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Purpose: The extent of tumor regression varies widely among locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). The purpose of this retrospectively study is to assess prognostic factors in LARC patients with NCRT, and further to analyze survival outcomes in patients with different tumor regression grades (TRGs). Methods: This study includes LARC patients who underwent NCRT and TME at our institution. We retrospectively analyzed the clinicopathological characteristics and survival of all patients, and performed subgroup analysis for patients with different TRGs. Survival differences were compared using the Kaplan-Meier method and the log rank test. Additionally, a multiple Cox proportional hazard model was used to identify independent prognostic factors. Results: The study included 393 patients, with 21.1%, 26.5%, 45.5%, and 6.9% achieving TRG 0, TRG 1, TRG 2, and TRG 3, respectively. The overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 89.4% and 70.7%, respectively. Patients who achieved TRG 0–3 had different 5-year OS rates (96.9%, 91.1%, 85.2%, and 68.8%, P = 0.001) and 5-year DFS rates (80.8%, 72.4%, 67.0%, 55.8%, P = 0.031), respectively. Multivariate analyses showed that the neoadjuvant rectal (NAR) score was an independent prognostic indicator for both overall survival (OS) (HR = 4.040, 95% CI = 1.792–9.111, P = 0.001) and disease-free survival (DFS) (HR = 1.971, 95% CI = 1.478–2.628, P ˂ 0.001). In the subgroup analyses, the NAR score was found to be associated with DFS in patients with TRG 1 and TRG 2. After conducting multivariate analysis, it was found that ypT stage was a significant predictor of DFS for TRG 1 patients (HR = 4.384, 95% CI = 1.721–11.168, P = 0.002). On the other hand, ypN stage was identified as the dominant prognostic indicator of DFS for TRG 2 patients (HR = 2.795, 95% CI = 1.535–5.091, P = 0.001). However, none of these characteristics was found to be correlated with survival in patients with TRG 0 or TRG 3. Conclusion: NAR score, in particular, appears to be the most powerful prognostic factor. It is important to consider various prognostic predictors for patients with different TRGs. [ABSTRACT FROM AUTHOR]

Background: Inherited variations in DNA double-strand break (DSB) repair pathway are known to influence ovarian cancer occurrence, progression and treatment response. Despite its significance, survival-associated genetic variants within the DSB pathway remain underexplored. Methods: In the present study, we performed a two-phase analysis of 19,290 single-nucleotide polymorphisms (SNPs) in 199 genes in the DSB repair pathway from a genome-wide association study (GWAS) dataset and explored their associations with overall survival (OS) in 1039 Han Chinese epithelial ovarian carcinoma (EOC) patients. After utilizing multivariate Cox regression analysis with bayesian false-discovery probability for multiple test correction, significant genetic variations were identified and subsequently underwent functional prediction and validation. Results: We discovered a significant association between poor overall survival and the functional variant GEN1 rs56070363 C > T (CT + TT vs. TT, adjusted hazard ratio (HR) = 2.50, P < 0.001). And the impact of GEN1 rs56070363 C > T on survival was attributed to its reduced binding affinity to hsa-miR-1287-5p and the resultant upregulation of GEN1 mRNA expression. Overexpression of GEN1 aggregated EOC cell proliferation, invasion and migration presumably by influencing the expression of immune inhibitory factors, thereby elevating the proportion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and then constructing an immunosuppressive tumor microenvironment. Conclusions: In conclusion, GEN1 rs56070363 variant could serve as a potential predictive biomarker and chemotherapeutic target for improving the survival of EOC patients. Highlights: Inherited variations in DSB repair pathway are known to influence ovarian cancer occurrence, progression and treatment response. In the present study, we performed a two-phase analysis of 19,290 SNPs in 199 genes in the DSB repair pathway among 1,039 ovarian cancer patients. Ultimately, we identified that the poor overall survival was significantly associated with functional variant GEN1 rs56070363 C > T. Further investigations revealed the mechanism underlying this association: the C > T transition resulted in decreased binding affinity to hsa-miR-1287-5p and subsequent upregulation of GEN1 mRNA expression. Overexpression of GEN1 aggregated EOC cell proliferation, invasion and migration presumably by influencing the expression immune inhibitory factors, thereby elevating the proportion of PMN-MDSCs and then constructing an immunosuppressive tumor microenvironment. Our findings thus provide novel molecular targets and a theoretical basis for individualized treatment approaches in ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: As gastric cancer patients aged ≥ 85 years have a short life expectancy and often die from other diseases such as pneumonia, indications for surgery are controversial. In this study, we retrospectively analyzed the prognostic factors of elderly patients with gastric cancer who are candidates for curative gastrectomy. Methods: Among 114 patients aged ≥ 85 years with gastric cancer at our hospital between 2010 and 2019, prognostic factors were examined using the Cox proportional hazards model in 76 patients excluding those with cStage IVB or endoscopic submucosal dissection. We also analyzed the factors of pneumonia death. Results: cStage was I/IIA/IIB/III/IVA in 37/6/14/14/5 patients, respectively. Treatment included distal gastrectomy in 28 patients, total gastrectomy in 6, local resection in 9, others in 3, and no surgery in 30. In univariate analyses of overall survival, Eastern Cooperative Oncology Group Performance Status, physiological score of Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), Onodera's prognostic nutritional index, cStage, and treatment were prognostic factors. In a multivariate analysis, POSSUM physiological score, cStage, treatment method {no surgery vs. distal gastrectomy: hazard ratio (HR) 5.78, 95% confidence interval (CI) 2.33–14.3}, (total gastrectomy vs. distal gastrectomy: HR 4.26, 95% CI 1.22–14.9) were independent prognostic factors. In univariate analyses of pneumonia-specific survival, treatment (total gastrectomy vs. distal gastrectomy: HR 6.98, 95% CI 1.18–41.3) was the only prognostic factor. Conclusions: The prognosis of distal gastrectomy was better than that of non-surgery even in patients aged ≥ 85 years. However, total gastrectomy was considered to be avoidable due to the high rate of postoperative pneumonia death. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. Methods: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. Results: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). Conclusions: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common malignancy with poor survival and requires long-term follow-up. Hence, we collected information on patients with Primary Hepatocellular Carcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a deep learning with a multilayer neural network (the NMTLR model) for predicting the survival rate of patients with Primary Hepatocellular Carcinoma. HCC patients pathologically diagnosed between January 2011 and December 2015 in the SEER (Surveillance, Epidemiology, and End Results) database of the National Cancer Institute of the United States were selected as study subjects. We utilized two deep learning-based algorithms (DeepSurv and Neural Multi-Task Logistic Regression [NMTLR]) and a machine learning-based algorithm (Random Survival Forest [RSF]) for model training. A multivariable Cox Proportional Hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into a training set and a test set in a 7:3 ratio. The training dataset underwent hyperparameter tuning through 1000 iterations of random search and fivefold cross-validation. Model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-year, 3-year, and 5-year survival rates was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Area Under the Curve (AUC). The primary outcomes were the 1-year, 3-year, and 5-year overall survival rates. Models were developed using DeepSurv, NMTLR, RSF, and Cox Proportional Hazards regression. Model differentiation was evaluated using the C-index, calibration with concordance plots, and risk stratification capability with the log-rank test. The study included 2197 HCC patients, randomly divided into a training cohort (70%, n = 1537) and a testing cohort (30%, n = 660). Clinical characteristics between the two cohorts showed no significant statistical difference (p > 0.05). The deep learning models outperformed both RSF and CoxPH models, with C-indices of 0.735 (NMTLR) and 0.731 (DeepSurv) in the test dataset. The NMTLR model demonstrated enhanced accuracy and well-calibrated survival estimates, achieving an Area Under the Curve (AUC) of 0.824 for 1-year survival predictions, 0.813 for 3-year, and 0.803 for 5-year survival rates. This model's superior calibration and discriminative ability enhance its utility for clinical prognostication in Primary Hepatocellular Carcinoma. We deployed the NMTLR model as a web application for clinical practice. The NMTLR model have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with primary liver cancer. [ABSTRACT FROM AUTHOR]

