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Simple Summary: This study assessed the prognostic impact of sarcopenic obesity (SO) in colorectal cancer patients. Among 211 sarcopenic patients, those with obesity (SO group) demonstrated significantly shorter cancer-related relapse-free survival (CRRFS) compared to their non-obese counterparts (non-SO group). While cancer-specific survival (CSS) was also poorer in the SO group, this difference did not reach statistical significance. Additionally, there was no significant difference in overall survival (OS) between the two groups. Multivariate analysis identified sarcopenic obesity, elevated CEA levels, and unfavorable histological types as independent predictors of poor CRRFS. These findings underscore the importance of routine assessment of both sarcopenia and obesity in clinical practice. Moreover, they highlight the potential benefits of interventions aimed at increasing muscle mass and reducing visceral fat to enhance patient outcomes. Background: Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods: We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results: CRRFS was significantly shorter in the SO group than in the non-SO group (p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions: Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the impact of intraoperative opioid use and anesthesia type on outcomes for patients undergoing radical cystectomy for bladder cancer. Data from 508 patients treated between 2015 and 2022 were analyzed. Most (82%) received combined intravenous and epidural anesthesia, while the rest received intravenous-only anesthesia. Results showed that combined anesthesia was linked to better overall survival and fewer intensive care unit admissions. However, opioid dosage and type did not significantly affect survival, recurrence rates, or major perioperative outcomes. The findings are limited by the study's single-center, retrospective nature, and further research is needed to confirm the safety of opioids in patients undergoing radical cystectomy. Background: An increased intraoperative opioid dose seems to lead to worse outcomes in several types of cancer. We assessed the effect of intraoperatively administered opioids as well as the type of anesthesia on survival, recurrence rates and major perioperative outcomes in patients who underwent radical cystectomy (RC) for urothelial carcinoma of the urinary bladder. Methods: We included patients who underwent open RC at our center between 2015 and 2022. The role of the type and dosage of intraoperative opioid agents, such as remifentanil, sufentanil and morphine milligram equivalents (MME), as well as the type of anesthesia (intravenous only versus intravenous/epidural), was assessed regarding perioperative and long-term outcomes after RC. Results: A total of 508 patients with a median age of 73 years (IQR: 64–78) were included. Overall, 92 (18%) patients received intravenous anesthesia, whereas 416 (82%) received combined anesthesia. At a median follow-up of 270 days (IQR: 98–808), 108 (21%) deaths and 106 (21%) recurrences occurred. Combined anesthesia was associated with better survival (HR:0.63, 95% CI: 0.4–0.97, p = 0.037) and lower intensive care unit admission rates (OR: 0.49, 95% CI: 0.31–0.77, p = 0.002) in the univariate analysis (unadjusted). The type and dosage of intraoperative opioid agents did not affect long-term survival and recurrence rates, as well as major perioperative outcomes. Nevertheless, the findings of our study were limited by its single-center, retrospective design. Conclusion: The use of intraoperative opioids was not associated with worse outcomes in our cohort, while the use of additional epidural anesthesia seems to be beneficial in terms of overall survival and intensive care unit admissions. Nevertheless, further research is mandatory to validate the safety of opioids in patients undergoing RC. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcomas are rare and diverse tumors that develop in various tissues like bone, muscle, and fat. This study examines the outcomes of two types of surgical removal of these tumors: planned resections (PEs), where the tumor is diagnosed a-priori and surgically removed with a plan, and unplanned resections (UEs), where the tumor is removed without prior diagnosis. We found that planned surgeries, while better at completely removing the tumor initially, are associated with more advanced tumors that have a higher chance of spreading and leading to cancer-related deaths. On the other hand, unplanned surgeries tend to have higher chances of the tumor coming back locally but do not significantly affect long-term survival. These findings highlight the importance of early detection and timely treatment at specialized centers to improve patient outcomes. Our research aims to help develop better tools for predicting and managing sarcomas to enhance patient care. Background: Sarcomas, a diverse group of malignant tumors arising from mesenchymal tissues, pose significant diagnostic and therapeutic challenges. This study compares the outcomes of planned resections (PEs) and unplanned resections (UEs) to inform better clinical practices. Methods: Data were analyzed from the Swiss Sarcoma Network (SSN), including patients with soft tissue and bone sarcomas treated at two major hospitals. This study utilized logistic regression and Cox regression models to examine the odds of UEs and their impact on local recurrence-free survival. Results: Among 429 patients registered by SSN members, 323 (75%) underwent PEs and 106 (25%) experienced UEs. PEs were associated with significantly larger tumors (94 mm vs. 47 mm, p < 0.001) and higher-grade tumors (Grade 3: 50.5% vs. 37.4%, p = 0.03). Despite achieving superior resection margins (R0: 78.8% vs. 12.6%, p < 0.001), PEs showed higher metastasis rates at follow-up (31.0% vs. 10.4%, p < 0.001) and greater cancer-specific mortality (16.7% vs. 6.6%, p = 0.01). UEs, while linked to higher local recurrence, did not significantly affect metastasis-free survival (MFS) or overall survival (OS). Conclusions: PEs achieve superior immediate surgical outcomes but are linked to higher metastasis and cancer-specific mortality due to the advanced stage of tumors. UEs, while associated with higher local recurrence rates, do not significantly impact MFS or OS. Early detection, comprehensive diagnostics, and timely referrals to specialized sarcoma hubs are essential to avoid UEs and reduce metastatic risk. Future research should focus on developing diagnostic tools using individual tumor and patient characteristics to improve sarcoma management. [ABSTRACT FROM AUTHOR]

Simple Summary: In a retrospective study of 86 patients, we identified independent predictors of recurrence-free survival (RFS) and overall survival (OS) after the resection of liver metastases of uveal melanoma using a multivariable Cox model. A disease-free interval of ≤24 months and a chromosome 8q surgain were associated with worse survival. With these two parameters, we built a novel clinico-genetic score that defined three risk groups with distinct prognoses. This novel score identified patients with a high risk of relapse after surgery. These patients may benefit from neoadjuvant or adjuvant systemic therapy following complete surgical resection with the hope of improving survival outcomes. Surgical treatment of liver metastases of uveal melanoma (LMUM) could be proposed for selected patients. This retrospective study examined the prognostic significance of the genetic profiles of liver metastases after LMUM resection. A total of 86 patients treated with resection for LMUM, who underwent genetic analysis of liver metastasis, were included. A multivariable Cox model identified the independent predictors of recurrence-free survival (RFS) and overall survival (OS). The disease-free interval (DFI) and a chromosome 8q surgain (>3 copies) were independent predictors and categorized patients into three risk groups with distinct postoperative prognoses. For the low-, intermediate-, and high-risk scores of recurrence, the median RFS values were 15 months (95% CI: 10–22), 6 months (95% CI: 4–11), and 4 months (95% CI: 2–7), and the median OS values were 86 months (95% CI: 55-NR), 25 months (95% CI: 17–48), and 19 months (95% CI: 12–22), respectively. The predictive accuracy of this scoring system was demonstrated by a mean area under the curve (AUC(t)) of 0.77 (95% CI: 0.65–0.90) for RFS and 0.81 (95% CI: 0.70–0.92) for OS. This novel score, based on a DFI of ≤24 months combined with a chromosome 8q surgain, identifies patients at a high risk of early recurrence and could help clinicians to propose perioperative treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This research was conducted to evaluate the impact of ipilimumab treatment in patients with metastatic melanoma when monotherapy with PD-1 inhibitors has failed. In particular, the aim was to evaluate the efficacy of ipilimumab in this setting based on the presence or absence of BRAF or NRAS mutations. The present study could allow us to understand when salvage treatment with ipilimumab would have the best impact, although an analysis on a larger patient cohort would be necessary. Background: When monotherapy with PD-1 inhibitors in metastatic melanoma fails, there are currently no standard second-line choices. In case of the unavailability of clinical trials, ipilimumab represents a possible alternative treatment. Methods: We collected data of 44 patients who received ipilimumab after the failure of PD-1 inhibitors from July 2017 to May 2023 at our Institute. Overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) based on BRAF or NRAS mutation