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Objective: Radiological prediction of Ki-67 plays a crucial role in determining the clinical outcomes of meningioma patients. The aim of this review is to comprehensively review the literature to synthesize evidence on how accurate radiological prediction of the Ki-67 proliferation index is to determine the Ki-67 index's association with clinical outcomes of meningioma. Materials and methods: A narrative synthesis systematic review followed PRISMA guidelines. The literature was searched using database-specific, relevant keywords, text words, and MeSH terms (controlled vocabulary) such as "Meningioma," "ki-67," "Ki 67 proliferation index," "proliferation index," "Radiomics," and "clinical outcomes" on electronic databases PubMed, Web of Science, and Google Scholar from 2014 to April 2024. Results: Out of 218 publications identified initially, only 03 moderate-quality studies were included in this paper after methodological quality assessment using the Newcastle–Ottawa scale. Discussion: The evidence synthesis by systematic review emphasizes the importance of radiographic approaches in predicting the Ki-67 proliferation index and their consequences for prognosis and treatment results in meningioma patients. Various radiological techniques, such as pre-operative MRI with clinical and radiomic analysis and machine learning algorithms, show promise for accurately predicting Ki-67 status, with significant associations between radiological features and clinical outcomes such as recurrence, survival, and progression-free survival. The radiomics models were compared and found that Lasso with LDA radiomic models outperformed other radiomics models in terms of accuracy, sensitivity, specificity, and predictive power. Lasso with LDA model also showed significant improvements in performance when the clinical datasets of meningiomas patients were combined to predict ki-67 levels. However, the comparison to histological evaluation emphasizes the necessity for additional validation and standardization. While these approaches provide non-invasive and possibly time-saving alternatives, drawbacks such as inherent biases, methodological limits, and practical challenges with automated selection procedures highlight future research and development topics. [ABSTRACT FROM AUTHOR]

Background: It is controversial whether there is a survival difference between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for esophageal cancer (EC). Therefore, this study aimed to compare the differences in survival and safety between two surgical approaches in patients with node-negative esophageal squamous cell carcinoma (ESCC). Methods: This ambispective cohort study included 1104 patients with node-negative ESCC who received OE or TE treatment at a Grate-A tertiary hospital in Henan Province between January 2015 and December 2016. The primary endpoint was 5-year overall survival (OS) and disease-free survival (DFS), and the secondary endpoint was surgical safety. Multivariable Cox regression analysis was used to analyze the effect of surgical approaches on OS and DFS, and propensity score matching (PSM) was performed to match confounding factors between two groups. Results: Patients were followed up ranged from 1.03 to 91.60 months, with a median follow-up time of 67.37 months. Kaplan–Meier survival analysis showed statistically significant differences between OE and TE in OS (70.05% vs 83.73%, P < 0.001) and DFS (67.15% vs 77.76%, P < 0.001). Furthermore, multivariate Cox regression analysis also demonstrated significant differences in long-term survival between the two groups (OS, HR (95% CI): 0.54 (0.41, 0.70); DFS, HR (95% CI): 0.68 (0.54, 0.86)). TE was associated with a reduction in intraoperative bleeding (median: 100 ml vs. 200 ml, P < 0.001), and an increase in the number of lymph nodes dissection (median: 23 vs. 28, P < 0.001). Similar results were found after PSM. Conclusion: In a selected cohort of patients with node-negative ESCC, TE surgical treatment was safer and had better long-term survival outcomes compared to OE. This provided corresponding clinical guidance to enhance survival benefits for patients. In the future, we hope to further explore the reasons for TE achieving higher survival rates. [ABSTRACT FROM AUTHOR]

Purpose: In Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE of gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) a question remains open about the potential benefits of personalised dosimetry. This observational prospective study examines the association of individualized dosimetry with progression free survival (PFS) in G1-G2 GEP NETs patients following the standard [177Lu]Lu-DOTATATE therapeutic regimen. Methods: The analysis was conducted on 42 patients administered 4 times, and on 165 lesions. Dosimetry was performed after the first and the forth cycle, with two SPECT/CT scans at day 1 and 7 after administration. Global mean Tumour absorbed Dose of each patient (GTD) was calculated after cycle 1 and 4 as the sum of lesion doses weighted by lesion mass, normalized by the global tumour mass. Cumulative GTD_TOT was calculated as the mean between cycle 1 (GTD_1) and 4 (GTD_4) multiplied by 4. Patients were followed-up for median 32.8 (range 18–45.5) months, through blood tests and contrast enhanced CT (ceCT). This study assessed the correlation between global tumour dose (GTD) and PFS longer or shorter than 24 months. After a ROC analysis, we stratified patients according to the best cut-off value for two additional statistical analyses. At last a multivariate analysis was carried out for PFS > / < 24 months. Results: The median follow-up interval was 33 months, ranging from 18 to 45.5 months. The median PFS was 42 months. The progression free survival rate at 20 months was 90.5%. GTD_1 and GTD_TOT were statistically associated with PFS > / < 24 m (p = 0.026 and p = 0.03 respectively). The stratification of patients on GTD_1 lower or higher than the best cut-off value at 10.6 Gy provided significantly different median PFS of 21 months versus non reached, i.e. longer than 45.5 months (p = 0.004), with a hazard ratio of 8.6, (95% C.I.: [2 – 37]). Using GTD_TOT with the best cut-off at 43 Gy, the same PFS values were obtained as after cycle 1 (p = 0.035). At multivariate analysis, a decrease in GTD_1 and, with lower impact, a higher global tumour volume were significantly associated with PFS < 24 months. We calculated the Tumour Control Probability of obtaining PFS > 24 months as a function of GTD_1. Discussion: Several statistical analyses seem to confirm that simple tumour dosimetry with 2 SPECT/CT scans after the first administration allows to predict PFS values after 4 × 7.4 GBq administrations of 177Lu[Lu]-DOTATATE in G1-G2 GEP NETs. This result qualitatively confirms recent findings by a Belgian and a French study. However, dosimetric thresholds are different. This probably comes from different cohort baseline characteristics, since the median PFS in our study (42 m) was longer than in the other studies (28 m and 31 m). Conclusion: Tumour dosimetry after the first administration of [177Lu]Lu-DOTATATE offers an important prognostic value in the clinical decision-making process, especially for the future as alternative emitters or administration schedule may become available. [ABSTRACT FROM AUTHOR]

Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2–81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13–1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34–1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27–1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27–2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56–2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57–2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. Clinical trial registration: NCT02358031. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancer (BTC) comprises a heterogeneous group of malignancies with poor prognosis because of the limited treatment options. With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests have been widely introduced into daily clinical practice. Patients and methods: We performed a retrospective, multicenter, observation cohort study. The genomic and clinical data of 85 BTC patients, who underwent CGP testing from August 2021 to September 2023, were analyzed. Results: There were 62 (73%) cases in which treatment recommendations were raised during expert meetings, including 34 intrahepatic cholangiocarcinoma (ICC), 20 extrahepatic cholangiocarcinoma (ECC) and 8 gall bladder carcinoma (GBC). The drug accessibility rate of the BTC patients was 15.3% (13 cases): ten ICCs, two ECCs, and one GBC. Five ICC patients (three male and two female) with the FGFR2 fusion gene were treated with pemigatinib. Those patients who received a genomically matched therapy had significantly longer median overall survival than those patients who not received. (n = 13; not reached [95% CI not reached-not reached] vs n = 72; 8.6 months [95% CI 6.6–10.0]; hazard ratio 0.24 [95% CI 0.12–0.49], p = 0.013). The median observation period of pemigatinib treatment was 15.4 months (range 10.1–27.4). The responses were classified as PR in three patients, SD in one patient and PD in one patient. The median progression free survival is 9.0 months. No patient had grade 3/4 AEs requiring discontinuation of the treatment. Conclusion: The drug accessibility rate of ICC is high and pemigatinib is effective and well-tolerated in ICC patients harboring FGFR2 gene fusions. [ABSTRACT FROM AUTHOR]

Background: FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. Methods: We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. Results: Out of 104 patients who met the criteria, the median age was 58 years (range, 16–72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4–12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6–15.0) and 27.9 months (95% CI 21.6–34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. Conclusion: In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials. [ABSTRACT FROM AUTHOR]