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

Background: Watch and wait (W&W) in complete clinical responders after neoadjuvant chemoradiotherapy has increasingly robust data supporting its oncological safety. Recently, studies have assessed the real‐world costs of this strategy compared to surgical resection. Our aim was to compare our oncological safety and costs associated with operative and surveillance strategies to international literature. Methods: Data were retrospectively collected and analysed via electronic health records from March 2014 to March 2021 in Christchurch, New Zealand. Two cohorts were created based on intention to treat. All hospital events were recorded and costed, as well as oncologic outcomes. Our primary endpoints were the cumulative cost of both strategies, 3‐year survival rate, and disease‐free survival. Results: Forty‐eight patients were identified who had rectal cancers resected (OT) with a yPT0N0 pathology, and 42 who were on the wait‐and‐watch (W&W) audit after having a clinical complete response. After exclusions, we identified 38 OT and 23 W&W patients; the W&W group were more co‐morbid (P = 0.05), had worse functional status (P = 0.008), higher BMI (P = 0.34) and more favourable clinical tumour staging (P = 0.01). The operative treatment (OT) group (n = 38) had more acute admissions (34% versus 13% in W&W, P = 0.08, OR 0.29). There was a 35.7% (n = 8 of 23) local recurrence in W&W and none in the OT group (P ≤ 0.001), with successful salvage in the W&W with local recurrence in 71.5% (n = 5 of 7). Three‐year distant metastasis‐free rate was 97.3% in the OT group and 90.9% in W&W (p = 0.05). Overall survival was 100% (W&W) and 94.7% (OT); (P = 0.019). Care in the OT group cost more than W&W, accounting for local regrowth management; $NZ70,759.56 versus $NZ47,905.52 (P = 0.014). Conclusion: This study found better oncological outcomes in the OT group, whilst the W&W group had reduced morbidity and acute bed days. The cost of wait and watch was approximately two‐thirds that of operative treatment, even accounting for salvage procedures for local regrowth. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of neoadjuvant endocrine therapy in female HR‐positive/HER2‐negative breast cancer patients. Data and Methods: We identified female patients aged ≥18 years with cT1‐4N0‐XM0, HR(+), and HER2(−) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery‐first," while those who received NET before surgery were classified as "NET." Propensity score‐matching, Cox proportional‐hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. Results: Among 432,387 cases, 2914 NET patients and 2914 surgery‐first patients were matched. Compared with the surgery‐first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery‐first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery‐first vs. NET: HR 2.17, 95% CI: 1.93–2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(−), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). Conclusion: NET may be a more effective treatment procedure than surgery‐first in female HR‐positive/HER2‐negative, non‐metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher‐level evidence‐based data. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this meta-analysis is to evaluate the potential benefits of postoperative radiotherapy (PORT) in patients with pN1 oral cavity squamous cell carcinoma. Methods: A literature search through major databases was conducted until January 2023. The adjusted hazard ratio (aHR) or risk ratio (RR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled. Results: Ten studies published between 2005 and 2022, with a pooled patient population of 2888, were included in this meta-analysis. Due to differences in study design and reported outcomes, the studies were categorized into distinct groups. In pN1 patients without extranodal extension (ENE), PORT was associated with a significant improvement in overall survival (OS) (aHR 0.76, 95% CI: 0.61-0.94). In pN1 patients without ENE and positive margins, PORT improved OS (aHR 0.71, 95% CI: 0.56-0.89) and was associated with a lower regional recurrence rate (RR 0.35, 95% CI: 0.15-0.83). However, in pN1 patients without ENE, positive margins, perineural invasion, and lymphovascular invasion, there were no significant differences observed between the PORT and observation groups in either 5-year OS (RR 0.48, 95% CI: 0.07-3.41) or 5-year disease-free survival (RR 0.37, 95% CI: 0.07-2.06). Conclusions: The current study demonstrated that PORT has the potential to improve OS in pN1 disease. However, the decision of whether to administer PORT still hinges on diverse clinical scenarios, and additional research is necessary to furnish a more conclusive resolution. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between the human papillomavirus (HPV) infection and overall survival rate in patients with oral cancer. Methods: This retrospective cohort study examined HPV status in 454 patients who were diagnosed with oral squamous cell carcinoma (OSCC) using the records of patients who underwent an initial treatment for OSCC between 2012 and 2021 at our institution as retrieved from the Cancer Registry database. The survival rates of the HPV-positive and HPV-negative groups were assessed and compared, and independent factors associated with survival were analyzed using multivariate Cox regression models. Results: Of the 454 patients with OSCC included in this study, 73 were excluded for invalid HPV tests. Of the remaining patients, 39 and 342 patients were categorized into HPV-positive and HPV-negative groups, respectively. The prevalence of HPVpositive in the patients with OSCC was 10.2% (95% confidence interval 7.2%-13.2%). The 3-year overall survival rates were 56.2% and 53.9% in the HPV-positive and HPV-negative groups, respectively. The 3-year disease-specific survival rates in the HPV-positive and HPV-negative groups were 60.2% and 56.9%, respectively. The survival differences were not statistically significant. HPV-positive status was not a significant predictor of overall survival in the multivariable Cox regression analyses (p = 0.728). Conclusion: The prevalence of HPV-positivity among patients with OSCC in the study was 10.2%. No association was found between HPV-positive status and 3-year overall survival in patients with oral cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy or combined chemoimmunotherapy is currently first-line therapy for patients with metastatic NSCLC without a driver mutation. Despite immunotherapy contributing to improved survival outcomes, the estimated 5-year OS rate for metastatic NSCLC remains poor. The aim of our retrospective study was to assess how patients with different anatomical metastatic sites respond or develop resistance to immunotherapy, combination chemoimmunotherapy, or chemotherapy alone. We confirmed that patients with bone metastases have poorer survival outcomes compared to those without bone metastases. This highlights a group of patients that may benefit from a specific clinical trial evaluation to assess the benefit of additional novel therapeutics or upfront radiotherapy. Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients with unresectable stage III/IV NSCLC who received first-line systemic therapy, we sought to assess the association between the site of metastases with patterns of response and progression. Data regarding demographics, tumour characteristics (including site, size, and volume of metastases), treatment, and outcomes were examined at two cancer care centres. The endpoints included organ site-specific response rate, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Two-hundred and eighty-five patients were included in the analysis. In a multivariate analysis, patients with bone metastases had a reduced ORR, PFS, and OS. Primary resistance was also more likely in patients with bone metastases. Patients with bone or liver metastases had a shorter OS when receiving ICIs with or without chemotherapy, but not with chemotherapy alone, suggesting an immunological basis for therapeutic resistance. A directed assessment of the tumour microenvironment in these locations and a deeper understanding of the drivers of organ-specific resistance to immunotherapy are critical to optimise novel combination therapies and sequencing in these patients. [ABSTRACT FROM AUTHOR]