status, sex, and the presence of brain metastases were estimated using the Kaplan–Meier method. Cox regression was used to evaluate independence in multivariate analysis. The objective response rate (ORR) was estimated based on RECIST 1.1. Results: Among the 44 patients enrolled in this study, 28 BRAF-wildtype, 9 BRAF-mutated, and 7 NRAS-mutated patients were identified. OS analysis showed a significant difference between wildtype and BRAF- or NRAS-mutated patients: 23.2 months vs 5.3 and 4.59, respectively, p = 0.017. The presence of brain metastases and BRAF or NRAS mutation were independent factors for mortality in multivariate analysis. Conclusions: In case of failure to enroll patients in innovative clinical trials, second-line ipilimumab still represents an effective therapy in patients with metastatic wildtype melanoma and in the absence of brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the real-world efficacy and safety of combining pembrolizumab, a novel immunotherapy agent, with chemotherapy in early-stage triple-negative breast cancer treatment. We specifically aimed to validate clinical trial results in routine practice. A total of 108 Turkish patients receiving neoadjuvant therapy were examined. The combined regimen demonstrated high efficacy, with 64% of patients achieving pathological complete response, and exhibited generally favorable safety profiles with predominantly mild adverse events. These findings support the use of this combination as a standard treatment for this aggressive breast cancer subtype. However, the results underscore the need for further research to identify optimal patient selection criteria, which can inform oncologists' decision-making and potentially enhance outcomes for patients with triple-negative breast cancer. Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in Türkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1–2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab–chemotherapy in early-stage TNBC, complementing evidence from randomized trials. [ABSTRACT FROM AUTHOR]

Simple Summary: This epidemiological study of adenoid cystic carcinoma (ACC) using data from the SEER system aims to investigate independent predictors of late mortality, including factors such as age, stage, and tumor location, as well as racial differences, geographical distribution, and lack of social support (being unmarried). A total of 5150 patients were identified. Our study revealed that stage, tumor location in the thoracic region, and treatment modalities, in addition to geographical distribution (Western region) and lack of social support (being unmarried), were identified as independent predictors of late mortality. While the SEER data are not designed to explain why disease patterns occur, they provide valuable insights into health-related issues that cannot be overlooked. Further studies are needed to determine why the Western region of the USA is associated with poorer survival compared to the Northeast. Objective: Adenoid cystic carcinoma (ACC) is a rare malignant tumor that mainly arises in the head and neck area. We aimed to compare the long-term survival of patients with ACC based on their geographic regions within the United States using the Surveillance, Epidemiology, and End Results (SEER) registry data. Methods: We queried the SEER database to evaluate the geographic distribution of ACC patients based on inpatient admissions. The states included in the study were divided into four geographical regions (Midwest, Northeast, South, and West) based on the U.S. Census Bureau-designated regions and divisions. Demographic and clinical variables were compared between the groups. Kaplan–Meier curves and Cox regression were used to assess late mortality. Results: A total of 5150 patients were included (4.2% from the Midwest, 17.2% from the Northeast, 22.5% from the South, and 56.1% from the West regions). The median follow-up was 12.3 (95% CI: 11.6–13.1 years). Median overall survival was 11.0 (95% CI: 9.2-NR years), 14.3 (95% CI: 12.4–16.4 years), 11.3 (95% CI: 9.7–14.8 years), and 12.0 (95% CI: 11.3–13.0 years) for Midwest, Northeast, South, and West regions, respectively. In multivariable analysis, older age, male sex, thoracic cancer, the presence of regional and distal disease, receiving chemotherapy, not undergoing surgical resection, and being treated in the West vs. Northeast region were found to be independent predictors of poor survival. We identified a significant survival difference between the different regions, with the West exhibiting the worst survival compared to the Northeast region. Conclusions: In addition to the well-known predictors of late mortality in ACC (tumor location, stage, and treatment modalities), our study identified a lack of social support (being unmarried) and geographic location (West region) as independent predictors of late mortality in multivariable analysis. Further research is needed to explore the causal relationships. [ABSTRACT FROM AUTHOR]

Simple Summary: This structured review evaluated prospective trials that included non-metastatic advanced stage (Stage III) non-small cell lung cancer patients to determine if survival was different for high radiation dose per day (>2 Gy per day), given over a shortened number of radiation treatments (less than 30), known as hypofractionation, as compared to the usual standard radiation regimen, known as conventionally fractionated radiation therapy (2 Gy radiation dose, given once daily on weekdays for 30 daily treatments). There was no evidence that hypofractionation improves survival as compared to conventionally fractionated radiation therapy. Toxicity varied among the studies. Larger trials are needed to assess whether hypofractionated radiation is equivalent to conventional radiation. It is unclear whether the use of systemic therapy will improve survival outcomes with hypofractionated radiation and how the use of systemic therapy may negatively affect radiation toxicity with hypofractionation. Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. Methods: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients. Results: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months–42.5 months) and toxicities such as grade 3 or higher esophagitis (0–42%) and grade 3 or higher pneumonitis (0–18%) were reported. Conclusions: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: There is no literature that compares the clinical outcomes between intraperitoneal chemotherapy without bevacizumab and triweekly intravenous chemotherapy plus bevacizumab. The aim of this study was to elucidate whether, in the frontline treatment of advanced ovarian, fallopian tube and primary peritoneal cancer, intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab will confer an improved survival benefit when compared with the combination of triweekly intravenous carboplatin/paclitaxel chemotherapy and bevacizumab. We found that intraperitoneal chemotherapy without bevacizumab is associated with better survival when compared with intravenous chemotherapy with bevacizumab. Objectives: To compare the clinical outcomes of intravenous carboplatin/paclitaxel chemotherapy plus bevacizumab versus intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab as the frontline treatment in women with advanced ovarian, fallopian tube and primary peritoneal cancer. Methods: Between November 2012 and January 2024, medical records of all consecutive women with stage II~IV cancer treated with either frontline adjuvant intraperitoneal cisplatin/paclitaxel without bevacizumab (IP group), intravenous carboplatin/paclitaxel without bevacizumab (IV group) or intravenous carboplatin/paclitaxel with bevacizumab (IVB group) at a tertiary referral center were reviewed. Results: A total of 143 women (IP group, n = 57; IVB group, n = 23; IV group, n = 63) were reviewed. The IP group had greater progression-free survival compared to the IVB group (49.1 months, 95% confidence interval [CI] = 27.8 months to infinity, versus 11.9 months, 95% CI = 11.2 to 16.2 months; adjusted hazard ratio [HR] = 0.45, 95% CI = 0.24 to 0.87, p = 0.017). Additionally, the IP group also had a higher overall survival compared to the IVB group (not reached, 95% CI = 55.6 months to infinity, versus 38.9 months, 95% CI = 21.9 months to infinity; adjusted HR = 0.34, 95% CI = 0.15 to 0.79, p = 0.012). Conclusions: Intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab seems to offer a survival advantage when compared with intravenous carboplatin/paclitaxel with bevacizumab in the frontline treatment of women with advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) are commonly used for acid reduction in patients with peptic ulcer disease or esophageal reflux. Previous studies have shown that acid-reducing agents (ARAs) might affect bevacizumab treatment. This study found that PPI use worsened the oncological outcomes in patients with metastatic colorectal cancer (mCRC) undergoing bevacizumab treatment. There was a negative dose–response relationship when compared to H2RA use. Physicians should consider the benefits and risks of long-term use of ARAs, especially PPIs, in mCRC patients treated with bevacizumab. Background: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. Methods: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose–response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. Results: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09–1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09–1.31). A similar dose–response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. Conclusions: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab. [ABSTRACT FROM AUTHOR]