Marginal mandibulectomy is indicated for oral cavity squamous cell carcinomas that involve floor of mouth, abut or minimally erode the mandible without gross invasion. Successful outcomes after Marginal mandibulectomy is predicated on accurate patient selection and appropriate adjuvant treatment based on specific host and tumor characteristics. To study the onclogical outcomes in terms of loco-regional recurrence free survival and disease specific survival of marginal mandibulectomy done for oral squamous cell carcinomas. Study Design—Retrospective study. Setting—The study was done from January 2018 to January 2021 at our tertiary care centre Madras Medical College, Chennai. Subjects—30 cases were included in our study who underwent Marginal Mandibulectomy for oral cavity SCC. Methods—The decision to perform a marginal mandibulectomy was taken based on preoperative clinical examination, contrast enhanced computed tomography (CECT) findings and intra-operative assessment under anesthesia. Disease-free survival, cause-specific survival, and local control rates were plotted using the Kaplan-Meier method. Oncologic outcomes in terms of Overall survival and Disease-specific survival at the end of 1 year and 3 years for the gingival, buccal, tongue, floor of mouth cancers were analyzed. Independent impacts including the site of tumor, T and N stage, microscopic bony invasion, grade of differentiation, adjuvant radiotherapy on the loco-regional control and cause-specific survival were evaluated using Kaplan meier method. Our study group was comprised of 20(66.67%) males and 10 (33.33%) females of mean age 54 years. None of them had prior radiotherapy to the head and neck region. A total of 7 (23.33%) marginal mandibulectomies were carried out for SCC in the gingival region, 11(36.67%) for buccal mucosa, 8(26.67%) for tongue, 2(6.67%) for floor of mouth SCC, 1(3.33%) involving lip, 1(3.33%) in Retromolar trigone. Clinically 2 (6.67%) patients had T1 cancer, 18 (54.54%) had T2, 6 (18.18%) had T3, 4(13.33%) had T4 tumor. Clinically Neck nodes were not palpable in 17 (56.67%) patients, 10 (33.33%) had N1 disease and 3 (10%) had N2 disease. T and N stage distributions for tongue/floor of mouth and gingival buccal complex cancers are summarized in the table and there were no statistically significant differences between the 2 groups. 19 (63.33%) had selective neck dissection (levels I–III), and 11 (36.67%) had comprehensive neck dissection. Well-differentiated tumors were encountered in 12 (40%) cases, moderately differentiated tumors in 16 (53.33%) cases, and poorly differentiated tumors in 2 (6.67%) cases. Bone was microscopically involved in 4 (13.33%) cases and mucosal margin of excision was less than 5 mm from the tumor in 2 (6.67%) cases. Cumulative hazard of local recurrence was not significantly affected by mandibular involvement. On histopathologic examination, positive nodes were seen in 6(20%) cases that included 3 (10%) with pN1 and the rest with pN2 disease. Adjuvant radiotherapy (56 to 64 Gy) was given to 13 (43.33%) patients. In carefully selected patients, marginal mandibulectomy in oral squamous cancer achieves good oncological outcome in terms of locoregional control and overall survival rates. [ABSTRACT FROM AUTHOR]

Background: Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC. Methods: This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted. Results: A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5–13.1) and 5.4 (95% CI: 3.8–7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016). Conclusion: Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. Methods and Materials: Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45–50.4 Gy/25–28 Fx, 5 fractions weekly), followed by brachytherapy (24–30 Gy/3–5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS). Results: All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%. Conclusions: Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer. [ABSTRACT FROM AUTHOR]

Background and Objective: Durvalumab plus tremelimumab (Durva/Treme) has recently been approved as a first-line or later-line treatment for patients with unresectable hepatocellular carcinoma (u-HCC) in Japan. We assessed the real-world outcomes of Durva/Treme for u-HCC, with a focus on treatment efficacy and safety. Methods: We retrospectively evaluated 22 patients with u-HCC treated with Durva/Treme at Iwate Medical University during the period from 2023 to 2024, with a comparison of the clinical outcomes between patients who received Durva/Treme as first-line and later-line treatments. We further evaluated changes in the modified albumin-bilirubin (mALBI) grade during treatment. Results: There were 10 patients in the first-line group and 12 patients in the later-line treatment group. During the follow-up with a median duration of 7.6 months, the median progression-free survival (first-line versus later-line: 4.7 months versus 2.9 months, p = 0.85), the objective response rate (0.0% versus 16.7%, p = 0.48), the disease control rate (60.0% versus 58.4%, p = 1.00), and the incidence of any adverse event (50.0% versus 75.0%, p = 0.38) were not statistically different between the two groups. The changes in the mALBI scores were not statistically significant (p = 0.75). Conclusions: Durva/Treme may be effective and safe for patients with u-HCC, even in patients who receive Durva/Treme as a later-line treatment. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer has improved significantly since the advent of EGFR tyrosine kinase inhibitors (EGFR-TKIs). We aimed to investigate the relationship between patient characteristics, EGFR genotype, therapeutic agents, and the prognosis of the patients with EGFR mutation-positive lung cancer. Methods: This retrospective cohort study analyzed 198 Japanese patients with unresectable EGFR mutation-positive lung cancer who were treated with EGFR-TKIs at Toho University Sakura Medical Center from April 2006 to December 2021. Factors associated with overall survival (OS) were analyzed using Cox proportional hazards analysis. Results: Patients who received osimertinib had a significantly longer OS than did those not receiving it (median OS, 36.2 versus 20.7 months; p < 0.001).There were significant differences in OS between patients with EGFR mutation who received osimertinib as first-line treatment, T790M-positive patients who received osimertinib as second- or later-line treatment, and those who did not receive it (median OS, 28.2 versus 40.2 versus 20.7 months; p = 0.003). However, in T790M-negative patients, no significant difference in OS was noted between those who did and did not receive osimertinib as post-treatment (median OS, 28.0 versus 40.0 months; p = 0.619). Multivariate Cox proportional hazards analysis showed that osimertinib treatment was associated with longer OS (hazard ratio, 0.480; 95% confidence interval, 0.326–0.707; p < 0.001). Conclusion: The patients who were T790M-positive in the first-line treatment with first or second-generation EGFR-TKIs and were given osimertinib as the second or later line treatment had a better prognosis than the patients who were T790M-negative in the first-line treatment with first or second-generation EGFR-TKIs and could not receive osimertinib. [ABSTRACT FROM AUTHOR]

Introduction: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity. Methods: Patients aged ≥ 18 years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8 Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis. Results: Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4–5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0 months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression. Conclusion: SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought. Trial Registration: EudraCT: 2017–003404-52; ClinicalTrials.gov: NCT04098432. [ABSTRACT FROM AUTHOR]

Introduction: Sacituzumab govitecan (SG) is approved for patients with previously treated metastatic or locally advanced triple-negative breast cancer (TNBC), as per the ASCENT trial results. Real-world studies (RWSs) cover more diverse patients than clinical trials, offering crucial data for healthcare policies. This study aimed to investigate the safety and efficacy of SG in real-world Polish patients with previously treated metastatic TNBC. Methods: In this ambispective multicenter cohort study, we collected demographic and clinical data. Premedication, adjustments in SG dosage, and treatment regimen adhered to the product's characteristics. Results: We included 79 female patients. The median age at SG initiation was 53 years; 32% of patients were initially diagnosed with a non-TNBC subtype. The median number of previous palliative lines was 2. Seven patients presented with brain metastases. The median overall survival was 10.3 months, and the median progression-free survival (PFS) was 4.4 months. The overall response rate was 35%, with a median time to response of 2 months. SG was discontinued by 70% of patients, primarily due to disease progression (95%). Treatment delays due to adverse events (AEs) occurred in 67% and dose reductions in 25% of patients, with neutropenia being the most common. Grade ≥ 2 AEs included neutropenia (43%), anemia (10.1%), and diarrhea (4%). A longer interval between breast cancer diagnosis and SG initiation or between metastasis diagnosis and SG initiation correlated with improved PFS, likely reflecting the disease's biological aggressiveness rather than treatment efficacy. Conclusion: In this RWS, SG demonstrated effectiveness and safety in patients with previously treated metastatic TNBC, consistent with ASCENT trial outcomes. Further research is needed to explore the efficacy of SG in different patient populations and healthcare systems. [ABSTRACT FROM AUTHOR]

