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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]

Identifying clinical features that are associated with recurrence of endometrioid endometrial carcinoma (EEC) in patients with diabetes mellitus (DM). A single-center retrospective cohort study was performed on patients with a diagnosis of both DM and Stage I EEC. Clinical and pathologic features were analyzed in relation to 5-year progression free survival (PFS). Kaplan-Meier Curves and Cox proportional hazard ratios were utilized to assess effect on 5-year PFS. A total of 539 patients were included, with biopsy proven recurrence in 86 (18 %), and 456 (82 %) with no evidence of recurrence. Age, BMI, HgbA1c, metformin use, number of antihyperglycemic medications, use of adjuvant radiation, and surgical approach were not associated with differences in PFS. Presence of end-organ complications associated with diabetes was correlated with worse PFS (HR 1.78, 95 % CI 1.1–2.9, P = 0.02), and specifically diabetic neuropathy was associated with higher rates of recurrence (HR 3.6, 95 % CI 2.1–6.2, P < 0.01). In this cohort, PFS was independently associated with extent of myoinvasion (HR 2.33, 95 % CI 1.4–3.7, P < 0.01) as well as both microsatellite instability (HR 3.43, 95 % CI 1.8–6.6, P < 0.01), and no specific molecular profile (HR 0.3, 95 % CI 0.2–0.6, P < 0.01) molecular subtypes. In patients with DM and EEC, extent of myoinvasion and TCGA molecular subtype correlated with worse PFS. Control of DM as evidenced by HgbA1c, BMI, and use of antihyperglycemic medications did not correlate with PFS in our cohort of patients with Stage I EEC, while the presence of diabetic neuropathy was associated with a higher risk of recurrence. These results highlight importance of evaluating diabetes severity and molecular subtype in endometrial cancer patients. • Diabetic neuropathy is associated with higher rates of endometrioid endometrial carcinoma (EEC) recurrence. • Obesity, hemoglobin A1C, and use of antihyperglycemic medications is not associated with EEC recurrence rates. • Myoinvasion, microsatellite instability, and no specific molecular subtype is associated with increased EEC recurrence. [ABSTRACT FROM AUTHOR]

We assessed real-world trends in the use of maintenance therapy [MT] (i.e., polyADP-ribose polymerase inhibitors (PARPi) and/or bevacizumab following platinum-based chemotherapy), among U.S. patients with ovarian cancer. Using Medicare and commercial administrative health claims data from Optum's de-identified Clinformatics® Data Mart Database, we identified patients who had been diagnosed with ovarian cancer between January 1, 2010, and March 31, 2021, and received platinum-based chemotherapy and MT. Multivariable logistic regression and Cox proportional hazards regression were used to evaluate associations between demographic and clinical characteristics and MT use. Our study included 6339 patients, with a median age of 70 years. The majority were White (70.1 %), Medicare-insured (71.9 %), and were treated in the South (42.5 %). Of the 31.5 % who received MT, 18.1 % received bevacizumab alone, 10.2 % PARPi alone, and 3.3 % both. After adjusting for insurance type, PARPi and bevacizumab use increased significantly from 2017 to 2020. Patients with a high Elixhauser comorbidity index were more likely to receive MT than were patients with a low index [OR (95 % CI): 1.46 (1.28–1.67), p < 0.0001]. PARPi use was significantly associated with treatment in the South [1.42 (1.10–1.83), p = 0.01]. Compared to patients who received neither agents, those who received bevacizumab, alone or in combination with PARPi, had a higher risk of death [HR = 2.02 (95 % CI: 1.70–2.28, p < 0.0001) and 1.66 (1.24–2.23), p = 0.001, respectively]. The majority of patients with ovarian cancer are not utilizing maintenance therapy after platinum-based chemotherapy. Age, comorbidity status, and geographic region of treatment were associated with MT use. Understanding the factors and real-world outcomes associated with MT use is important to support patients in making value concordant and informed decisions. • Age, comorbidity status, and geographic region of treatment were associated with ovarian cancer maintenance therapy use. • After adjusting for insurance type, both PARPi and bevacizumab use increased significantly from 2017 to 2020. • We found relatively low use of PARPi plus bevacizumab, despite being associated with a longer progression-free survival. [ABSTRACT FROM AUTHOR]

To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC). We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000–12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation. Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33–91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1–234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94). Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated. • Radiation only was the most common (38%) adjuvant therapy in patients with stage I-II endometrial clear cell carcinoma (ECCC) • Positive cytology impacted risk of recurrence and age > 65 years impacted overall survival in this cohort of patients • Survival outcomes of surgically staged patients with stage I-II ECCC were not impacted by receipt of adjuvant treatment • Patients with tumors of "pure" clear cell vs "mixed" clear cell histology had no difference in survival [ABSTRACT FROM AUTHOR]

To evaluate the significance of response assessment with magnetic resonance imaging (MRI) during chemoradiotherapy (CRT) for outcomes of adenocarcinoma of the cervix. A retrospective analysis of 102 patients diagnosed with FIGO 1B3-IVa cervical adenocarcinoma was conducted. Patients underwent definitive CRT and brachytherapy. Mid-treatment MRI-assessments were used to evaluate tumor response during radiotherapy, focusing on tumor volume reduction rate (TVRR), which was defined as an optimal reduction rate from initial tumor volume for tumor progression. Locoregional recurrence (LRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS) rates according to the tumor response were analyzed. Forty-five (44.1 %) of 102 patients experienced tumor downstaging during CRT, with 72 (70.5 %) demonstrating a complete response on post-treatment MRI three months after radiotherapy. With a median follow-up of 35.5 months, the 3-year PFS and overall OS rates for all patients were 60.0 % and 84.0 %, respectively. LRR and DM rates at 3 years were 25.2 % and 23.3 %, respectively. Patients with TVRR≥81.8 % had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) and OS (93.2 % vs. 69.0 %, P = 0.002) rates than the other patients with TVRR<81.8 %. LRR (10.6 % vs. 45.6 %, P = 0.003) and DM (14.6 % vs. 33.5 %, P = 0.008) rates at 3 years were significantly lower in TVRR≥81.8 % group compared to TVRR<81.8 % group. In the multivariate analysis, positive initial lymph node (hazard ratio [HR], 2.11; confidence interval [CI], 1.25–3.87; P = 0.02] and TVRR (HR, 0.42; CI, 0.19–0.93; P = 0.03) were significantly associated with PFS. Mid-treatment MRI assessment is crucial and higher rates of tumor volume reduction during radiotherapy indicates better prognosis for tumor recurrence and patient survival in cervical adenocarcinoma. [Display omitted] • We conducted a multicenter retrospective study on the significance of mid-treatment MRI in cervical adenocarcinoma. • The optimal tumor volume reduction rate using mid-treatment MRI for tumor progression was 81.8 %. • Higher tumor volume reduction rate patients had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) than non-downstaged patients. • Positive lymph node and tumor downstaging were significant factors for PFS in the multivariate analysis (P = 0.02). [ABSTRACT FROM AUTHOR]

In patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2 -mutated PSROC patients, focusing on the type and location of PV. We assessed the outcomes of 100 BRCA1/2 -mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS). PFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects. In summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients. Trial registration number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015. • BRCA1/2 mutation location impacts the outcome of relapsed ovarian cancer patients on olaparib maintenance monotherapy (OMT). • Patients on OMT with BRCA1 pathogenic variant (PV) had shorter progression free survival (PFS) compared to BRCA2 PV. • Patients on OMT with PV in BRCA2 or in BRCA1 DNA binding domain had better PFS compared to PV in BRCA1 RING domain. • No significant difference in PFS between patients on OMT with germline or somatic BRCA1/2 PV was observed. • Adverse events in patients on OMT were not significantly different between germline and somatic PV in BRCA1/2. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the optimal monitoring after initial treatment of ovarian clear cell carcinoma (OCCC) using data from patients enrolled in the Japanese Gynecologic Oncology Group (JGOG) 3017 study. The JGOG study evaluated the efficacy of an irinotecan and cisplatin combination regimen compared with that of a paclitaxel and carboplatin regimen for OCCC patients who underwent primary surgery. Yielding 619 total patients in this study, to analyze progression-free and overall survival, the hazards over time were estimated using kernel smoothing curves to identify the peak of event occurrence. The number of progression events was summed by progression site, and the cumulative incidence proportion was estimated for the major progression sites, considering competing risks. The peak hazard for progression or death was observed at 12 months post-treatment, and most events were observed by 24 months. The hazard for death peaked at 18 months post-treatment, with most events being observed by 48 months. The hazard for lung, liver, and spleen metastases remained constant for 18 months post-treatment, with a decreasing trend thereafter; most events were observed by 18 months. The hazard for peritoneal dissemination was constant for 12 months, with a decreasing trend thereafter, with most exacerbations observed by 24 months. The risk of pelvic recurrence peaked at 6 months, with most exacerbations observed by 24 months. The incidence of progression events for OCCC peaked at 12 months and most progression events occurred within 24 months. Close follow-up for the initial 24 months post-treatment and fewer visits thereafter may be acceptable. However, closely monitoring symptoms and examining patients based on differences in progression rates at different sites may be important. • The incidence of progression events for OCCC peaked at 12 months after initial treatment. • Most progression events for OCCC occurred within 24 months after initial treatment. • Close follow-up for OCCC during the initial 24 months after treatment with fewer visits thereafter may be acceptable. [ABSTRACT FROM AUTHOR]

We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks. Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m2 IV with C AUC 6 IV and D8 nab-P 100 mg/m2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. From 08/2016–03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months. The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC. • Dose-dense nab-paclitaxel on day 1, 8 with day 1 carboplatin every 3 weeks is feasible (6-cycle completion rate of 82.6%). • In advanced/recurrent cases, median progression free survival was 23.2 months (95% CI: 12.1, not reached). • The regimen had tolerable toxicity, with 61% with grade 1 neuropathy and no patients with grade 3 or 4 neuropathy. • Nab-paclitaxel can be an acceptable taxol replacement for regimens with immunotherapy to avoid use of concomitant steroids. [ABSTRACT FROM AUTHOR]

To elucidate the clinicopathological characteristics and oncological outcomes of a special group of patients with gestational trophoblastic neoplasia (GTN) initially presenting with isolated lung lesions, elevated human chorionic gonadotropin (hCG) levels, and unobserved pelvic lesions. Overall, 2358 patients with GTN treated at our hospital between 2000 and 2023 were retrospectively reviewed, and 40 patients were evaluated. The demographic characteristics, clinicopathological features, treatment data, and follow-up information of each patient were collected. The primary outcome was progression free survival. Kaplan-Meier analysis and univariate and multivariate Cox proportional hazard analyses were used to identify the risk factors. Among the 40 patients, 95.0 % had solitary lung lesions, with a median size of 1.9 cm. Moreover, 72.5 % of patients were pathologically confirmed as epithelioid trophoblastic tumors (ETT). During a median follow-up period of 53.5 months (range, 2–143), 11 patients experienced recurrence, including all patients who received chemotherapy alone as the initial treatment, and no death was observed. Relapse treatment involved lung segmentectomy and lobectomy combined with chemotherapy and immunotherapy. Univariate and multivariate Cox analyses identified comparing with surgery±chemotherapy, chemotherapy alone as the initial treatment (hazard ratio [HR] =7.738, 95 % confidence interval [CI] 1.698–35.269, P = 0.008) as independent risk factor for recurrence. In patients with a history of pregnancy exhibiting isolated pulmonary lesions, elevated hCG levels (mostly <1000 mIU/mL), and unobserved pelvic lesions, ETT should be considered first. Surgical resection of lung lesion is crucial for optimal management. When chemotherapy is considered, multidrug regimen is recommended. • Gestational trophoblastic neoplasia (GTN) comprises a group of pregnancy-associated malignancies. • Most patients with isolated GTN of the lung had a pathological diagnosis of epithelial trophoblastic tumors (ETT). • Surgical resection of lung lesions is crucial, adjuvant and multidrug chemotherapy is recommended when needed. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). Methods: Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. Results: Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29–41), DCR was 67% (95%CI 58–76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11–9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78–100) and 37% (95%CI 19–57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68–91), 74% (57–88), 73% (35–98) and 57% (46–68), respectively. Conclusion: As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation. [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]

Background: Acute myeloid leukemia (AML) has a heterogeneous molecular profile, clinical presentations, and response to treatments and outcomes. DNA methylation is conducted by DNA methyltransferases including DNMT3B. Poly ADP-ribose polymerase 1 belongs to a family of enzymes that mediate important cellular processes including DNA repair, transcription, and cell death/cell proliferation, and it is involved in the development, spread, treatment, and prognosis of some cancers. The objective of this study is to assess the impact of PARP1 and DNMT3B genes expression on laboratory characteristics, response to treatment and survival in Egyptian cytogenetically normal AML patients. Methods: This study included 67 Egyptian CN-AML patients in addition to 8 healthy bone marrow donors. Measurement of DNMT3B and PARP1 gene expression was done on bone marrow samples via real-time semiquantitative polymerase chain reaction. Result: Expression of both DNMT3B and PARP1 genes was significantly upregulated in AML (P =.001, P =.036, respectively). Upregulated DNMT3B was associated with higher total leukocyte count (TLC), PB, and BM blast cell%. Also, upregulated PARP1 correlated with higher TLC, PB, and BM blast cell%. High expression of both DNMT3B and PARP1 correlated with greater frequencies of FLT3-ITD. High DNMT3B expression, and combined upregulation of both PARP1 and DNMT3B genes associated significantly with ELN stratification. But no correlation was found with response (CR), overall survival (OS), disease-free survival (DFS), or event-free survival (EFS). Conclusion: Our findings highlight the importance of considering DNMT3B and PARP1 expression levels as potential prognostic biomarkers for progression and aggressiveness of CN-AML patients in AML. Assessing their expression levels could be an indicator to guide treatment decisions and potentially improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: This retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People's Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed. Results: The ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, P = 0.005; DCR: 88.1% vs. 67.8%, P = 0.039; PFS: 10 months vs. 6 months, P < 0.0001; OS: 24 months vs. 16 months, P = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (P > 0.05). Conclusion: Compared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients. [ABSTRACT FROM AUTHOR]

Lung enteric-type adenocarcinoma (ETAC) is a rare subtype of non-small cell lung cancer (NSCLC), comprising approximately 0.6% of all primary lung adenocarcinomas. It is characterized by a tendency for early metastasis and a prognosis comparable to that of common lung adenocarcinoma. This case report described a patient with lung-ETAC who developed gastric metastasis. The patient underwent treatment with chemotherapy and a PD-1 inhibitor, resulting in disease remission with a progression-free survival (PFS) of 8 months. The follow-up time was 13 months. This case report was aimed to enhance understanding of the biological behavior of this rare tumor and provide insights into potential future treatment strategies. [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]

