For many years, androgen deprivation therapy (ADT) alone was considered the established standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). A paradigm shift was initiated by the CHAARTED trial, which for the first time demonstrated a significant overall survival benefit with the addition of docetaxel to ADT. Further randomized trials also revealed a clinical benefit from intensifying ADT with the modern hormonal agents abiraterone, apalutamide, darolutamide and enzalutamide. Moreover, the triplet combination of darolutamide, ADT and docetaxel was shown to provide a survival advantage compared with chemo-hormonal therapy alone. These combination approaches are now considered the standard of care in mHSPC. Although the introduction of these treatment strategies has substantially prolonged median overall survival in patients with mHSPC, a considerable proportion of patients still experience early mortality during the course of the disease. Consequently, a significant unmet need for novel therapeutic options remains. This article aims to review first-line treatment options in the mHSPC setting and highlight their differences to support evidence-based therapeutic decision-making. In addition, emerging developments are discussed with the goal of further improving clinical outcomes.

Survival benefit of platinum-based chemotherapy in non-surgically treated advanced ovarian cancer: A nationwide study.

Abstract Background and objective: HER2 0 compared to HER2 low (1+ or 2+) is associated with worse survival in HER2-negative metastatic breast cancer (MBC). We explored the impact of HER2 status on survival in patients withe HER2-negative breast cancer (HER2-) and germline BRCA1, BRCA2, and PALB2 mutations. Methods: We evaluated outcomes among women with HER2- patients with breast cancer treated at MD Anderson Cancer Center from August 1996 to May 2024. Patient characteristics were analyzed using descriptive statistics and standard tests of association. Cox proportional hazard models evaluated factors associated with overall survival (OS). Results: PALB2. Among 93 patients with PALB2, median age at diagnosis was 49.5 years old (st.dev 10.5). 20 (21.5%) had Stage I, 21 (22.6% Stage II), 18 (19.4%) Stage III, 4 (4.3%) de novo Stage IV disease. ER was weakly positive in 4 (4.3%), negative in 28 (30.1%), positive in 61 (65.6%). PR was negative in 41 (45.2%), positive in 51 (54.8%). 48 (51.6%) were HER2 0, while 45 (48.3) were HER2 low (1+ or 2+). Of the 48 patients who were HER2 0, 5 died at last follow-up, with OS 89.6%. Of the 45 patients with HER2 low, 4 died with OS 91.1%. Median OS for HER2 0 patients was 130.06 months (95% CI 114.65, 145.465 months) compared to 261.96 months for HER2 low (95% CI 219.21, 297.89) (p < 0.05). BRCA1 and BRCA2. For 752 patients with BRCA1 and 2, median age was 44.5 years (st.dev 11.20). 224 (29.8%) had Stage I disease, 332 (44.1%) Stage II, 144 (19.1%) Stage III, and 42 (5.6%) de novo Stage IV. ER was negative in 374 (49.7%), positive in 377 (50.1%). PR was negative in 460 (61.2%) and positive in 289 (38.4%). HER2 was 0 in 443 (58.9%), 1+ in 208, 2+ in 101 (13.4%). BRCA1. Among 424 patients with BRCA1, 266 (62.7%) were HER2 0 and 158 HER2 low. Among 266 who were HER2 0, 49 died, with OS 81.6%. Among those who were HER2 low, 26 died, with OS 83.5%. Median OS was 289.34 (95% CI 229.66, 548.80) for patients with HER2 0 compared to 175.54 (95% CI 158.05,193.03) for HER2 low (p<0.05). BRCA2. Among 327 patients with BRCA2, 177 (54.1%) were HER2 0 and 150 HER2 low. Among 177 who were HER2 0, 26 died with OS 85.3%. Among those with HER2 low, 25 have died with OS 83.3%. For Her2 0, median OS was 384.46 months (95% CI 199.54, 441.99) compared to 172.927 for HER2 low (95% CI 107.98, 291.4) (p > 0.05). Conclusions: HER2 0 was associated with worse OS compared to HER2 low in patients with PALB2 mutations and with better OS compared to HER2 low in patients with BRCA1 and BRCA2, though the association for BRCA2 was not statistically significant. Future studies should address the impact of targeted therapy and tumor biology in these populations. Citation Format: D. Kizub, A. Gutierrez, R. K. Murthy, C. Albarracin, B. K. Arun. Association of HER2 0 vs HER2 low with median OS in patients with breast cancer and BRCA1, BRCA2, and PALB2 pathogenic mutations [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-03-24.