Background: Although selpercatinib has shown clinical benefits for rearranged during transfection (RET) fusion–positive non-small cell lung cancer (NSCLC), its cost-effectiveness requires further evaluation. Aim: This study aimed to evaluate the cost-effectiveness of selpercatinib versus chemotherapy and pembrolizumab in the first-line treatment of RET fusion–positive NSCLC from the perspective of the United States (US) payer. Method: A partitioned survival model was developed based on data from the LIBRETTO-431 trial. Cost and utility values for the health state were obtained from database data or published literature. The measured outcomes included quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analyses (PSA) were conducted to assess the uncertainty of the model. Results: Selpercatinib increased QALYs in patients with RET fusion–positive NSCLC by 0.90 compared to chemotherapy plus pembrolizumab, with an additional cost of $542,517.45, resulting in an ICER of $603,286.49/QALY, which exceeded the willingness-to-pay (WTP) threshold ($150,000) in the US. One-way sensitivity analysis suggested that the utility of progressed disease, the utility of progression-free survival, the price of selpercatinib, the discount, the price of pemetrexed, and the price of pembrolizumab had the greatest influence on the cost- effectiveness analysis process. In the PSA, 99.9% of the scatter points were distributed above the US WTP threshold of $150,000. Conclusion: From the perspective of the US payer, selpercatinib is not cost-effective compared to chemotherapy and pembrolizumab for first-line treatment in patients with RET fusion-positive NSCLC. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy provides new hope to individuals with small cell lung cancer (SCLC). Predicting biomarkers for clinical effects is crucial for SCLC patients receiving programed death-ligand 1 (PD-L1) inhibitor treatment. Aim: The aim of this study was to clarify the value of serum lipids as predictors of immune related adverse events (irAEs) and the anti-tumour effects in SCLC patients who received PD-L1 inhibitors as first-line treatment. Method: This study included patients with SCLC who received at least one cycle of PD-L1inhibitors at Shanghai Pulmonary Hospital from August 2020 to December 2023. We collected the clinical data of the SCLC patients, including basic information and serum lipid levels, before immunotherapy. Results: The irAEs rate was 16.1% of 124 enrolled patients. In multivariate analysis, the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio was an independent predictor of irAEs (p = 0.045). Tumour response analysis indicated that the objective response rate (ORR) was 43.4% and the disease control rate (DCR) was 79.5%. Seventy-seven patients experienced any progression-free survival (PFS) event. The median PFS was longer in the HDL-C-high group (10.03 months) than in the HDL-C-low group (6.67 months) (p = 0.043). In Cox regression analysis, the serum HDL-C level was an independent predictor of PFS (p = 0.002). For patients of the high TG/HDL-C ratio, the ORR significantly differed between patients who suffered from any irAEs and those who did not (p = 0.0139). Conclusion: This study found that serum lipid levels might predict the responses to anti-PD-L1 as first-line treatment for SCLC. [ABSTRACT FROM AUTHOR]

Background and purpose: The role of local ablative radiotherapy (stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS)) in the management of metastatic breast cancer (mBC) patients remains unclear. This study aimed to assess the efficacy of SBRT/SRS in oligometastatic and oligoprogressive breast cancer patients. Methods: Totally 80 mBC patients with oligometastatic disease (OMD) and 80 with oligoprogressive disease (OPD) to ≤5 metastatic lesions were retrospectively analyzed. The endpoint was overall survival and progression-free survival, and univariate and multivariate analyses were performed for survival analysis. Results: Totally 160 mBC cases (80 OMD and 80 OPD cases) were analyzed, with a total of 291 treated metastases. In the study of OMD, we analyzed 30 cases with oligo-recurrence and 50 cases with sync-oligometastases. The median follow-up time was 46 months, and 1-, 2-, and 3-year OS rates for all patients were 89.8%, 77.6%, and 67.3%, respectively, and the 1-, 2-, and 3-year PFS rates were 71.4%, 44.9%, and 34.7% respectively. In multivariate analysis (MVA), treatment for oligometastases and non-triple-negative status predicted favorable OS. In patients with oligometastases, median OS was 58 months, and 1-, 2-, and 3-year OS rates were 100%, 91.7%, and 83.3%, respectively; median OS in patients with oligoprogression was 35 months, and 1-, 2-, and 3-year OS rates were 80%, 64%, and 52%, respectively. In mBC cases with limited brain metastases administered SRS, poor OS was detected in patient age under 45 years (P = 0.041), triple-negative cases (P = 0.025), and those with OPD (P = 0.022). In OMD, a significant improvement in PFS was observed in the oligo-recurrence group compared to the sync-oligometastases group (P = 0.013). Conclusion: Patients administered local ablative radiotherapy (SBRT/SRS) for oligometastases have better overall survival than those treated for oligoprogression. SBRT/SRS may be beneficial for young and non-triple-negative mBC cases. The presence of oligo-recurrence can predict a favorable prognosis of oligometastases in patients with mBC treated with SBRT/SRS. [ABSTRACT FROM AUTHOR]

We aimed to compare FOLFIRI and bevacizumab with FOLFIRI and aflibercept in terms of overall survival (OS), progression-free survival (PFS) and safety in patients with RAS-mutant metastatic colon cancer who progressed after first-line FOLFOX or XELOX and bevacizumab treatment. This retrospective study included 243 patients from 15 different centres in Turkey. The endpoints of the study were OS, PFS and safety and side effect outcomes. The median age of the patients included in the study was 60 (21–85) years. Of the patients enrolled in the study, 114 patients (46.9%) received aflibercept and 129 patients (53.1%) received bevacizumab. Median OS was 11.2 (95% CI: 9.1–13.2) months in patients receiving FOLFIRI + aflibercept and 14.1 (95% CI: 11.2–17.1) months in patients receiving FOLFIRI + bevacizumab. The median PFS was 5.7 (95% CI: 4.9–6.5) months in the aflibercept arm and 7.7 (95% CI: 7.1–8.3) months in the bevacizumab arm. Grade 3–4 side effects were observed in 58 (50.9%) patients in the aflibercept arm and 33 (25.6%) patients in the bevacizumab arm. As a result of our study, in patients with metastatic RAS-mutant colon cancer who progressed after first-line oxaliplatin-based doublet chemotherapy and bevacizumab, better OS and PFS results were obtained in patients receiving bevacizumab with FOLFIRI compared to patients receiving aflibercept with FOLFIRI. In addition, the side effect profile was more tolerable in the bevacizumab arm. [ABSTRACT FROM AUTHOR]

Purpose: Grade 3 meningiomas, although rare, are associated with high morbidity and mortality. The respective impacts of extent of surgical resection and adjuvant radiotherapy are still debated. Moreover, anaplastic meningiomas are studied in heterogenous cohort of de novo and progressive anaplastic tumors. Methods: We conducted a retrospective multicentric study on patients operated from a de novo anaplastic meningioma between 1999 and 2021. A centralized pathological review using 2016 WHO criteria was performed for all cases. Patients with history of radiotherapy or NF2-related Schwannomatosis were excluded. Results: Sixty-five patients were included in the study. Median progression free survival was 23 months and median overall survival was 2 years. Neither quality of resection nor adjuvant radiotherapy alone were predictive of better overall survival. Progression free survival were impacted by combination of gross-total resection and adjuvant radiotherapy (HR = 0.47 CI95% = [0.24–0.92], p = 0.027) and age at diagnosis (HR = 2.92 CI95% = [1.38–6.21], p = 0.005) in univariate analyses. Within anaplastic tumors, those graded on mitosis number had a poorer prognosis than those graded on overt anaplasia. Among anaplastic tumors with high mitotic score (> 20/10HPF), progression free survival were impacted by postoperative radiotherapy (HR = 0.44 CI95% = [0.22–0.88], p = 0.020) and gross total resection and adjuvant radiotherapy association (HR = 0.44 CI95% = [0.21–0.90], p = 0.024) in univariate analyses. Conclusion: Simpson grade didn't show any impact on overall survival. Gross total resection + adjuvant radiotherapy favorably impacted progression free survival in our cohort of de novo anaplastic meningiomas. [ABSTRACT FROM AUTHOR]

