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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]

Purpose: Thyroid dysfunction is the most common immune-related adverse event during anti-programmed cell death 1 (anti-PD-1) therapy. In this study, we monitored patients with advanced malignant tumors who received anti-PD-1 therapy to observe the characteristic of anti-PD-1 therapy-induced thyroid dysfunction and its correlation with prognosis. Methods: Patients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study. Results: Among these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1-induced thyroid dysfunction occurred 63 (26–131) days after administration; thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan–Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the no thyroid dysfunction group (227 (95% confidence interval (CI) 50.85–403.15) days vs 164 (95% CI 77.76–250.24) days, p = 0.026). Male patients had better PFS than female patients (213 (95% CI 157.74–268.26) days vs 74 (95% CI 41.23–106.77) days, p = 0.031). In cox proportional hazards regression model, anti-PD-1-induced thyroid dysfunction remained an independent predictor of better PFS (hazard ratio (HR) = 0.339(0.136–0.848), p = 0.021). Conclusion: Thyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis. Trial registration: This study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022. [ABSTRACT FROM AUTHOR]

Background: As a phosphorylated protein, NOLC1 is mainly located in the nucleus and is highly expressed in a variety of tumors, participating in the regulation of cell proliferation and aging. This study further investigated the role of NOLC1 in colorectal cancer tumors, aiming to provide sufficient scientific evidence for the clinical treatment of colorectal cancer. Methods: We used TCGA, GEO, TNMplot, GEPIA, and other databases to explore the expression level of NOLC1 in colorectal cancer patients, as well as the correlation between the clinical characteristics of colorectal cancer patients and their expression, and conducted the prognostic analysis. Immunohistofluorescence (IHF) staining verified the analytical results. Subsequently, KEGG and GO enrichment analysis was used to identify the potential molecular mechanism of NOLC1 promoting the occurrence and development of colorectal cancer. The influence of NOLC1 expression on the immune microenvironment of colorectal cancer patients was further investigated using the TIMER database. GDSC database analysis was used to screen out possible anti-colorectal cancer drugs against NOLC1. Finally, we demonstrated the effect of NOLC1 on the activity and migration of colorectal cancer cells by Edu Cell proliferation assay and Wound Healing assay in vitro. Results: Our results suggest that NOLC1 is overexpressed in colorectal cancer, and that overexpression of NOLC1 is associated with relevant clinical features. NOLC1, as an independent risk factor affecting the prognosis of colorectal cancer patients, can lead to a poor prognosis of colorectal cancer. In addition, NOLC1 may be associated with MCM10, HELLS, NOC3L, and other genes through participating in Wnt signaling pathways and jointly regulate the occurrence and development of colorectal cancer under the influence of the tumor microenvironment and many other influencing factors. Related to NOLC1: Selumetinib, Imatinib, and targeted drugs such as Lapatinib have potential value in the clinical application of colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Conclusions: High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Further studies and clinical trials are needed to confirm the role of NOLC1 in the development and progression of colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to explore which therapeutic strategy is more beneficial for elderly esophageal cancer (EC) patients with distant metastasis, the treatment utilization status and the screening of factors related to prognosis, so as to better guide the treatment of these patients. Methods: Patients in the Surveillance Epidemiology and End Results (SEER) database were divided into chemoradiotherapy (Group A), chemotherapy (Group B), radiotherapy (Group C), and no treatment (Group D) according to different treatment methods. Propensity score matching (PSM) was performed to adjust for baseline differences between the two groups. Overall survival (OS) and esophageal cancer-specific survival (ECSS) was calculated using the Kaplan–Meier method and compared using the log-rank test. Results: A total of 7027 patients were included in this study, 5739 males (81.7%) and 1288 females (18.3%) with the median age was 70 (60–98). In the original cohort, the number of patients in the four groups was 2260 (Group A), 2087 (Group B), 945 (Group C) and 1735 (Group D), respectively. After PSM, there was no significant difference in mean OS (A vs B, 13.5 months VS 13.4 months, P = 0.511) and mean ECSS (A vs B, 15.6 vs 15.5 months, P = 0.374), while both OS (B vs C, 7 vs 3 months, P < 0.001) and ECSS (B vs C, 8 vs 3 months, P < 0.001) of chemotherapy alone were significantly better than those of radiotherapy