Abstract Background: The phase 3 MONALEESA-3 trial reported a statistically significant improvement in PFS with RIB + FUL over placebo (PBO) + FUL as first-line (1L) or second-line (2L) treatment (tx) in postmenopausal patients with HR+/HER2- ABC at the primary analysis (median: 20.5 months vs 12.8 months; HR: 0.59; 95% CI: 0.48-0.73; P < 0.001). Additionally, a statistically significant OS benefit with RIB + FUL was seen at the final protocol-specified analysis (HR: 0.72; 95% CI: 0.57-0.92), which was maintained with extended follow up (median follow-up time: 56.3 months; HR, 0.73; 95% CI: 0.59-0.90). Patients with the ILC subtype, who account for 10-15% of all breast cancer patients, show unique clinicopathological characteristics. This exploratory analysis examined the PFS and OS in a subgroup of MONALEESA-3 patients with ILC, including those receiving tx in the 1L setting. Methods: Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. PFS and OS were evaluated by log-rank test and Cox proportional hazards model stratified per interactive response technology by lung/liver metastasis status and previous endocrine therapy. PFS and OS were summarized using Kaplan-Meier methods. The data cutoff for this analysis was January 11, 2023. Results: Among all MONALEESA-3 patients (N=726), 120 (16.5%) had the ILC subtype, 77 of whom were treated with RIB + FUL and 43 with PBO + FUL. Additionally, of the 354 MONALEESA-3 patients receiving 1L tx, 56 (15.8%) had the ILC subtype, with 38 treated with RIB + FUL and 18 with PBO + FUL. Patient demographics and disease characteristics were balanced between the two tx arms in this subgroup. Patients had a median age of 63 y (RIB arm: 64 y; PBO arm: 63 y); 17.5% of patients had de novo ABC (RIB arm: 18.2%; PBO arm, 16.3%), and 81.7% patients had experienced relapse >12 months after completion of (neo)adjuvant therapy (RIB arm: 80.5%; PBO arm, 83.7%); 83.3% of patients had bone metastasis (RIB arm: 81.8%; PBO arm, 86.0%), and 45.0% had visceral metastasis (RIB arm: 48.1%; PBO arm: 39.5%). The baseline characteristics were similar among those with ILC receiving 1L tx and remained balanced between the two tx arms. Patients with ILC receiving RIB + FUL showed a longer PFS (median: 20.5 months) than those receiving PBO + FUL (median: 9.4 months, HR: 0.56; 95% CI: 0.37-0.86). The median PFS was further prolonged in patients with ILC receiving 1L tx with RIB + FUL (median: 26.3 months) over PBO + FUL (median: 18.1 months; HR: 0.78; 95% CI: 0.39-1.59). Additionally, patients with ILC receiving RIB + FUL had a longer OS (median: 51.2 months) than those receiving PBO + FUL (median: 30.8 months, HR: 0.62; 95% CI: 0.39-0.98); the median OS in patients with ILC receiving 1L tx with RIB + ET vs PBO + FUL was 59.6 months vs 40.0 months (HR: 0.54; 95% CI: 0.25-1.19). Rates of adverse events (AEs) including neutropenia, alanine aminotransferase elevation, and aspartate aminotransferase elevation in RIB + FUL-treated patients in the ILC subgroup (and in the 1L tx ILC subgroup) were comparable to those observed in the overall MONALEESA-3 population. Conclusions: Similar to the overall MONALEESA-3 population, RIB + FUL tx demonstrated an improvement in PFS and OS over PBO + FUL in patients with ILC, including among those treated in the 1L setting. The efficacy benefit of RIB observed in patients with HR+/HER2- ABC with the ILC subtype, including those receiving 1L tx, further supports the use of RIB in this patient population. Citation Format: M. De Laurentiis, J. Mouabbi, S. Im, M. Kruse, S. Chia, S. Brucker, C. Villanueva, G. Jerusalem, M. Gao, G. Sopher, J. Wu, J. Zarate, J. Beck. Progression-free survival (PFS) and overall survival (OS) results from the phase 3 MONALEESA-3 trial of postmenopausal patients with hormone receptor-positive (HR+)/HER2-negative (HER2−) advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL): A subgroup analysis of patients with invasive lobular carcinoma (ILC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-27.