Post-neoadjuvant therapy (post-NAT) and post-surgical circulating tumor DNA (ctDNA) risk stratification may enhance the management of patients with locally advanced rectal cancer (LARC). In this study, we assessed the prognostic value of ctDNA-based MRD detection in LARC patients using a personalized, tumor-informed ctDNA assay. Plasma samples from LARC patients (N = 30) were analyzed retrospectively using the Signatera™ assay. The neoadjuvant rectal (NAR) score was calculated and compared to ctDNA status to predict recurrence risk and survival outcomes. ctDNA-positive patients post-NAT and post-surgery had worse Disease Free Survival (DFS) (HR: 7.82; p = 0.001, HR: 19.65; p = 0.001) when compared to ctDNA-negative patients. In the post-NAT setting, patients who responded to NAT had superior DFS compared to patients who did not clear their ctDNA or showed no radiological response (HR: 24.7, p = 0.001 and HR: 5.1, p = 0.054, respectively). When ctDNA status is used alongside the NAR score in the post-NAT setting, patients who were ctDNA-positive with an intermediate or high NAR score showed significantly worse DFS (HR: 47.5, p < 0.001) compared to ctDNA-negative patients with either a low or intermediate/high NAR score (HR: 9.8, p = 0.0301). Post-NAT ctDNA status, whether used alone or in combination with the NAR score, may predict NAT response, and improve risk stratification. [ABSTRACT FROM AUTHOR]

The efficacy of loncastuximab tesirine (lonca) following chimeric antigen receptor T-cell therapy (CAR-T) progression/failure is unknown. Hence, we sought to examine real-world use and outcomes of lonca following CAR-T in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the USA. In this retrospective study, we included adults (age ≥ 18 years) with R/R DLBCL who received lonca monotherapy as third- (3 L) or fourth line (4 L) treatment after progressing on second line (2 L) or 3 L CAR-T, respectively. Post-CAR-T lonca outcomes included response rates (overall response rate [ORR] and complete response [CR] rate), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 118 patients were included in the analysis with 95 receiving lonca following 2 L CAR-T (median age:66 years; 61% male) and 23 following 3 L CAR-T (median age:57 years; 43% male). Patients with 2 L CAR-T/3 L lonca had an ORR of 73% (CR rate of 34%). With a median follow-up of 8.5 months following lonca initiation, median DOR, PFS, and OS were not reached. The DOR, PFS, and OS at 12 months were 68%, 77%, and 84%, respectively. Patients with 3 L CAR-T/4 L lonca had an ORR of 78% (CR rate of 17%). With a median follow-up of 13 months following lonca initiation, the median DOR and PFS were 7.6 and 12.0 months, while median OS was not reached. OS at 12 months was 95%. In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings including those who were resistant to or progressed after CAR-T. [ABSTRACT FROM AUTHOR]

The International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab–pomalidomide–dexamethasone vs. pomalidomide–dexamethasone) and IKEMA (isatuximab–carfilzomib–dexamethasone vs. carfilzomib–dexamethasone) studies provide large datasets for retrospectively validating the prognostic value of the R2-ISS in relapsed/refractory multiple myeloma. Of 609 pooled patients, 68 (11.2%) were reclassified as R2-ISS stage I, 136 (22.3%) as R2-ISS stage II, 204 (33.5%) as R2-ISS stage III, 55 (9.0%) as stage IV, and 146 (24.0%) "Not classified". Median progression-free survival was shorter among those reclassified as R2-ISS stage II (HR 1.52, 95% CI 0.979–2.358), stage III (HR 2.59, 95% CI 1.709–3.923), and stage IV (HR 3.51, 95% CI 2.124–5.784) versus stage I. Adding isatuximab led to longer progression-free survival versus doublet therapy (adjusted HR 0.544 [95% CI 0.436–0.680]), with a consistent treatment effect observed across all R2-ISS stages. This is the first study to validate the R2-ISS with novel agents, including anti-CD38 monoclonal antibodies, and to show that R2-ISS, as a prognostic scoring system, can be applied to patients with relapsed/refractory multiple myeloma. [ABSTRACT FROM AUTHOR]

Preoperative peritumoral edema (PTE) in intracranial meningiomas is known to be a risk factor for postoperative recurrence. However, there are two groups: those in which preoperative PTE remains and those in which preoperative PTE receded after tumor removal. We aimed to investigate whether postoperative PTE could improve the prediction of prognosis of meningioma with preoperative PTE. We retrospectively reviewed postoperative MRI scans in 3 months after operation of 371 patients with preoperative PTE of meningioma that underwent surgery between 2015 and 2017. All the patients were classified into two different groups according to whether had postoperative PTE receded within 3 months after operation. Clinical manifestations, histopathology characteristics, radiology data and follow-up outcomes were noted. student's t-test and chi-square test for independence were used to compare clinical characteristics. Univariate and multivariate Cox analysis and Kaplan‒Meier methods were utilized to determine the independent effect of postoperative PTE on postoperative recurrence. Multivariate Cox analyses showed that the risk factors of meningioma recurrence: high WHO grades (HR = 4.989, P<0.001), superior sagittal sinus invasion (HR = 2.290, P = 0.047), postoperative PTE in 3 months after operation (HR = 1.804, P = 0.044) and STR (HR = 3.940, P = 0.003). Kaplan-Meier model showed that the progression-free survival of patients with postoperative PTE are shorter than who with postoperative PTE receded in 3 months after operation (HR = 3.30, P = 0.006). According to our research, we found that postoperative PTE in 3 months after operation is related to the outcomes of meningioma with preoperative PTE. Besides, we demonstrated that there were also some factors for recurrence: male, high WHO grades, superior sagittal sinus invasion and STR. These findings highlight the need for prospective study. [ABSTRACT FROM AUTHOR]

The clinical significance of FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) plus anti-EGFR monoclonal antibody using cetuximab for metastatic colorectal cancer (mCRC) remains controversial. We report results from a randomized phase 2 DEEPER trial (UMIN000018217, jRCTs061180022) to test the superiority of modified (m)-FOLFOXIRI plus weekly cetuximab over bevacizumab in patients with RAS wild-type (wt) mCRC. Primary endpoint was depth of response (DpR). Secondary endpoints included objective response rate (ORR), early tumor shrinkage (ETS) at week 8, progression-free survival (PFS), overall survival (OS), time to tumor growth (TTG), time to treatment failure (TTF), association between tumor shrinkage and prognosis, association between TTG and prognosis, R0 resection rate, and safety. In 359 enrolled patients with RAS wt mCRC, median DpR was significantly better in cetuximab (57.3% vs 46.0%, p = 0.0029); however, ORR, ETS, R0 resection rate, TTG, TTF, PFS and OS were similar between 2 treatments. There was a weak association between DpR and survival time in both treatments. The correlation between TTG and OS was slightly stronger in cetuximab. The post-hoc exploratory analysis showed that cetuximab produced greater PFS (15.3 vs 11.7 months; HR 0.68) and OS (53.6 vs 40.2 months; HR 0.54) in patients with left-sided and RAS/BRAF wt tumors. m-FOLFOXIRI plus cetuximab has clinical benefit for tumor shrinkage in RAS wt mCRC. The survival benefit for RAS/BRAF wt and left-sided mCRC needs further investigation. Anti-EGFR therapy plus doublet chemotherapy is standard of care for patients with RAS wild-type metastatic colorectal cancer (mCRC) but the role of triplet chemotherapy is unclear. Here, the authors report a randomised phase 2 trial testing the superiority of adding cetuximab (anti-EGFR) over bevacizumab (anti-VEGF) to modified FOLFOXIRI (5-FU, leucovorin, oxaliplatin and irinotecan) in patients with RAS wild-type mCRC. [ABSTRACT FROM AUTHOR]