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

Simple Summary: In spontaneous tumor regression, tumors shrink and disappear without conventional treatments. This phenomenon challenges the view that cancer is an irreversible genetic disease and that the only treatment option is to kill cancer cells or surgically remove them. In tumor reversion, cancer cells have been shown to return to normal cells when they are transplanted into a normal cellular environment. Additionally, people consuming a Western diet ingest excessive amounts of dietary phosphate, and a dysregulated oversupply of phosphate can be transported into cells, stimulating the cellular growth that forms tumors. Based on reviewed evidence, this paper proposes that reducing excessive dietary phosphate potentially activates tumor regression and reversion, as components of cancer cells are self-digested. Furthermore, fevers and fasting-mimicking diets are associated with tumor regression, which also may be initiated by reduced phosphate intake. Studies are needed to test dietary phosphate reduction in tumor regression and reversion to improve cancer patient survival. Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and an increased transport of phosphate into tumor cells, potentially mediated by phosphate overload from excessive dietary phosphate intake, a significant problem in Western societies. This paper proposes that reduced dietary phosphate overload and reregulated phosphate metabolism may reverse an imbalance of kinases and phosphatases in cell signaling and cellular proliferation, thereby activating autophagy in tumor regression and reversion. Dietary phosphate can also be reduced by sickness-associated anorexia, fasting-mimicking diets, and other diets low in phosphate, all of which have been associated with tumor regression. Tumor reversion has also been demonstrated by transplanting cancer cells into a healthy microenvironment, plausibly associated with normal cellular phosphate concentrations. Evidence also suggests that the sequestration and containment of excessive phosphate within encapsulated tumors is protective in cancer patients, preventing the release of potentially lethal amounts of phosphate into the general circulation. Reducing dietary phosphate overload has the potential to provide a novel, safe, and effective reversion therapy for cancer patients, and further research is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to elucidate whether osteopenia predicts clinicopathological findings in patients with hepatocellular carcinoma. Bone mineral density was assessed using computed tomography scan images taken within 3 months before surgery. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. The overall survival of osteopenia patients was shorter than that of non-osteopenia patients, regardless of gender. Osteopenia was an independent risk factor for overall survival and recurrence-free survival. The pathological factor associated with osteopenia was microvascular portal vein invasion. Background: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival. Methods: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan–Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox's proportional hazard model. Results: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion. Conclusion: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion. [ABSTRACT FROM AUTHOR]