Simple Summary: Since no randomized clinical trial has compared surgery to chemoradiotherapy (CTRT) in FIGO stage IB3 cervical cancer patients, the optimal management remains controversial. In our study, nerve-sparing laparoscopic radical hysterectomy (nsLRH) proved to be safe and effective. The encouraging results on toxicity and survival, when compared to CTRT, warrant further investigation and reinforce the idea that surgery is a valid option for these patients. (1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4–5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to develop and validate a radiomic model for predicting overall survival (OS) in glioblastoma multiforme (GBM) patients using pre-treatment MRI images. A retrospective dataset of 289 patients from multiple institutions was used to extract 660 radiomic features (RFs) from each patient's tumor volume. The initial model was enhanced by incorporating clinical variables and validated through repeated three-fold cross-validation. The final clinical–radiomic model utilized primary gross tumor volume (GTV) and T2-FLAIR MRI modality and includes the age variable and two robust RFs. The model achieved a moderately good discriminatory performance (C-Index: 0.69) and significant patient stratification (p = 7 × 10−5) on the validation cohort. Notably, the trained model exhibited the highest integrated area under curve (iAUC) at 11 months (0.81) in the literature. The study concluded that the validated clinical–radiomic model can effectively stratify GBM patients into low and high-risk groups based on OS. Future work will focus on integrating deep learning-based features and standardized convolutional filters to improve OS predictions. Purpose: To develop and validate an MRI-based radiomic model for predicting overall survival (OS) in patients diagnosed with glioblastoma multiforme (GBM), utilizing a retrospective dataset from multiple institutions. Materials and Methods: Pre-treatment MRI images of 289 GBM patients were collected. From each patient's tumor volume, 660 radiomic features (RFs) were extracted and subjected to robustness analysis. The initial prognostic model with minimum RFs was subsequently enhanced by including clinical variables. The final clinical–radiomic model was derived through repeated three-fold cross-validation on the training dataset. Performance evaluation included assessment of concordance index (C-Index), integrated area under curve (iAUC) alongside patient stratification into low and high-risk groups for overall survival (OS). Results: The final prognostic model, which has the highest level of interpretability, utilized primary gross tumor volume (GTV) and one MRI modality (T2-FLAIR) as a predictor and integrated the age variable with two independent, robust RFs, achieving moderately good discriminatory performance (C-Index [95% confidence interval]: 0.69 [0.62–0.75]) with significant patient stratification (p = 7 × 10−5) on the validation cohort. Furthermore, the trained model exhibited the highest iAUC at 11 months (0.81) in the literature. Conclusion: We identified and validated a clinical–radiomic model for stratification of patients into low and high-risk groups based on OS in patients with GBM using a multicenter retrospective dataset. Future work will focus on the use of deep learning-based features, with recently standardized convolutional filters on OS tasks. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated whether the anatomical location of metastases from posterior uveal melanoma affects survival. We found that patients with newly diagnosed metastatic posterior uveal melanoma who only have extrahepatic metastases had a significantly longer survival compared to patients with liver metastases. This insight could help clinicians improve the prediction of patient outcomes and enhance the selection of patients in clinical trials. Background/Objectives: Metastatic posterior uveal melanoma (PUM) is one of the deadliest types of melanomas. Though the median survival is short, some patients with metastatic disease live for a long time. In this study, we investigated whether the anatomical location of the metastatic lesions is associated with differences in survival. Methods: One hundred and seventy-eight patients with metastatic PUM with baseline whole-body imaging were retrospectively included. The patients were divided into three groups based on the anatomical location of metastases: (1) exclusive liver metastases (hepatic pattern), (2) both hepatic and extrahepatic metastatic lesions (hepatic–extrahepatic pattern), and (3) exclusive extrahepatic lesions (extrahepatic pattern). Survival was investigated using Kaplan–Meier plots, log-rank test, and the Cox proportional hazard model. Results: In total, 95 patients (53%) presented with hepatic pattern, 66 patients (37%) presented with hepatic–extrahepatic pattern, and 17 patients (10%) presented with extrahepatic pattern. Overall survival was significantly longer in patients with extrahepatic pattern (median 17.0 months) compared to those with hepatic pattern (median 11.0 months) and hepatic–extrahepatic pattern (median 7.0 months) (p < 0.001, log-rank test). Multivariate Cox regression analysis showed increased hazard ratios (HR) for hepatic pattern (HR 2.37, 95% CI 1.08–5.17, p = 0.031) and hepatic–extrahepatic pattern (3.25, 95% CI 1.42–7.41, p = 0.005) compared to extrahepatic pattern. Most patients with hepatic (95%) and hepatic–extrahepatic patterns (82%) were diagnosed with metastases by liver ultrasonography screening, whereas 81% of patients with extrahepatic pattern developed symptoms that led to the diagnosis. Conclusions: Extrahepatic pattern was associated with prolonged survival in patients with metastatic PUM, despite there being a larger proportion of symptomatic patients. It is therefore important to consider the anatomical location of the metastatic lesions when stratifying patients into clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Inclusion of Black patients and other racial minorities has been limited (<2%) in urothelial carcinoma clinical trials. On meta-analysis of all recent ICIs, ADCs and targeted therapy phase III trials in UC (n = 17), women had inferior OS to men (RR 0.89; p = 0.04) on investigational agents. No OS differences by race or age were observed on meta-analysis. Background: Urothelial carcinoma (UC) is one of the most common cancers diagnosed worldwide. However, minority populations, such as female, elder, and Black patients, may have disparate outcomes and are commonly neglected in randomized prospective trials. This review aims to study the relationship between age, sex, and race on urothelial cancer prognosis, particularly focusing on contemporary therapy and its effect on overall survival. Methods: Phase III prospective trials since 2016 of immune checkpoint inhibitors, antibody-drug conjugates, or targeted therapies in urothelial carcinoma were identified from PubMed. Trials that did not report on survival by race, sex, or age distribution were excluded, and remaining trials (n = 17) were compared by subgroup. Results: Women were reported to have inferior OS on investigational agents compared to men in 9/17 trials. In a meta-analysis, women had inferior OS to men (OR 0.89 [95% CI: 0.78–0.99]; p = 0.04). Asian/Pacific Islander patients had inferior outcomes to White patients on investigational agents in 3/5 trials. In a meta-analysis, OS was not significant by race (OR 1.18 [0.90–1.46], p = 0.38). Black patients composed <2% of all trial patients, and no subgroup data were reported. Both 65 (n = 7) and 75 (n = 2) were reported as age cut-offs in trial subgroups, and survival data were mixed. Conclusions: Women in UC trials may have inferior survival outcomes to men. Racial diversity was poor and thus limited any conclusions on survival disparities. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examined the outcomes of lung metastasectomy in urothelial carcinoma patients using data from a Japanese multi-institutional database. The study included 100 patients who underwent the procedure between 1985 and 2021. Results showed 5-year overall survival and disease-free survival rates of 59% and 46%, respectively. Larger tumor diameter and presence of distant metastases at primary cancer treatment were identified as significant adverse prognostic factors. The authors claim that this is the largest published case series on this topic, providing benchmark data for assessing long-term outcomes. Background/objectives: The efficacy of lung metastasectomy in patients with urothelial carcinoma remains inconclusive, as there is only limited evidence from small studies. In this study, we aimed to assess the prognostic outcomes of excising pulmonary metastases from urothelial carcinoma. Methods: In this study, we utilized data from the Metastatic Lung Tumor Study Group of Japan database, a multi-institutional prospective database of pulmonary metastasectomies. We examined the data of patients who had undergone pulmonary metastasectomy for urothelial carcinoma between 1985 and 2021. Exclusion criteria included insufficient clinical information and follow-up of <3 months. Results: The study cohort comprised 100 patients (63 bladder cancer, 37 renal pelvic and ureteral cancer), with a median follow-up of 34 months. There were 70 male and 30 female patients of average age 66.5 ± 10.4 years at lung metastasectomy. The median interval from treatment of the primary lesion to metastasectomy was 19 months and the maximum tumor diameter was 21 ± 15 mm. Three- and five-year overall survival rates were 69% and 59%, respectively. Three- and five-year disease-free survival rates were 56% and 46%, respectively. Multivariate analysis identified larger tumor diameter (hazard ratio: 1.62, 95% confidence interval: 1.21–2.17) and distant metastases at the time of treatment of the primary cancer (hazard ratio: 4.23; 95% confidence interval: 1.54–11.6) as significant adverse prognostic factors for overall survival. Conclusions: To our knowledge, this is the largest published case series of pulmonary resection for metastatic urothelial carcinoma, providing benchmark data for the assessment of long-term outcomes of this rare entity. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a significant gap in research and guidelines for treating octogenarian multiple myeloma (MM) patients. This retrospective study examined 101 MM patients, median age 84 years (80–98), treated outside clinical studies at TASMC between 2010 and 2023, aiming to review real-world practices and outcomes experienced by this vulnerable group of patients. Of these patients, 87% received a bortezomib-based regimen; 20% received lenalidomide ± bortezomib; 44% were treated with novel agent-based doublets, and 51% with triplets/quadruplets. Despite the employment of reduced doses of steroids and lenalidomide, treatment-related toxicity was high, including 9% who suffered grade 5 events. Of these patients, 67% received subsequent lines, resulting in an impressive median overall survival of 42 months (1–141) in the entire cohort. These results highlight the effectiveness of personalized therapy for octogenarian multiple myeloma (MM) patients and emphasize the need for further real-time studies to establish guidelines for the management of this vulnerable and growing population. Background: Data on the outcome of octogenarian multiple myeloma (MM) patients (pts), especially if treated outside clinical studies, are scanty. Aims and Methods: MM pts ≥ 80 years, treated at TASMC with first-line therapy between 2010 and 2023, were reviewed. Characteristics and outcomes were analyzed. Results: A total number of 101 pts, of whom 54 were males with a median age of 84 years (80–98), were included. Among them, 67.4% had a Charlson comorbidity index of ≥5, 37% had ISS-3 (International staging system) and 20% had Revised-ISS-3. In our study, 44.5% received doublets and 50.5% received triplets/quadruplets. A bortezomib-based regimen was applied in 87%, and IMiDs were used in 27.7%. Despite an upfront employment of a low lenalidomide dose, dose reductions were required in 48%. Grade ≥ 3 adverse events (AEs) (mainly infections) were documented in 36.6% of patients, including grade 5 events in 9%, all attributed to infections. The overall response rate was 69%, including 31% ≥ VGPRs (Very good partial response). Sixty-seven percent (67%) received second-line therapy, administered within a median period of 12 months (1–84). Within a median follow-up period of 36 m (1–141), the median overall survival (OS) approached 42 m (range: 1–141); being shorter in pts > 84 years (HR = 1.7, p = 0.03), pts with lung disease (HR = 1.8, p = 0.044) and pts with ISS = 3 and R-ISS = 3 (HR = 1.65, p = 0.0016 and HR = 2.45, p = 0.006, respectively); Conclusions: Octogenarians treated outside clinical studies often have a lower tolerance to treatment. Nevertheless, upfront administration of low doses of anti-MM agents provided a response in the majority of patients, translated into impressive OS. Nevertheless, mortality due to AEs was high, emphasizing the need for new, "octogenarian-oriented" treatment protocols. [ABSTRACT FROM AUTHOR]

Simple Summary: Histopathological and molecular factors could play a role in determining LNM in colon cancer. Extended lymphadenectomies in right-sided patients have been associated with complications. We demonstrated that histopathological and molecular analysis can be useful in predicting LNM and therefore identify high risk patients which could potentially benefit from D3 lymphadenectomy/CME. Background: Lymphadenectomy plays a central role in the treatment of localized colon cancer. While in left colon cancer the D3 lymphadenectomy/CME is considered the standard of care, lymphatic stations to be removed in right colon cancer are still a matter of discussion. The individuation of LNM risk factors could help in choosing the lymphadenectomy in right-sided tumors. This study aims to analyze the correlation of histopathological and molecular characteristics with lymph node metastasis, both in right- and left-sided colon cancer, and their impact on survival; Methods: We conducted a single-center observational retrospective study. The following data were collected and analyzed for each patient: demographics, histopathological and molecular data, and intraoperative and perioperative data. Statistical analyses were performed, including descriptive statistics, multivariate logistic regression and survival analysis; Results: An association between tumor size (pT, p < 0.001), grading (p = 0.013), budding (p < 0.001), LVI (79,4% p < 0.001) and LNM was observed. A multivariate analysis identified pT4 (OR 5.45, p < 0.001) and LVI+ (OR 10.7, p < 0.001) as significant predictors of LNM. Right-sided patients presented a worse OS when associated with LNM, while no significant difference was observed in N0 patients; Conclusions: histological and molecular analysis can help identify high risk patients, which could benefit from extended lymphadenectomies. These patients could be ideal candidates for the D3 lymphadenectomy/CME. [ABSTRACT FROM AUTHOR]

Simple Summary: We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with clinicopathologic features and survival in 627 pancreatic cancer patients who received neoadjuvant therapy (NAT). We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, and better tumor response. Both ESOT and ESOP were associated with less frequent recurrence/metastasis, better disease-free survival (DFS), and overall survival (OS) in the overall study population. ESOP was associated with better DFS and OS in patients with ypT0/ypT1 or ypN0 tumors and better OS in patients with complete or near-complete response. ESOT was associated with better OS in patients with ypT0/ypT1 or ypN0 tumors. Both ESOT and ESOP were independent prognostic factors for OS in multivariate survival analyses. Therefore, ESOP and ESOT are associated with the prognosis of PDAC patients with complete or near-complete response and a ypT0/ypT1 tumor after NAT. Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, and better tumor response (p < 0.05). ESOP was also associated with a smaller tumor size (p < 0.001), more lymph nodes (p < 0.001), a lower ypN stage (p < 0.001), better differentiation (p = 0.02), and less frequent lymphovascular invasion (p = 0.009). However, since ESOP and ESOT were primarily conducted for cases with no grossly identifiable tumor or minimal residual carcinoma in initial sections, potential bias cannot be excluded. Both ESOT and ESOP were associated with less frequent recurrence/metastasis and better DFS and OS (p < 0.05) in the overall study population. ESOP was associated with better DFS and better OS in patients with ypT0/ypT1 or ypN0 tumors and better OS in patients with complete or near-complete response (p < 0.05). ESOT was associated with better OS in patients with ypT0/ypT1 or ypN0 tumors (p < 0.05). Both ESOT and ESOP were independent prognostic factors for OS according to multivariate survival analyses. Therefore, accurate pathologic evaluation using ESOP and ESOT is associated with the prognosis in PDAC patients with complete or near-complete pathologic response and ypT0/ypT1 tumor after NAT. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates racial disparities in the stage of gastric cancer at diagnosis and overall survival among different racial groups using data from the SEER database (2018–2021). The retrospective cohort study of 18,984 patients found that Hispanics are 19% more likely to be diagnosed at a later stage of gastric cancer compared to non-Hispanics. Additionally, both Hispanics and Black patients showed poorer overall survival compared to Non-Hispanic Whites. The disparities are attributed to factors such as healthcare access, insurance coverage, language barriers, and preventive health service utilization. These findings highlight the need for targeted interventions to address these disparities in cancer outcomes. Introduction: Racial disparities in gastric cancer outcomes, including stage at diagnosis and overall survival, continue to affect Hispanic and non-Hispanic populations. This study aims to evaluate these disparities across different racial groups. Patients and methods: We conducted a retrospective cohort study using SEER data from 2018 to 2021, including 18,984 patients diagnosed with gastric cancer. Patients were selected based on ICD-O-3 codes for "stomach" with malignant behavior. Using ordered logistic regression, the association between race and stage at diagnosis was analyzed, while Cox proportional hazards models were used to assess OS and CSS. Results: Hispanic patients were significantly more likely to be diagnosed at a later stage compared to non-Hispanic patients (OR: 1.19; 95% CI: 1.10–1.28). Both Hispanic and Black patients had worse OS compared to Non-Hispanic Whites (HR 1.10 CI 1.03–1.17, p = 0.003 and HR 1.13 CI 1.04–1.22, p = 0.002, respectively) as well as CSS. Conclusions: Hispanic patients are more likely to be diagnosed with advanced-stage gastric cancer and have poorer survival outcomes compared to non-Hispanic Whites. These disparities may be linked to differences in healthcare access, insurance, language barriers, and preventive care utilization. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal cancer is the eighth most frequent cancer in Europe, and its prevalence is increasing. Surgery is the treatment of choice for localised renal cell carcinoma requiring interventional management, but less invasive treatment methods are emerging. Stereotactic body radiotherapy (SBRT) utilises precise delivery of high doses of radiation to ablate the primary cancer. In our systematic review and meta-analysis, we pooled data from available prospective trials, including 13 studies involving 308 patients. The results of the meta-analysis show that SBRT for localised renal cell carcinoma is highly effective in controlling local diseases and has low complication rates. In the second year, 97% of patients were free from local recurrence. Only 3% experienced severe adverse events, which included abdominal pain and fatigue. SBRT presents a valuable treatment for patients who require treatment but cannot undergo surgery; however, it has not been yet confirmed to be equieffective to surgery as trials directly comparing these methods are missing. Context: Surgery is the gold standard for the local treatment of primary renal cell carcinoma (RCC), but alternatives are emerging. We conducted a systematic review and meta-analysis to assess the results of prospective studies using definitive stereotactic body radiotherapy (SBRT) to treat primary localised RCC. Evidence acquisition: This review was prospectively registered in PROSPERO (CRD42023447274). We searched PubMed, Embase, Scopus, and Google Scholar for reports of prospective studies published since 2003, describing the outcomes of SBRT for localised RCC. Meta-analyses were performed for local control (LC), overall survival (OS), and rates of adverse events (AEs) using generalised linear mixed models (GLMMs). Outcomes were presented as rates with corresponding 95% confidence intervals (95% CIs). Risk-of-bias was assessed using the ROBINS-I tool. Evidence synthesis: Of the 2983 records, 13 prospective studies (n = 308) were included in the meta-analysis. The median diameter of the irradiated tumours ranged between 1.9 and 5.5 cm in individual studies. Grade ≥ 3 AEs were reported in 15 patients, and their estimated rate was 0.03 (95%CI: 0.01–0.11; n = 291). One- and two-year LC rates were 0.98 (95%CI: 0.95–0.99; n = 293) and 0.97 (95%CI: 0.93–0.99; n = 253), while one- and two-year OS rates were 0.95 (95%CI: 0.88–0.98; n = 294) and 0.86 (95%CI: 0.77–0.91; n = 224). There was no statistically significant heterogeneity, and the estimations were consistent after excluding studies at a high risk of bias in a sensitivity analysis. Major limitations include a relatively short follow-up, inhomogeneous reporting of renal function deterioration, and a lack of prospective comparative evidence. Conclusions: The short-term results suggest that SBRT is a valuable treatment method for selected inoperable patients (or those who refuse surgery) with localised RCC associated with low rates of high-grade AEs and excellent LC. However, until the long-term data from randomised controlled trials are available, surgical management remains a standard of care in operable patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with brain metastases from non-small cell lung cancer are often managed by various treatment approaches including surgery, chemotherapy/immunotherapy, and radiation therapy. While patients with a good performance status and a limited burden of disease are often candidates for surgical resection, the selection of the optimal adjuvant treatment paradigm, in light of the development of novel treatments for tumors with actionable mutations, remains a challenge. In this study, we sought to examine the benefit of radiation therapy, systemic therapy, or a combination of treatments following surgery with respect to in-brain progression-free survival and overall survival. Our data demonstrate that a combination of radiation therapy and systemic therapy has a benefit in improving progression-free survival in patients with non-small cell lung cancer who have developed brain metastases. Background/Objectives: Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. Methods: We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. Results: In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively (p = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively (p = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ2 test, p = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ2 test, p = 0.0018). Conclusions: We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary myelofibrosis and secondary myelofibrosis after polycythemia vera and essential thrombocythemia are sub-entities of myeloproliferative neoplasms with poor prognosis for long-term survival. Allogeneic stem-cell transplantation remains the only potentially curative therapy, but the risk of serious side effects and possible treatment-related mortality must be considered. In recent years, efforts have been made to optimize conditioning therapy, donor selection, and supportive therapy in order to improve the outcomes of stem-cell transplantation. We report on 36 patients with myelofibrosis who underwent stem-cell transplantation in our center. We compared the outcomes in earlier and more recent years and evaluated the influence of certain transplant- and patient-specific variables. Pretreatment with a JAK inhibitor, intensified conditioning, and the preferential use of haploidentical instead of mismatched unrelated donors for patients lacking an HLA-identical donor are most likely responsible for the improved outcome after allogeneic stem-cell transplantation in myelofibrosis in recent years. (1) Background: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is the only treatment with the potential for cure in patients with myelofibrosis (MF). However, the risk of graft rejection, which is particularly high in MF, and the risk of significant non-relapse mortality must be considered. (2) Methods: In this retrospective, single-center study, we compared allo-HSCT outcomes in 36 adult patients with MF transplanted at two-time intervals (2001–2015 versus 2016–2021). (3) Results: The estimated median overall survival was 48.9 months (95%CI 0.00–98.2) in the cohort transplanted before 2016 and not reached in the more recent years (p = 0.04) due to markedly lower non-relapse mortality (p = 0.02). The 3-year relapse incidence was low in both cohorts (11.1% and 12.5%, p > 0.99). When comparing only subgroups within the more recent cohort based on the presence or absence of total body irradiation (TBI) or the use of sequential regimens, OS and PFS were comparable. (4) Conclusion: Pretreatment with ruxolitinib, intensified conditioning, and the preferential use of haploidentical related instead of mismatched unrelated donors for patients lacking an HLA-identical donor are most likely responsible for the improved outcome after allo-HCT in MF in recent years. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the impact of radiation doses to the heart and lungs on overall survival (OS) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) treated with radiotherapy. An analysis of 120 patients, each with exactly three years of follow-up, revealed that higher radiation doses to the heart and lungs were significantly associated with worse OS. Importantly, the combination of heart and lung radiation doses provided enhanced and more detailed risk stratification, making it a more powerful predictor of poor survival than individual doses alone. These findings suggest that minimizing combined radiation exposure to both organs may improve survival outcomes in LA-NSCLC patients. Background/Objectives: Despite advancements in treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), overall survival (OS) remains poor. The specific effects of varying heart and lung doses on OS in LA-NSCLC patients have not been thoroughly investigated, especially their combined impact on survival. This study aimed to examine the impact on OS of both individual and combined heart and lung doses in patients with LA-NSCLC treated with radiotherapy over a three-year follow-up period. Methods: A total of 120 patients who received definitive radiotherapy for LA-NSCLC (stage III, 92.5%) from January 2015 to January 2020 were retrospectively reviewed. The endpoint in this study was OS. Each patient was followed for a fixed period of three years. Results: Univariate Cox regression analysis showed that OS was significantly related to mean heart dose (MHD, hazard ratio [HR], 3.4 [1.8–6.3]; p < 0.001), pericardium V40 (HR, 3.2 [1.7–6.0]; p < 0.001), and total lung V20 (HR, 2.6 [1.4–5.0]; p = 0.003), and these were independent predictors for worse OS in multivariate analysis. Kaplan–Meier curve analysis with log-rank tests revealed that survival was significantly worse in patients with higher MHD (p < 0.001), pericardium V40 (p < 0.001), and total lung V20 (p = 0.002). Combining MHD and total lung V20, and pericardium V40 and total lung V20 provided enhanced risk stratification for OS (p < 0.001 for both combinations). Conclusions: The combination of heart and lung doses provided enhanced and more detailed risk stratification in prediction of OS for a fixed period of three years in LA-NSCLC patients treated with radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Although some of the novel systemic treatments, especially the group of tyrosine kinase inhibitors, have shown a durable central nervous system response, ionizing radiation remains the mainstay in the management of brain metastases (BM). Recent technological advancements have enabled the replacement of whole-brain radiotherapy with localized stereotactic radiotherapy (SRT) for treating up to 10 BM, either as a primary or combined treatment, reducing neurotoxicity and improving local control (LC). The delivered target dose and patient selection play