Background and objectives: Minimally invasive esophagectomy (MIO) offers a less traumatic resection for cancer patients resulting in improved quality of life. Concerns about the oncological efficacy of the procedure and potential impact on survival may have limited its wider adoption. This study reports survival outcomes fifteen years after patients underwent a total MIO for esophageal cancer. Methods: A single-centre analysis of survival outcomes was conducted on all patients who underwent MIO between 2004 and 2010 and had completed at least 15-years follow-up. Actual overall survival (OS) and disease-free survival (DFS) were evaluated with the Kaplan–Meier method. The pattern of association of patient factors with survival was assessed with the Cox regression analysis. Results: A total of 121 patients underwent resection, with 4 (3.3%) in-patient deaths. With a median follow-up time of 15.2 years, the median OS was 41 months. At 15-years there were 20 survivors (17.1%), with numbers at 10 and 5 years being 34 (29.1%) and 45 (38.5%) respectively. Median DFS was 27 months, with 19 (16.2%) patient disease free at 15 years, and 32 (27.4%) and 38 (32.5%) at 10 and 5 years respectively. Predictors of poor survival were the intracorporeal fashioning of the gastric conduit, perioperative blood transfusions, advanced disease stage and recurrence. Conclusions: Long term survival outcomes following MIO support its increasing recognition as the standard of care as for curative resection in esophageal cancer. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Despite advances in treatment, mechanisms underlying GBM invasion remain incompletely understood. This systematic review synthesizes findings from laboratory and clinical studies to elucidate the molecular mechanisms driving GBM invasion and their implications for prognosis and therapy. This review adhered to PRISMA guidelines, conducting a comprehensive search of PubMed/Medline for studies published up to October 16, 2023. Inclusion criteria focused on studies investigating molecular mechanisms of GBM invasiveness with reported clinical outcomes (overall survival (OS) and progression-free survival (PFS). Exclusion criteria included systematic reviews, case reports, small case series, and studies limited to preclinical data. Risk of bias was assessed using the ROBINS-I tool. From 831 records, 21 studies (2198 patients) met the criteria. Key GBM invasion mechanisms included ECM degradation, vascular invasion, EMT, apoptotic regulation, cytoskeletal organization, and RNA sequencing. Vascular mechanisms were most studied. Bevacizumab resistance linked to poorer outcomes. EMT markers like TWIST and ECM degradation via MMPs such as CD147 correlated with decreased survival. Cytoskeletal and RNA studies highlighted the prognostic significance of tumor subtypes and microenvironmental interactions. This systematic review elucidates the molecular mechanisms underlying GBM invasiveness and their clinical implications. Integrating molecular profiling into routine clinical assessment may enhance prognostic accuracy and therapeutic efficacy, paving the way for personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The Skeletal Muscle Index (SMI) serves as an objective metric for assessing nutritional status in patients with malignant tumors. Research has found baseline nutritional status can influence both the efficacy and prognosis of targeted anti-tumor therapies, with growth factor tyrosine kinase inhibitors frequently inducing drug-related sarcopenia. Fruquintinib has received approval for the treatment of metastatic colorectal cancer. This study examines the prognostic significance of baseline SMI in patients with metastatic colorectal cancer undergoing treatment with fruquintinib. Additionally, the study investigates the incidence of SMI reduction following fruquintinib therapy to assess its impact on patient prognosis. Methods: A retrospective multicenter study was conducted to analyze patients with metastatic colorectal cancer who received fruquintinib treatment across eight medical centers in Eastern China. The muscle area at the third lumbar vertebra was assessed, and both baseline and post-treatment SMI values were calculated independently. The relationship between SMI and patient survival was subsequently examined. Results: The median progression-free survival (PFS) for the cohort of 105 patients was 4.2 months (95% CI, 3.7 to 4.9 months), while the median overall survival (OS) was 10.2 months (95% CI, 9.0 to 12.7 months). Notably, the baseline SMI prior to the initiation of fruquintinib therapy exhibited a significant correlation with OS (P = 0.0077). Multivariate analysis indicated that baseline SMI serves as an independent prognostic factor for OS (P = 0.005). Furthermore, after Propensity Score Matching (PSM) analysis, there was still a significant correlation between baseline SMI and OS. Among the patients, 28.87% developed sarcopenia following oral administration of fruquintinib. However, no statistically significant difference in OS was observed between the group with reduced SMI and the group without SMI reduction after treatment with fruquintinib. Conclusion: The baseline SMI was identified as an independent prognostic factor for OS and may influence the survival outcomes of patients with metastatic colorectal cancer undergoing treatment with fruquintinib. Despite the potential of fruquintinib to induce sarcopenia, no significant correlation was observed between changes in SMI following treatment and patient survival. [ABSTRACT FROM AUTHOR]

Background: This multicentre retrospective observational study aims to develop imaging-based prognostic and predictive models for relapsed/refractory (R/R) B-cell lymphoma patients undergoing CAR-T therapy by integrating clinical data and imaging features. Specifically, our aim was to predict 3- and 6-month treatment response, overall survival (OS), progression-free survival (PFS), and the occurrence of the immune effector cell-associated neurotoxicity syndrome (ICANS). Results: Sixty-five patients of R/R B-cell lymphoma treated with CAR-T cells in two centres were included. Pre-infusion [18F]FDG PET/CT scans and clinical data were systematically collected, and imaging features, including kurtosis, entropy, maximum diameter, standardized uptake value (SUV) related features (SUVmax, SUVmean, SUVstd, SUVmedian, SUVp25, SUVp75), total metabolic tumour volume (MTVtotal), and total lesion glycolysis (TLGtotal), were extracted using the Quibim platform. The median age was 62 (range 21–76) years and the median follow-up for survivors was 10.47 (range 0.20–45.80) months. A logistic regression model accurately predicted neurotoxicity (AUC: 0.830), and Cox proportional-hazards models for CAR-T response at 3 and 6 months demonstrated high accuracy (AUC: 0.754 and 0.818, respectively). Median predicted OS after CAR-T therapy was 4.73 months for high MTVtotal and 37.55 months for low MTVtotal. Median predicted PFS was 2.73 months for high MTVtotal and 11.83 months for low MTVtotal. For all outcomes, predictive models, combining imaging features and clinical variables, showed improved accuracy compared to models using only clinical variables or imaging features alone. Conclusion: This study successfully integrates imaging features and clinical variables to predict outcomes in R/R B-cell lymphoma patients undergoing CAR-T. Notably, the identified MTVtotal cut-off effectively stratifies patients, as evidenced by significant differences in OS and PFS. Additionally, the predictive models for neurotoxicity and CAR-T response show promising accuracy. This comprehensive approach holds promise for risk stratification and personalized treatment strategies which may become a helpful tool for optimizing CAR-T outcomes in R/R lymphoma patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the efficacy and safety of Selinexor combined bortezomib, lenalidomide, and dexamethasone (XVRd) protocol in newly diagnosed multiple myeloma with extramedullary disease. Methods: This is a single-arm, open, observational clinical study. For induction/consolidation(21-day cycles), patients received 8 cycles of XVRd protocol. In maintenance (28-day cycles), patients received XR (Selinexor + Lenalidomide) at least 2 years until disease progression, death or withdrawal. The primary endpoints were overall response rates and minimal residual disease negative rates. Results: The median age of the 10 patients was 62 (range 55–81) years. R-ISS stage 3 was present in 2 (20%) patients. 3 patients had high risk cytogenetic and 1 patient with plasma cell leukocyte. According to IMWG criteria, the ORR of 10 patients with NDMM was 100%, including 2 stringent complete response (sCR), 2 complete remission (CR), 4 very good partial response (VGPR) and 2 partial response (PR). Median progression-free survival and overall survival were not achieved. The most common grade 3–4 treatment-emergent adverse events (occurring in 10% of patients) were thrombocytopenia. The most common non-hematological adverse events were grade 1 or 2, including nausea (30%), fatigue (40%), and anorexia (20%). Overall, the severe toxicities were manageable. Conclusion: The XVRd regimen had good efficacy and safety in newly diagnosed multiple myeloma with extramedullary disease. [ABSTRACT FROM AUTHOR]

Recently, emerging evidence suggests an association between MECOM (MDS1 and EVI1 complex locus) and cancers. However, a comprehensive pan-cancer analysis to fully investigate this relationship is lacking. Herein, public platforms with large-scale genomics, including The Cancer Genome Atlas, Gene Expression Omnibus dataset, and the Human Protein Atlas were explored to investigate the prognostic and immunological roles of MECOM across certain cancer types. Our findings revealed differential expression of MECOM in various cancer types, indicating its potential to predict diverse clinical outcomes, such as overall survival time and disease-free survival time in patients with various malignancies. Additionally, we observed an association between the mutation burden in MECOM in various cancers and patient survival. Furthermore, the mechanism of MECOM-mediated oncogenesis was tentatively explored by immune infiltration analysis. This study provided a relatively comprehensive overview of the prognostic and immunological roles of MECOM in multiple cancers. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) are a promising biomarker for assessment of prognosis. The study was to analyse the relationship between preoperative and postoperative peripheral blood CTC and clinical features and prognosis in patients with tongue squamous cell carcinoma (TSCC). Methods: 85 with TSCC and 30 tongues with benign disease who underwent surgical treatment from May 2016 to May 2023 were retrospectively analysed. CTC testing was performed twice for TSCC group before and after surgery and only before the surgery for the benign disease group, only one test was performed before surgery.The association of CTCs with clinical features and progression-free survival (PFS) was also analyzed. Results: The positive rates of CTCs in patients with TSCC were 90.6% before treatment and 72.9% after treatment, respectively. CTCs were not detected in patients with benign disease group before treatment. There was no significant difference in the number of CTCs before and after treatment in patients with disease progression (P > 0.05). However, the number of CTCs after treatment in patients with disease remission (DR) and stable disease (SD) was significantly lower than before treatment, and the difference was statistically significant (P < 0.05). The results of the log-rank test demonstrated that the postoperative CTC was associated with the PFS (P < 0.05), whereas the preoperative CTC was not related to the PFS. The Cox proportional hazard regression model indicated that postoperative CTC and lymph node metastasis were independent risk factors. Conclusions: Postoperative CTCs may be an independent risk factor for a poor prognosis in patients with TSCC and CTC may serve as a valuable biomarker for prognostic monitoring for TSCC patients. [ABSTRACT FROM AUTHOR]