Simple Summary: Telomerase reverse transcriptase promoter (TERTp) mutation is commonly observed in brain tumors and are known to contribute to the acquisition of immortality in tumors via maintaining telomere length. In this study, we aimed to investigate the prognostic impact of several known prognostic factors, including TERTp mutations, in 528 adult-type diffuse gliomas classified according to the 2021 WHO criteria. Our data showed that TERTp mutation status had a significant impact on prognosis in the combined group of glioblastoma, IDH-wildtype and astrocytoma, IDH-mutant, but was not a predictor of prognosis within any individual tumor groups. We also showed that several known clinicopathologic factors have different prognostic significance depending on the type of tumor. This supports the need for systematic tumor diagnosis based on molecular pathology classification and indicates that multiple factors, not just TERTp mutation status, should be considered in the prognosis of tumors. Mutation in the telomerase reverse transcriptase promoter (TERTp)is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan–Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Different immunotherapy combinations improved prognosis for advanced non-oncogene driven NSCLC, but they were not directly compared. The aim of our study is to present the real-world data for 122 patients treated at the Institute of Oncology in Cluj-Napoca with three different consecutive immunotherapy combinations (dual immunotherapy—18 patients, dual immunotherapy plus short course chemotherapy—33 patients, mono-immunotherapy plus full course chemotherapy—71 patients). Efficacy results using different immunotherapy combination strategies were in line with those from the registration trials, with 22.2 months median overall survival and 49% actuarial 2-year survival. Results were not significantly different between the three protocols. Older age, impaired performance status, corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate survival analysis. Long-term data are available for the dual immunotherapy cohorts, with 30.5% and 18.8% of patients alive at 5 years. Purpose. Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. Methods. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. RESULTS. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0–1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Conclusions. Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Hereditary breast cancer represents a significant proportion of breast cancer cases worldwide, and BRCA1 and BRCA2 explain the majority of these. Less frequent genes with variable penetrance remain less characterized in Colombia. This study explores the characteristics and outcomes of 82 breast cancer patients with germline pathogenic/likely pathogenic variants (PVs) treated and followed at the Instituto Nacional de Cancerología, Colombia (INC-C) from 2018 to 2021 as part of an Institutional Hereditary Cancer Program implementation. We described the distribution of germline PVs among the different breast cancer molecular subtypes in this cohort of carriers. We observed that most PVs were in known breast cancer susceptibility genes, and PVs in BRCA2 were the most frequent. Notably, we observed that patients with disease progression were predominantly carriers of PVs in the BRCA2 gene. This study aimed to investigate prognosis and survival differences in 82 breast cancer patients with germline pathogenic/likely pathogenic variants (PVs) treated and followed at the Breast Unit of the Instituto Nacional de Cancerología, Colombia (INC-C) between 2018 and 2021. Median age at diagnosis was 46 years, with 62.2% presenting locally advanced tumors, 47.6% histological grade 3, and 35.4% with triple-negative breast cancer (TNBC) subtype. Most carriers, 74.4% (61/82), had PVs in known breast cancer susceptibility genes (i.e., "associated gene carriers" group, considered inherited breast cancer cases): BRCA2 (30), BRCA1 (14), BARD1 (4), RAD51D (3), TP53 (2), PALB2 (2), ATM (2), CHEK2 (1), RAD51C (1), NF1 (1), and PTEN (1). BRCA1-2 represented 53.7%, and homologous recombination DNA damage repair (HR-DDR) genes associated with breast cancer risk accounted for 15.9%. Patients with PVs in non-breast-cancer risk genes were combined in a different category (21/82; 25.6%) (i.e., "non-associated gene carriers" group, considered other breast cancer cases). Median follow-up was 38.1 months, and 24% experienced recurrence, with 90% being distant. The 5-year Disease-Free Survival (DFS) for inherited breast cancer cases was 66.5%, and for other breast cancer cases it was 88.2%. In particular, for carriers of PVs in the BRCA2 gene, it was 37.6%. The 5-year Overall Survival (OS) rates ranged from 68.8% for those with PVs in BRCA2 to 100% for those with PVs in other HR-DDR genes. Further studies are crucial for understanding tumor behavior and therapy response differences among Colombian breast cancer patients with germline PVs. [ABSTRACT FROM AUTHOR]

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

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

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

Simple Summary: Meningiomas are classified pathologically by the World Health Organization (WHO) grading system, with WHO grade 2 and 3 tumors considered "high-grade". These tumors are characterized microscopically by high mitotic rates and macroscopically by a brain invasion. The goal of the surgical treatment of these tumors is maximal safe resection to minimize surgical morbidity and extend patient survival. Surgical resection is made difficult by frequently indistinct boundaries between normal brain layers and the encasement of blood vessels and cranial nerves. Surgeons and scientists must continue to collaborate to offer patients the highest quality operative and post-operative medical care. Maximal resection with the preservation of neurological function are the mainstays of the surgical management of high-grade meningiomas. Surgical morbidity is strongly associated with tumor size, location, and invasiveness, whereas patient survival is strongly associated with the extent of resection, tumor biology, and patient health. A versatile microsurgical skill set combined with a cogent multimodality treatment plan is critical in order to achieve optimal patient outcomes. Continued refinement in surgical techniques in conjunction with directed radiotherapeutic and medical therapies will define future treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment options for children with recurrent medulloblastoma are often limited due to extensive previously received treatments after initial diagnosis. Especially, repeated radiotherapy is associated with significant side-effects. In this study, we study the impact on survival of repeated radiotherapy at recurrence for patients with previous irradiation, as well as first irradiation at recurrence when no previous radiotherapy was applied. We find that repeated radiotherapy provides a short-time benefit in terms of survival, but survival ten years after recurrence is not significantly improved. At the same time, we find that applying radiotherapy at recurrence when patients received no previous irradiation did significantly improve survival, both short and long term. Background: Radiotherapy (RT) involving craniospinal irradiation (CSI) is important in the initial treatment of medulloblastoma. At recurrence, the re-irradiation options are limited and associated with severe side-effects. Methods: For pre-irradiated patients, patients with re-irradiation (RT2) were matched by sex, histology, time to recurrence, disease status and treatment at recurrence to patients without RT2. Results: A total of 42 pre-irradiated patients with RT2 were matched to 42 pre-irradiated controls without RT2. RT2 improved the median PFS [21.0 (CI: 15.7–28.7) vs. 12.0 (CI: 8.1–21.0) months] and OS [31.5 (CI: 27.6–64.8) vs. 20.0 (CI: 14.0–36.7) months]. Concerning long-term survival after ten years, RT2 only lead to small improvements in OS [8% (CI: 1.4–45.3) vs. 0%]. RT2 improved survival most without (re)-resection [PFS: 17.5 (CI: 9.7–41.5) vs. 8.0 (CI: 6.6–12.2)/OS: 31.5 (CI: 27.6–NA) vs. 13.3 (CI: 8.1–20.1) months]. In the RT-naïve patients, CSI at recurrence improved their median PFS [25.0 (CI: 16.8–60.6) vs. 6.6 (CI: 1.5–NA) months] and OS [40.2 (CI: 18.7–NA) vs. 12.4 (CI: 4.4–NA) months]. Conclusions: RT2 could improve the median survival in a matched cohort but offered little benefit regarding long-term survival. In RT-naïve patients, CSI greatly improved their median and long-term survival. [ABSTRACT FROM AUTHOR]