Introduction: Chemoradiotherapy in head and neck cancer patients has a curative intent but often deteriorates nutritional status leading to sarcopenia and cachexia. Methods: In this observational and single-centered study, a prospective evaluation of several biochemical and anthropometrical parameters, weight loss, handgrip strength, visual analogue scale of appetite, questionnaires associated with malnutrition & quality of life and body composition (obtained by Bioelectrical Impedance Vector Analysis) was performed before and after high-dose cisplatin chemotherapy combined with radiotherapy in 60 patients affected by head and neck cancer. Oral nutritional supplements were used to reach the correct number of daily calories and proteins. Results and discussion: All patients completed radiotherapy as planned and the 96,4% of them did not interrupt chemotherapy for toxicity, reaching a total dose of at least 200mg/m2. Despite a rapid deterioration of body composition during treatment, nutritional support helped patients to maintain (or in some cases improve) anthropometric parameters from the end of chemoradiotherapy to the following 3 months. Low prealbumin and albumin pre-treatment led to higher risk of toxicities with consequent reduction of cisplatin dose intensity, whereas weight at the end of the treatment seems to be an interesting predicting factor for disease free and overall survival (p=0.007; p=0.015). [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is associated with a high risk of endometrial cancer (EC). However, its impact on EC progression remains unclear. This meta-analysis examined the association between MetS and survival outcomes in EC patients. Methods: A comprehensive search of PubMed, EMBASE, and Web of Science databases up to May 22, 2024, was conducted. Two independent reviewers performed study selection, data extraction, and quality assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results: Nine studies comprising 13,579 endometrial cancer (EC) patients were included. Among these, 2,896 patients (21.3%) had MetS at the time of enrollment. The follow-up durations ranged from 3.4 to 14.2 years. The results showed that EC patients with MetS at baseline demonstrated significantly poorer overall survival (HR = 1.57, 95% CI = 1.19-2.07, p = 0.002; I² = 25%) and progression-free survival (HR = 1.33, 95% CI = 1.08-1.63, p = 0.007; I² = 16%). A similar association was observed for cancer-specific survival (HR = 1.26, 95% CI = 1.10-1.44, p = 0.001; I² = 0%). Subgroup analyses based on study characteristics showed consistent results across studies conducted in countries with different follow-up durations. Conclusion: This meta-analysis suggests that MetS is associated with poor survival outcomes in EC patients. Further prospective studies are required to validate our findings. Systematic review registration: PROSPERO, identifier CRD42024561654. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the preoperative haemoglobin, albumin, lymphocyte, and platelet score as a prognostic indicator in oral squamous cell carcinoma treated by radical surgery. Subjects and Methods: Patients (83 men, 32 women; 65.80 ± 11.47 years) who underwent radical surgery between 2012 and 2022 were included. Factors affecting overall survival and disease‐free survival according to the haemoglobin, albumin, lymphocyte, and platelet score were examined. Patients were categorised into low‐ and high‐score groups using optimal cut‐off values obtained from receiver operating characteristic curve analysis. Results: The low‐score group had poorer overall and disease‐free survival (p < 0.001 each). Multivariate analysis identified alcohol consumption (hazard ratio [HR], 3.83; 95% confidence interval [CI]: 1.56–9.41, p = 0.003); vascular invasion (HR, 3.97; 95% CI: 1.60–9.85, p = 0.003); and the haemoglobin, albumin, lymphocyte, and platelet score (HR, 0.39; 95% CI: 0.20–0.78, p = 0.007) as independent prognostic factors for overall survival and vascular (HR, 3.66; 95% CI: 1.79–7.50, p < 0.001) and lymphovascular (HR, 2.44; 95% CI: 1.36–4.41, p = 0.003) invasion as independent prognostic factors for disease‐free survival. Conclusion: The preoperative haemoglobin, albumin, lymphocyte, and platelet score may be a significant prognostic factor for patients with oral squamous cell carcinoma undergoing radical surgery. [ABSTRACT FROM AUTHOR]

Background: Minimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications. Methods: We retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed. Results: In a cohort of 220 patients with NDMM, attainment of MRD--offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD-duration ≥ 12 months was associated with an 83 % (95 % confidence interval (CI), 0.09-0.34; P < 0.0001) or 69 % (95 % CI, 0.13-0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD--was sustained, the better the outcome was. Loss of MRD--led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0-0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0-0.24, P = 0.0008). Most patients (70 %) who lost MRD--status carried high-risk cytogenetic abnormalities (HRCAs). While MRD--was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging). Conclusions: Longitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status. [ABSTRACT FROM AUTHOR]

BACKGROUND: Both radical prostatectomy and radiation therapy are effective in controlling the condition of patients with hormone-resistant prostate cancer (HRPCa). However, there is limited research on the prognosis and quality of life of HRPCa patients after different treatment modalities. OBJECTIVE: To explore the efficacy of radical prostatectomy (RP) and radiotherapy (RT), when treating high-risk prostate cancer (HRPCa). METHODS: Overall 103 HRPCa patients were included and were divided into RP group and RT group according to different treatment methods. The propensity score matching method (PSM) was used to balance the baseline data of the two groups and match 34 patients in each group. The prognosis, quality of life, and basic efficacy of patients were compared. RESULTS: After intervention, the disease-free survival rate of the RT group was higher than that of the RP group (79.41% vs. 55.88%, p = 0.038). Quality of life scores between the two treatment methods had no difference before intervention (p > 0.05), but higher in RT group than that of the RP group after intervention (p < 0.05). After treatment, there was no statistically significant difference in total effective rate of treatment between two groups (44.12% vs. 58.82%, p > 0.05), but the disease control rate was significantly higher in RT group (94.12% vs. 76.47%, p = 0.040). CONCLUSION: Radical radiotherapy is effective in the clinical treatment of HRPCa patients, with a higher disease-free survival rate and improved quality of life after treatment, and is worth promoting. [ABSTRACT FROM AUTHOR]

Motivation Integrating multiple omics datasets can significantly advance our understanding of disease mechanisms, physiology, and treatment responses. However, a major challenge in multi-omics studies is the disparity in sample sizes across different datasets, which can introduce bias and reduce statistical power. To address this issue, we propose a novel framework, OmicsNMF, designed to impute missing omics data and enhance disease phenotype prediction. OmicsNMF integrates Generative Adversarial Networks (GANs) with Non-Negative Matrix Factorization (NMF). NMF is a well-established method for uncovering underlying patterns in omics data, while GANs enhance the imputation process by generating realistic data samples. This synergy aims to more effectively address sample size disparity, thereby improving data integration and prediction accuracy. Results For evaluation, we focused on predicting breast cancer subtypes using the imputed data generated by our proposed framework, OmicsNMF. Our results indicate that OmicsNMF consistently outperforms baseline methods. We further assessed the quality of the imputed data through survival analysis, revealing that the imputed omics profiles provide significant prognostic power for both overall survival and disease-free status. Overall, OmicsNMF effectively leverages GANs and NMF to impute missing samples while preserving key biological features. This approach shows potential for advancing precision oncology by improving data integration and analysis. Availability and implementation Source code is available at: https://github.com/compbiolabucf/OmicsNMF. [ABSTRACT FROM AUTHOR]

To describe our experience in the resection of gliomas involving the insula and analyze the variables implicated in the management and prognosis of these tumors. This retrospective, single-center, analytic study included a cohort of 83 patients who underwent surgery for insular gliomas by the same surgeon in a third-level Argentine center, in the period between 2010 and 2023. We analyzed the population's demographic, clinical, and radiologic features and surgical variables associated with postoperative results and prognosis using multivariate regression analysis. A total of 53 patients (54% men) were included, with a mean follow-up of 40.7 months. The mean age at surgery was 41 years (range, 21–73) and 66.1% corresponded to low-grade gliomas (LGGs). Seizures were the initial symptom in most cases. There was evidence of tumor extension over the insula to the temporal or/and frontal lobe in 64.2% of patients. An extent of resection >90% was achieved in 62.3% of cases (27% of gross total resection), with an average resected volume of 89.4%. Awake craniotomy was indicated in 47% of patients and intraoperative magnetic resonance imaging was performed in 24%. Recurrence was observed in 44% of patients, with a mean progression-free survival of 31 months (42 months in LGG and 10 months in high-grade glioma [HGG]). Nine patients underwent reoperation. By the time of 2 years, survival was 100% for LGG and 46% for HGG, whereas 4-year overall survival was 92% for patients with LGG and 15.4% for those with HGG. Surgery for insular gliomas is a complex task that needs to be managed with adequate preoperative and intraoperative assessment to achieve maximum safe resection with low morbidity for better functional and oncologic outcomes. Adequate anatomic understanding, radiologic analysis, awake craniotomy, and cortical and subcortical mapping are paramount to pursue this aim. [ABSTRACT FROM AUTHOR]