alone. Subgroup analysis of patients older than 80 years showed that the median OS (A vs B, 7 vs 6 months) and median ECSS (A vs B, 8 vs 7 months) of Group A were significantly better than those of Group B (P < 0.05). In addition, all patients were randomly divided into a training set and a validation set with a ratio of 7:3. Based on the independent risk factors for OS, a nomogram model was constructed and validated. Conclusion: For elderly EC patients with distant metastasis, aggressive treatment was still necessary after a comprehensive assessment of the patient's physical condition, especially for patients over 80 years old, and chemoradiotherapy maybe still the first choice. In addition, a nomogram model was constructed to intuitively and accurately evaluate the prognosis of this population. [ABSTRACT FROM AUTHOR]

Purpose: Our study intended to explore the correlation between HER2 alterations and 18F-FDG PET/CT metabolic parameters and their prognostic value in EGFR-negative non-small-cell lung cancer (NSCLC) patients detected by next-generation sequencing (NGS). Methods: NGS assay was performed in 1737 NSCLC patients, a total of 88 HER2 alterations and 176 negative HER2 with EGFR-negative patients were randomly selected for this study. Results: When the HER2 status with EGFR-negative group was analyzed, multivariate analysis showed that smoking status, primary tumor SUVmax (pSUVmax) < 13.03 and stage were the independent deterministic factors of HER2 alterations. Multivariate cox regression analysis revealed that HER2 status, age, smoking status and stage were independent risk factors for overall survival (OS) in EGFR-negative NSCLC patients with different HER2 status. When the HER2 alterations group was separately analyzed, multivariate analysis demonstrated that low pSUVmax < 15.32 and histology were the independent deterministic factors of HER2 mutation. Multivariate cox regression analysis revealed that pSUVmax, smoking status, nodal involvement and treatment methods were independent risk factors for OS in EGFR-negative NSCLC patients with HER2 alterations. Conclusion: The study revealed that low pSUVmax was associated with HER2 alterations in EGFR-negative NSCLC patients, moreover HER2 mutation and HER2 amplification exhibited distinct 18F-FDG metabolic and clinical characteristics. Furthermore, it explored the prognostic value of HER2 alterations and 18F-FDG PET/CT metabolic parameters of pSUVmax in EGFR-negative NSCLC patients. [ABSTRACT FROM AUTHOR]

Objective: To wholly evaluate the prognostic value of CHT for pT1-3N0-1 breast cancer patients with HR+, HER2− subtype using the Surveillance, Epidemiology, and End Results (SEER) database. Method: A total of 126,102 eligible cases diagnosed between January 2010 and December 2018 were included in the SEER database. A propensity-score matched (PSM) study with competing risk analysis was conducted. The Kaplan–Meier method was used to visualize the survival disparities between chemotherapy (CHT) and no CHT groups. The cumulative incidences of different subgroups were compared by Fine-Gray's test. Results: Before PSM, patients in the CHT group had worse OS and CSS (both P < 0.001). After PSM, we were surprised that patients in the CHT group had a better OS than those in the no CHT group (HR 0.74, 95% CI 0.68–0.80, P < 0.001), while no significant survival disparities were observed for CSS (HR 1.00, 95% CI 0.89–1.12, P = 0.952). In the competing risk analysis, the OS disparities between the CHT and no CHT groups were mainly attributed to deaths of other causes (subdistribution HR [95% CI] 0.50 [0.44–0.57]). After adjusting for other competitive risk events, there was no significant difference in cumulative death risk of breast cancer between the CHT and no CHT groups (subdistribution HR [95% CI] 1.01 [0.90–0.1.13]). Conclusion: The present study is the first, to our knowledge, to wholly evaluate the prognostic value of CHT for pT1-3N0-1 breast cancer patients with HR+, HER2− subtype using a propensity-score matched study with competing risk analysis. All pT1-3N0-1 breast cancer patients with HR+, HER2− subtype do not benefit from CHT. Genetic testing may be the only effective tool to determine the need for CHT at the present. [ABSTRACT FROM AUTHOR]

Introduction: Currently, the prognosis of resected N2 non-small cell lung cancer patients undergoing neoadjuvant radiotherapy is poor. The goal of this research was to develop and validate a novel nomogram for exactly predicting the overall survival (OS) of resected N2 NSCLC patients undergoing neoadjuvant radiotherapy. Methods: The data applied in our research were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. We divided selected data into a training cohort and a validation cohort using R software, with a ratio of 7:3. Univariate Cox regression and multivariate Cox regression were utilized to select significant variables to build the nomogram. To validate our nomogram, calibration curves, receiver operating characteristic curves (ROC), decision curve analysis (DCA), and Kaplan–Meier survival curves were employed. The nomogram model was also compared with the