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

Introduction: Nectin-4 is a member of the nectin family and a calcium-independent immunoglobulin-like transmembrane protein that contributes to tumor growth and angiogenesis in malignant tumors. A nectin-4-directed antibody drug conjugate, enfortumab vedotin-ejf, has recently been approved for treatment in urothelial cancer and is currently under investigation in other tumor entities such as breast, lung, and prostate cancer. In non-clear cell renal cell carcinoma (RCC), vascular endothelial growth factor (VEGF)-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. However, due to the rarity of disease treatment recommendations for chromophobe RCC (chRCC) are limited and new therapeutic agents urgently needed. In this study, we investigated the expression and prognostic impact of nectin-4 in a large cohort of chRCC. Methods: Patients who underwent renal surgery due to chRCC were recruited. Clinical data were retrospectively evaluated. Tumor specimen was analyzed for nectin-4 expression by immunohistochemistry. Results: Eighty-one chRCC patients were eligible for analysis. In 15 (18.5%) samples, tumors were positive for nectin-4. No significant associations were found for nectin-4 expression and clinical attributes in patients with chRCC. Kaplan-Meier analysis disclosed a 5-year overall survival for nectin-4-negative and nectin-4-positive tumors of 91.8% versus 100.0% (p = 0.316, log rank). Conclusions: In chRCC, a small subset of tumors expresses nectin-4 potentially amenable to nectin-4-directed treatment. Expression of nectin-4 is not associated with parameters of aggressiveness or survival. Due to the rare incidence of chRCC, further studies with larger cohorts are warranted. [ABSTRACT FROM AUTHOR]

Introduction: It is unclear whether a lower lobe origin is a risk factor for early recurrence of non-small cell lung cancer (NSCLC) in patients who underwent pulmonary resection. Methods: The risk factors for early recurrence, defined as recurrence occurring within 1 year after surgery, were analyzed in 476 patients with NSCLC who underwent pulmonary resection without wedge resection. Results: The proportion of men, Brinkman's index, carcinoembryonic antigen levels, and the maximum standardized uptake value (SUVmax) were significantly higher in patients with early recurrence than in those without early recurrence. Furthermore, the rates of lower lobe origin, extended resection beyond lobectomy, lymphatic invasion, vascular invasion, and advanced-stage disease were significantly higher in patients with early recurrence. Age (odds ratio [OR] = 4.46, p < 0.01), SUVmax (OR = 5.78, p = 0.02), a lower lobe origin (OR = 3.06, p = 0.01), and pathological stage (OR = 3.34, p = 0.01) were risk factors for early recurrence in multivariate analysis. Furthermore, only early recurrence (OR = 3.34, p = 0.01) was a risk factor for overall survival in multivariate analysis, and overall survival outcomes and prognoses significantly differed between patients with and without early recurrence (p < 0.01). Conclusion: Age, SUVmax, a lower lobe origin, and pathological stage are risk factors for early recurrence. These results suggest that for patients with NSCLC who underwent pulmonary resection, SUVmax and a lower lobe origin are important for deciding the indication for adjuvant chemotherapy in addition to pathological stage. [ABSTRACT FROM AUTHOR]

Background: Altered body composition has been attributed to major health problems globally, particularly in patients with cancer. To date, there have not been sufficient indices for body compositions in predicting the survival of locally advanced breast cancer (LABC). Purpose: To assess the association between body composition and overall survival (OS) as well as disease-free survival (DFS) in patients with LABC. Material and Methods: A retrospective study was conducted of patients with LABC diagnosed between 2010 and 2018. Body composition parameters, including skeletal muscle and adiposity parameters, were measured using computed tomography at the L3 vertebra using in-house software developed by MATLAB and freeware Python 3.6.13. The association between body composition and OS and DFS were analyzed using a log-rank test and multivariate Cox-proportional hazard regression. Results: Of 199 patients, 72 (36%) died during the follow-up period (range = 3.8–150.7 months). Median survival was 101 months. Low visceral-to-subcutaneous ratio ≤0.3 (adjusted hazard ratio [aHR] = 2.57, 95% confidence interval [CI] = 1.51−4.37; aHR = 2.46, 95% CI = 1.33−4.56), and high composite fat (aHR = 3.26, 95% CI = 1.69−6.29; aHR = 2.19, 95% CI = 1.11−4.3) were associated with lower OS and DFS. Positive lymph nodes ≥3, progesterone receptor negative, and total radiation dose >5000 cGy significantly decreased both OS and DFS. A history of previous treatment before body composition assessment and surgery had a protective effect on OS and DFS. No association of sarcopenia, body mass index, and adiposity areas with survival outcomes was observed. Conclusion: Low visceral-to-subcutaneous ratio and high composite fat were independent prognostic factors for OS and DFS in patients with LABC. However, other body composition parameters showed no effect on survival. [ABSTRACT FROM AUTHOR]

Background: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. Methods: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. Results: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20–50) vs. 35 (30–59) mL, median difference (95%CI) − 5 (− 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) − 1.19 (− 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II–III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5–32.5) vs. 32 (27–38.5) days, median difference (95%CI) − 3 (− 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. Conclusion: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2. [ABSTRACT FROM AUTHOR]

