12–15 months with a 5% 5 year survival despite them undergoing a harsh and brutal treatment regimen involving surgery, radiation and chemotherapy. This is because GBMs are impossible to completely resect and almost always recur at the borders of the resection margin, while the presence of the blood–brain barrier limits the amount of chemotherapy that can access the brain, requiring the patient to receive high and extremely toxic doses of chemotherapy. In this study, we demonstrate that local delivery of the chemotherapeutic drug irinotecan directly into the border of the resection margin offers a safe route of administration with none of the normal side effects associated with traditional chemotherapy. Glioblastomas are impossible to completely resect and almost always recur at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur, while systemic treatment is hampered by the blood–brain barrier. Here, we report on the first evaluation in humans of the intraparenchymal injection of irinotecan into the resection cavity after surgical resection of recurrent glioblastoma patients. The cytotoxicity of irinotecan was compared to SN-38 in primary cells from recurrent glioblastoma patients. Irinotecan was injected at multiple (~30) sites of the resection cavity wall at a depth of 3 to 5 mm. SN-38 was more cytotoxic than irinotecan at concentrations below 1 µM due to enzyme kinetics. The intraparenchymal administration of irinotecan was safe, with good wound healing and an absence of swelling, inflammation, or pseudo-abscess formation. The median survival post irinotecan administration was 32.6 weeks. The median overall survival was 30.5 months, with a two-year survival rate of 56%. This study demonstrates that local delivery of irinotecan into the brain parenchyma offers a safe route of administration over systemic delivery in the treatment of recurrent glioblastoma. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes of lung metastasectomy in 147 patients with pulmonary metastases from primary liver tumors at three medical centers. Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. These findings can guide thoracic surgeons in patient selection and predicting surgical outcomes. Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide Receptor Radionuclide Therapy (PRRT) and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). In clinical practice, most patients receive more than one regimen, and the optimal sequence of treatments for these patients remains poorly understood. We present a real-world comparison of progression-free survival (PFS) between PRRT and CAPTEM in PNETs. Our analysis found that clinical outcomes were comparable to previously reported data in the real-world setting and were similar for both regimens. PFS for patients without extrahepatic metastases and those with MEN1, DAXX, and/or ATRX mutations might be prolonged with PRRT. Patients with grade 3 disease might fare better with CAPTEM initially. Candidates for surgical debulking or those with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to the shorter time to response. Background: Peptide Receptor Radionuclide Therapy (PRRT), a form of Radioligand Therapy (RLT), and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). Data regarding comparative efficacy are lacking. Herein, we compare the efficacy of PRRT vs. CAPTEM as second-line/beyond regimens and treatment sequencing. Methods: Clinicopathologic, radiographic, and genomic data were captured for metastatic PNETs seen in our multi-disciplinary NET clinic between 2013 and 2023. The primary outcome was progression-free survival (PFS) after progression on a previous line of systemic therapy. The secondary outcomes were objective response rate (ORR), time to response (TTR), and overall survival (OS). Results: Fifty-nine cases were included. PFS was similar in the PRRT (n = 29) and CAPTEM (n = 30) groups (PRRT = 21.90 months vs. CAPTEM = 20.03 months; HR 0.99; p = 0.97). On subgroup analysis, PRRT had longer PFS in cases without extrahepatic metastases (26.47 months vs. 17.67 months; p = 0.03) and cases with a mutation in the MEN1, DAXX, and/or ATRX genes (28.43 months vs. 18.67 months; p = 0.03). PRRT had reduced PFS in patients with grade 3 disease (7.83 months vs. 16.33 months; p = 0.02). ORR did not vary significantly (34.78% vs. 40.91%; p = 0.67). CAPTEM responders showed shorter TTR (6.03 months vs. 11.15 months; p = 0.03). In patients who received both, OS did not vary based on the sequence (HR 1.20; p = 0.75). Conclusions: PFS, ORR, and OS are similar when using PRRT vs. CAPTEM as second-line-and-beyond therapy for patients with metastatic PNETs. However, patients with MEN1, DAXX, and/or ATRX mutations or without extrahepatic metastases might better benefit from PRRT and patients with grade 3 disease from CAPTEM. Candidates for surgical debulking or with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to shorter TTR. [ABSTRACT FROM AUTHOR]

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]

Simple Summary: Vulvar cancer is a rare cancer but has a high cure rate if diagnosed early and treated appropriately. In the early 20th century, 5-year survival rates were only 15–20% because of inadequate treatment of both the primary cancer and the groin lymph nodes. By the mid-20th century, 5-year survival rates rose to 60–70% with the introduction of the radical resection of the vulva, together with the radical resection of the groin and usually pelvic lymph nodes. Although cure rates were good, physical and psychological morbidity were high with this extensive surgery. Hence, various modifications have been proposed over the past 50 years to decrease this morbidity without compromising survival, including modifications to the extent of both the vulvectomy and lymph node dissection. This paper looks at the results these modifications have on both survival and morbidity. Vulvar cancer is a rare disease, and cure rates were low until the mid-20th century. The introduction of an en bloc radical vulvectomy and bilateral groin and pelvic lymph node dissection saw them rise from 15–20% to 60–70%. However, this very radical surgery was associated with high physical and psychological morbidity. Wounds were usually left open to granulate, and the average post-operative hospital stay was about 90 days. Many attempts have been made to decrease morbidity without compromising survival. Modifications that have proven to be successful are as follows: (i) the elimination of routine pelvic node dissection, (ii) the use of separate incisions for groin dissection, (iii) the use of unilateral groin dissection for lateral, unifocal lesions, (iv) and radical local excision with 1 cm surgical margins for unifocal lesions. Sentinel node biopsy with ultrasonic groin surveillance for patients with node-negative disease has been the most recent modification and is advocated for patients whose primary cancer is <4 cm in diameter. Controversy currently exists around the need for 1 cm surgical margins around all primary lesions and on the appropriate ultrasonic surveillance for patients with negative sentinel nodes. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies analyzing specific treatment-related prognostic factors can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. The aim of our retrospective study was to determine the prognostic performance of clinicopathological factors and blood biomarkers in patients with unresectable metastatic melanoma treated with BRAF and MEK inhibitors. A total of 199 patients were included in the multivariate analysis of the risk of progression and death. We found that primary tumor localization on the limbs, Clark invasion level V, M1c stage or M1d stage at the start of therapy, and elevated baseline serum S100B level were independently and significantly associated with poor outcomes. The present study suggests that clinicopathological factors, including primary tumor characteristics and stage of metastatic disease, as well as serum markers may provide information on the probability of survival in patients with advanced melanoma treated with BRAF and MEK inhibitors. Prognostic studies can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. Methods: A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. Results: We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Conclusion: Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents a significant fraction of head and neck cancers, with a challenging five-year survival rate of only 50%. Key risk factors include tobacco and alcohol consumption and infection with human papillomavirus (HPV), particularly HPV16. Distinct biological differences exist between HPV-positive and HPV-negative OPSCC, including differences in mutation patterns and gene expression profiles. This study focuses on aldo-keto reductases (AKRs), specifically AKR1C2, which are involved in cellular stress management and detoxification processes, particularly in cisplatin-resistant tumors. This study investigates the role of AKR1C2 in HPV-positive OPSCC and its effect on patient outcomes. The findings indicate that increased levels of AKR1C2 are linked to unfavorable prognosis, particularly in male patients, while higher levels in female patients indicate a favorable prognosis. Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53WT). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification (p = 0.009) as well as positive HPV status (p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal carcinomatosis is a term for cancer cells spreading from tumors of internal organs and massively invading a large part of the membrane lining the abdomen and pelvis. For most patients, peritoneal carcinomatosis suggests only several months of life left. Current medicine can offer only alleviation of symptoms from this incurable disease. Researchers are intensely exploring some new therapeutic targets. Among promising candidates are non-coding RNAs, short molecules serving as important regulators in cells. When a disease such as cancer develops in the body, it is accompanied by typical changes in levels of non-coding RNAs. In this review, we provide an overview of current state of knowledge regarding the changes of non-coding RNA levels in peritoneal carcinomatosis. Deeper understanding of this topic could lead to the identification of non-coding RNAs as feasible specific biomarkers or novel therapeutic targets in the treatment of peritoneal carcinomatosis. Peritoneal carcinomatosis represents an advanced stage of tumors within the peritoneal cavity. Once considered an incurable terminal cancer metastasis, contemporary medicine is on the hunt for certain potentially curative options alongside the present day's palliative disease management. However, for most patients, peritoneal carcinomatosis continues to pose a fatal late-stage prognosis with a grim future outlook. Over the past two decades, non-coding RNAs have garnered significant attention due to their undeniable significance in regulating cellular processes across all levels. Disruption of the intricate regulation led by non-coding RNAs has been demonstrated to have a substantial impact on various human diseases, particularly in cancer, including solid tumors originating from the organs of the peritoneal cavity. This review aims to offer a comprehensive overview of the current state of knowledge in the under-researched field of peritoneal carcinomatosis, focusing specifically on the role of non-coding RNAs in the development of this condition and delineating potential avenues for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the most common cancer in men and a major cause of cancer-related deaths around the world. Prostate cancer that has spread to other parts of the body (advanced prostate cancer) is often treated with a drug called enzalutamide, which is a type of hormone therapy. Enzalutamide works by blocking the effect of the testosterone hormone on prostate cancer cells to stop them from growing. While this can be effective for several years, unfortunately, many patients being treated with enzalutamide eventually go on to become resistant to treatment, and the therapy stops working. Here, we show that prostate cancer cells that have become resistant to enzalutamide have increased levels of a type of sugar (known as sialic acid) on their surfaces. We set out to test whether stripping sialic acid from the surface of prostate cancer cells could help keep enzalutamide working for longer. Excitingly, our experiments show that treating prostate cancer cells with a drug to block sialic acid can partially reverse enzalutamide resistance. These findings suggest that drugs targeting sialic acid could be used in combination with enzalutamide therapy to disarm drug resistance and provide urgently needed new treatment options for men with prostate cancer. Prostate cancer is a lethal solid malignancy and a leading cause of cancer-related deaths in males worldwide. Treatments, including radical prostatectomy, radiotherapy, and hormone therapy, are available and have improved patient survival; however, recurrence remains a huge clinical challenge. Enzalutamide is a second-generation androgen receptor antagonist that is used to treat castrate-resistant prostate cancer. Among patients who initially respond to enzalutamide, virtually all acquire secondary resistance, and an improved understanding of the mechanisms involved is urgently needed. Aberrant glycosylation, and, in particular, alterations to sialylated glycans, have been reported as mediators of therapy resistance in cancer, but a link between tumour-associated glycans and resistance to therapy in prostate cancer has not yet been investigated. Here, using cell line models, we show that prostate cancer cells with acquired resistance to enzalutamide therapy have an upregulation of the sialyltransferase ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) and increased levels of α2,6-sialylated N-glycans. Furthermore, using the sialyltransferase inhibitor P-SiaFNEtoc, we discover that acquired resistance to enzalutamide can be partially reversed by combining enzalutamide therapy with sialic acid blockade. Our findings identify a potential role for ST6GAL1-mediated aberrant sialylation in acquired resistance to enzalutamide therapy for prostate cancer and suggest that sialic acid blockade in combination with enzalutamide may represent a novel therapeutic approach in patients with advanced disease. Our study also highlights the potential to bridge the fields of cancer biology and glycobiology to develop novel combination therapies for prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic renal cell carcinoma (RCC) represents a significant challenge in oncology, and systemic therapy remains the primary treatment modality. Radiation therapy (RT) offers a non-invasive ablative approach to the management of oligometastatic disease, and the use of Stereotactic Ablative Radiotherapy (SABR) has demonstrated remarkably high disease control. Within the broad spectrum of oligometastatic disease, we evaluated the efficacy of SABR on oligorecurrent RCC systemic treatment-naïve, and we aimed to identify predictive factors for long-term disease control. We demonstrated the potential of SABR to delay the need for systemic therapy and confirmed the long-term efficacy of SABR for oligometastatic RCC patients, with a superior benefit for patients with single lung metastasis, potentially refining patient selection processes to tailor treatments. Background: Stereotactic ablative radiotherapy (SABR) is emerging as a potential local treatment option for oligometastatic RCC. This study aims to evaluate the efficacy of SABR in patients with oligorecurrent RCC. Methods: A total of 50 patients with histologically confirmed RCC underwent SABR for oligorecurrence between 2006 and 2022. Eligible patients had up to five extracranial metastases and were systemic treatment-naïve at the time of irradiation. The primary endpoints of the analysis were overall survival (OS), local control (LC), distant metastasis–free survival (DMFS), and time to systemic therapy initiation. Results: The median OS was not reached, with 1- and 3-year OS rates of 93.8% and 77.5%, respectively. LC rates at one and three years were 95.8% and 86.5%, respectively. The median time to systemic therapy initiation was 63.8 months, and the median DMFS was 17.9 months, with one- and three-year rates of 63.4% and 36.6%, respectively. Multiple metastases were a negative predictive factor for DMFS (HR 2.39, p = 0.023), whereas lung metastases were associated with a more favorable outcome (HR 0.38, p = 0.011). Conclusions: SABR offers a valuable treatment option for oligometastatic RCC, demonstrating significant potential for achieving long-term disease control and delaying the need for systemic therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Induction regimens using 4-drugs for patients with newly diagnosed multiple myeloma have shown impressive results in multiple trials. However, trials of 4-drug regimens typically use a 3-drug regimen as their comparator, which limits our ability to determine whether the benefit is from the specific combination of drugs or just the addition of more agents. We performed a meta-analysis to compare all trials that compared 4-drug to 3-drug regimens and found that the addition of an anti-CD38 antibody (daratumumab or isatuximab) resulted in improved responses, while 4-drug regimens without an anti-CD38 antibody performed similarly to 3-drug regimens. While the addition of an anti-CD38 antibody led to increased adverse effects, these were predominantly mild and easily managed. These data suggest that an anti-CD38 antibody should be part of all 4-drug induction regimens for newly diagnosed myeloma patients. The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examined the outcomes of patients with gallbladder cancer over 20 years in Saskatchewan, Canada, focusing on geographic, demographic, and clinical factors. A total of 331 patients diagnosed between 2000 and 2019 were included. The majority (64%) had advanced stage 4 