tumor–node–metastasis (TNM) staging system by utilizing net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: Eight variables—age, sex, operative type, LN removed number, chemotherapy, AJCC stage, M stage, histology—were statistically significant in the multivariate Cox regression analysis and were selected to develop our nomogram. Based on ROC curves, calibration curves, and DCA analysis, our novel nomogram demonstrated good predictive accuracy and clinical utility. Using Kaplan–Meier (KM) survival curves and log-rank tests, the risk stratification system was able to stratify patients based on their estimated mortality risk. The nomogram performed better than the TNM staging system based on the NRI and IDI indexes. Conclusions: We developed and validated a nomogram to predict prognosis of resected N2 NSCLC patients undergoing neoadjuvant radiotherapy. Using this nomogram, clinicians may find this nomogram useful in predicting OS of targeted patients and making more appropriate treatment decisions. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to construct two web-based nomograms to predict the probability of bone metastasis (BM) in esophageal cancer (EC) patients and the prognostic of EC patients with BM (ECBM). Methods: We collected the data of EC and ECBM patients in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015. Independent risk variables for the development of BM in EC patients were identified using univariate and multivariate logistic regression analyses. Univariate and multivariate Cox regression analyses were used to assess independent prognostic variables in ECBM patients. And then, constructed two nomograms to predict the risk of bone metastases and overall survival (OS) of ECBM patients. Survival differences were studied by Kaplan–Meier (K–M) survival analysis. The predictive efficacy and clinical applicability of these two nomograms were assessed by using receiver operating characteristic (ROC) curve, the area under curve (AUC), calibration curve and decision curve analysis (DCA). Results: We selected a total of 6839 patients with EC, of which 326 (4.77%) had BM at the time of initial diagnosis. The results of K–M survival and Cox regression analysis showed significant effects of BM on the OS in EC patients. Age, N stage, tumor size and brain/liver/lung organ metastasis were identified as BM-related risk variables. Chemotherapy and brain/liver organ metastasis were identified as ECBM-related prognostic variables. The ROC, AUC, calibration curves and DCA of two nomograms all showed excellent predictive efficacy and clinical applicability. Conclusions: These two nomograms were constructed and validated, which could objectively predict the risk of BM in EC patients and the prognostic in ECBM patients. These tools are expected to make valuable contributions in clinical work, informing surgeons in making decisions about patient care. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to construct a novel clinical risk stratification for overall survival (OS) prediction in adolescent and young adult (AYA) women with breast cancer. Method: From the Surveillance, Epidemiology, and End Results (SEER) database, AYA women with primary breast cancer diagnosed from 2010 to 2018 were included in our study. A deep learning algorithm, referred to as DeepSurv, was used to construct a prognostic predictive model based on 19 variables, including demographic and clinical information. Harrell's C-index, the receiver operating characteristic (ROC) curve, and calibration plots were adopted to comprehensively assess the predictive performance of the prognostic predictive model. Then, a novel clinical risk stratification was constructed based on the total risk score derived from the prognostic predictive model. The Kaplan–Meier method was used to plot survival curves for patients with different death risks, using the log-rank test to compared the survival disparities. Decision curve analyses (DCAs) were adopted to evaluate the clinical utility of the prognostic predictive model. Results: Among 14,243 AYA women with breast cancer finally included in this study, 10,213 (71.7%) were White and the median (interquartile range, IQR) age was 36 (32–38) years. The prognostic predictive model based on DeepSurv presented high C-indices in both the training cohort [0.831 (95% CI 0.819–0.843)] and the test cohort [0.791 (95% CI 0.764–0.818)]. Similar results were observed in ROC curves. The excellent agreement between the predicted and actual OS at 3 and 5 years were both achieved in the calibration plots. The obvious survival disparities were observed according to the clinical risk stratification based on the total risk score derived from the prognostic predictive model. DCAs also showed that the risk stratification possessed a significant positive net benefit in the practical ranges of threshold probabilities. Lastly, a user-friendly Web-based calculator was generated to visualize the prognostic predictive model. Conclusion: A prognostic predictive model with sufficient prediction accuracy was construct for predicting OS of AYA women with breast cancer. Given its public accessibility and easy-to-use operation, the clinical risk stratification based on the total risk score derived from the prognostic predictive model may help clinicians to make better-individualized management. [ABSTRACT FROM AUTHOR]