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

Despite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain regions, prompting concern over both durable disease control and the morbidity associated with large volume radiation therapy. This study audits volumetric response, survival and functional outcomes in this 'large volume' subgroup that undergoes intensity modulated radiation therapy (IMRT). From a prospective database of 187 patients with IDH-mutant grade 3 gliomas managed with IMRT between 2008 and 2020, recorded PTV was divided into quartiles. The top quartile, termed the 'large volume cohort' (LVC), was identified. IMRT involved FET-FDG guided integrated boost (59.4/54Gy in 33 fractions). Manual volumetric segmentation of baseline, four months and 13 months post-IMRT tumour were performed for T1, T2 and T1gd MRI sequences. The primary endpoint was volumetric reduction on the T1 and T2 sequences at 13 months and analysed with relapse-free survival (RFS) and overall survival (OS). Morbidity endpoints were assessed at year four post-IMRT and included performance status (ECOG PS) and employment outcomes. The fourth quartile (LVC) identified 44 patients for whom volumetric analysis was available. The LVC had median PTV of 320cm3 compared to 186.2cm3 for the total group. Anaplastic astrocytoma and oligodendroglioma were equally distributed and tumour sites were frontal (54%), temporal (18%) and parietal lobes (16%). Median follow-up for survivors was 71.5 months. Projected 10-year RFS and OS in LVC was 40% and 62%, compared to 53% and 62% respectively in the overall cohort. The RFS (p = 0.06) and OS (p = 0.65) of the LVC was not significantly different to other PTV quartiles; however the impact of PTV volume reached significance when analysed as a continuous variable (RFS p < 0.01; OS p = 0.02). Median T1 volumes were 26.1cm3, 8.0cm3 and 5.3cm3 at months +0, +3 and +12, respectively. The corresponding T2 volumes were 120.8cm3, 29.1cm3 and 26.3cm3. The median T1 and T2 volume reductions were 77% (q1–3: 57–92%) and 78% (q1–3: 60–85%) at 13 months post-IMRT. Initial T2 volume was associated with worse RFS (p = 0.04) but not OS (p = 0.96). There was no association between median T2 volume reduction and RFS (p = 0.77). For patients assessable at year 4 post-IMRT, no late CTCAE Grade 3/4 toxicity events were recognised. 92% of patients were ECOG PS 0–1, 45% were employed at prior capacity and 28% were working with impairment. Patients with large volume IDH-mutant Grade 3 glioma demonstrated significant tumour reduction post-IMRT, and good long-term outcomes with respect to survival and functional status. Although larger IMRT volumes were associated with poorer RFS, this was also associated with the initial volume of non-enhancing tumour. • IDH-mutant Grade 3 glioma are brain tumours with good prognosis. • Standard management consists of surgery, radiotherapy and temozolamide. • Large tumours pose challenge of achieving local control with acceptable morbidity. • PET imaging and modern radiotherapy techniques allow conformal tumour delineation. • These techniques allow for good long-term control, survival and function. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical impact of suspicious extra-abdominal lymph nodes (EALNs) identified preoperatively on CT and/or PET/CT images in advanced ovarian cancer. Methods: A retrospective study was conducted with 122 patients diagnosed with stage III or IV ovarian cancer with preoperative CT and/or PET/CT images from 2006 to 2022. Imaging studies were evaluated for the presence, size and location of suspicious EALNs. Suspicious lymph node enlargement was defined by a cut-off ≥5mm short-axis dimension on CT and/or lesions with maximum standardized uptake values of ≥2.5 on PET/CT. This study only included patients who did not have their EALNs surgically removed. Results: A total 109 patients met the inclusion criteria; 36 (33%) had suspicious EALNs and were categorized as "node-positive". The median overall survival (OS) was 45.73 months for the "node-positive" and 46.50 months for the "node-negative" patients (HR 1.17, 95% CI 0.68–2.00, p = 0.579). In multivariate analysis, after adjusting for other variables selected by process of backward elimination using a significance level of p<0.20, suspicious EALNs still showed no clinical significance on OS (aHR 1.20, 95% CI 0.67–2.13, p = 0.537) as well as progression-free survival (aHR 1.43, 95% CI 0.85–2.41, p = 0.174). Old age (aHR 2.23, 95% CI 1.28–3.89, p = 0.005) and platinum resistance (aHR 1.92, 95% CI 1.10–3.36, p = 0.023) affects adversely on OS. Conclusion: Suspicious EALNs did not worsen the prognosis of patients with advanced ovarian cancer. However, its impact on survival is not yet clarified. Further investigation is required to assess the clinical significance of suspicious EALNs on preoperative imaging studies. [ABSTRACT FROM AUTHOR]

Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography–tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a tumor with high morbidity and mortality. The importance of inflammatory and metabolic parameters affecting progression-free survival (PFS) and overall survival (OS) has been investigated more intensively recently. We aimed to investigate the effect of glucose/c-reactive protein (CRP) ratio [GCR], which shows these two parameters together, on PFS in cervical cancer. Methods: We retrospectively included 90 patients with adenocarcinoma and squamous cell carcinoma of the cervix. The effects of clinical variables, inflammatory and glycemic parameters on PFS and OS were analyzed by Kaplan-Meier method. The data were compared with the healthy control group of 90 individuals using the independent t test. The effect of parameters on mortality was analyzed using ROC curves and cut off values were determined. Results: Glucose, CRP, CRP/lymphocyte ratio (CLR) and GCR were statistically significant in predicting mortality (p < 0.05). Disease stage, glucose, CRP, CLR and GCR were associated with overall survival. CRP, CLR and GCR were associated with progression-free survival (p < 0.05). In multivariate analysis, GCR was prognostic for PFS (p = 0.025). GCR was statistically significant while compared with the patient and healthy control group (p < 0.001). Conclusion: In cervical cancer, GCR rate was found to be prognostic independent of stage. Higher GCR rate was associated with longer PFS duration. [ABSTRACT FROM AUTHOR]

Background: For advanced non‐small cell lung cancer (NSCLC), combination therapies including a PD‐1 inhibitor plus chemotherapy or a PD‐1 inhibitor, CTLA‐4 inhibitor, and chemotherapy are standard first‐line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real‐world setting. Methods: In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first‐line therapies in 182 patients with stage IIIB–IV NSCLC. Primary outcomes were overall survival (OS) and progression‐free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan–Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD‐L1 expression. Results: In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3–4 adverse events occurred comparably, but immune‐related adverse events were numerically more frequent in the CNI group. Conclusions: In real‐world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: The modeled CA-125 elimination constant K (KELIM) is a potential marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy (NACT) before interval surgery. The objective of this study was to externally validate the KELIM (rate of elimination of CA-125) score in patients with high-grade serous ovarian cancer (HGSC) undergoing NACT and explore its relation to the completeness of IDS and survival. Methods: The study was based on a retrospective cohort of 133 patients treated for advanced HGSC, International Federation of Gynecology and Obstetrics (FIGO) stages III–IV, with neoadjuvant chemotherapy, folllowed by interval surgery, in two centres in China. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. We used standardized (std) KELIM for subsequent analysis. Clinicopathologic parameters were collected, and Kaplan‒Meier survival analyses were performed for PFS and OS. Results: KELIM was an independent predictor of the probability of complete surgery and survival in our cohort. The median std KELIM score of patients with complete surgery was significantly higher than that of patients with incomplete IDS (1.20 vs. 0.71, P < 0.001). Multivariate analysis showed that a std KELIM score 0.925 was an independent predictive factor for achieving complete resection (OR = 5.480; 95% CI, 2.409–12.466, P < 0.001) and better PFS (HR = 0.544; 95% CI: 0.349–0.849, P = 0.007) and OS (HR = 0.484; 95% CI: 0.251–0.930, P = 0.030). Conclusions: The tumor-primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during NACT, is a major parameter to consider for decision-making regarding IDS attempts and predicting patient survival. [ABSTRACT FROM AUTHOR]