OBJECTIVES To analyse impact of segmentectomy on oncological outcomes of different peripheral early-stage lung adenocarcinoma patterns. METHODS Retrospective multicentre study including patients who underwent either lobectomy or segmentectomy in 6 European centres from 2015 to 2021, for ≤2 cm pathological peripheral lung adenocarcinoma. Overall and disease-free survivals were assessed by cox-regression and lung cancer-specific survival by competing regression analyses to adjust for patient- and tumour-related factors both in the entire dataset and the in aggressive adenocarcinoma patterns dataset. RESULTS Lobectomy and segmentectomy were performed in 481 (71%) and 193 (29%) patients, respectively. Propensity score matching was performed (n  = 191). One hundred and 8 patients had a least an aggressive pattern. Five-year disease-free, overall and lung cancer-specific survivals were similar between patients who underwent lobectomy or segmentectomy in both entire and aggressive pattern datasets. In patients with aggressive pattern, 5-year disease-free (lobectomy 87.3%; segmentectomy 86.6%, P  = 0.62), overall (lobectomy 86.4%; segmentectomy 95.6%, P  = 0.61) and lung cancer-specific (lobectomy 100%; segmentectomy 95.6%, P  = 0.13) survivals did not differ. Segmentectomy was not an independent risk factor for disease-free survival, neither for overall survival nor for lung cancer-specific survival in any of the 2 datasets. In patients with aggressive pattern, loco-regional recurrence (linearized risks: lobectomy 8.21; segmentectomy 11.3) was higher in patients who underwent segmentectomy. CONCLUSIONS Resection should not be extended (to lobectomy) on patients who underwent segmentectomy for pathologically proven early-stage adenocarcinoma with aggressive patterns. [ABSTRACT FROM AUTHOR]

OBJECTIVES Ascending aortic length has recently been recognized as a novel predictor of adverse events in aortic diseases, but its prognostic value in type A intramural haematoma is unknown. We aimed to evaluate the association between ascending aortic length and outcomes in patients with type A intramural haematoma initially managed medically. METHODS We retrospectively analysed patients with acute type A intramural haematoma. Ascending aortic length was measured by computed tomography. The primary outcome was aortic progression, defined as aortic intervention or aortic-related death. RESULTS A total of 98 patients were enrolled. During a median follow-up of 2.6 years, aortic progression occurred in 27 patients (27.6%), i.e. 9 events per 100 patient-years. Patients with ascending aortic length ≥11 cm had significantly higher rates of aortic progression [54.2% (20.9 events per 100 patient-years) vs 18.9% (6.1 events per 100 patient-years), P  = 0.001], surgical intervention (45.8% vs 12.2%, P  = 0.001) and presence of ulcer-like projection (25.0% vs 2.7%, P  = 0.002) compared to those with ascending aortic length <11 cm. Kaplan–Meier analysis demonstrated lower progression-free survival in the ascending aortic length ≥11 cm group (P  = 0.0021). Ascending aortic length had a sensitivity of 61.9% and specificity of 77.8% for predicting aortic progression, with an area under the curve of 0.756 (95% confidence interval 0.649–0.862). CONCLUSIONS Ascending aortic elongation may identify a high-risk subgroup of acute type A intramural haematoma patients initially managed medically who could potentially benefit from early surgery. Ascending aortic length should be considered in the risk stratification and management of these patients. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is a highly aggressive malignancy accounting for the majority of kidney cancers. Despite recent advancements in therapeutic options, the prognosis for advanced-stage RCC remains poor. Niemann–Pick C1-Like 1 (NPC1L1) plays a crucial role in cholesterol absorption and has been implicated in cancer progression across various cancers. However, its expression patterns and prognostic significance in RCC remain unclear. Methods: In this study, NPC1L1 expression in normal and RCC tissues, including subtypes, was compared using TCGA, GEPIA2, and The Human Protein Atlas. Clinical correlations were assessed, and the impact of NPC1L1 on overall survival (OS) and progression-free survival (PFS) was evaluated. Gene effect scores were analyzed using the DepMap tool to determine the involvement of NPC1L1 in RCC progression. Results: NPC1L1 expression was significantly lower in RCC tissues compared to normal tissues, particularly in the clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) subtypes, but increased in advanced tumor stages. Higher NPC1L1 expression was associated with worse OS and PFS in RCC patients. Multivariable Cox regression confirmed NPC1L1 as an independent prognostic marker. Additionally, gene effect scores showed that NPC1L1 is essential for the survival of specific RCC cell lines. Conclusions: This study determines NPC1L1 as an independent prognostic indicator in RCC, with higher expression associated with poor survival outcomes. These findings suggest that NPC1L1 could serve as a valuable marker for identifying high-risk RCC patients. Further research is required to investigate the molecular mechanisms underlying the role of NPC1L1 in RCC progression. [ABSTRACT FROM AUTHOR]

Background: The role of brain metastases (BM) surgery is of paramount importance for patients' progression-free and overall survival. "En-bloc" and "piecemeal" resection represent the main surgical techniques. Although en-bloc resection remains the best surgical option, it is not widely adopted or feasible as the first choice. We describe our point of view about the en-bloc surgical technique with an illustrative case and discuss its indications with pros and cons through a comprehensive literature review. Materials and methods: A Medline search up to December 2023 in the Embase and PubMed online electronic databases was made and PRISMA statement was followed. An illustrative case of "en-bloc" resection from our surgical series was also added as a technical note. Results: We describe tips and tricks of our surgical technique and added a surgical video from our series. The literature review disclosed 19 studies. Resulting data suggested that "en-bloc" resection, when feasible, provides lesser risk of leptomeningeal dissemination, local recurrence rates, intraoperative bleeding occurrence and perioperative complications; in addition, it preserves the normal anatomy. Conclusions: En-bloc resection is the gold standard technique for surgical treatment of brain metastases especially for patients with superficial lesions that are small in size and far from eloquent areas. [ABSTRACT FROM AUTHOR]

Introduction: This retrospective study aimed to determine the effect of pre-treatment hemoglobin (Hgb) value on the prognosis of patients with advanced rectal carcinoma undergoing neoadjuvant chemoradiotherapy (nCRT) in terms of pathologic complete response (pCR). Methods: A total of 192 individuals with rectal cancer who underwent nCRT were included in the study between 2011 and 2019. The patients were separated into anemic and non-anemic categories based on pretreatment Hgb values (Hgb <11 gr/dL). Results: The Hgb threshold for defining anemia was assessed using receiver operating characteristic curve analysis. Of the 48 (25%) patients, 144 (75%) were in the non-anemic group. The median overall survival (OS) time was 27 months in the anemic group and 69 months in the non-anemic group patients (p=0.028). No statistically significant difference was observed in disease-free survival between the groups. When comparing the two groups "patients" pCR and partial response ratio was elevated in the non-anemic group (p<0.001). In anemic groups patients, female, median age, >60 years, and CA19-9 value was high (p=0.021, p=0.042, p=0.014 and p=0.030). In logistic regression analysis for pCR, tumor regression grade (0-1 vs. 2-3) and pathologic T-stage (0 vs. 1-2) was statistically significant (p<0.001 and p=0.03), anemia (Hgb <11 gr/dL vs. >11 gr/dL) was not statistically significant (p=0.219). Conclusion: In the group with lower pretreatment Hgb values (<11 gr/dL), the pCR, partial response, and OS time were lower. However, Hgb levels with a cut-off of 11 gr/dL were not statistically proven to be prognostic factors for rectal carcinoma treated with nCRT. [ABSTRACT FROM AUTHOR]