a crucial role in enhancing treatment efficacy. However, there is still limited evidence supporting which factors most affect LC and which patients derive the greatest benefit from SRT. This retrospective single-institutional study evaluated treatment outcomes in a heterogeneous patient population treated with Linac-based SRT, with the aim of identifying potential dosimetric and clinical prognostic factors to better inform the decision-making process. Background/Objectives: To report on predictive factors in Linac-based SRT for single and multiple BM. Methods: Consecutive patients receiving either one or three fractions of single-isocenter coplanar VMAT SRT were retrospectively included. The GTV-PTV margin was 1–2 mm. The delivered target dose was estimated by recalculating the original plans on roto-translated CT according to errors recorded by post-treatment CBCT. The Kaplan–Meier method estimated local progression-free survival (LPFS), intracranial progression-free survival (IPFS), and overall survival (OS). Log-rank and Wilcoxon–Mann–Whitney tests evaluated inter-group differences, whereas Cox regression analysis assessed prognostic factors. Results: Fifty females and fifty males, with a median age of 69 years, received 107 SRTs. A total of 213 BM (range, 1–10 per treatment) with a median volume of 0.22 cc were irradiated with a median minimum BED of 59.5 Gy. The median delivered GTV D95 reduction was −0.3%. The median follow-up was 11 months. Nineteen LP events and a 1-year LC rate of 90.1% were observed. The GTV coverage did not correlate with LC, while the GTV volume was a risk factor for LP, with the 1-year rate dropping to 73% for volumes ≥ 0.88 cc. The median LPFS, IPFS, and OS were 6, 5, and 7 months, respectively. Multivariate analysis showed that patients with melanoma histology and those receiving a second or subsequent systemic therapy line had the worst outcomes, whereas patients with adenocarcinoma histology and mutations showed better results. Conclusions: The accuracy and efficacy of the Linac-based SRT approach for BM were confirmed, but the dose distribution alone failed to predict the treatment response, suggesting that other factors must be considered to maximize SRT outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Myxoid liposarcoma (MLPS) is a rare soft tissue sarcoma, often affecting the proximal extremity. There is currently limited literature describing MLPS in older individuals. This retrospective study describes treatment outcomes and tolerability in older patients treated for non-metastatic MLPS. The study shows that older patients with MLPS tolerated systemic therapy, radiation therapy, and surgery with few toxicities. Background: Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. Methods: This single institution retrospective study included patients aged 70 years and older with localized (non-metastatic) myxoid liposarcoma. Results: Sixteen patients were included. The median age was 75 years, and 9 (56%) were female. Fourteen (88%) were extremity tumors and two (12%) were trunk. The median tumor size was 10.4 cm (range, 3.6 to 28 cm). Five (31%) tumors had a round cell component. All patients had surgery. Fourteen (88%) had perioperative radiation, and three (19%) had perioperative chemotherapy. One patient had postoperative infection, and one patient had neutropenic fever from preoperative chemotherapy. The median follow up from surgery was 6.3 years. Eight (50%) patients died from MLPS. The median relapse-free survival and overall survival were 34 months and 75 months, respectively. Conclusions: Most older patients with localized MLPS received perioperative radiation therapy with surgery, and few serious toxicities were reported. Even with treatment, half of the patients relapsed. [ABSTRACT FROM AUTHOR]

Simple Summary: In this article, we report the results of an interim analysis of 81 early-stage lung cancer patients undergoing stereotactic ablative radiotherapy with the CyberKnife M6 robotic radiosurgery system, with the endpoints being treatment efficacy and tolerance. Within a median follow-up of 20 months, a grade 2/3 lung toxicity of no clinical significance was reported in 6% of the patients. A higher biological effective dose and larger irradiation lung volumes were associated with increased toxicity. The projected 24-month local progression-free survival rate was 95%. These results confirm the safety and efficacy and further cement the role of robotic stereotactic ablative radiotherapy for early-stage lung cancer patients as an eventual alternative to surgery. Background/Objectives: Surgery is the primary treatment for early-stage lung cancer. Patients with medically inoperable lung carcinomas and patients who refuse to undergo surgery are treated with definite radiotherapy. Stereotactic ablative radiotherapy (SABR) is a compelling non-invasive therapeutic modality for this group of patients that confers promising results. Methods: We report an interim analysis of an ongoing trial. Eighty-one patients with medically inoperable early-stage (T1,2N0) lung cancer underwent SABR in our institution. SABR was delivered via the CyberKnife M6 robotic radiosurgery system. The endpoints of the analysis were treatment efficacy and tolerance. Results: There were no acute or late toxicities from the skin or the connective tissue of the thorax. A grade 2/3 lung injury of non-clinical significance was noted in 6% of patients, which was directly related to a higher biologically effective dose (BEDα/β = 3) and larger irradiation lung volumes in both univariate and multivariate analyses. A local control (LC) was achieved in 100% of the patients at the first follow-up, and the projected 24-month local progression-free survival (LPFS) rate was 95%. The projected 24-month disease-specific overall survival (OS) was 94%. Conclusions: High LC and OS rates can be achieved with SABR for early-stage lung cancer, with minimal toxicity. This study continues to recruit patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Traditional methods for predicting patient outcomes rely heavily on the physical characteristics of tumors. Our research aims to develop a new, simple risk score that uses three specific molecular markers found in tumor tissues. By examining the presence and levels of these markers, we hope to better predict which patients have a higher risk of poor outcomes. This can help doctors make more informed decisions about treatment options. Our findings may lead to improved survival rates by identifying high-risk patients who need more aggressive treatment and sparing low-risk patients from unnecessary procedures. Introduction: Several new molecular markers in colorectal carcinomas have been discovered; however, classical histopathological predictors are still being used to predict survival in patients. We present a novel risk score, which uses molecular markers, to predict outcomes in patients with colorectal carcinoma. Methods: The immunohistochemistry of tissue micro arrays was used to detect and quantify H2BUB1, RBM3 and Ki-67. Different intensities of staining were categorized for these markers and a score was established. A multivariate analysis was performed and survival curves were established. Results: 1791 patients were evaluated, and multivariate analysis revealed that our risk score, the 3-biomarker classifier, is an independent marker to predict survival. We found a high risk-score to be associated with dismal median survival for the patients. Conclusions: A more personalized score might be able to better discriminate low- and high-risk patients and suggest adjuvant treatment compared to classical pathological staging. Our score can serve as a tool to predict outcomes in patients suffering from colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The no specific molecular profile (NSMP) subtype of endometrial cancers remains a poorly understood class from a molecular standpoint, with a wide range of prognoses due to their internal heterogeneity. In this article, we confirm the value of a previously proposed further subdivision of NSMP into two risk classes: low-risk and high-risk; they are characterized by marked differences in oncological outcomes, including both the risk of recurrence and mortality. We are confident that this subdivision could bring significant benefits in the near future, not only in terms of modulating adjuvant therapy but also in standardizing research cohorts for more consistent and reproducible data. (1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we collected data on 51 patients diagnosed with NSMP EC following the introduction of molecular profiling at our institution. Patients were retrospectively analyzed for estrogen receptor (ER) status, histotype, and grade to identify potential prognostic subgroups. (3) Results: Our analysis identified two distinct subgroups within NSMP EC: low-risk and high-risk, based on ER status, histotype, and grade. The low-risk NSMP group demonstrated significantly better survival outcomes compared to the high-risk group. With a median follow-up time of 16 moths (IQR 13.0–29.7), the disease-free survival (DFS) and overall survival (OS) for the low-risk group were 100%. For the high-risk group, the DFS and OS were 71.4% and 78.6%, respectively, which showed a statistically significantly difference (Log-Rank Mantel-Cox < 0.001). In the high-risk group, four patients experienced recurrence, and three of these patients died. (4) Conclusions: Stratifying NSMP EC into low-risk and high-risk categories based on ER status, histotype, and grade can lead to more accurate prognostic assessments. In time, it may require tailored adjuvant therapies and a personalized treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Real-world studies comparing TNT and CRT are vital for advancing the treatment of LARC. Our study provides valuable insights reflecting the diverse patient populations and varied clinical practices encountered and demonstrates the advantage of TNT, providing a superior alternative to standard CRT and potentially enhancing treatment outcomes and quality of life. Total neoadjuvant therapy (TNT) has emerged as a promising approach for managing locally advanced rectal cancer (LARC), aiming to enhance resectability, increase pathological complete response (pCR), improve treatment compliance, survival, and sphincter preservation. This study compares the clinical outcomes of TNT, with either induction or consolidation chemotherapy, to those of the standard chemoradiotherapy (CRT). In this retrospective multi-institutional study, patients with stage II-III LARC who underwent CRT or TNT from seven oncology centers between 2021 and 2024 were retrospectively analyzed. The TNT group was categorized into induction or consolidation groups based on the sequence of chemotherapy and radiotherapy. Clinical and pathological data and treatment outcomes, including pCR, event-free survival (EFS), and overall survival (OS), were analyzed. Among the 276 patients, 105 received CRT and 171 underwent TNT. The TNT group showed significantly higher pCR (21.8% vs. 2.9%, p < 0.001) and lower lymphatic (26.3% vs. 42.6%, p = 0.009), vascular (15.8% vs. 32.7%, p = 0.002), and perineural invasion rates (20.3% vs. 37.6%, p = 0.003). Furthermore, 16.9% of TNT patients opted for non-operative management (NOM), compared to 0.9% in the CRT group (p < 0.001). The median interval between the end of radiotherapy and surgery was longer in the TNT group (17.6 weeks vs. 8.8 weeks, p < 0.001). The 3-year EFS was 58.3% for CRT and 71.1% for TNT (p = 0.06). TNT is associated with higher pCR, lower lymphatic and vascular invasion rates, and higher rates of NOM compared to CRT. This supports the use of TNT as a viable treatment strategy for LARC, offering potential benefits in quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Upfront novel androgen receptor signaling inhibitors (ARSIs) are the first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). However, there are a certain number of cases in which androgen deprivation therapy (ADT) is more effective in patients of Asian descent. If we can identify patients who show a marked response to ADT within 12 weeks after ADT, which is the inclusion criterion for upfront ARSI clinical trials, it would be valuable from an economic standpoint. A total of 218 patients who received ADT treatment at Kanazawa University Hospital between 2000 and 2020 were included in this study. Multivariate analysis revealed that a decrease in PSA levels of <95% at 12 weeks after ADT initiation was a predictor of short time to castration resistance (TTCR) in low-risk patients. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs, based on the rate of PSA reduction at 12 weeks. Background: The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. Methods: A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan–Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. Results: The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. Conclusion: The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary treatment for operable pancreatic cancer involves surgery followed by adjuvant therapy, with an increasing use of perioperative or neoadjuvant chemotherapy. We performed a network meta-analysis to assess the comparative efficacy of various treatment approaches for resectable pancreatic cancer. A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone. Excluding Asian studies, the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen. The findings endorse the utilization of perioperative and multi-agent chemotherapy as the favored intervention for operable PC in Western nations. The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations. [ABSTRACT FROM AUTHOR]

Simple Summary: The most common adverse events (AEs) that occurred in response to targeted therapy for hepatocellular carcinoma were appetite loss (adverse event grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). Among these, appetite loss and general fatigue negatively affect overall survival (OS) and progression-free survival (PFS). Increasing AE grades of hypertension, proteinuria, and hypothyroidism were associated with better OS, whereas hypertension, HFS, and hypothyroidism were associated with better PFS. To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532–1.450–2.361 (p for trend 0.037), 1.057–1.691–3.364 (p for trend 0.004), 1.176–0.686–0.281 (p for trend 0.002), 0.639–0.759–1.820 (p for trend 0.462), 1.030–0.959–0.147 (p for trend 0.011), and 0.697–0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592–1.073–2.811 (p for trend 0.255), 1.161–1.282–4.324 (p for trend 0.03), 0.965–0.781–0.655 (p for trend 0.095), 0.737–0.623–2.147 (p for trend 0.153), 1.061–0.832–0.800 (p for trend 0.391), and 1.412–0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the nationwide real-world outcomes of chemotherapy in 8651 patients with metastatic pancreatic cancer. Overall survival improved from 2012 to 2019 and was evident after the introduction of gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX. Propensity score matching revealed no difference in overall survival between these two regimens. The findings demonstrate that advances in chemotherapy have improved survival outcomes nationally, comparing the effectiveness of GnP and FOLFIRINOX using real-world data. Background/Objectives: This nationwide population-based study investigated the overall survival (OS) of patients with metastatic pancreatic cancer (mPC) receiving first-line chemotherapy. Methods: Data from the National Health Insurance Service linked to the Korea Central Cancer Registry were used. Patients with mPC receiving first-line chemotherapy (2012–2019) were included and followed up until 2020. The gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX groups were matched according to age, sex, and comorbidities. Results: In total, 8652 patients with mPC were treated with chemotherapy. GnP and FOLFIRINOX have been administered since 2016 and 2017, respectively. The median OS increased annually from 6 months in 2012–2013 to 10 months in 2018–2019. The median OSs in the GnP and FOLFIRINOX groups were significantly longer than those in patients receiving gemcitabine ± erlotinib. A total of 1134 patients from both the GnP and FOLFIRINOX groups were selected using propensity score matching. Before matching, the median OS was longer in the FOLFIRINOX group than in the GnP group (p = 0.0029). After matching, however, there was no significant difference in the median OS between the two groups (11 vs. 11 months, respectively, p = 0.2438). Conclusions: Patients with mPC receiving chemotherapy have shown improved OS since the introduction of GnP and FOLFIRINOX. After matching, OS did not differ between the GnP and FOLFIRINOX groups. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 40% of all diagnoses of rectal cancer in Spain are locally advanced. A multimodal treatment is needed, and one of its pillars is radiotherapy, with a classic dose scheme of up to 50–50.4 Gy concomitantly with oral capecitabine or 5-fluorouracil. Dose escalation is being explored to achieve higher rates of a pathological complete response, but the optimal dose and its impact on the outcomes are unclear. Our study aimed to evaluate the percentage of complete pathological responses obtained with an intensified neoadjuvant radiotherapy treatment scheme. We confirmed in a homogeneous population (49 patients treated with standard radiotherapy vs. 50 patients treated with dose-escalated radiotherapy) higher rates of a pathological complete response with a dose of up to 54 Gy concomitantly with oral capecitabine. Neoadjuvant radiotherapy intensification is useful for specimen sterilization and should be offered to selected patients. Locally advanced rectal cancer requires a multimodal treatment. Radiotherapy is being explored for intensification to improve the rates of pathological complete responses (ypCR rates) which are correlated with better outcomes. This study reports a comparison between standard versus escalated doses in a preoperative scenario. The ypCR rates, toxicity, postoperative complications, and disease-free and overall survival at 5 years are described. From 2012 to 2019, 99 patients were analyzed retrospectively: standard arm (mean of 47.5 Gy) vs. dose-escalated arm (mean of 54.3 Gy). All patients were treated with 3DRT in 25 fractions, with concomitant capecitabine and surgery performed according to the total mesorectal excision principles in both arms. The ypCR was reported using the "College of American Pathologist grades"; the gastrointestinal (GI) and genitourinary (GU) toxicity was reported using the "Common Terminology Criteria for Adverse Events" (CTCAE 4.0). The ypCR rates were higher in the dose-escalated group (25% vs. 10.64%; p = 0.07), with a lower rate of non-treatment response (61.36% vs. 38.64%; p = 0.11). No statistical differences between the arms were found in terms of the oncological outcomes, postoperative complications (p = 0.15), second surgeries (p = 0.62), or deaths (p = 0.62). The CTCAE acute GI and GU toxicity were grade I or II in both arms. Our study presents a long-term follow-up in comparative cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluates the long-term oncological outcomes of sentinel lymph node biopsy (SLNB) compared to axillary lymph node dissection (ALND) in clinically node-positive (cN+) breast cancer patients