Background: The validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients. Methods: The clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed. Results: The mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01–1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups. Conclusions: ESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient's general condition. [ABSTRACT FROM AUTHOR]

Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, p = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, p = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the increased risk of developing renal cell carcinoma (RCC) in patients with advanced chronic kidney disease (ACKD), little is known about the patient clinical characteristics and genetic mutations found in these RCC tumors. Using a multi-institutional research network, this study compiled clinical records and somatic tumor whole exome sequencing data of 296 adult patients with RCC, 61 of whom had ACKD. Patients with RCC and ACKD were more likely to be male, present with earlier stage RCC at diagnosis, and have lower rates of BAP1 mutations. Median overall survival was not reached in either group over a median follow-up of 31.3 months. These findings suggest RCC in patients with ACKD develops via a BAP1-independent mutational driver and further support BAP1 loss as a marker of disease aggressiveness. Background: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined. Patients and Methods: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care® protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.5 mg/dL prior to RCC diagnosis. Results: Of 296 patients with RCC, 61 met the criteria for ACKD. The most common somatic mutations in the overall cohort were in VHL (126, 42.6%), PBRM1 (102, 34.5%), and SETD2 (54, 18.2%). BAP1 had a decreased mutational frequency in RCC specimens from patients without ACKD as compared to those with ACKD (10.6% versus 1.6%), but this was not statistically significant in univariable (OR 0.14, p = 0.056) or multivariable (OR 0.15, p = 0.067) analysis. Median OS was not reached in either cohort. Conclusions: Using the clinicogenomic ORIEN database, our study found lower rates of BAP1 mutations in RCC specimens from patients with ACKD, which may reflect a BAP1-independent mutational driver of RCC in patients with ACKD. [ABSTRACT FROM AUTHOR]

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

Simple Summary: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has been successfully used as a conditioning regimen in acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. In this study, we investigated how increased doses of melphalan impact the safety of HDCT with TreoMel and patient outcomes. A total of 51 AML patients were included in the analysis: 31 (60.8%) received standard-dose treosulfan combined with melphalan 140 mg/m2 (TreoMel 140) and 20 (39.2%) received melphalan 200 mg/m2 (TreoMel 200). There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohorts. The side effect profile was comparable between both patient groups. Our results show that a higher melphalan dose is well tolerated. No significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and short follow-up. Longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. (1) Background: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has shown promising safety and efficacy as a conditioning regimen for acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. The aim of this study was to compare two melphalan dose schedules in regard to the safety of TreoMel HDCT and patient outcomes. (2) Methods: We retrospectively analyzed the safety and efficacy of two melphalan dose schedules combined with standard-dose treosulfan in AML patients undergoing HDCT and ASCT at the University Hospital of Bern, Switzerland, between August 2019 and August 2023. Patients received treosulfan 42 g/m2 combined with either melphalan 140 mg/m2 (TreoMel 140) or melphalan 200 mg/m2 (TreoMel 200). Co-primary endpoints were progression-free survival (PFS), overall survival (OS), as well as safety profile. (3) Results: We included a total of 51 AML patients: 31 (60.8%) received TreoMel 140 and 20 (39.2%) TreoMel 200. The patients' basal characteristics were comparable between both cohorts. No significant differences in the duration of hospitalization or the adverse event profile were identified. There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohort. (4) Conclusions: A higher dose of melphalan (TreoMel 200) was well tolerated overall. No statistically significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and the short follow-up. A longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is predicted to be the second-highest cause of cancer mortality in the US by 2040. It is driven by various mutations including KRAS, TP53, SMAD4, and CDKN2A. Roughly 1 in 10 patients with pancreatic cancer have wildtype KRAS (KRASWT). We studied 27 patients with KRASWT to better understand their molecular characteristics and potential for precision medicine. Our findings revealed that KRASWT PDAC is enriched with potentially treatable genetic alterations, including those affecting the MAPK pathway, DNA repair pathway, and kinase fusion genes. One of our KRASWT PDAC patients was found to have a specific, targetable TFG-MET mutation and they responded well to treatment with a cMET inhibitor. This suggests that KRASWT PDAC has unique genetic characteristics that could be targeted with specific treatments tailored to each patient, highlighting the importance of comprehensive genetic profiling in KRASWT PDAC. Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics. [ABSTRACT FROM AUTHOR]

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

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

Background: Neoadjuvant therapy (NAT) is an important tool for the treatment of patients with breast cancer. The aim of NAT is to make it operable for patients with locally advanced breast cancer, to shrink early-stage tumors - thus allowing for breast conservation. Pathological complete response achieved by post-chemotherapy is an independent factor in the long-term survival of patients. Thus, the histopathological components of post-chemotherapy changes such as cellularity and lymph node (LN) tumor deposits, when combined, help to assess residual carcinoma burden. Aims and Objectives: This study aims to analyze various histopathological changes in the breast after neoadjuvant chemotherapy with the objective of evaluating post-chemotherapy response and residual cancer burden. Materials and Methods: A total of 34 cases of post-chemotherapy modified radical mastectomy specimens were analyzed for pathological response (pCR) and residual cancer burden were evaluated. Tumor cellularity, stromal changes, lymphovascular invasion, and LN involvement were noted. Results: The age group of presentation of 34 cases ranged from 30 to 75 years of age with the mean age being 43.5 years. The most common histomorphological finding was fibrosis/elastosis and vacuolation with 26 (76.5%) and 24 (70.6%) cases, respectively. The number of cases that showed partial pCR was 30 (88.2%) and 1 (2.9%) case showed a pathological complete response which belonged to Stage 0, pathological no response was shown by 3 (8.8%) cases which belonged to Stage II and Stage IV. Conclusion: Post-chemotherapy response of neoadjuvant chemotherapy in breast carcinoma is important for prognosis and predictive information for disease relapse. [ABSTRACT FROM AUTHOR]