Background: To date, the only potential curative treatment for multiple myeloma (MM) remains allogeneic (allo) hematopoietic cell transplant (HCT), although, most patients will eventually relapse. In relapsed patients, donor lymphocyte infusions (DLIs) have been reported to control disease, but the optimal strategy prior to and doses of DLIs remain unclear. With this study (NCT03413800), we aimed to investigate the efficacy and toxicity of lenalidomide and dexamethasome (Len/Dex) followed by escalating pre-determined doses of DLIs in MM patients who relapsed after allo HCT. Methods: Patients aged 18–65 years with relapsed MM following upfront tandem autologous (auto)/allo HCT were eligible. Treatment consisted of six cycles of Len/Dex followed by three standardized doses of DLIs: 5 × 106 CD3+/kg, 1 × 107/kg and 5 × 107/kg every 6 weeks. Bone marrow minimal measurable disease (MRD) using flow cytometry (10−5) was performed at enrolment, then every 3 months for 2 years or until disease progression, in a subset of patients. The primary endpoint was efficacy as measured by progression-free survival (PFS) at 2 years following Len/Dex/DLIs. Secondary objectives were safety including GVHD, response including MRD status and overall survival (OS). Results: A total of 22 patients participated in this study, including 62% with high-risk cytogenetics. With a median follow-up of 5.3 years (range: 4.1–6.1), PFS and OS were 26.5% (95% CI: 10.4–45.9%) and 69.2% (95% CI: 43.3–85.1%), respectively. Overall, the best responses achieved post-Len/Dex + DLIs were complete remission in 9.1%, very good partial response in 50%, and progressive disease in 40.9%. Among the nine patients tested for MRD, only two achieved a negative status after receiving DLIs. Six patients died, all due to disease progression. No acute GVHD was observed after DLIs. We report a very low incidence of moderate/severe chronic GVHD of 18.2% with no need for systemic immunosuppressants one year after diagnosis. No unexpected adverse events were observed. Interestingly, a positive correlation between response to Len/Dex re-induction and response to DLIs was found (p = 0.0032). Conclusions: Our findings suggest that Len/Dex/DLIs in second line treatment after upfront tandem auto/allo HCT in relapsed MM patients remains feasible and safe. With a potential correlation between induction chemotherapy and DLI responses, more potent induction regimens together with higher doses of DLIs should be considered in the future. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a prevalent liver cancer with poor prognosis, often linked to hepatitis B (HBV) and C (HCV) infections. This meta-analysis evaluates the efficacy of immunotherapy in HCC, particularly in cases arising from viral hepatitis. Methods: In adherence to PRISMA Statement 2020 guidelines, the immunotherapeutic outcomes comprised objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Data were analyzed from randomized controlled trials up to April 2024 using the fixed-effects models in R (V.4.3.3.) and RevMan (Cochrane). Results: This study included 9 trials with 5316 patients. The ORR was slightly higher in the viral group at 27.93% compared to 24.07% in the non-viral group, though this difference was not significant (p = 0.15). Viral HCC patients exhibited a median PFS of 7.3 months (IQR: 6.2–8.4) compared to 5.8 months (IQR: 5.48–6.13) in non-viral patients, a significant improvement (p = 0.005). Similarly, median OS was longer in the viral group at 16.8 months (IQR: 12.99–20.61) versus 15.2 months (IQR: 13.25–17.15) for non-viral HCC, which was also significant (p < 0.0001). The median OS for viral HCC was 16.8 months (IQR: 14.11–19.49 months), with HBV patients experiencing slightly higher survival at 17.15 months (IQR: 14.3–20 months) compared to 16.8 months (IQR: 12.99–20.61 months) for HCV patients; this difference was not statistically significant (p = 0.89). Conclusions: Immunotherapy shows potential in treating HCC, with significantly better outcomes in viral HCC, particularly HBV-associated cases. The heterogeneity highlights the need for personalized treatment approaches based on the viral background of HCC patients. Further research should aim to optimize these therapies to improve survival rates. [ABSTRACT FROM AUTHOR]

Introduction: Radium-223 dichloride (radium-223) is a bone-targeting radioisotope therapy that aids in the survival of patients with metastatic castration-resistant prostate cancer (mCRPC) to bones. This study aimed to describe the clinical characteristics and outcomes of patients with mCRPC treated with radium-223 in a real-world setting. Methods: This was a retrospective study of patients with mCRPC treated with radium-223 between 2016 and 2020 at the London Health Sciences Centre in London, Canada. The baseline characteristics between the patients receiving 1–3 and 4–6 treatment cycles were compared using a two-sample t-test and Chi-square test. ANOVA was used to determine if there was a difference in each diagnostic variable per treatment cycle. Kaplan–Meier curves were generated to estimate progression-free survival (PFS) and overall survival in the patients treated with different numbers of cycles. Results: Fifty eligible patients were identified. The median age was 71 years (IQR: 66–76). Most patients (62%) received radium-223 beyond the third-line treatment. The mean number of radium-223 treatments was four. While 60% of the patients received 4–6 injections, 40% received 1–3 injections. Fifty-eight percent (58%) of the patients demonstrated a clinical benefit, with the remainder expressing either disease progression (28%) or stable disease (10%). The patients treated with 4–6 cycles had a delay to disease progression compared to those given 1–3 cycles of radium-223 (F5,35 = 10.52, p < 0.001). A higher alkaline phosphatase level prior to treatment was associated with a longer PFS (z33 = 2.362, p = 0.018). Treatment-related hospitalization for skeletal-related events was noted in 8% of the patients, and 14% required treatment discontinuation due to hematologic toxicity. Conclusions: This study confirms the safety of radium-223 in patients with mCRPC in a real-world setting. The radium-223 treatment was associated with a clinical benefit in the majority of the patients, particularly in those with higher pre-treatment serum alkaline phosphatase levels. Further studies to identify the predictive biomarkers are warranted to better guide the contemporary use of radium-223. [ABSTRACT FROM AUTHOR]

Background: Peripheral nodal B‐cell lymphomas (PNBCL) represent the most common presentation of lymphomas in dogs. Multiagent CHOP (C = cyclophosphamide, H = hydroxydaunorubicin [Doxorubicin], O = Oncovin, P = prednisolone)‐based chemotherapy protocols have been widely accepted as gold standard 1st‐line treatment. CHOP‐25 and CHOP‐19 are most commonly prescribed but have never been directly compared. Objectives: Our primary aim was to compare outcomes of dogs diagnosed with PNBCL, treated using a 1st‐line CHOP‐19 or CHOP‐25 protocol. A secondary objective was to determine the impact of protocol‐related variables on outcomes. Animals: Five hundred two dogs from 16 European oncology referral centers. One hundred fifty‐five dogs were treated with CHOP‐19 and 347 dogs with CHOP‐25. Methods: Retrospective, multicentric cohort study of dogs diagnosed with PNBCL between 2014 and 2021. Results: The 6‐month, 1‐year, and median progression‐free survival (PFS) were 56.5% (95% confidence interval [CI], 49.2‐65.0), 14.1% (95% CI, 9.4‐21.0), and 196 days (95% CI, 176‐233) with CHOP‐19; and 56.4% (95% CI, 51.4‐61.9), 17% (95% CI, 13.4‐21.6), and 209 days (95% CI, 187‐224) with CHOP‐25. The 1‐year, 2‐year and median overall survival (OS) were 36.9% (95% CI, 29.7‐46.0), 13.5% (95% CI, 8.6‐21.1), and 302 days (95% CI, 249‐338) with CHOP‐19; and 42.8% (95% CI, 37.7‐48.7), 15.4% (95% CI, 11.7‐20.4), and 321 days (95% CI, 293‐357) with CHOP‐25. No significant difference in PFS and OS was found between the 2 protocols. Conclusions and Clinical Importance: Our study confirmed similar outcomes for dogs with PNBCL treated with 1st‐line CHOP‐19 or CHOP‐25. Both protocols therefore could be used as a standard of care in future trials. [ABSTRACT FROM AUTHOR]