Purpose: Postmastectomy radiotherapy (PMRT) in patients with T1–2N1 breast cancer is still controversial. This study was to evaluate the survival prognosis of T1-2N1 patients with or without PMRT. Patients and methods: From January 2006 to May 2017, 2606 female breast cancer patients underwent mastectomy in our medical center, among whom 402 patients of T1-2N1 stage with or without PMRT were finally analyzed. The median follow-up duration was 59.5 months. The primary endpoint was overall survival (OS). The secondary endpoint was disease-free survival (DFS). Results: In the study of our center, no statistically significant difference was observed between the T1-2N1 PMRT and non-PMRT subgroups for the 5-year OS (94.4% vs 95.4%, p = 0.667) and DFS (90.1% vs. 91.1%, p = 0.798). By the date of the last follow-up, 8.96% (n = 36) of the patients experienced any recurrence. Univariate analysis revealed that PMRT was not a prognostic factor for either OS (p = 0.667) or DFS (p = 0.798) in T1-2N1 patients. We then did a meta-analysis on the current treatment patterns, in which 2606 PMRT and 4281 non-PMRT T1-2N1 breast cancer patients with mastectomy were included. The meta-analysis showed that PMRT didn't improve the OS of the patients (HR = 0.85, p = 0.11), but patients with PMRT had better DFS than those in the non-PMRT group (HR = 0.62, p < 0.001). Conclusion: PMRT did not affect the survival of T1-2N1 breast cancer patients who underwent mastectomy, suggesting that radiotherapy may be safely omitted for them. [ABSTRACT FROM AUTHOR]

Purpose: To predict the risk of radiation pneumonitis (RP), a multiomics model was built to stratify lung cancer patients. Our study also investigated the impact of RP on survival. Methods: This study retrospectively collected 100 RP and 99 matched non-RP lung cancer patients treated with radiotherapy from two independent centres. They were divided into training (n = 175) and validation cohorts (n = 24). The radiomics, dosiomics and clinical features were extracted from planning CT and electronic medical records and were analysed by LASSO Cox regression. A multiomics prediction model was developed by the optimal algorithm. Overall survival (OS) between the RP, non-RP, mild RP, and severe RP groups was analysed by the Kaplan‒Meier method. Results: Sixteen radiomics features, two dosiomics features, and one clinical feature were selected to build the best multiomics model. The optimal performance for predicting RP was the area under the receiver operating characteristic curve (AUC) of the testing set (0.94) and validation set (0.92). The RP patients were divided into mild (≤ 2 grade) and severe (> 2 grade) RP groups. The median OS was 31 months for the non-RP group compared with 49 months for the RP group (HR = 0.53, p = 0.0022). Among the RP subgroup, the median OS was 57 months for the mild RP group and 25 months for the severe RP group (HR = 3.72, p < 0.0001). Conclusions: The multiomics model contributed to improving the accuracy of RP prediction. Compared with the non-RP patients, the RP patients displayed longer OS, especially the mild RP patients. [ABSTRACT FROM AUTHOR]

PARP inhibitors in ovarian cancer have been a breakthrough therapy of the past decade, driven by positive trial results, and supported by an original pharmacological rationale. However, with mature data, detrimental survival results led to the withdrawals, in 2022, of all approved PARP inhibitors in the most advanced settings' indication (as monotherapy in third or subsequent lines) by the US Food and Drug Administration (FDA). Two other indications, as maintenance after relapse, were also restricted. In this work, based on pooled meta-analysis in each setting, we question a unique situation in oncology: a survival benefit is seen in front-line settings, with, at the same time, a survival decrement in later lines. Either this original feature is explained by the unique biological action of PARP inhibitors—through synthetic lethality—in patients with ovarian cancer and homologous repair deficiency. Another explanation may be trial design: decrement in later lines could partly explain why beneficial results were seen in early settings, simply by avoiding late exposure to PARP inhibitors in the experimental arm in those trials. High crossover rates seen in some trials further support this alternate hypothesis. We contend our analysis and recent survival results of PARP inhibitors warrant a whole reassessment of the place of these compounds in the landscape of ovarian cancer treatments. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, several new targeted therapies have emerged for advanced breast cancer (aBC). However, real-life data specific to aBC and different breast cancer subtypes are scarce. This retrospective cohort study was designed to describe the distribution of aBC subtypes, incidence, treatment patterns, survival, and PIK3CA hotspot mutation frequency. Methods: The study included all patients in the Hospital District of Southwest Finland diagnosed with aBC between 2004 and 2013 and with a sample available in Auria Biobank. In addition to registry-based data collection, 161 HR+/HER2− aBCs were screened for PIK3CA mutations. Results: Altogether, 54.7% of the 444 patients included in the study had luminal B subtype. The smallest representations were in HR−/HER2+ (4.5%) and triple-negative (5.6%) subgroups. The percentage of aBC among all diagnosed breast cancers increased until 2010, after which it remained stable. The triple-negative cancers were associated with shorter median overall survival (5.5 months) compared to other subgroups (16.5–24.6 months). Most (84%) triple-negative cancers also metastasized during the first two years, whereas this was more evenly distributed over time in other subgroups. Of the HR+/HER2− tumors, 32.3% harbored a PIK3CA hotspot mutation. These patients, however, did not have inferior survival compared to patients with PIK3CA wild-type cancers. Conclusion: This study described real-world aBC subgroups and indicated that the clinical outcomes of subgroups vary. Although PIK3CA hotspot mutations did not lead to inferior survival, they are relevant as possible treatment targets. Overall, these data could be utilized to further evaluate the subgroup-specific medical needs in breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Tumor location and tumor node metastasis (TNM) stage guide treatment decisions in colorectal cancer (CRC) patients. However, patients with the same disease stage do not benefit equally from adjuvant therapy. Hence, there remains an urgent clinical need to identify prognostic and/or predictive biomarker(s) to personalize treatment decisions. In this exploratory study, we investigated whether our previously defined metabolic Warburg-subtypes can predict which CRC patients might derive survival benefit from adjuvant therapy. Methods: Information regarding treatment (surgery only: n = 1451; adjuvant radiotherapy: n = 82; or adjuvant chemotherapy: n = 260) and Warburg-subtype (Warburg-low: n = 485, -moderate: n = 641, or –high: n = 667) was available for 1793 CRC patients from the Netherlands Cohort Study (NLCS). Kaplan–Meier curves and Cox regression models were used to investigate survival benefit from adjuvant therapy compared to surgery-only for the different Warburg-subtypes. Results: Patients with Warburg-moderate CRC (HRCRC-specific 0.64; 95% CI 0.47–0.86, HRoverall 0.61; 95% CI 0.47–0.80), and possibly Warburg-high CRC (HRCRC-specific 0.86; 95% CI 0.65–1.14, HRoverall 0.82; 95% CI 0.64–1.05), had survival benefit from adjuvant therapy. No survival benefit was observed for patients with Warburg-low CRC (HRCRC-specific 1.07; 95% CI 0.76–1.52, HRoverall 0.95; 95% CI 0.70–1.30). There was a significant interaction between Warburg-subtype and adjuvant therapy for CRC-specific survival (p = 0.049) and overall survival (p = 0.035). Conclusion: Our results suggest that Warburg-subtypes may predict survival benefit from adjuvant therapy in CRC patients. A survival benefit from adjuvant therapy was observed for patients with Warburg-moderate and possibly Warburg-high CRC, but not for patients with Warburg-low CRC. Future prospective studies are necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Purpose: We analyzed clinical features and the representative HE-stained pathologic images to predict 5-year overall survival via the deep-learning approach in cervical cancer patients in order to assist oncologists in designing the optimal treatment strategies. Methods: The research retrospectively collected 238 non-surgical cervical cancer patients treated with radiochemotherapy from 2014 to 2017. These patients were randomly divided into the training set (n = 165) and test set (n = 73). Then, we extract deep features after segmenting the HE-stained image into patches of size 224 × 224. A Lasso–Cox model was constructed with clinical data to predict 5-year OS. C-index evaluated this model performance with 95% CI, calibration curve, and ROC. Results: Based on multivariate analysis, 2 of 11 clinical characteristics (C-index 0.68) and 2 of 2048 pathomic features (C-index 0.74) and clinical–pathomic model (C-index 0.83) of nomograms predict 5-year survival in the training set, respectively. In test set, compared with the pathomic and clinical characteristics used alone, the clinical–pathomic model had an AUC of 0.750 (95% CI 0.540–0.959), the clinical predictor model had an AUC of 0.729 (95% CI 0.551–0.909), and the pathomic model AUC was 0.703 (95% CI 0.487–0.919). Based on appropriate nomogram scores, we divided patients into high-risk and low-risk groups, and Kaplan–Meier survival probability curves for both groups showed statistical differences. Conclusion: We built a clinical–pathomic model to predict 5-year OS in non-surgical cervical cancer patients, which may be a promising method to improve the precision of personalized therapy. [ABSTRACT FROM AUTHOR]