disease, with a significant proportion (66%) being rural residents. Key factors associated with poorer overall survival included stage 4 disease, lack of surgery, older age, a higher neutrophil-to-lymphocyte ratio, and no referral to a regional cancer center. Among early-stage patients, stage III disease and urban residence were associated with worse disease-free survival. The findings highlight the late-stage diagnosis and referral challenges impacting the outcomes of gallbladder cancer. Background: Gallbladder cancer (GBC) is an uncommon cancer. This study aimed to determine the outcomes of GBC in relation to geographic, demographic, and clinical factors in a Canadian province from 2000 to 2019. Methods: This population-based retrospective cohort study included all patients diagnosed with gallbladder cancer (GBC) in Saskatchewan, Canada, from 2000 to 2019. Cox proportional multivariate regression analysis was conducted to identify factors associated with poorer outcomes. Results: In total, 331 patients with a median age of 74 years and male–female ratio of 1:2 were identified. Of these patients, 305 (92%) had a pathological diagnosis of GBC. Among patients with documented staging data, 64% had stage IV disease. A total of 217 (66%) patients were rural residents, and 149 (45%) were referred to a cancer center. The multivariate analysis for patients with stage I–III GBC showed that stage III disease [hazard ratio (HR), 2.63; 95% confidence interval (CI), 1.09–6.34)] and urban residence (HR, 2.20; 95% CI, 1.1–4.39) were correlated with inferior disease-free survival. For all patients, stage IV disease (HR, 3.02; 95% CI, 1.85–4.94), no referral to a cancer center (HR, 2.64; 95% CI, 1.51–4.62), lack of surgery (HR, 1.63; 95% CI, 1.03–2.57), a neutrophil–lymphocyte ratio of >3.2 (HR, 1.57; 1.05–2.36), and age of ≥70 years (HR, 1.51; 95% CI, 1.04–2.19) were correlated with inferior overall survival. Conclusions: In this real-world context, the majority of patients with GBC were diagnosed at a late stage and were not referred to a cancer center. For those with early-stage GBC, living in an urban area and having stage III disease were linked to worse outcomes. Across all stages of GBC, stage IV disease, older age, absence of surgery, lack of referral to a cancer center, and a high neutrophil-to-lymphocyte ratio were associated with poorer survival. [ABSTRACT FROM AUTHOR]

Simple Summary: This research aims to identify preoperative factors that may predict positive resection margins in patients undergoing breast-conserving surgery for early-stage breast cancer. By retrospectively analyzing patient records from 2009 to 2017, the study investigates preoperative factors associated with positive resection margins. The findings indicate that neoadjuvant chemotherapy and the presence of ductal carcinoma in situ are significantly associated with positive resection margins. These results underscore the importance of these preoperative factors in surgical planning and management, potentially leading to improved outcomes for breast cancer patients. The primary objective of this study was to identify preoperative factors that could be associated with positive resection margins. We also tried to analyze the local recurrence and overall survival in patients who received conservative treatment for early-stage breast cancer and correlate these parameters with preoperative factors. A retrospective examination was conducted on the medical records and pathological reports of 143 patients who underwent breast-conserving surgery (BCS) for breast cancer in our department from 2009 to 2017. Postoperative outcomes were assessed through phone contact and statistical analyses, including GraphPad Prism, and Fisher's exact test, the Chi-square test, and the log-rank test were employed. The results revealed positive resection margins in 7.69% (11 cases) of the 143 patients, with an overall mortality rate of 16.66% for those with positive margins and 6.59% for those with negative margins. Statistical analysis indicated no significant differences in the overall (p = 0.5) or specific (p = 0.53) survival between the positive and negative margin groups. The positive margins were significantly associated with neoadjuvant chemotherapy (p < 0.0001) and the presence of ductal carcinoma in situ (DCIS) (p = 0.01). Among the analyzed factors, two out of sixteen were significantly linked to positive resection margins in BCS, emphasizing their importance in surgical management planning for early-stage breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The Fas/Fas ligand (FasL) system is an apoptosis-regulating pathway that holds a key role in tumor immune surveillance and metastasis. Although this pathway has been extensively investigated in pre-clinical models and in primary tumor tissues, however its role in the periphery is largely unexplored. To this end, the expression of Fas/FasL was for the first time assessed on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) in the peripheral blood of patients with metastatic breast cancer (BC). The results show that Fas and FasL are frequently expressed on BC patients' CTCs, with Fas/FasL-co-expressing CTCs emerging as a poor prognostic marker predicting a high risk for disease progression. On the other hand, Fas and FasL were also frequently expressed on BC patients' PBMCs, and Fas/FasL co-expression on PBMCs emerged as a favorable prognostic marker associated with a low risk for death. These results show that the assessment of Fas/FasL expression on CTCs and PBMCs can provide valuable prognostic information for patients with metastatic BC, and highlight their potential role in the peripheral immune response and metastatic progression of BC. The Fas/Fas ligand (FasL) system is a major apoptosis-regulating pathway with a key role in tumor immune surveillance and metastasis. The expression of Fas/FasL on mammary tumor tissues holds prognostic value for breast cancer (BC) patients. We herein assessed Fas/FasL expression on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) from 98 patients with metastatic BC receiving first-line treatment. Fas+, FasL+, and Fas+/FasL+ CTCs were identified in 88.5%, 92.3%, and 84.6% of CTC-positive patients, respectively. In addition, Fas+/FasL+, Fas-/FasL+, and Fas-/FasL- PBMCs were identified in 70.3%, 24.2%, and 5.5% of patients, respectively. A reduced progression-free survival (PFS) was revealed among CTC-positive patients (median PFS: 9.5 versus 13.4 months; p = 0.004), and specifically among those harboring Fas+/FasL+ CTCs (median PFS: 9.5 vs. 13.4 months; p = 0.009). On the other hand, an increased overall survival (OS) was demonstrated among patients with Fas+/FasL+ PBMCs rather than those with Fas-/FasL+ and Fas-/FasL- PBMCs (median OS: 35.7 vs. 25.9 vs. 14.4 months, respectively; p = 0.008). These data provide for the first time evidence on Fas/FasL expression on CTCs and PBMCs with significant prognostic value for patients with metastatic BC, thus highlighting the role of the Fas/FasL system in the peripheral immune response and metastatic progression of BC. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. This study investigates the clinical interest of whole exome sequencing for analyzing somatic mutational signatures in patients with advanced or metastatic NSCLC treated with the current standard of care. Investigating somatic mutational signatures as well as structural variations, we evaluated the association between genomic features and patient outcomes in a cohort of 132 patients. This study identified specific signatures associated with poor response to immune checkpoint inhibitor (ICI) therapy and chemotherapy, potentially aiding treatment selection and identifying patients unlikely to benefit from these approaches. Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. This study investigates the clinical interest of whole exome sequencing (WES) for analyzing somatic mutational signatures in patients with advanced or metastatic NSCLC treated with the current standard of care. Methods: Exome sequencing data and clinical characteristics from 132 patients with advanced or metastatic NSCLC were analyzed. Somatic mutational signatures including single base substitutions (SBSs), double base substitutions (DBSs), and copy number signatures were evaluated. Structural variations including tumor mutational burden (TMB), the number of neoantigens, TCR clonality, homologous recombination deficiency (HRD), copy number alterations (CNAs), and microsatellite instability (MSI) score were determined. The association between these genomic features, NSCLC subtypes, and patient outcomes (progression-free and overall survival) was evaluated. Conclusions: Exome sequencing offers valuable insights into somatic mutational signatures in NSCLC. This study identified specific signatures associated with a poor response to immune checkpoint inhibitor (ICI) therapy and chemotherapy, potentially aiding treatment selection and identifying patients unlikely to benefit from these approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Older patients with locally advanced non-small cell lung cancer may not be candidates for standard treatment due to their poor performance status. Immunotherapy and radiotherapy are well tolerated and may become the treatment of choice for those patients. This hypothesis should be confirmed in future clinical trials. The standard of care for locally advanced non-small-cell lung cancer (NSCLC) is either surgery combined with chemotherapy pre- or postoperatively or concurrent chemotherapy and radiotherapy. However, older and frail patients may not be candidates for surgery and chemotherapy due to the high mortality risk and are frequently referred to radiotherapy alone, which is better tolerated but carries a high risk of disease recurrence. Recently, immunotherapy with immune checkpoint inhibitors (ICIs) may induce a high response rate among cancer patients with positive programmed death ligand 1 (PD-L1) expression. Immunotherapy is also well tolerated among older patients. Laboratory and clinical studies have reported synergy between radiotherapy and ICI. The combination of ICI and radiotherapy may improve local control and survival for NSCLC patients who are not candidates for surgery and chemotherapy or decline these two modalities. The International Geriatric Radiotherapy Group proposes a protocol combining radiotherapy and immunotherapy based on the presence or absence of PD-L1 to optimize the survival of those patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Treating non-small cell lung cancer (NSCLC) patients with brain metastases (BM) is challenging, especially when brain involvement is the first sign of cancer. This study retrospectively analyzed 25 patients with newly diagnosed brain metastatic NSCLC without EGFR or ALK alterations. The findings suggest that patients with symptomatic BM at diagnosis may have better survival outcomes due to increased use of multimodal local treatments. Combining local approaches with first-line immune checkpoint inhibitors (ICI) and chemotherapy appears to improve survival in these patients. Additionally, a nonsystematic literature review was conducted to better understand the topic and explore the potential benefits of various immunotherapy-based combinations for brain metastatic NSCLC. This research aims to highlight the survival outcomes of this underrepresented population and provide insights into optimal treatment strategies. In the era of immune checkpoint inhibitors (ICI), managing non-oncogene driven non-small cell lung cancer (NSCLC) with brain metastases (BM) is challenging, especially when brain involvement is the initial sign. Patients with newly diagnosed brain metastatic NSCLC without epidermal growth factor receptor (EFGR) nor anaplastic lymphoma kinase (ALK) alterations were retrospectively included. Twenty-five patients were analyzed; 15 (60%) had symptomatic BM as the first sign (group 1), while 10 (40%) had BM discovered during complementary examinations (group 2). Fourteen patients (56%) had concomitant extracerebral metastases, primarily in group 2. Eight (32%) had oligometastatic disease, with seven in group 1. Over half received chemotherapy and pembrolizumab as first-line treatment. BM surgical resection occurred in twelve (80%) patients in group 1 and one in group 2. Median cerebral progression-free survival was 10 months: 12 in group 1 and 5 in group 2. Median overall survival was 25 months: not reached in group 1 and 6 months in group 2. This case series highlights survival outcomes for patients with inaugural BM, a demographic underrepresented in pivotal trials. Oligometastatic disease and symptomatic BM as initial signs seem associated with better prognosis due to increased use of multimodal local approaches. Combining local approaches with first-line ICI+/− chemotherapy appears to improve survival in brain metastatic NSCLC. A literature review was conducted to explore key questions regarding upfront ICI alone or in combination with systemic drugs or local approaches in brain metastatic NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant therapy with targeted therapy or immunotherapy has become the standard of care for fully resected stage III–IV melanoma. In this scenario, real-world data are needed to relate the actual effectiveness and safety of these regimens with the evidence provided in the clinical trials. This study provides clinicians and researchers with the results of an Italian single-center real-world experience on the use of adjuvant therapy in resected stage III–IV melanoma patients. Our findings confirm the real-world effectiveness and safety of adjuvant regimens, yet underscores the need for further research to explore biomarker-based predictors for relapse and to assess the translation of improved relapse-free survival into long-term overall survival benefit. This study was carried out at the Dermatologic Clinic of the University of Turin, Italy, to assess the effectiveness and safety of adjuvant therapy in patients who received either targeted therapy (TT: dabrafenib + trametinib) or immunotherapy (IT: nivolumab or pembrolizumab) for up to 12 months. A total of 163 patients participated, including 147 with stage III and 19 with stage IV with no evidence of disease. The primary outcomes were relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). At 48 months, both TT and IT approaches yielded comparable outcomes in terms of RFS (55.6–55.4%, p = 0.532), DMFS (58.2–59.8%, p = 0.761), and OS (62.4–69.5%, p = 0.889). Whilst temporary therapy suspension was more common among TT-treated patients compared to IT-treated individuals, therapy discontinuation due to adverse events occurred at comparable rates in both groups. Predictors of relapse included mitoses, lymphovascular invasion, ulceration, and positive sentinel lymph nodes. Overall, the proportion of BRAF-mutated patients receiving IT stood at 7.4%, lower than what was observed in clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Azacytidine and donor lymphocyte infusions were combined effectively in a single-center high-risk patient cohort (n = 29) for post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome. Bone marrow Wilms tumor gene 1 (WT1) expression was measured at time of transplant and post-transplant relapse. By using the Cox proportional hazards model, cut-off values for WT1 at both time points were obtained. The disease risk index incorporating initial cytogenetics and the disease stage at transplant as well as WT1 expression was significantly associated with overall survival, indicating that WT1 may represent a minimal residual disease marker in this context of cell therapy response evaluation, especially in high-risk patients currently considered to be in complete remission. Cut-off values for bone marrow WT1 expression for the two decisive treatment time points were proposed. Introduction: Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine–donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. Methods: A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. Results: An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, p = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, p = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, p = 0.0002. Conclusions: DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk. [ABSTRACT FROM AUTHOR]

Simple Summary: The study analyzed income disparities in 5-year survival rates (5YSR) among cancer patients in South Korea from 2002 to 2018. Overall, 5YSR improved from 2002–2006 to 2014–2018, particularly for lung, liver, and stomach cancers. The Slope Index of Inequality (SII) indicated significant income-related disparities, with higher survival rates associated with higher incomes, notably for lung and liver cancers. The SII for lung, liver, and stomach cancer increased, while that of thyroid, breast, cervical, prostate, and colorectal cancer decreased over the study period. The findings highlight persistent income-related gaps in cancer survival despite overall improvements, emphasizing the need for targeted interventions to address socioeconomic inequalities in cancer care outcomes. Background: The overall survival rates among cancer patients have been improving. However, the increase in survival is not uniform across socioeconomic status. Thus, we investigated income disparities in the 5-year survival rate (5YSR) in cancer patients and the temporal trends. Methods: This study used a national cancer cohort from 2002 to 2018 that was established by linking the Korea Central Cancer Registry and the National Health Insurance Service (NHIS) claim database to calculate the cancer survival rate by income level in the Republic of Korea. Survival data were available from 2002 onward, and the analysis was based on the actuarial method. We compared the survival of the earliest available 5-year period of 2002–2006 and the latest available 5-year period of 2014–2018, observing until 31 December 2021. Income level was classified into six categories: Medical Aid beneficiaries and five NHIS