treated with neoadjuvant therapy (NAT). Analyzing data from 322 patients, the study found that SLNB is associated with better long-term outcomes, including recurrence-free survival (RFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS), compared to ALND. The axillary recurrence rates for SLNB ranged between 0.9% and 2.1%, comparable to those reported in other studies. Despite the high false-negative rates previously associated with SLNB, this study's findings support its safety and effectiveness in this patient population. Overall, SLNB is a viable alternative to ALND, offering better long-term oncological outcomes without increasing the risk of axillary recurrence. Backgrounds: This study compares the long-term outcomes of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy (SLNB) in clinically node-positive (cN+) breast cancer (BC) patients treated with neoadjuvant therapy (NAT).Methods: We conducted a retrospective analysis of 322 cN+ BC patients who became clinically node-negative (ycN0) post-NAT. Patients were categorized based on the final type of axillary surgery performed: ALND or SLNB. Recurrence-free survival (RFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were evaluated and compared between the two groups. Results: Patients in the SLNB group had significantly better 3-, 5-, and 10-year RFS, DDFS, OS, and BCSS compared to those in the ALND group. The SLNB group also had a higher proportion of patients achieving pathologic complete response (pCR). Multivariate analysis identified pCR, ypN0 status, and SLNB as favorable prognostic factors for all survival metrics. Axillary recurrence rates were low for both groups (0.6–2.1%). Conclusions: SLNB may be a safe and effective alternative to ALND for selected cN+ BC patients who convert to ycN0 after NAT. These findings suggest that careful patient selection is crucial, and further research is needed to validate these results in more comparable populations. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the optimal timing and effectiveness of radiotherapy in treating oligometastatic prostate cancer (OMPC), which is characterized by limited metastatic spread. We evaluated the impact of early intervention with radiotherapy, targeting both the primary tumor and metastatic sites, on patient survival. Our results show that early radiotherapy to oligometastatic sites, particularly when combined with primary tumor treatment, significantly enhances survival outcomes. These findings underscore the critical importance of timely and personalized treatment strategies in improving the management and care of patients with OMPC. Background/Objectives: Oligometastatic prostate cancer (OMPC) represents an early stage of metastatic disease characterized by a limited number of lesions. Recent advancements in imaging and treatment have revived interest in personalized therapies, including metastasis-directed radiotherapy (OMDRT) and primary prostate radiotherapy (PPR). This study evaluates the impact of OMDRT timing and the role of PPR on survival outcomes in OMPC patients; Methods: In this retrospective cohort study, 82 patients with OMPC who underwent OMDRT between 2010 and 2019 were analyzed. Patients were classified based on OMDRT timing (early vs. late) and disease type (synchronous vs. metachronous). Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, assessed via Kaplan-Meier analysis and Cox proportional hazards models; Results: Among the patients, 36 (43.9%) had synchronous and 46 (56.1%) had metachronous OMD. With a median follow-up of 32 months, the 5-year PFS and OS rates were 77.5% and 88.5%, respectively. Early OMDRT significantly improved PFS (HR 0.461, 95% CI: 0.257–0.826, p = 0.009) and OS (HR 0.219, 95% CI: 0.080–0.603, p = 0.003). Subgroup analysis showed the most favorable outcomes for synchronous OMD patients receiving early OMDRT, with a median PFS of 22.2 months and a 5-year survival rate of 42.1%. The treatment of the primary prostate provided a survival benefit in the OS of synchronous OMD patients (5-year 83.1% vs. 50%, p = 0.025), and there was a further improvement in OS after PPR (5-year 87.7% vs. 50%, p = 0.015). Conclusions: Early OMDRT significantly enhances survival outcomes in OMPC, in both synchronous and metachronous cases. The integration of PPR can further improve results, emphasizing the importance of early intervention and personalized treatment strategies. To more definitively clarify our findings across various clinical situations, further studies with larger cohorts or prospective designs are necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: The survival of patients with colorectal cancer liver metastasis can be prognosticated based on the presence or absence of desmoplastic histopathologic growth patterns. Patient survival is improved if the liver tumor has at least a 50% desmoplastic histopathologic growth pattern. Determing the patients tumor histopathological features is essential to prognosis outcomes and treatment management. Introduction: Colorectal cancer liver metastasis (CRCLM) remains a lethal diagnosis, with an overall 5-year survival rate of 5–10%. Two distinct histopathological growth patterns (HGPs) of CRCLM are known to have significantly differing rates of patient survival and response to treatment. We set out to review the results of 275 patients who underwent liver resection for CRCLM at the McGill University Health Center (MUHC) and analyze their clinical outcome, mutational burden, and pattern of cancer progression in light of their HGPs, and to consider their potential effect on surgical decision making. Methods: We performed a retrospective multivariate analysis on clinical data from patients with CRCLM (n = 275) who underwent liver resection at the McGill University Health Center (MUHC). All tumors were scored using international consensus guidelines by pathologists trained in HGP scoring. Results: A total of 109 patients (42.2%) were classified as desmoplastic and angiogenic, whereas 149 patients (57.7%) were non-desmoplastic and vessel co-opting. The 5-year survival rates for angiogenic patients compared with vessel co-opting patients were 47.1% and 13%, respectively (p < 0.0001). Multivariate analysis showed patients with vessel co-opting CRCLM had a higher incidence of extrahepatic metastatic disease (p = 0.0215) compared with angiogenic CRCLM. Additionally, KRAS mutation status was a marker of increased likelihood of disease recurrence (p = 0.0434), as was increased number of liver tumors (p = 0.0071) and multiple sites of extrahepatic metastatic disease (p < 0.0001). Conclusions: Multivariate analysis identified key clinical prognostic and molecular features correlating with the two HGPs. Determining liver tumor HGPs is essential for patient prognostication and treatment optimization. [ABSTRACT FROM AUTHOR]

Simple Summary: HER2-low breast cancer is a newly recognized subtype that has shown promising responses to treatment with antibody–drug conjugates (ADCs). However, there is still little known about its clinical and molecular characteristics. In this study, we examined the clinical and pathological features, survival rates, and expression of HER2-related genes in Colombian patients with HER2-low breast cancer, comparing them to HER2-negative and positive groups. We found that HER2-low tumors were better differentiated and had a lower proliferation index compared to HER2-positive tumors. Additionally, compared to HER2-negative cases, HER2-low patients had higher mRNA expression of the ERBB2 gene and longer overall survival rates. Despite these findings, there were no significant differences in survival when adjusted for estrogen receptor status and clinical stage. These results highlight the need for further research on HER2-low breast cancer to optimize treatment strategies for this unique group. HER2-low tumors have shown promise in response to antibody–drug conjugates (ADCs) in recent clinical trials, underscoring the need to characterize this group's clinical phenotype. In this study, we aimed to explore the clinicopathological features, survival rates, and HER2 amplicon mRNA expression of women affected with HER2-low breast cancer, compared with HER2-negative and HER2-positive groups. We included 516 breast cancer patients from Colombia, for whom we compared clinicopathological features, mRNA expression of three HER2 amplicon genes (ERBB2, GRB7 and MIEN1), survival and risk of mortality between HER2-low cases (1+ or 2+ with negative in situ hybridization (ISH) result) with HER2-positive (3+ or 2+ with positive ISH test) and HER2-negative (0+) cases. A higher proportion of patients with better-differentiated tumors and a lower proliferation index were observed for HER2-low tumors compared to the HER2-positive group. Additionally, HER2-low tumors showed higher mRNA expression of the ERBB2 gene and longer overall survival rates compared to HER2-negative cases. Nonetheless, a Cox-adjusted model by ER status and clinical stage showed no statistically significant differences between these groups. Our results show differences in important clinicopathological features between HER2-low and both HER2-positive and negative tumors. Given this unique phenotype, it is crucial to evaluate the potential advantages of ADC therapies for this emerging subtype of breast cancer. [ABSTRACT FROM AUTHOR]

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: 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: 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: 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: 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 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: 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]