Background: Small bowel adenocarcinoma (SBA) remains a rare malignancy accounting for less than 5% of all the gastrointestinal tract cancers. However, only limited data and expert guidelines are available for this entity. As a result, treatment concepts are predominantly derived from colorectal cancer. Methods: To substantiate data on the course of disease, diagnosis and treatment of SBA, we performed a population-based analysis from a Bavarian population of 2.2 million people. Results: We identified 223 patients with SBA. Mean age at diagnosis was 67.8 years and patients were diagnosed rather late (34.5% UICC stage IV). Largest proportion of these patients were diagnosed with adenocarcinoma of the duodenum (132 patients, 59.2%) and most patients were diagnosed with late stage cancer, stage IV (70 patients, 31.4%). With respect to treatment, most patients underwent primary surgery (187 patients, 84.6%). Systemic therapy seemed to have an impact in UICC stage IV patients but not in UICC stage IIB or III. The 5-year survival rate was 29.0%. This was significantly less compared to colon cancer in the same cohort, which was 50.0%. Furthermore, median survival of patients with small bowel cancer was only 2.0 years (95% CI 1.4–2.5) compared to 4.9 years (95% CI 4.8–5.1) of patients with colon cancer. Conclusion: SBA showed a distinct epidemiology compared to colon cancer. Thus, data acquisition particularly on systemic treatment are paramount, with the objective to complement the available guidelines. [ABSTRACT FROM AUTHOR]

Purpose: Data from randomized controlled trials in high-grade endometrial cancer are scarce due to its low prevalence. Therefore, guideline recommendations in this cancer subtype rely on relatively few randomized trials and data from retrospective studies. The aim of this study was to evaluate the benefits from guideline-concordant therapy in high-grade endometrial cancer in a real-world patient group. Methods: The effect of treatment according to German S3 guidelines and the former S2k guideline on overall survival (OS) and recurrence-free survival (RFS) was evaluated in a cohort of 293 high-grade endometrial cancer patients. Results: Treatment concordant with the S3 guideline significantly improved OS (HR 0.623, CI 0.420–0.923, p = 0.018) and RFS (HR 0.578, CI 0.387–0.863, p = 0.007). Treatment concordant with the S2k guideline did not result in a significantly higher OS (HR 0.783, CI 0.465–1.316, p = 0.335) or RFS (HR 0.741, CI 0.347–1.740, p = 0.242). Conclusion: Therapy according to the German S3 guideline improved OS and RFS in univariate as well as multivariate analysis in this cohort of high-grade endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: As one of the most effective analgesics, opioids are essential for patients with cancer-related pain, even in the context of the opioid abuse crisis. The current meta-analysis aimed to identify whether concomitant exposure to opioids can affect the efficacy of ICIs and lead to a worse prognosis. Methods: PubMed, Embase, and the Cochrane Library were searched based on the PRISMA checklist, through April 2022, for the following terms: ("opioids" OR "concomitant medication") AND ("Neoplasm" OR "Carcinoma" OR "Cancer" OR "Tumor") AND ("Immunotherapy" OR "Immune Checkpoint Inhibitor" OR "PD-L1 Inhibitor" OR "PD-1 Inhibitor" OR "CTLA-4 Inhibitor"). The outcomes considered were overall survival (OS) and progression-free survival (PFS) calculated using the random-effects or fixed-effects model. Results: After screening 531 studies, a total of 7 articles involving 2690 patients were eligible for quantitative analysis. The use of opioids was negatively correlated with OS (HR 1.75, 95%CI 1.32–2.31, P < 0.001; I2 = 81%, P < 0.001) and significantly reduced the PFS (HR 1.61, 95%CI 1.41–1.83, P < 0.001; I2 = 0%, P = 0.63) of patients treated with ICIs. Similar results were obtained in each subgroup analysis. While NSAIDs could lead to poor OS (HR 1.25, 95% CI 1.03–1.51, P = 0.02; I2 = 0%, P = 0.60) but not PFS (HR 1.11, 95% CI = 0.89–1.39, P = 0.36) for ICIs patients. And sensitivity analyses confirmed the reliability of the results. Conclusion: Opioids significantly reduced OS and PFS in patients receiving ICI therapy. Thus, the use of different types of opioids should be considered with caution, and it is necessary to actively develop alternative treatments. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate the safety and efficacy of immune checkpoint inhibitors in small cell lung cancer patients with brain metastases. Methods: We retrospectively reviewed the records of small cell lung cancer patients with brain metastases treated with chemotherapy and radiotherapy for brain metastases with or without immune checkpoint inhibitors at our institution from January 2019 to January 2021. Patients were divided into two groups. In Group A, patients received chemotherapy and radiotherapy for brain metastases. In Group B, patients received chemotherapy, radiotherapy for brain metastases and at least four cycles of immunotherapy. Overall survival and intracranial progression-free survival were assessed using Kaplan–Meier estimates and Cox regression models. Results: A total of 282 patients