Introduction: The predictive utility of laboratory markers in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) is an ongoing area of research. The predictability of the platelet-lymphocyte ratio (PLR) on survival outcomes depending on the generation of EGFR TKI is undetermined. Methods: 151 patients treated with EGFR TKIs in Los Angeles were grouped according to generation of TKI. Differences in progression free survival (PFS) by stratification by PLR was determined using Kaplan–Meier analysis. Differences in median change in laboratory markers by generation of TKI was analyzed using Mann–Whitney tests. Cox Hazard Regression was used to perform multivariate analysis. Results: Median PFS of those managed with 1st or 2nd generation TKIs was significantly lower in patients with a PLR ≥ 180 (10.5 months) compared to those with PLR < 180 (16.6 months, p = 0.0163). Median PFS was comparable in those treated with osimertinib regardless of PLR. Patients managed with osimertinib had a significant decrease in absolute lymphocyte count (ALC) at 6 weeks and in platelets at 6 weeks and 3 months compared to those managed with 1st or 2nd generation TKIs. Discussion: The predictive value of PLR was more apparent in patients treated with 1st or 2nd generation TKIs compared to those treated with osimertinib. Third generation EGFR TKIs may be more efficacious in treating patients with laboratory findings previously shown to predict poor survival. The significant changes in peripheral cell counts suggest variable tumor microenvironment changes dependent on the generation of TKI received. [ABSTRACT FROM AUTHOR]

Little is known about changes in the abundance of tumor-infiltrating lymphocytes (TILs) and immune phenotype (IP) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We aimed to compare the TILs and IP between initial and recurrent HNSCCs using paired analysis. Thirty-seven patients who experienced recurrence after surgical resection and received treatment with immune checkpoint inhibitors (ICIs) between June 2014 and June 2023 were included. Changes in intratumoral TIL (iTILs), stromal TIL (sTILs), and IPs were subjected to paired analysis between the initial and recurrent tumors. We investigated their relationship with the outcomes of ICIs. The density of iTIL and sTIL in the recurrent tumors was significantly lower compared to initial tumors. IP was significantly different; the proportion of desert IP was higher in recurrent tumors (83.8% vs. 35.1%, P < 0.001). Increased sTIL was a favorable indicator for overall response to ICIs and progression-free survival. Our findings suggest TILs decrease during recurrence compared with the initial tumor, resulting in a transition toward desert IP. Therefore, careful evaluation of TIL density in both initial and recurrent tumors is recommended when using ICIs in patients with R/M HNSCC. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as a vital component in the contemporary landscape of cancer treatment. Recent studies have indicated that CEP55 plays an oncogenic role; however, its specific mechanisms in promoting tumor proliferation and its potential value in prognosis and immunotherapy prediction across various cancers remain to be elucidated. CEP55 was significantly overexpressed in 22 cancer types compared with their adjacent normal tissues. Elevated CEP55 expression was positively correlated with younger onset age, worse tumor stage, lower response rate to the first treatment, lower tumor-free survival rate, and poorer overall survival (OS) and disease-free survival (DFS) prognosis in most cancers. Moreover, CEP55 expression was positively correlated with its binding and related genes, such as KIF11 (R = 0.83, P < 0.001), CDK1 (R = 0.77, P < 0.001) and CCNA2 (R = 0.76, P < 0.001), and the classic proliferation markers, including MKI67 and PCNA. Enrichment analyses indicated that CEP55 was predominantly associated with cell division, cell cycle activities and proliferation. Immune cell infiltration analysis by TIMER2.0 revealed that CEP55 expression was positively correlated with many kinds of infiltrating cells, such as Th2 cells and some CD4+ T cell subsets. The CEP55 expression was positively associated with increased MSI and TMB in various cancers. Our analyzation indicated that the CEP55 expression level in patients with complete remission (CR) or partial remission (PR) to anti-PDL1 therapy was significantly higher than patients with stable disease (SD) or progressive disease (PD) based on IMvigor210 cohort. We also used Gene Set Cancer Analysis (GSCA) to predict a serious of small molecule CEP55 targeted drugs, such as AZ628, SB52334, SB590885, A-770,041, AZD7762, Elesclomol, panobinostat, BRD-A94377914, and LRRK2-IN-1. Furthermore, the patients with high level of CEP55-posivie tumor epithelial cells had inferior overall survival in ccRCC according to single-cell analysis. Finally, our wet lab experiments verified that the CEP55-positive rate in ccRCC tissues (19/30, 63.3%) was significantly higher than that in renal adjacent tissues (10/30, 33.3%). The clinicopathologic analysis revealed that CEP55 protein level was significantly associated with tumor size (P = 0.044), histology grade (P < 0.001) and stage (P = 0.034). Our study indicated that CEP55 overexpression in most caner types was associated with poor prognosis. Notably, CEP55 was closely relevant to immune cell infiltration and impacted the response to immunotherapy and small molecule drugs against cancers. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are currently the first line of tumor immunotherapy for the treatment of a wide range of tumors. However, the main side effect of immune checkpoint inhibitors is that they cause immune-related adverse events (irAEs) in patients. The relationship between the occurrence of immune side effects in patients and efficacy is controversial. The objective of this study was to confirm the relationship between patients who develop thyroid dysfunction after immune checkpoint inhibitors and efficacy. Methods: This study was a retrospective real-world clinical study, and a total of 50 patients with advanced tumors treated with immune checkpoint inhibitors at Anqing People's Hospital from 2020.8 to 2022.5 were retrospectively collected. Among them, 30 patients with hypothyroidism and 20 patients with normal or hyperthyroidism occurred, and the treatment effects and prognostic differences between the two groups were compared. Finding: After PD1 treatment in all patients, there were 10 cases of partial remission(PR), 18 cases of stable disease(SD) and 2 cases of progressive disease(PD) in patients who developed hypothyroidism, with a disease control rate(DCR) of 93.3% and objective remission rate(ORR) of 33.3%. There were 0 complete remission (CR) patient, 3 PR patients, 11 SD patients, 6 PD patients, 70.0% DCR and 15.0% ORR in patients who did not develop hypothyroidism. The DCR and ORR of patients who developed hypothyroidism were better than those of non-hypothyroid patients, and the difference was statistically significant (P < 0.05). Kaplan–Meier survival analysis showed that progression-free survival (PFS) reached 9.2 months (95% CI 7.726–10.779) in patients who developed hypothyroidism and did not hypothyroidism patients have a PFS of 7.3 months (95% CI 5.604–8.505), with a statistically significant difference (P = 0.0341 < 0.05). Further subgroup analysis revealed that among patients who developed hypothyroidism, PFS was 3.3 months (95% CI 0.630–5.440) in patients with cholangiocarcinoma, 6.89 months (95% CI 5.604–8.505) in patients with non-small cell lung cancer, > 12 months in patients with hepatocellular carcinoma, and 11.05 months (95% CI 9.308–12.792) in patients with esophageal cancer months and PFS for patients with gastric cancer was 9.74 months (95% CI 6.979–12.502). Interpretation: When patients with advanced tumors were treated with immune checkpoint inhibitors, DCR and ORR were higher in patients who developed hypothyroidism, and patients had better PFS. The benefits were greater in patients with gastric, esophageal, and hepatocellular carcinomas. [ABSTRACT FROM AUTHOR]