Background and Aim: A growing number of studies have demonstrated that neoadjuvant chemotherapy can improve the prognosis of patients with resectable colorectal liver metastases (CRLM). However, the routine use of postoperative adjuvant chemotherapy (POAC) for patients with CRLM after simultaneous resection remains controversial. This retrospective study investigated the impact of POAC on outcomes in patients with CRLM who underwent simultaneous resection of colorectal cancer tumors and liver metastases using propensity score matching (PSM) analysis. Methods: From January 2009 to November 2020, patients with CRLM who underwent simultaneous resection were retrospectively enrolled. The confounding factors and selection bias were adjusted by 2:1 PSM. Patients were stratified into the POAC and non‐POAC groups. Kaplan–Meier curves were utilized to compare overall survival (OS) and progression‐free survival (PFS) between the groups. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors before and after PSM analysis. The utility of the model was evaluated using receiver operating characteristic (ROC) and calibration curves after PSM analysis. Results: In total, 478 patients with resectable CRLM were enrolled and assigned to the POAC (n = 212, 60.9%) or non‐POAC group (n = 136, 39.1%). After 2:1 PSM, there was no significant bias between the groups. Kaplan–Meier survival analysis revealed a significant effect of POAC on OS (P < 0.001) but not PFS. Multivariate Cox regression analysis identified T stage (T3–T4), lymph node metastasis, radiofrequency ablation during surgery, operative time ≥ 325 min, and the receipt of postoperative adjuvant chemotherapy (hazard ratio = 0.447, 95% confidence interval = 0.312–0.638, P < 0.001) as independent prognostic factors for OS. The areas under the ROC curves for the nomogram model for predicting 1‐, 3‐, and 5‐year survival were 0.653, 0.628, and 0.678, respectively. Subgroups analysis suggested that POAC can enhance OS in patients with resectable CRLM with either low (1–2, P < 0.001) or high clinical risk scores (3–5, P = 0.020). Conclusions: Overall, this study identified POAC as a prognostic factor to predict OS in patients with CRLM undergoing simultaneous resection. [ABSTRACT FROM AUTHOR]

Background: PET–CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care. Methods: Staging PET–CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET–CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUVmean of liver to the average SUVmean of the bilateral rectus femoris muscles. Kaplan–Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS. Results: Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET–CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56–0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009). Conclusions: Elevated LRF ratio, a patient-specific PET–CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Management of early‐stage gallbladder cancer is becoming more important as the rate of early detection is increasing. Although there have been many studies about the clinical implication of the invasion depth or peritoneal/hepatic location of gallbladder cancers, there is no study on the clinical implication of the geometric location of cancer along the longitudinal length of the gallbladder. Methods: The location of gallbladder cancer was defined as the geometric center of the primary site of a tumour, which lies on the longitudinal diameter of the surgical specimens. We compared the oncologic outcomes following surgery between gallbladder cancers located on the fundal end and those located on the cystic ductal end. We also analysed patients with stage 1 gallbladder cancer who recurred after surgery. Results: A total of 575 patients with gallbladder cancer were included in this study. Patients with gallbladder cancer on the cystic ductal end had significantly lower rates of recurrence‐free survival (P = 0.016) and overall survival (P = 0.023) compared to those with gallbladder cancer on the fundal end. Among 90 patients with stage 1 gallbladder cancer, three patients had a recurrence, all of whom had cystic ductal end gallbladder cancer and showed cystic duct invasion or concomitant xanthogranulomatous cholecystitis in permanent pathology. Conclusions: Gallbladder cancers on the cystic ductal end had worse postoperative oncologic outcomes compared with those on the fundal end. [ABSTRACT FROM AUTHOR]

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

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

• Chemotherapy response score is a valuable tool that helps determine patients at risk of earlier relapse and death. • The importance of debulking surgery remains significant even in those with minimal response to chemotherapy. • Survival differences of CRS 1-2 vs CRS 3 patients were similar to those of patients with platinum resistant vs sensitive disease. The chemotherapy response score (CRS) has been widely adopted as a predictive tool for ovarian cancer survival. In the present study, we seek to define differences in survival rates among patients grouped in the traditionally established three-tiered system and those who have not been offered debulking surgery. We designed a retrospective cohort study involving women treated with chemotherapy and offered interval or late debulking surgery for ovarian cancer. Twenty-eight women were not considered for a debulking procedure for various reasons. Of the 89 women who were finally offered interval debulking or late debulking surgery, 28 had a CRS 1 score, 34 had a CRS 2 score and 27 had a CRS 3 score. Significant differences were noted in the progression-free survival (PFS) and overall survival (OS) of patients based on the CRS stratification, although survival rates were considerably longer for all three groups compared to those of patients who were not offered surgery. Cox regression univariate analysis revealed that suboptimal debulking and CRS 1 or no surgery had a significant negative impact on PFS and OS rates. The binary stratification of CRS (CRS 1–2 vs CRS 3) revealed comparable differences in the PFS and OS to those in the groups that were stratified as platinum resistant and platinum sensitive. The chemotherapy response score is a significant determinant of ovarian cancer survival that helps evaluate the risk of early disease relapse and death and may soon be useful in guiding patient-tailored treatment. [ABSTRACT FROM AUTHOR]

• FDG-PET/CTs detects a higher rate on lymph node metastasis compared with conventional CT in ovarian cancer patients. • In the literature, CT positive lymph nodes show an inverse effect on complete resection rate, PFS and OS. • In our Cohort FDG-PET/CT positive lymph node show no correlation with intra- and perioperative outcomes or the OS. Compared to conventional computed tomography (CT), fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) detects higher rates of lymph node and distant metastases in patients with ovarian cancer. However, FDG-PET/CT is not routinely performed during preoperative work-up. Therefore, we investigated the prognostic value of preoperative FDG-PET/CT in advanced epithelial ovarian cancer (EOC) and its predictive value for surgical resection in patients with no residual disease. The potential significance of PET-positive supradiaphragmatic lymph nodes (SDLNs) for these parameters was evaluated. All patients with FIGO IIA-IVB EOC diagnosed between March 2014 and January 2021 at our certified gynaecological cancer centre, who underwent FDG PET/CT before primary surgery were retrospectively included. Fifty-three consecutive patients were included in the study. Eighteen (34 %) patients had PET-positive SDLNs. We could not demonstrate a significant correlation between PET-positive SDLNs and median overall survival (OS; SDLN-positive: 58.76 months, SDLN-negative: 60.76 months; p = 0.137) or intra- or perioperative outcomes. FDG PET/CT has a higher detection rate for SDLNs in patients with ovarian cancer than CT has, as described in the literature. Moreover, PET-positive SDLNs failed to predict intraoperative outcomes or overall survival. [ABSTRACT FROM AUTHOR]