were enrolled in our study. At the end of the study (May 12, 2021), the median overall survival was 13.3 months among 218 patients in Group A and 33.4 months among 64 patients in Group B (hazards ratio [HR] 0.320, 95% confidence interval [CI], 0.189–0.545, P < 0.001). Both univariate and multivariate analyses suggested that two factors were significantly correlated with overall survival: the inclusion of immunotherapy in the regimen and the presence of extracranial metastases. The median intracranial progression-free survival was 6.93 months in Group A and 10.73 months in Group B (HR = 0.540, 95% CI, 0.346–0.841, P = 0.006). The intracranial objective response rate of Group B was greater than that of Group A, but the intracranial disease control rate was similar between the groups. Conclusion: Immunotherapy plus chemotherapy and radiotherapy for brain metastases showed promising efficacy for small cell lung cancer patients with brain metastases. [ABSTRACT FROM AUTHOR]

Objective: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC). Methods: A total of 1133 patients with GC (812 male and 321 female, average age: 59.43 years) were evaluated. Receiver-operating characteristic curves were used to determine the best cutoff values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. Results: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.07; 95% CI 0.97–1.19; adjusted P = 0.179). In patients with SII > 1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI 0.29–1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score was, the worse the OS (P < 0.001). Conclusion: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC. [ABSTRACT FROM AUTHOR]

Background: To date, information on risk factors and temporal patterns of recurrences in patients with vulvar cancer is sparse. Conclusive data for an optimal surveillance strategy are lacking. Methods: This multicenter, retrospective population-based register study included 1412 patients who have been treated from 2000 to 2017 for vulvar cancer in the German districts of Upper Palatinate, Lower Bavaria, and Saxony-Anhalt. Kaplan–Meier method, and univariate and multivariate Cox regression were employed to evaluate prognostic factors and temporal course of overall survival, cumulative recurrence, and recurrence-free survival rates. Results: After exclusion, the final study cohort comprised 829 patients. Most recurrences occurred within the first 3 years after diagnosis. Notably, a significant subset of patients were recurrent even after 5 years. The cumulative recurrence rate from all relapses was 18.6% 1 year after primary diagnosis. The recurrence rate increased to 34.7% after 3, to 41.8% after 5, and to 56.6% after 10 years post-diagnosis. The risk of relapse was significantly increased in patients over 70 years of age (hazard ratio (HR) = 2.7; p < 0.001; 95% CI 1.6–4.4), and in patients with positive nodal status N1 (HR = 2.0; p = 0.019; 95% CI 1.1–3.5) and N2/3 (HR = 2.2; p = 0.033; 95% CI 1.1–4.4). Conclusion: Our study provides compelling evidence that follow-up care should be carried out for longer than 5 years, especially for high-risk patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival. Methods: Preoperative frailty status was assessed by the G8 geriatric screening tool (G8 Score), Lee Schonberg prognostic index, Charlson Comorbidity index and American Society of Anesthesiologists Physical Status System in women older than 60 years with EC. Univariable and multivariable Cox-regression analyses, as well as Kaplan–Meier survival analyses were performed to determine the prognostic impact. Statistical analyses were adjusted for cancer entity-specific risk factors such as conventional histopathological tumor characteristics and relevant anamnestic life style parameters. Results: 153 patients with all stages of EC who were operated at the University Medical Center Mainz between 2008 and 2019 were included. In multivariable analyses, only the G8 Score retained independent significance as a prognostic factor for disease-specific survival (DSS) (HR:4.58; 95% CI [1.35–15.51]) and overall survival (OS) (HR:2.89; 95% CI [1.31–6.39]. 92 patients (61.3%) were classified as G8-non-frail with a significantly increased DSS and OS rate compared to the 58 G8-frail patients (DSS:93.8% vs. 60.8%; p < 0.001 and OS:88.2% vs. 49.7%; p < 0.001; respectively). Conclusions: This is the first study demonstrates the substantial clinical and prognostic impact of the G8 Score on survival in elderly women with EC. Assessing the frailty status to estimate the individual vulnerability of elderly cancer patients could be useful in preoperative decision-making to individualize treatment plans such as the surgical radicality and to improve pre- and postoperative morbidity. [ABSTRACT FROM AUTHOR]