Background: SLIT and NTRK-like protein 2 (SLITRK2) encodes a transmembrane protein that regulates neurite outgrowth. Some studies have demonstrated that SLITRK2 overexpressed in glioma. But the expression pattern, prognostic value and immunologic function of SLITRK2 in tumors remains unknown. Methods: The expression pattern of SLITRK2 among pan-cancers was examined through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). We analyzed the association between SLITRK2 expression level and tumor stage among pan-cancers. Kaplan–Meier survival analysis was utilized to investigate the prognostic relevance of SLITRK2 across 33 different types of cancers. Moreover, the correlations among SLITRK2 expression, immune cell infiltration, immunomodulatory related genes, tumor mutation burden (TMB), microsatellite instability (MSI) were evaluated. The relationship between SLITRK2 expression and crucial genes mutations was also illustrated. By using tissue microarray (TMA), the expression of SLITRK2 in 89 paired gastric cancer (GC) tissues was investigated. Results: Our study indicated that SLITRK2 expression varied across cancers. Elevated SLITRK2 expression was positively related to advanced tumor stage, poor overall survival (OS) and reduced disease-free survival (DFS). Bioinformatic analyses underscore SLITRK2's role in immune response, with its expression significantly tied to immune cell infiltration and marker expression. Based on TMA data, SLITRK2 expression level was positively associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients. Conclusion: Our findings provided that SLITRK2 may function as a biomarker by regulating immune cell infiltration. In addition, we verified that high SLITRK2 expression was correlated with poor prognosis in GC. [ABSTRACT FROM AUTHOR]

To investigate the prognostic factors of recurrent meningioma patients who underwent reoperation, so as to make relevant recommendations for the treatment. A retrospective analysis was performed on 73 patients with recurrent meningioma. Patients' clinical data were obtained from their medical records. Progression-free Survival (PFS) was defined as the interval from the date of surgery to the date of tumor recurrence, or to the date of the last imaging review. Overall survival (OS) was defined as the time from the date of surgery to death from any cause, or to the date of the last follow-up. The multivariate COX regression showed that dural attachment length (HR = 1.238, 95%CI1.011–1.516, P = 0.039) and WHO grade (HR = 2.184, 95%CI1.135–4.203, P = 0.019) were independent risk factors for tumor progression. The factors associated with survival in multivariate regression analysis were preoperative Karnofsky Performance Scale (KPS) (HR = 0.951, 95%CI0.923–0.979, P = 0.001), dural attachment length (HR = 1.520, 95%CI1.124–2.057, P = 0.007) and WHO grade (HR = 4.829, 95%CI1.891–12.331, P = 0.001). The dural attachment length (OR = 1.843, 95%CI1.236–2.748, P = 0.003) was the only risk factor associated with postoperative pulmonary infection. No correlation was observed between Simpson's grade and either PFS or OS. The dural attachment length is closely related to the prognosis of recurrent meningioma, which should be given importance during the perioperative assessment. [ABSTRACT FROM AUTHOR]

In myelodysplastic syndromes (MDS), the IL-1β pathway is upregulated, and previous studies using mouse models of founder MDS mutations demonstrated that it enhances hematopoietic stem and progenitor cells' (HSPCs') aberrant differentiation towards the myeloid lineage at the expense of erythropoiesis. To evaluate whether targeting the IL-1β signaling pathway can rescue ineffective erythropoiesis in patients with MDS, we designed a phase 2 non-randomized single-arm clinical trial (NCT04239157) to assess the safety profile and efficacy of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS patients. We enrolled 25 patients with a median age of 74 years; 60% were male, 16% had lower-risk MDS, 84% had intermediate-1 risk MDS according to the International Prognostic Scoring System score, and 80% failed hypomethylating agent therapy. The study met the primary endpoint of defining the clinical activity of canakinumab, and the secondary objective of determining the safety profile, including the rate of transfusion independence, the duration of response, progression-free survival, leukemia-free survival, and overall survival. The overall response rate was 17.4%, with all responses including hematological improvement. Sequential post-hoc prospective single-cell RNA sequencing analyses of HSPCs and bone marrow mononuclear cells at different time points during therapy showed that canakinumab's on-target effects in hematopoietic populations expressing the IL-1β receptor decreased the TNF-mediated inflammatory signaling pathway but rescued ineffective erythropoiesis only in the context of lower genetic complexity. This study demonstrates that better stratification strategies could target lower-risk MDS patients more effectively. The IL-1β pathway is upregulated in patients with myelodysplastic syndromes (MDS). Here the authors report the results of a phase 2 clinical trial of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS. [ABSTRACT FROM AUTHOR]

Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment. Patients in this analysis received front-line RVd for ≥3 cycles and were grouped by transplant status and baseline renal function. As of August 4, 2021, 344 transplanted and 289 non-transplanted patients had received RVd for ≥3 cycles at induction. Improved renal function was observed at 3, 6, and 12 months in patients with all severities of RI at baseline. In patients with >60 and ≤60 creatinine clearance mL/min at baseline, median progression-free survival was 49.4 months and 47.6 months in transplanted patients and 35.7 months and 29.1 months in non-transplanted patients, respectively. These results provide real-world evidence that patients with NDMM and RI who receive front-line RVd for ≥3 cycles may have improved renal function regardless of transplant status, with renal function no longer affecting the long-term outcome. Clinical trial information: NCT01081028. [ABSTRACT FROM AUTHOR]

Patients with advanced and recurrent cervical cancer often lack satisfactory treatment outcomes. Thus, it is necessary to seek reliable biomarkers that provide the ability to identify the disease at an early stage and predict the patient prognosis, providing new strategies for the treatment of cervical cancer. The sequencing data of ITGA3 were retrieved from public datasets. Immune infiltration and sensitivity of potential immunotherapy and chemotherapy have been analyzed between two subgroups. Functional analysis was applied to excavate the related pathways of ITGA3 in cervical cancer. Furthermore, the impact of ITGA3 in tumor progression has been verified in vitro. The results revealed that the level of ITGA3 was upregulated in cervical cancer, and was positively correlated with worse prognosis. The tumor microenvironment of patients in the high-risk group was immunosuppressed. Patients in high-risk group may not benefit from immunotherapy, but be may be sensitive to several chemotherapy drugs. Notably, the angiogenesis, epithelial mesenchymal transition, and PI3K pathway were increased in high-risk group. Collectively, ITGA3 is a marker of poor prognosis and promotes tumor progression by regulating PI3K/AKT pathway in cervical cancer. Our results provide new insights for potential molecular targeted therapy and prognostic prediction of cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer. Methods: We retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020. Results: Overall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien–Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan–Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892–37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076–8.340; p = 0.036) were independent prognostic factors for disease-free survival. Conclusion: Postoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, yet it carries significant risks, including acute kidney injury (AKI). In this study, we investigated the risk factors and clinical impact of AKI in patients undergoing CAR-T cell therapy. This retrospective study involved hematologic patients treated with CAR-T therapy. Clinical and laboratory data were collected, and clinical outcomes were monitored during follow-up after CAR-T infusion. AKI was defined according to KDIGO criteria. The outcome measures included early mortality, overall survival (OS), and disease-free survival (DFS). Among the 48 patients analyzed, 14 (29%) developed AKI, with a mean onset of 6 days after CAR-T infusion. The risk of AKI was associated with baseline performance status (OR 8.65, IC95% 6.2–12, p = 0.032) and the development of severe cytokine release syndrome post-therapy (OR 16.4 95%CI 1.9-138.5, p = 0.01). Patients with AKI more frequently required intensive care. Furthermore, severe AKI was independently associated with worse clinical outcomes, including reduced OS and DFS (HR 18.2, 95%CI 2.6–27.3, p = 0.003). Additionally, patients who developed AKI post-CAR-T therapy were more likely to progress to chronic kidney disease during follow-up. In conclusion, frail patients undergoing CAR-T therapy are at an increased risk of developing AKI, which can significantly affect both short- and long-term outcomes. Preventive strategies and early recognition of AKI are essential in these patients. [ABSTRACT FROM AUTHOR]