The prognosis of recurrent cervical cancer tends to be poor and there are limited effective treatments currently available for these patients. This study was developed to find a safe and effective treatment for patients with central pelvic recurrent cervical cancer. This retrospective study analyzed patients with central pelvic recurrent cervical cancer who received 3D-printed individual template (3D-PIT) brachytherapy between February 2019 and June 2023. Analyses of dosimetric parameters, toxicity-related complications, and survival were conducted based on the data of these patients. Twenty-one patients with central pelvic recurrent cervical cancer patients were enrolled. All of them received 3D-printed individual template (3D-PIT) brachytherapy. The mean respective adjusted cumulative HRCTV-D90 and HRCTV-D98 values for these patients were 86.9 Gy and 75.4 Gy. And the local control (LC) rate of these patients was 57.1%. In these 21 patients, only 2 (9.5%) of them experienced grade 3–4 rectal adverse reactions, while 7 (33.3%) patients experienced grade 3–4 bladder adverse reactions. 5(23.8%) patients had fistula, while 3 of these 5 patients had undergone prior anti-VEGF targeted drug treatment which is a risk factor of fistula. The respective 2-year rates of overall and progression-free survival (OS and PFS) for these patients were 72.9% and 57.4%, with a 26-month median PFS. These single-institution data highlight the potential viability of 3D-PIT brachytherapy as an approach to managing intractable central pelvic recurrent cervical cancer following first-line treatment. [ABSTRACT FROM AUTHOR]

The microvessel compartment is crucial in the tumour microenvironment of endometrioid adenocarcinoma (EA). This study investigated the role of vasculogenic mimicry (VM), CD146, and CD105 microvessel density in the clinical prognosis of EA. A total of 188 EA cases were analyzed, with VM channels and microvessels detected using PAS/CD31, CD146, and CD105 staining. Mann-Whitney and Fisher exact tests were used to compare the study groups according to the evaluated criteria. ROC analysis included determination of the confidence interval (CI) and area under the ROC curve. The Mantel-Cox test was used to analyze progression-free survival. Multivariate Cox proportional hazard analysis was performed using stepwise regression. Results showed that VM channels and CD146 and CD105 microvessels were significantly higher (p < 0.0001) in cases with unfavourable prognosis. Univariate survival analysis highlighted the significant role of these factors in progression-free survival, while multivariate Cox analysis identified VM and CD146+ vessels as predictive factors. This study demonstrates, for the first time, that VM, CD146, and CD105-positive vessels are involved in EA prognosis, suggesting their potential as independent prognostic indicators and targets for antiangiogenic therapy. However, these findings require further validation through large-scale studies. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to retrospectively analyse the response and prognosis factors for patients with lung adenocarcinoma exhibiting brain metastasis and epidermal growth factor receptor (EGFR) mutations, who were treated with a combination of EGFR-tyrosine kinase inhibitor (TKI) and brain radiotherapy (RT). Methods: Clinicopathological data of patients with lung adenocarcinoma were collected from January 2021 to January 2024 at the First Affiliated Hospital of Hebei North University. Statistical analysis was performed using SPSS version 26.0, with significance set at p < 0.05. Results: A total of 105 patients were included. The overall survival (OS) rates at 1, 2, and 3 years were 82.9%, 61.2%, and 33.7%, respectively. The progression-free survival 1 (PFS1) rates at 1, 2, and 3 years were 62.7%, 36.6%, and 22.1%, respectively. The progression-free survival 2 (PFS2) rates at 1, 2, and 3 years were 80.8%, 54.6%, and 31.4%, respectively. The median OS, PFS1, and PFS2 were 29.8, 18.0, and 28.1 months, respectively. Cox multivariate analysis identified gene mutation status and brain radiation dose as independent prognostic factors for OS. For PFS1, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors. Clinical stage, gene mutation status, brain radiation dose, and initial treatment response were independent prognostic factors for PFS2. Conclusion: The combination of TKIs and brain RT is effective for patients with lung adenocarcinoma with EGFR mutations and brain metastases. Patients with exon 19 Del or exon 21 L858R mutations and brain radiation doses ≥40 Gy exhibit longer OS, PFS1, and PFS2. Additionally, complete remission + partial remission is associated with extended PFS1 and PFS2, while patients in stage IVA show longer PFS2. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiotherapy (CCRT) is used as the primary treatment modality for currently limited cervical cancer and lacks non-invasive quantitative parameters to assess clinical outcomes of treatment for cervical cancer treatment. Purpose: To develop nomograms based on clinical prognostic factors and apparent diffusion coefficient (ADC) in predicting downstaging and progression-free survival (PFS) after CCRT for cervical cancer. Material and Methods: X-tile was used to calculate the optimal threshold for ΔADCmean(%) for prognostic stratification. Kaplan–Meier curves were used to calculate the difference in PFS between high- and low-risk groups. Univariate and multivariate Cox proportional risk regression models were used to identify clinical and radiological risk factors for prognosis and construct a prognostic nomogram model. Results: ΔADCmean(%) was significantly correlated with tumor downstaging; the area under the receiver operating characteristic curve (AUC) was 0.868. X-tile showed that the optimal threshold for ΔADCmean(%) to diagnose prognosis was 40.8. Kaplan–Meier curves showed that the low-risk population in the training group had significantly longer PFS within 3 years (P < 0.001). Multivariate Cox regression showed that ΔADC (%) is independent risk factor for PFS. The C-index of ΔADC(%) predicting 3-year PFS in the training set is 0.761 and the C-index of the nomogram model is 0.862. Conclusion: ΔADCmean(%) is a non-invasive biomarker for predicting tumor downstaging in cervical cancer after CCRT. The nomograms based on ΔADCmean(%) predict PFS of patients with cervical cancer with moderate accuracy. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and Aims: Outcome analysis of patients with Wilms' tumors (WT) is presented. Materials and Methods: A retrospective analysis of 23 children having WT managed by a single surgeon over 3 years (2021–2024) using the International Society of Paediatric Oncology Umbrella protocol was done. Results: The median age at presentation was 36 months; 32 months and 24 months for the unilateral WT (uWT) (n = 19) and bilateral WT (bWT) (n = 4), respectively. M: F ratio was 2.3: 1. WTs were localized in 19 (uWT-16; bWT-3) and metastatic in 4 (uWT-3; bWT-1) patients. Core-needle biopsy was done in 22 patients (26 renal units). Pre-therapy contrast-enhanced computed tomography volumetry (n = 20) showed a median tumor volume of 1023 ml (range: 47–2680 ml). Post-neoadjuvant chemotherapy (NACT) median tumor burden (n = 19) was 612 ml (range 59–3775 ml). Post-NACT, tumor volume decreased in 11/18 patients but increased in seven patients. NACT was avoided in one neonate. Nephroureterectomy (including one with excision of bladder cuff) and nephron-sparing surgery were done in 17 and 10 renal units including 3 with multifocal WT, respectively. Risk stratification was intermediate in 21 and High in 2. Overall staging in 19 uWT included Stage I-7, Stage II-5, Stage III-4, and Stage IV-3 (local staging-stage I in 1 and stage II in 2). Local staging in 8 renal units with bWT was Stage I in 7 and II in 1. One stage IV uWT had bilateral pulmonary metastatectomy. Adjuvant chemotherapy has been completed in 18 patients; two patients are still on adjuvant chemotherapy; flank radiation was administered in six patients. Three patients with synchronous bWT died; two due to acute kidney injury in the immediate postoperative period and one with metastatic disease who had abandoned adjuvant chemotherapy after the 1st cycle. Another patient died of a huge metachronous tumor in the contralateral kidney after a year of completion of therapy. One patient had successful multimodality treatment of local relapse with liver metastasis. 1-year overall and event-free survivals are 84% and 76%, respectively. Conclusions: Excellent short-term results for localized uWT from a center in a low-middle-income country are reported. [ABSTRACT FROM AUTHOR]