subtypes according to insurance premium. The slope index of inequality (SII) and relative index of inequality were used to measure absolute and relative differences in 5YSR by income, respectively. Results: The 5YSR between the 2002–2006 and 2014–2018 periods for all cancers improved. A significant improvement in 5-year survival rates (5YSR) over the study period was observed in lung, liver, and stomach cancer. The SII of survival rates for lung (17.5, 95% confidence interval (CI) 7.0–28.1), liver (15.1, 95% CI 10.9–19.2), stomach (13.9, 95% CI 3.2–24.7), colorectal (11.4, 95% CI 0.9–22.0), and prostate (10.7, 95% CI 2.5–18.8) cancer was significantly higher, implying higher survival rates as income levels increased. The SII for lung, liver, and stomach cancer increased, while that of thyroid, breast, cervical, prostate, and colorectal cancer decreased over the study period. Conclusions: Although substantial improvement in the 5YSR was observed across cancer types and income levels from 2002 to 2018, this increase was not uniformly distributed across income levels. Our study revealed persistent income disparities in the survival of cancer patients, particularly for lung and liver cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is one of the deadliest cancers due to its subtle onset and advanced stage at diagnosis. With most patients having inoperable cancer at diagnosis, survival rates remain low despite existing treatments. Our review aims to map and summarize current studies on FGFR inhibitors, a promising new treatment targeting specific cancer pathways. We found that while there are many preclinical studies, clinical research is still emerging, focusing mainly on the efficacy and safety of these treatments. Although FGFR alterations are relatively rare in pancreatic cancer, the few available real-life data are promising. Future research should aim to better identify the genetic drivers of this cancer and gather more data on long-term outcomes. This could lead to improved treatments and better survival rates for patients with pancreatic cancer. Pancreatic cancer is a highly lethal disease, often diagnosed at advanced stages, with a 5-year overall survival rate of around 10%. Current treatments have limited effectiveness, underscoring the need for new therapeutic options. This scoping review aims to identify and summarize preclinical and clinical studies on FGFR (Fibroblast Growth Factor Receptor) inhibitors, including tyrosine kinase inhibitors (TKIs) and FGFR-specific inhibitors, in pancreatic cancer with FGFR alterations. We included studies analyzing efficacy, safety, and survival outcomes in various populations. A comprehensive search across major databases identified 73 relevant studies: 32 preclinical, 16 clinical, and 25 from gray literature. The clinical trials focused primarily on efficacy (20 studies) and safety (14 studies), with fewer studies addressing survival outcomes. FGFR1 was the most studied alteration, followed by FGFR2 and FGFR4. Although FGFR alterations are relatively rare in pancreatic cancer, the available data, including promising real-life outcomes, suggest significant potential for FGFR inhibitors. However, more extensive research is needed to identify the correct genetic drivers and gather robust survival data. Ongoing and future trials are expected to provide more comprehensive insights, potentially leading to improved targeted therapies for pancreatic cancer patients with FGFR alterations. [ABSTRACT FROM AUTHOR]

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

Simple Summary: 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: The medical field is increasingly interested in using machine learning (ML) to analyse data, sparking a debate on whether ML is better than traditional statistical modelling. The aim of our retrospective study was to investigate the use of statistical models versus ML to predict survival in patients with osteosarcoma using low-dimensional data from the EURAMOS-1 trial. Results showed that ML did not add much value in this context, which involved data from nearly 2000 patients and eight predictors. Traditional statistical models worked well without needing extensive complex training, unlike ML, and they showed better effectiveness overall because they are easy to understand and use. The article helps healthcare researchers assess different prediction models in similar low-dimensional contexts. Since the mid-1980s, there has been little progress in improving survival of patients diagnosed with osteosarcoma. Survival prediction models play a key role in clinical decision-making, guiding healthcare professionals in tailoring treatment strategies based on individual patient risks. The increasing interest of the medical community in using machine learning (ML) for predicting survival has sparked an ongoing debate on the value of ML techniques versus more traditional statistical modelling (SM) approaches. This study investigates the use of SM versus ML methods in predicting overall survival (OS) using osteosarcoma data from the EURAMOS-1 clinical trial (NCT00134030). The well-established Cox proportional hazard model is compared to the extended Cox model that includes time-varying effects, and to the ML methods random survival forests and survival neural networks. The impact of eight variables on OS predictions is explored. Results are compared on different model performance metrics, variable importance, and patient-specific predictions. The article provides comprehensive insights to aid healthcare researchers in evaluating diverse survival prediction models for low-dimensional clinical data. [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: Relapse and treatment-related side effects pose significant challenges for older patients with high-risk blood cancers (myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)) undergoing hematopoietic stem cell transplants from HLA-haploidentical donors. We compared two preparative treatment regimens to identify the most tolerable and effective approach: one using fludarabine, cyclophosphamide, and melphalan, and the other using fludarabine, cyclophosphamide, and treosulfan. Our goal was to determine which treatment offers better survival rates and fewer side effects. We found that both regimens resulted in similar survival outcomes. However, the melphalan regimen was associated with fewer relapses but more treatment-related deaths, while the treosulfan regimen had fewer side effects but exhibited poorer disease control. These findings suggest that treosulfan may be safer, though higher doses might improve disease control, providing valuable insights for future treatments. Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated the feasibility of treosulfan-based conditioning, noting stable engraftment and low non-relapse mortality (NRM) in patients undergoing HLA-matched allo-HSCT. However, data on treosulfan-based conditioning in the HLA-haploidentical transplantation (HaploT) setting are limited. We retrospectively compared conditioning with fludarabine–cyclophosphamide (FC)–melphalan (110 mg/m2) and FC-treosulfan (30 g/m2) prior to HaploT using post-transplantation cyclophosphamide (PTCy) in patients with high-risk MDS/AML patients ≥ 50 years, transplanted from 2009–2021 at our institution (n = 80). After balancing patient characteristics by a matched-pair analysis, we identified twenty-one matched pairs. Two-year OS and LFS were similar among the groups (OS 66% and LFS 66%, p = 0.8 and p = 0.57). However, FC-melphalan was associated with a significantly lower probability of relapse compared to FC-treosulfan (0% vs. 24%, p = 0.006), counterbalanced by a higher NRM (33% vs. 10%, p = 0.05). Time to engraftment and incidences of acute and chronic graft-versus-host disease (GvHD) did not differ significantly. In conclusion, HaploT using FC-treosulfan in combination with PTCy in patients aged ≥50 years with MDS/AML appears safe and effective, particularly in advanced disease stages. We confirm the favorable extramedullary toxicity profile, allowing for potential dose intensification to enhance antileukemic activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Regorafenib offers longer survival for patients with refractory metastatic colorectal cancer (mCRC). We aimed to identify biomarkers for regorafenib through preclinical and translational studies. In silico analysis identified matrix metalloproteinase (MMP)-14 and MMP-9 as key biomarkers. Validation in patients receiving regorafenib or FTD/TPI showed that high MMP-14 levels were correlated with a better response to regorafenib. Additionally, lower MMP-9 levels before the second cycle were linked to improved disease control and survival. These findings suggest that MMP-14 and MMP-9 could serve as prognostic markers for regorafenib efficacy. In identifying biomarkers for anticancer drugs, the lack of objectivity in selecting candidate factors makes interpretation difficult. We performed preclinical analysis and a translational validation study to identify candidate biomarkers for regorafenib efficacy in metastatic colorectal cancer (mCRC). Using in silico COMPARE analysis with a human cancer cell line panel, JFCR39, we selected candidate biomarkers whose expression correlates with regorafenib sensitivity. We validated predictive values in mCRC patients receiving regorafenib (discovery, n = 53) and FTD/TPI (control, n = 16). Blood samples were obtained at baseline (BL), before the second cycle (2nd), and at progressive disease (PD), and biomarker levels were measured using ELISA. Our analysis showed that high matrix metalloproteinase (MMP)-14 expression was associated with a high sensitivity to regorafenib. In the discovery cohort, high MMP-14 levels at BL and PD were correlated with tumor shrinkage and longer progression-free survival (PFS). A subsequent analysis of other related factors further indicated that the patients with decreased MMP-9 levels at the 2nd had higher disease control rates, tumor shrinkage, longer PFS, and overall survival than those with increased changes. These findings were not observed in the control cohort. Our study suggests MMP-14 and MMP-9 may serve as prognostic markers for regorafenib and provide insights into novel combination therapies with anti-MMP-9 agents or FTD/TPI. [ABSTRACT FROM AUTHOR]