Background: Combining Trastuzumab with chemotherapy for HER2-positive gastric cancer shows treatment promise but may raise costs. We aimed to evaluate the cost-effectiveness of combining Trastuzumab with chemotherapy for HER2-positive gastric cancer treatment in Iran. Methods: We employed a partitioned survival model (PSM) to evaluate the cost-effectiveness of trastuzumab plus chemotherapy versus chemotherapy alone. The PSM framework included three distinct health states: progression-free, post-progression, and death. Clinical data, including overall survival and progression-free survival rates, were derived from the ToGA trial, a randomized controlled study. A bottom-up approach was used to calculate costs by considering drug costs, adverse event management costs and other disease management costs separately for the progression-free and post-progression states. The analysis was conducted from the Iranian healthcare system's perspective, considering direct medical costs. We performed a cost-effectiveness analysis to determine the optimal strategy by comparing the incremental cost-effectiveness ratio (ICER) to Iran's cost-effectiveness threshold, set at one to three times the GDP per capita. Additionally, we conducted sensitivity analyses to assess the robustness of our findings. Results: Both FOLFOX-based regimens were strongly dominated. In comparison, the CAPOX regimen cost $2,811.11 for 0.75 QALYs. Adding Trastuzumab to CAPOX increased the cost to $6,128 and improved effectiveness to 0.92 QALYs, resulting in an ICER of $19,089.94 per QALY, which is between 2 and 3 times the GDP per capita in 2022. Conclusion: The addition of trastuzumab to chemotherapy regimens improved clinical outcomes in HER2-positive gastric cancer patients. From an economic perspective, the CAPOX regimen is the most cost-effective option when considering a cost-effectiveness threshold of up to two times Iran's GDP per capita. However, when the threshold increases to three times the GDP per capita, the CAPOX + Trastuzumab regimen becomes the preferred choice. These findings provide valuable insights for healthcare policymakers in Iran. [ABSTRACT FROM AUTHOR]

High-dose melphalan at 200 mg/m2 (MEL-200) is the standard conditioning regimen before autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Busulfan (BU) and cyclophosphamide (CY) can be used as alternatives when MEL is unavailable. However, most studies on BU/CY conditioning regimens were conducted before proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) were available. This non-interventional comparative cohort study compared progression-free survival (PFS) between the MEL-200 and BU/CY in patients with MM treated with PIs and/or IMIDs. A total of 137 patients were analyzed (MEL-200,113 patients; BU/CY, 24 patients). The BU/CY group had a higher rate of PI and/or IMID use and very good partial response (VGPR) or complete remission (CR) at ASCT and post-ASCT maintenance. Median PFS was 29.7 and 46.8 months in the MEL-200 and BU/CY groups, respectively. In the multivariate analysis, PFS was significantly better in the BU/CY group. International Staging System Stage I and VGPR or CR at ASCT were significantly associated with longer PFS. No treatment-related mortality was observed in either group by day 100. The BU/CY conditioning regimen may be a viable alternative to the MEL-200 regimen in patients with MM who undergo ASCT after treatment with PIs and/or IMIDs. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the interfractional volume changes of large (≥ 10 cm3) brain metastases (BMs) during fractionated gamma knife radiosurgery (FGKRS) to assess its predictive value for tumor control outcomes. Methods: The patients who underwent FGKRS for large BMs between January 2017 and December 2022 in our center were reviewed. The interfractional volume change was defined as the disparity in tumor volume (TV) measured between the magnetic resonance images acquired on the first treatment day and those obtained after 2 or 3 fractions during the course of FGKRS. Results: A total of 73 lesions in 70 patients with various primary pathologies were included. Over a median follow-up period of 11 months (range 1–77), the tumor control rate was 63%. Initial TV (cm3) was associated with progression free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses (p = 0.01). Interfractional TV changes revealed an increase in 13 (17.8%) lesions, no change in 14 (19.2%) lesions, and a decrease in 46 (63.0%) lesions, with a mean volume reduction of 5% ± 0.12. Three cut-offs (5%, 10% and 15% volume decrement) were established and patients were divided into two groups based on each reference point. However, there were no significant differences in PFS and OS between the two groups, irrespective of the chosen cut-off value used. Conclusion: Interfractional volume changes of large BMs were not found to be associated with tumor control outcomes. Neither significant interfractional volume reduction nor significant volume increase necessarily predicts the tumor control, making early close monitoring essential after FGKRS. [ABSTRACT FROM AUTHOR]

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting. [ABSTRACT FROM AUTHOR]

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32–72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14–40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting. [ABSTRACT FROM AUTHOR]

We propose a novel framework that addresses the deficiencies of Randomized clinical trial data subgroup analysis while it transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision medicine. Our approach counters the effects of unobserved confounding in observational data through a two-step process that adjusts predicted outcomes under treatment. These adjusted predictions train decision trees, optimizing treatment assignments for patient subgroups based on their characteristics, enabling intuitive treatment recommendations. Implementing this framework on gastrointestinal stromal tumors (GIST) data, including genetic sub-cohorts, showed that our tree recommendations outperformed current guidelines in an external cohort. Furthermore, we extended the application of this framework to RCT data from patients with extremity sarcomas. Despite initial trial indications of universal treatment necessity, our framework identified a subset of patients who may not require treatment. Once again, we successfully validated our recommendations in an external cohort. [ABSTRACT FROM AUTHOR]

Introduction: Desmoid tumors (DT) are rare, locally invasive tumors originating from connective tissue. Surgical intervention is no longer the standard treatment for DT, as systemic therapy gradually replaces it due to its superior efficacy. Despite the availability of various treatment modalities, there is a need for a first-line systemic treatment regimen that offers both effective disease control and acceptable safety profiles. Methods: To assess the efficacy and safety of different systemic treatment agents for DT, we conducted a systematic review and network meta-analysis. Eligible studies were identified through searches of PubMed, Embase, and the Cochrane Library databases, and data were extracted according to predefined inclusion criteria. Results: Three articles and clinical data from 295 patients with progressive and refractory DT were included in this Bayesian network meta-analysis. When considered by objective response rate (ORR), the efficacy of γ-secretase inhibitor versus placebo (OR 0.12, 95%CI 0.01–1.68) is superior to that of TKI (OR 0.49, 95%CI 0.03–7.62) and chemotherapy (OR 0.90, 95%CI 0.02–40.00). Vascular endothelial growth factor (VEGF)-TKI (OR, 0.09; 95% CI, 0.01–1.79) seemed to have the highest improvement in terms of 1-yr PFS rate, while chemotherapy seemed to have the highest improvement across all therapies in terms of 2-yr PFS rate across all therapies (OR, 0.06; 95 percent CI, 0.01–2.98). In terms of safety, the incidence of AEs is highest for γ-secretase inhibitor versus placebo (OR 0.16, 95%CI 0.02–1.55), while TKI is associated with the least AEs (OR 0.62, 95%CI 0.06–6.97). Conclusion: γ-secretase inhibitor provides superior local control of tumors, while chemotherapy and TKI may offer better long-term survival benefits. Among the three regimens, TKI demonstrated better treatment-related safety. These findings have important implications for guiding clinical practice in systemic treatment of DT. Highlights: The study conducted a systematic review and Bayesian network meta-analysis to evaluate the efficacy and safety of systemic treatment options for progressive and refractory desmoid tumors. The analysis included 3 RCT studies, and the primary clinical endpoints were progression-free survival and objective response rate. The network meta-analysis showed that γ-secretase inhibitors have better tumor response and more severe toxicity, while chemotherapy and TKI may have better long-term survival benefits. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a heterogeneous histiocytosis characterized by proliferation of Langerhans cells. While less common, manifestations of digestive tract involvement in LCH remain largely unrevealed. We conducted a retrospective analysis of demographics, clinical, endoscopic, genetic and follow-up data from 13 adult patients with pathologically confirmed gastrointestinal involvement of LCH (LCH-GI), in a single-center cohort of 465 patients. Digestive tract involvement was observed in 2.80% of LCH patients. At LCH-GI diagnosis, 7 patients (53.8%) had unifocal lesions, and 6 patients (46.2%) had multisystem disease. 6 patients (46.2%) experienced no gastrointestinal symptoms at LCH-GI onset, while others were symptomatic. Stomach was most commonly affected (61.5%), followed by esophagus (23.1%), colon (7.7%) and anus (7.7%). Endoscopic findings varied among 12 patients, including submucosal bulge (8 patients, 66.7%) and non-bulging lesions (4 patients, 33.3%) such as erosions, coarse granular mucosa, and regional abnormal coloration. Among 8 patients with genetic analysis, BRAFV600E mutation was detected in 5 patients (62.5%). The estimated 1-year overall survival rate was 91.7%. Progression-free survival of patients with submucosal bulges under endoscopy was significantly better than those with non-bulging lesions. This study presents 13 cases of LCH with digestive tract involvement. We emphasize the importance of endoscopy and biopsy for pathological examination of lesions such as submucosal bulges and erosions under endoscopy to assist in early detection of LCH. Comprehensive systemic assessment and regular endoscopic monitoring are essential in patient management. Treatment should be individualized with dynamic adjustments during follow-up. [ABSTRACT FROM AUTHOR]