Background The microbiome has been associated with chemotherapy and immune checkpoint inhibitor efficacy. How this pertains to resectable esophageal carcinoma is unknown. Our aim was to identify microbial signatures in resectable esophageal carcinoma associated with response to neoadjuvant chemoradiotherapy with or without an immune checkpoint inhibitor. Methods From 2 prospectively collected esophageal carcinoma cohorts (n = 172 in total) treated with neoadjuvant chemoradiotherapy alone (n = 132) or a combination of neoadjuvant chemoradiotherapy and an immune checkpoint inhibitor (n = 40), fecal samples were available at baseline, during treatment, and presurgery. Additionally, in the immune checkpoint inhibitor–treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor, and duodenal DNA were extracted for 16S ribosomal RNA sequencing. Associations were investigated between microbiome composition pathological complete response and progression-free survival (PFS). Results There was a statistically significant shift in the microbiota profile of the fecal, tumor, and duodenal microbiota over time. In the total cohort, patients with a pathological complete response had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment (P  = .036). Presurgery, lower alpha diversity (<4.12) was related to worse PFS (log-rank P  = .025). Baseline tumor biopsies of patients with short PFS had more Fusobacterium. A low baseline duodenal alpha diversity (<3.96) was associated with worse PFS (log-rank P  = .012). Conclusions Lower intestinal alpha diversity was associated with worse response and survival of esophageal carcinoma patients. In tumor biopsies, Fusobacterium was more abundant in patients with poor PFS. After further mechanistic validation, these findings may aid in response prediction and the design of novel microbiome modulating treatments for esophageal carcinoma patients. [ABSTRACT FROM AUTHOR]

Aim: The main aim of this study was to evaluate the effectiveness of 18F-fluorodeoxyglucose (18FDG) positron emission tomography/computerized tomography (PET/CT) parameters in predicting the Kristen rat sarcoma viral oncogene(KRAS) mutation status of patients with colon cancer. Materials and Methods: Between April 2013 and December 2020, 79 patients who were diagnosed with colon cancer by colonoscopy underwent staging 18FDG PET/CT with this diagnosis and met all the inclusion criteria were included in this study. Clinical and prognostic features and also imaging (18FDG PET/CT and magnetic resonance imaging) reports of the patients were collected and analyzed retrospectively. Results:KRAS mutation was seen in 32 of patients (40.5%). No significant difference was observed between KRAS mutant and wild-type patients in terms of clinical features (tumor location, findings regarding metastasis, T stage, and tumor differentiation grade in patients who underwent surgery) and overall survival. Progression-free survival was significantly shorter in KRAS mutant patients (p = 0.018). Primary tumor standardized uptake value (SUVmean) was significantly higher in KRAS mutant cases in the whole group (p = 0.024) and in patients in whom KRAS analysis was performed only in the primary lesion (p = 0.036). The cutoff value for predicting KRAS mutation status was 7.01 g/mL (area under the curve [AUC]: 0.650, confidence interval [CI] 95%, 0.56–0.74). Conclusions: When colon and rectal cancer cases were evaluated separately, the primary tumor SUVmean value was significantly higher in KRAS mutant colon cancer cases. However, its effectiveness in predicting KRAS mutation status was low, similar to other parameters in the literature. [ABSTRACT FROM AUTHOR]

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set (n = 290) and a validation set (n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a major global health challenge with a need for new biomarkers and therapeutic targets. This work investigated the biological mechanisms and clinical value of Ly1 antibody reactive (LYAR) in CRC. Methods: We analyzed LYAR mRNA expression across multiple public databases, including genotype-tissue expression, gene expression omnibus, Oncomine, and the cancer genome atlas, alongside in-house immunohistochemical data to evaluate LYAR protein expression in CRC and non-CRC colorectal tissues. Gene set enrichment analysis (GSEA) was used to elucidate LYAR's biological functions, and its impact on the tumor immune microenvironment was assessed using CIBERSORT, ESTIMATE, and single-cell RNA sequencing techniques. In addition, LYAR's association with clinicopathological features and patient prognosis was explored, and its influence on drug sensitivity was investigated using the Connectivity Map database. Results: LYAR was significantly upregulated in CRC tissues compared with non-CRC colorectal counterparts, associated with altered immune cell composition and enhanced RNA processing, splicing, and cell cycle regulation. High LYAR expression correlated with poor disease-free and overall survival, underscoring its prognostic value. GSEA revealed LYAR's involvement in critical cellular processes and pathways, including DNA repair, cell cycle, and mTORC1 signaling. Correlation analysis identified genes positively and negatively associated with LYAR, leading to the discovery of temsirolimus and WYE-354, mTOR inhibitors, as potential therapeutic agents for CRC. Furthermore, LYAR expression predicted increased sensitivity to cetuximab in RAS wild-type metastatic CRC, indicating its utility as a biomarker for treatment responsiveness. Conclusions: LYAR's upregulation in CRC highlights its potential as a biomarker for prognosis and therapeutic targeting, offering insights into CRC pathology and suggesting new avenues for treatment optimization. [ABSTRACT FROM AUTHOR]

Objective: Extragonadal germ cell tumours have a more unfavourable prognosis than gonadal germ cell tumours. We aimed to evaluate the survival analysis, response rates, and factors affecting responses to high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in patients with relapsed/refractory extragonadal germ cell tumours. Methods: This study included patients diagnosed with extragonadal germ cell tumours who underwent HDCT + ASCT between November 2016 and January 2023 at Gülhane Training and Research Hospital. Clinical characteristics and follow-up data from patient records and the hospital's electronic system were retrospectively analysed. Patients under 18 years of age and those without medical records were excluded. Patient characteristics, post-HDCT progression-free survival (PFS), overall survival (OS) data, and factors affecting survival were examined. The relationship between clinical factors and OS/PFS was analysed. Results: Twenty-five patients were included in this study. Complete response (CR) was observed in seven patients (28%), partial response (PR) was observed in nine patients (36%), stable disease (SD) was observed in one patient, and progressive disease (PD) was observed in eight patients (32%) after HDCT + ASCT. The median follow-up period was 25.4 months. The median PFS and OS after HDCT + ASCT were calculated as 6.1 months and 12.2 months, respectively. Conclusions: Salvage HDCT + ASCT is an option in the treatment of extragonadal germ cell tumours, offering the potential for prolonged survival and curing. [ABSTRACT FROM AUTHOR]