Simple Summary: The combination of chemoradiotherapy followed by surgery (trimodality therapy) is considered standard of care for patients with locally advanced esophageal adenocarcinoma, but many potential candidates for surgery receive curative-intent chemoradiotherapy alone. This study compared the outcomes of patients who received trimodality therapy to those who received curative-intent chemoradiotherapy. Our primary analysis found that trimodality therapy reduced the risk of local tumor recurrences, but we did not detect statistically significant differences in the risks of distant metastases or mortality. These results can help patients and clinicians make informed treatment decisions, although further studies are needed to refine our understanding of the trade-offs between the two treatment strategies. The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24–0.62; p < 0.001 ) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77–1.91; p = 0.40 ). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56–1.09; p = 0.14 ) or cancer-specific survival (HR, 0.83; 95% CI, 0.57–1.21; p = 0.33 ). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the protein expression levels of UCHL1, SNRNP200, and PAK4 in clear cell renal cell carcinoma (CCRCC) using advanced proteomic techniques. We found that UCHL1 and SNRNP200 are significantly upregulated, and PAK4 is downregulated in high-grade CCRCC, and all are involved in critical cellular pathways linked to cancer progression and poor clinical outcomes. Specifically, UCHL1 is implicated in the Akt signaling pathway, SNRNP200 plays a role in RNA splicing and cell cycle regulation, and PAK4 is associated with cell proliferation and invasion. The enhanced expression of UCHL1 and SNRNP200, and decreased expression of PAK4 correlate with shorter progression-free survival in CCRCC patients, suggesting their potential as prognostic markers and targets for therapeutic intervention. This research contributes to the understanding of CCRCC's molecular dynamics and opens new avenues for targeted treatments. Recent advancements in proteomics have enhanced our understanding of clear cell renal cell carcinoma (CCRCC). Utilizing a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by immunohistochemical validation, we investigated the expression levels of UCHL1, PAK4, and SNRNP200 in high-grade CCRCC samples. Our analysis also integrated Reactome pathway enrichment to elucidate the roles of these proteins in cancer-related pathways. Our results revealed significant upregulation of UCHL1 and SNRNP200 and downregulation of PAK4 in high-grade CCRCC tissues compared to non-cancerous tissues. UCHL1, a member of the ubiquitin carboxy-terminal hydrolase family, showed variable expression across different tissues and was notably involved in the Akt signaling pathway, which plays a critical role in cellular survival in various cancers. SNRNP200, a key component of the RNA splicing machinery, was found to be essential for proper cell cycle progression and possibly linked to autosomal dominant retinitis pigmentosa. PAK4's role was noted as critical in RCC cell proliferation and invasion and its expression correlated significantly with poor progression-free survival in CCRCC. Additionally, the expression patterns of these proteins suggested potential as prognostic markers for aggressive disease phenotypes. This study confirms the upregulation of UCHL1, SNRNP200, and PAK4 as significant factors in the progression of high-grade CCRCC, linking their enhanced expression to poor clinical outcomes. These findings propose these proteins as potential prognostic markers and therapeutic targets in CCRCC, offering novel insights into the molecular landscape of this malignancy and highlighting the importance of targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer in stages II and III is a significant health challenge, requiring ongoing improvements in treatment strategies. One promising approach is neoadjuvant therapy, which is given before surgery to shrink tumours and treat unseen cancer spread. This early treatment can help doctors see how well the tumour responds, which can guide further therapy after surgery. Testing for specific markers in the tumour, like certain gene mutations and protein levels, helps doctors choose the most effective treatments for each patient. By doing this, the chances of successful surgery and long-term survival improve. Managing this type of cancer requires a team of specialists working together to create personalised treatment plans. Despite its promise, neoadjuvant therapy comes with challenges, such as determining which tumours can be removed after treatment and recognising if a tumour appears larger due to treatment effects rather than actual growth. However, the medical community's ongoing research and dedication are essential to overcoming these obstacles and enhancing the benefits of neoadjuvant therapy. This approach aims to increase survival rates and improve the quality of life for patients with non-small cell lung cancer, making it a valuable advancement for society. Non-small cell lung cancer (NSCLC) poses a significant challenge in clinical oncology, necessitating continual refinement of treatment approaches in stages II and III. Recent advancements have highlighted the potential of neoadjuvant therapy in optimising patient outcomes. Biomarker testing guides neoadjuvant therapy decisions, including epidermal growth factor receptor (EGFR) mutation and programmed death-ligand 1 (PD-L1) expression testing. Neoadjuvant therapy aims to improve oncological outcomes by treating micrometastatic disease and assessing tumour response before surgery. Disease-free survival is a surrogate endpoint for overall survival in both neoadjuvant and adjuvant settings. Multidisciplinary collaboration is crucial for individualised treatment planning and optimising patient care. The management of NSCLC requires a comprehensive approach, integrating expertise across disciplines and tailoring treatment strategies to individual patient needs. Neoadjuvant therapy shows promise in improving long-term outcomes, with biomarker testing guiding treatment decisions. Challenges such as defining borderline resectability and differentiating pseudoprogression highlight the need for ongoing research and collaboration. [ABSTRACT FROM AUTHOR]

Simple Summary: There are no reliable prognostic biomarkers for ovarian cancer. The immune tumor suppressive marker interleukin-10 has been shown to be elevated in cancer, specifically in ovarian cancer. This study aims to correlate interleukin-10 levels in the ascites and sera of ovarian cancer patients to correlate with cancer-related data and outcomes. Our findings suggest a prognostic role for interleukin-10 that may be related to its immunosuppressive function in the tumor microenvironment. Future studies are needed to validate these results. This study highlights a potential target for novel therapeutic approaches. Interleukin-10 (IL-10) has been shown to be present at high levels in the ascites of ovarian cancer (OC) patients; however, little is known about its prognostic value. We sought to correlate IL-10 levels in ascites and sera of OC patients with clinicopathologic characteristics and oncologic outcomes. IL-10 levels and clinical data from biobanked ascites and serum samples of OC patients were evaluated. Receiver operating characteristic curves were used to quantify marker performance and identify IL-10-high and IL-10-low groups. Correlations between IL-10 levels and clinicopathologic data were performed. Survival outcomes were calculated, while the factors affecting them were also investigated. A total of 106 patients had ascites samples, of which 44 serum samples were also available. Mean ascites IL-10 levels were significantly higher in patients with serous histology compared to endometrioid histology (p = 0.024). Fold-change in ascites IL-10 during treatment positively correlated with clinical response, as determined by a change in serum cancer antigen (CA)-125 levels (p = 0.0126). Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with high compared with low ascites IL-10 levels (PFS: 18 versus 60 months; p = 0.007, OS: 42 versus 85 months; p = 0.029). A significant positive correlation was seen between ascites and sera IL-10 levels (p = 0.019). In multivariable analyses, a high ascites IL-10 level was associated with a significantly worse prognosis (PFS hazard ratio (HR) = 1.93; p = 0.02). Patients with high ascites levels of IL-10 have worse outcomes, which are likely reflective of the immunosuppressive effect of IL-10. This highlights its potential role as an immunomodulator in the tumor microenvironment, leading to OC immune evasion. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates how a condition called hydronephrosis—where the kidney swells due to blocked urine flow as a result of advanced bladder cancer—affects the outcomes of a surgical procedure called robot-assisted radical cystectomy, used to remove the bladder in this group of patients. The study analysed data from multiple Asian expert centers to see if patients with hydronephrosis before surgery had different outcomes compared to those without it. Results showed that patients with hydronephrosis tended to have worse survival rates and more complications following surgery. Understanding these impacts helps doctors better predict and improve treatment outcomes for bladder cancer patients. This study's findings can lead to more personalised and effective treatment plans, enhancing patient care. Introduction: Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. Patients and Methods: This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. Results: From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196–2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173–2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). Conclusions: The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Elderly cancer patients represent a population particularly susceptible to nutritional alterations, which can have an impact on overall survival and chemotherapy tolerance. The effects of nutritional interventions in this frail population have not been adequately examined in previous review studies. We conducted a systematic review of the existing literature on the effects of oral nutritional supplements (ONSs) and dietary counseling during chemotherapy in older oncology patients. Various types of ONS were investigated, including multimodal intervention with tailored nutritional counseling, whey protein supplements, amino acids supplements (including immune nutrition supplements), and fish oil omega-3-enriched supplements. ONSs showed promise in reducing chemotherapy side-effects and improving nutritional status in older cancer patients, but further studies are needed to explore their efficacy on chemotherapy adherence and overall survival. Further studies are needed to investigate the effects of ONS considering chronological age and frailty criteria, different dietary habits, and specific nutritional assessment like Bioelectrical Impedance Analysis. This study aims to review existing literature on the effect of oral nutritional supplements (ONSs) during chemotherapy in older cancer patients. Electronic databases were searched for relevant studies up to March 2024. The risk of bias in the included studies was evaluated using the Cochrane tool. Eligible studies included randomized, prospective, and retrospective studies evaluating the effect of ONSs in elderly (median age > 65 years) cancer patients during chemotherapy. Data regarding chemotherapy adherence, toxicity, overall survival, and nutritional status were extracted. A total of ten studies, involving 1123 patients, were included. A meta-analysis of the results was not conducted due to the scarcity and heterogeneity of results. Some ONSs were associated with reduced incidence of chemotherapy side-effects, particularly oral mucositis, and improved nutritional status. There was limited or no evidence regarding the impact of ONSs on chemotherapy adherence or overall survival. Various types of ONS were investigated, including multimodal intervention with tailored nutritional counseling, whey protein supplements, amino acids supplements (including immune nutrition supplements), and fish oil omega-3-enriched supplements. ONSs showed promise in reducing chemotherapy side-effects and improving nutritional status in older cancer patients, but further studies are needed to explore their efficacy on chemotherapy adherence and overall survival. Future research should consider both chronological age and frailty criteria, account for dietary habits, and use specific nutritional assessment like Bioelectrical Impedance Analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Although atezolizumab plus bevacizumab is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. In this meta-analysis, we examined the subsequent regimen after the failure of atezolizumab–bevacizumab and found that sequential multitargeted tyrosine kinase inhibitors, including sorafenib and lenvatinib, significantly prolonged the survival of patients, with a pooled OS of 11.45 months and a PFS of 3.78 months, respectively. Moreover, the subsequent use of sorafenib or lenvatinib has manageable toxicity. Therefore, our data indicate that sorafenib or lenvatinib treatment is a rational option for patients with advanced HCC after progression on atezolizumab–bevacizumab. Background: Although atezolizumab plus bevacizumab (hereinafter, atezolizumab–bevacizumab) is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. This study evaluated the efficacy and safety of sorafenib and lenvatinib in patients with advanced HCC that progressed under atezolizumab–bevacizumab treatment. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, Embase, and the Cochrane Library for articles published before November 2023. Random-effects meta-analysis was performed to determine the pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), comparing patients who received sorafenib versus lenvatinib. Results: Seven studies involving 387 patients were included. The pooled ORR, DCR, OS, and PFS for sorafenib and lenvatinib together were 26% (95% CI: 14–43%), 63% (95% CI: 47–77%), 11.45 months (95% CI: 7.12–15.77, I2 = 92%, p < 0.01), and 3.78 months (95% CI: 2.34–5.23, I2 = 67%, p = 0.02), respectively. Although lenvatinib users had a longer median OS (12.42 vs. 10.75 months) and PFS (5.15 vs. 2.58 months) than sorafenib users, the pooled ORR, DCR, median OS, and PFS for these medications were comparable. Additionally, the distributions of all-grade and grade ≥ 3 adverse events for sorafenib and lenvatinib were comparable to those for these two medications when used as first-line therapies. Conclusions: Sorafenib or lenvatinib can provide effective treatment with manageable toxicity in patients with advanced HCC after disease progression under atezolizumab–bevacizumab. [ABSTRACT FROM AUTHOR]

Simple Summary: Alterations in the SMARCB1/INI1 expression pattern have been detected in many tumors, including chordomas. We studied a large group of patients with conventional spinal chordomas, and the aims were to assess the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying alterations in the SMARCB1 gene and to investigate the correlation between clinicopathological features and patient survival. Partial SMARCB1/INI1 loss was identified in several patients, and this pattern correlated with mobile spine location and inadequate surgical margins. Moreover, mobile spine tumor location and inadequate surgical margins negatively impacted disease-free survival. The complete loss of SMARCB1/INI1 is currently ongoing as a target for molecular therapy; therefore, the partial loss of SMARCB1/INI1 in tumors could also have therapeutic implications. The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1/INI1 was correlated with cervical–thoracic–lumbar tumor location (p = 0.033) and inadequate surgical margins (p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of immune checkpoint inhibitors has revolutionized the treatment of lung cancer by becoming the standard therapy for advanced non-small cell lung cancer that lacks specific genetic mutations. However, not all patients respond equally, underscoring the need for biomarkers to predict treatment response. To address this, a study was conducted with 55 lung cancer patients treated with immune checkpoint inhibitors to investigate whether biomarkers like TCRβ diversity and certain cytokines linked to T cell activity could predict the response to immunotherapy. While higher TCRβ clonality and specific cytokine levels appeared to be associated with improved survival rates, the findings were not statistically significant. Specifically, higher levels of IL-2 and