Introduction: The role of CD147 as an important indicator of tumor prognosis remains controversially discussed in literature. We focused on the prognostic significance of CD147 expression in esophageal cancer patients. While some studies report that CD147 is an unfavorable prognostic factor in esophageal squamous cell carcinoma, others showed no significant correlation. However, only one study draws attention to the significance of CD147 in esophageal adenocarcinoma, which is one of the most rapidly increasing neoplasms in the western world. Methods: To finally clarify the impact of CD147 as a prognostic factor, especially for esophageal adenocarcinomas, we analyzed CD147 expression in a tissue microarray of 359 esophageal adenocarcinomas and 254 esophageal squamous cell cancer specimens. For the immuno-histochemical analysis, we used a primary antibody specific for CD147. Staining intensity and proportion of positive tumor cells were scored (negative, weak, moderate, strong staining). These findings were compared to normal esophageal tissue and correlated to the histopathological tumor phenotype and survival data. Results: CD147 expression was detectable in weak intensities in benign esophageal tissue (85.78%) and expressed in predominately moderate to strong intensities in esophageal cancer (88.34%). Strong CD147 immunostaining was linked to increased infiltration depth (p = 0.015) and differentiation (p = 0.016) in esophageal squamous cell cancer but revealed no significant correlation with histopathology of adenocarcinoma. Moreover, CD147 intensity was unrelated to overall survival in this collective for both subtypes of esophageal cancer. Conclusion: Thus, our data show that CD147 has no prognostic value, neither in esophageal adenocarcinoma nor squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess whether the whole body metabolic active tumour volume (MTVWB), quantified on staging [18F]FDG PET/CT, could further stratify stage IV non-small cell lung cancer (NSCLC) patients. Methods: A group of 160 stage IV NSCLC patients, submitted to staging [18F]FDG PET/CT between July 2010 and May 2020, were retrospectively evaluated. MTVWB was quantified. Univariate and multivariate Cox regressions were carried out to assess correlation with overall survival (OS). C-statistic was used to test predictive power. Kaplan–Meier survival curves with Log-Rank tests were performed to compute statistical differences between strata from dichotomized variables and to calculate the estimated mean survival times (EMST). Survival rates at 1 and 5 years were calculated. Results: MTVWB was a statistically significant predictor of OS on univariate (p < 0.0001) and multivariate analyses (p < 0.0001). The multivariate model with MTVWB (Cindex ± SE = 0.657 ± 0.024) worked significantly better as an OS predictor than the cTNM model (Cindex ± SE = 0.544 ± 0.028) (p = 0.003). An EMST of 29.207 ± 3.627(95% CI 22.099–36.316) months and an EMST of 10.904 ± 1.171(95% CI 8.609–13.199) months (Log-Rank p < 0.0001) were determined for patients with MTVWB < 104.3 and MTVWB ≥ 104.3, respectively. In subsamples of stage IVA (cut-off point = 114.5) and IVB patients (cut-off point = 191.1), statistically significant differences between EMST were also reported, with p-values of 0.0001 and 0.0002, respectively. In both substages and in the entire cohort, patients with MTVWB ≥ cut-off points had lower EMST and survival rates. Conclusion: Baseline MTVWB, measured on staging [18F]FDG PET/CT, further stratifies stage IV NSCLC patients. This parameter is an independent predictor of OS and provides valuable prognostic information over the 8th edition of cTNM staging. [ABSTRACT FROM AUTHOR]

Purpose: This phase I clinical trial is designed to assess the safety and feasibility of the epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR) T-cell generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer (NSCLC) patients. Compared to viral systems, the piggyBac transposon system is a simpler, more economical, and alternative way to introduce chimeric antigen receptor (CAR) transgenes into T cells. Methods: This study recruited nine patients with advanced relapsed/refractory EGFR-positive NSCLC for two cycles of the piggyBac-generated EGFR-CAR T cells at dose of 1 × 106 cells/kg or 3 × 106 cells/kg of body weight. The patients were monitored for adverse events, clinical response, and persistence of plasma GFR-CAR T cells. Results: Infusions of piggyBac-generated EGFR-CAR T cells were well tolerated in all nine patients. The most common adverse events were grade 1 to 3 fever and there were no patients who experienced grade 4 adverse events or serious cytokine release syndrome. After treatment, eight of nine patients showed detectable EGFR-CAR T cells in their peripheral blood. One patient showed a partial response and lasted for more than 13 months, while six had stable disease, and two had progressed disease. The progression-free survival of these nine patients was 7.13 months (95% CI 2.71–17.10 months), while the median overall survival was 15.63 months (95% CI 8.82–22.03 months). Conclusion: This Phase I clinical trial revealed that the non-viral piggyBac transposon system-engineered EGFR-CAR T-cell therapy is feasible and safe in treatment of EGFR-positive advanced relapsed/refractory NSCLC patients. Future study will assess it in more patients or even possibly with a higher dose. Trial registration number NCT03182816. [ABSTRACT FROM AUTHOR]