Background: In advanced-stage esophageal squamous cell carcinoma (ESCC), treatment of both the primary tumor and metastatic sites is imperatively required. Consequently, an optimal treatment modality should effectively control both aspects. Therefore, the benefits of concurrent chemoradiotherapy (CCRT) in cases of advanced-stage ESCC should be evaluated. Methods: This retrospective study compared the efficacy and safety of CCRT versus chemotherapy alone for advanced-stage ESCC patients from January 2012 to December 2023 at a university hospital in Southern Thailand. Survival was assessed using the Kaplan–Meier approach, with comparisons being made by the log-rank test. A p-value of <0.05 indicated statistical significance. Results: From a total of 196 patients with stage IV ESCC, 117 (59.7%) received CCRT, while 79 (40.3%) received chemotherapy alone. The median overall survival (OS) time was 9.04 months for CCRT and 5.79 months for chemotherapy (hazard ratio, HR: 0.58 [0.43–0.78]). CCRT significantly improved OS time in stage IVA patients (HR: 0.52 [0.29–0.93]), but not in stage IVB patients (HR: 0.76 [0.51–1.11]). The median progression-free survival (PFS) time was 6.04 months for CCRT and 3.50 months for chemotherapy (HR 0.48 [0.35–0.65]). The objective response rates (ORRs) were 43.6% and 22.8%, respectively (p = 0.003). Hematological toxicities were more common with CCRT, along with mild cases of treatment-associated pneumonitis and dermatitis. Conclusions: Although palliative chemotherapy is the standard treatment for advanced-stage ESCC, CCRT provides significant benefits for patients with stage IVA ESCC, improving OS, PFS, and ORRs, despite there being a higher incidence of adverse events. Thus, CCRT should be considered for patients with stage IVA ESCC with a good performance status. [ABSTRACT FROM AUTHOR]

Glucocorticoid receptor (GR) activation may promote metastasis in oestrogen receptor-negative and triple-negative breast cancer (TNBC). However, the role of the GRβ isoform, which has opposing effects to the main isoform, has not been studied in clinical samples. We aimed to analyse the intracellular localisation of total GR and GRβ in vitro using plasmid constructs and fluorescent immunocytochemistry. Additionally, our goal was to perform immunostaining for total GR and GRβ on two cohorts: (i) on 194 clinical breast cancer samples to compare the expression in different molecular subtypes, and (ii) on 161 TNBC samples to analyse the association of GR with survival. We supplemented our analysis with RNA data from 1097 TNBC cases. We found that in the absence of the ligand, GR resided in the cytoplasm of breast cancer cells, while upon ligand activation, it translocated to the nucleus. A negative correlation was found between cytoplasmic GRtotal and Ki67 in luminal A tumours, while the opposite trend was observed in TNBC samples. Tumours with strong lymphoid infiltration showed higher cytoplasmic GRtotal staining compared to those with weaker infiltration. Patients with high nuclear GRtotal staining had shorter progression-free survival in univariate analysis. High cytoplasmic GRβ was a marker for better overall survival in multivariate analysis (10-year overall survival HR [95% CI]: 0.46 [0.22–0.95], p = 0.036). As a conclusions, this study is the first to investigate GRβ expression in breast tumours. Different expression and cellular localisation of GRtotal and GRβ were observed in the context of molecular subtypes, underscoring the complex role of GR in breast cancer. An inverse association between cytoplasmic GRtotal and the Ki67 proliferation index was observed in luminal A and TNBC. Regarding the impact of GR on outcomes in TNBC patients, while cytoplasmic GRβ was associated with a better prognosis, patients with nuclear GRtotal staining may be at a higher risk of disease progression, as it negatively affects survival. Caution should be exercised when using glucocorticoids in patients with nuclear GR staining, as it may negatively impact survival. [ABSTRACT FROM AUTHOR]

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS). We analyzed baseline, randomization, and 6-month post-remission samples from 24 patients (median age of 71 and 12 males). High-throughput NGS targeted 350 myeloid malignancy-related genes, considering variants with a variant allele frequency ≥ 4%. At diagnosis, all patients had 5 to 17 (median = 10) mutations, with DNMT3A (42%), NPM1 (33%), and TET2 (33%) being most frequent. FANCA mutations in four patients were linked to a higher relapse risk (HR = 4.96, p = 0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-scale transcriptomic datasets. The resulting seven-gene signature (KMT5C, DPP4, TYMS, CDC25B, IRF5, MEN1, and DNMT3B) was validated across independent cohorts and patient-derived xenograft (PDX) models. This signature demonstrated strong prognostic value for progression-free, disease-free, relapse-free, metastasis-free, and overall survival. Importantly, the signature not only identified specific NEPC subtypes, such as large-cell neuroendocrine carcinoma, which is associated with very poor outcomes, but also predicted a poor prognosis for PCa cases that exhibit this molecular signature, even when they were not histopathologically classified as NEPC. This dual prognostic and classifier capability makes the seven-gene signature a robust tool for personalized medicine, providing a valuable resource for predicting disease progression and guiding treatment strategies in PCa management. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma, the predominant primary tumor among all central nervous systems, accounts for around 80% of cases. Prognosis in neuro-oncology involves assessing the disease's progression in different individuals, considering the time between the initial pathological diagnosis and the time until the disease worsens. A noninvasive therapeutic approach called radiomic features (RFs), which involves the application of artificial intelligence in MRI, has been developed to address this issue. This study aims to systematically gather evidence and evaluate the prognosis significance of radiomics in glioblastoma using RFs. Methods: We conducted an extensive search across the PubMed, ScienceDirect, EMBASE, Web of Science, and Cochrane databases to identify relevant original studies examining the use of RFs to evaluate the prognosis of patients with glioblastoma. This thorough search was completed on 25 July 2024. Our search terms included glioblastoma, MRI, magnetic resonance imaging, radiomics, and survival or prognosis. We included only English-language studies involving human subjects, excluding case reports, case series, and review studies. The studies were classified into two quality categories: those rated 4–6 were considered moderate-, whereas those rated 7–9 were high-quality using the Newcastle–Ottawa Scale (NOS). Hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS were combined using random effects models. Results: In total, 253 studies were found in the initial search across the five databases. After screening the articles, 40 were excluded due to not meeting the eligibility criteria, and we included only 14 studies. All twelve OS and eight PFS trials were considered, involving 1.639 and 747 patients, respectively. The random effects model was used to calculate the pooled HRs for OS and PFS. The HR for OS was 3.59 (95% confidence interval [CI], 1.80–7.17), while the HR for PFS was 4.20 (95% CI, 1.02–17.32). Conclusions: An RF-AI-based approach offers prognostic significance for OS and PFS in patients with glioblastoma. [ABSTRACT FROM AUTHOR]

Findings regarding the relationship between sarcopenia and lymphoma have been inconsistent across studies. This study investigated the association between sarcopenia and lymphoma. We systematically searched the Embase, Science Direct, Cochrane Library, and PubMed databases from inception to 31 March 2024 to identify relevant studies. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Twenty-six studies with 3659 participants were included. Sarcopenic lymphoma patients had poor overall survival (OS) (HR = 1.88; 95% CI: 1.47–2.41; p < 0.001). The heterogeneity was high (I2=80%). However, the result of the Egger test indicated a significant publication bias (p < 0.001). After employing the trim and fill method to adjust for this bias, the HR of OS became non-significant (p > 0.05). The progression-free survival (PFS) was worse in sarcopenic patients (HR = 1.77; 95% CI: 1.37–2.29; p < 0.001; I2=70%). There was no significant publication bias (p > 0.05). In the subgroup analyses, sarcopenia was a negative predictor of OS in lymphoma patients who undergo hematopoietic cell transplantation (HCT) (HR = 1.61;95% CI: 1.19–2.18; I2=30%). Male lymphoma patients with sarcopenia had a significantly worse OS (HR = 2.29; 95% CI:1.24–4.24; p = 0.009). Among patients with primary central nervous system lymphoma (PCNSL), those with sarcopenia defined by temporal muscle thickness (TMT) exhibited significantly worse OS (HR = 2.20; 95% CI:1.04–4.65; p = 0.039; I2=68%). Sarcopenia is associated with worse PFS in lymphoma patients. Subgroup analyses indicate that sarcopenia is a negative predictor of OS after HCT, and male lymphoma patients who suffer from sarcopenia have higher mortality. Sarcopenia defined by TMT is also a negative predictor of OS for patients with PCNSL. [ABSTRACT FROM AUTHOR]