IL-15 were linked to shorter overall survival, with high IL-15 levels increasing the risk of death threefold in multivariable analysis. Although further research with larger sample sizes is needed for confirmation, these results offer promising insights into potential markers for predicting responses to immune checkpoint inhibitors. The development of immune checkpoint inhibitors (ICIs) has changed the therapeutic paradigm of lung cancer (LC), becoming the standard of treatment for previously untreated advanced non-small cell lung cancer (NSCLC) without actionable mutations. It has allowed the achievement of durable responses and resulted in significant survival benefits. However, not all patients respond; hence, molecular biomarkers are needed to help us predict which patients will respond. With this objective, a prospective observational study was designed, including a cohort of 55 patients with NSCLC who received ICIs. We studied whether biomarkers such as TCRβ and specific cytokines involved in the regulation of T cell activity were related to the immunotherapy response. In the survival analysis, it was found that patients with higher TCRβ clonality, lower TCRβ evenness, higher TCRβ Shannon diversity and lower TCRβ convergence had higher overall survival (OS) and progression-free survival (PFS). However, no statistically significant association was observed. Regarding cytokines, those patients with higher levels of IL-2 and IL-15 presented statistically significantly shorter OS and PFS, respectively. In fact, in the multivariable analysis, the high IL-15 level increased the risk of death by three times. Although the sample size was small and more studies are needed to confirm our results, our study reveals promising markers of responses to ICIs. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the high mutation burden in small-cell lung cancer (SCLC) suggests that it should be responsive to immune checkpoint blockade (ICB), relatively few patients have shown durable clinical benefit (DCB). To identify biomarkers of responses, biopsies from 35 patients treated with ICB (21 first-line and 14 second-line) were subjected to transcriptomic analysis and gene signatures were studied. Patients with DCB were compared to those with no clinical benefit (NCB). The response to ICB in the second-line, but not the first-line, setting was associated with gene signatures of inflammation, antigen presentation, interferon responses, and increased CD8 T cells. Our data suggest that responses to ICB in the second-line setting can be predicted by the baseline inflammatory state of the tumor; however, this strong association with inflammation was not observed in the first-line setting, likely because chemotherapy alters the immune milieu allowing a response to ICB. Although immune checkpoint blockade (ICB) is currently approved for the treatment of extensive-stage small-cell lung cancer (SCLC) in combination with chemotherapy, relatively few patients have demonstrated durable clinical benefit (DCB) to these therapies. Biomarkers predicting responses are needed. Biopsies from 35 SCLC patients treated with ICB were subjected to transcriptomic analysis; gene signatures were assessed for associations with responses. Twenty-one patients were treated with ICB in the first-line setting in combination with platinum-based chemotherapy; fourteen patients were treated in the second-line setting with ICB alone. DCB after ICB in SCLC in the second-line setting (3 of 14 patients) was associated with statistically higher transcriptomic levels of genes associated with inflammation (p = 0.003), antigen presentation machinery (p = 0.03), interferon responses (p < 0.05), and increased CD8 T cells (p = 0.02). In contrast, these gene signatures were not significantly different in the first-line setting. Our data suggest that responses to ICB in SCLC in the second-line setting can be predicted by the baseline inflammatory state of the tumor; however, this strong association with inflammation was not seen in the first-line setting. We postulate that chemotherapy alters the immune milieu allowing a response to ICB. Other biomarkers will be needed to predict responses in first-line therapy patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Mutations in the gene, TP53, define the most treatment-resistant subtype of acute myeloid leukemia (AML). Patients with TP53-mutated AML invariably develop disease recurrence after treatment, leading to short survival times. Previous studies have shown that less than 10% of these patients survive beyond 2 years after diagnosis. Moreover, the best treatment approach for these patients is still unclear. Our study is the first to analyze therapy results beyond first-line treatment, highlighting the importance of therapy sequencing in managing these patients. We found that sequential treatment with intensive chemotherapy followed by a less-intensive regimen achieved the highest remission rate of over 65%. Eligible patients should then receive blood stem cell transplantation from a donor, which significantly improves long-term survival. Our study provides crucial data to guide management and optimize therapy sequencing for better survival in this treatment-resistant disease. Background: TP53 mutations (TP53m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients. Methods: This study was a single-center, retrospective cohort analysis. Results: Our cohort includes 86 TP53m and 337 TP53 wild-type (TP53wt) adult AML patients. TP53m AML patients presented with lower bone marrow and peripheral blasts; none presented with hyperleukocytosis. Patients who received intensive treatment up front demonstrated superior overall survival (OS) over those receiving first-line non-intensive therapy (2-year OS 22% versus 7%; p = 0.02). However, the complete remission (CR) rates among the first-line intensive and non-intensive therapy groups were comparable (21.9% and 29.4%, respectively, p = 0.49). The improved OS is therefore attributed to superior cumulative CR in the intensive group. First-line intensively treated patients were more likely to receive and respond to salvage, leading to a cumulative CR rate of 65.7% (versus 29.4%, p = 0.003). Achieving CR at any point is strongly associated with superior survival outcomes with 2-year OS of 31% versus 0% for those not achieving CR ever (p < 0.01). Conclusions: We find that TP53m AML rarely presents with oncological emergencies, suggesting that clinical trial enrollment is feasible in this group. Additionally, in our cohort, intensive induction therapies lead to superior survival outcomes attributed to successful salvage therapy. These data suggest that strategic therapy sequencing and salvage therapy may be important in optimizing outcomes for TP53m AML patients. [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: This study explores the involvement of the immune system in oral and lung squamous cell carcinoma. Given the increasing recognition of the immune system's significance in cancer, the study analyzes key components of both tumor macroenvironment and microenvironment. In detail, the focus is on systemic inflammation markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR). Additionally, this study investigates Tumor-Infiltrating Lymphocytes (TILs) and CD8+ cells in the tumor microenvironment. We aimed to better understand the impact of these prognostic factors on overall survival (OS) and disease-free survival (DSF) in order to enhance cancer risk stratification and guide therapeutic decisions. Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. Results: Associations were found between systemic inflammation markers—NLR, MLR, and PLR—and tumor microenvironment factors, such as TILs and CD8+ cell prevalence—elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. Discussion: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response's role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. Conclusions: Future integration into cancer classification could improve risk stratification and treatment guidance. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of metastatic lung cancer has been largely modified with targeted therapies and immunotherapies. Whether this survival benefit for subgroups of patients is beneficial to all patients treated for lung cancer has never been explored. The Institut Curie is an anti-cancer center in Paris, France, treating patients with lung cancer. Since the 2000s, Institut Curie has implemented dematerialized medical records, allowing for a large overview of the survival of patients with lung cancer according to treatment evolution. We found that the survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC (non-small cell lung cancer) but not in SCLC (small cell lung cancer). SCLC remains a disease with poor prognosis for which novel therapies are needed. Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1—2000 to 2009, 752 for Period 2—2010 to 2017, and 768 for Period 3—2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies. [ABSTRACT FROM AUTHOR]