Invasive fungal infections after CD19 chimeric antigen receptor T-cell therapy for B-cell lymphoma: a Lymphoma study association study from the DESCAR-T (Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells) registry.

The mesenchymal-epithelial transition (MET) receptor plays a key role in cell growth and survival. The MET exon 14 (METex14) skipping mutation occurs in 3% to 4% of patients with non-small cell lung cancer (NSCLC) and leads to prolonged MET signaling and oncogenesis. MET tyrosine kinase inhibitors (TKIs), such as tepotinib and capmatinib, are effective for METex14-altered NSCLC; however, their impact on patients with a poor performance status (PS) is unclear. We retrospectively analyzed clinical outcomes of MET-TKI treatment for NSCLC with the METex14 skipping mutation. We reviewed 59 cases of NSCLC with the METex14 skipping mutation diagnosed at the National Cancer Center Hospital between June 2020 and April 2024. Clinical data included demographics, PS, histology, PD-L1 expression, treatment response, progression-free survival (PFS), and overall survival (OS). Forty-nine patients (median age, 72 years; range=50-87 years; 53.1% male) received MET-TKIs (tepotinib or capmatinib). Thirty-seven patients and 12 patients had PS scores of 0 or 1 and ≥2, respectively. The median PFS and median OS of patients who received MET-TKI treatment were 5.6 months and 18.7 months, respectively. Thirty-seven patients who received first-line MET-TKI treatment had median PFS, median OS, and a median overall response rate (ORR) of 5.6 months, 21.3 months, and 48.6%, respectively. For patients with a PS score ≥2 (n=9), the median PFS, median OS, and median ORR were 0.95 months, 1.3 months, and 11.1%, respectively. A PS score ≥2 was strongly associated with shorter OS. Two of nine (22.2%) patients with a poor PS experienced improvement. MET-TKIs are effective for NSCLC with the METex14 skipping mutation; however, their efficacy for patients with a poor PS is limited.

Background:Patients with perihilar cholangiocarcinoma (pCCA) have high postoperative mortality and a poor prognosis. A reliable preoperative marker is needed to determine whether these patients are likely to benefit from surgical treatment.Objectives:This study aimed to verify the predictive value of preoperative albumin-bilirubin (ALBI) grades for 90-day mortality and long-term outcomes in these patients.Methods and design:This retrospective, multicenter, cohort study included patients with pCCA, surgically treated between January 2012 and December 2023. Patients were divided into ALBI 1–2 and ALBI 3 groups according to preoperative ALBI grade. Logistic and Cox regression analyses evaluated risk factors for 90-day death and overall survival (OS), respectively.Results:Of the 828 included patients, 243 (29.3%) had ALBI grade 3. In total, 744 (89.9%) and 89 (10.1%) patients underwent radical resection and palliative surgery, respectively. The 90-day mortality rate was 8.9% for the entire cohort and 16.5% for patients with ALBI 3, higher than that of ALBI 1–2 (5.8%). Age, extended hemihepatectomy, and ALBI 3 were independent risk factors for 90-day mortality. Patients with ALBI 3 had a higher postoperative intra-abdominal bleeding, bile leakage, and acute organ dysfunction. The median OS of patients with ALBI 3 (21.0 months) was shorter than that of ALBI 1–2 (29.0 months). In the radical resection subgroup, the median OS of ALBI 3 was 23.0 months, poorer than that of ALBI 1–2 (33.0 months).Conclusion:Preoperative ALBI grades can identify patients with pCCA who may benefit from surgical resection. Patients with ALBI 3 had a high risk of postoperative complications, 90-day mortality, and poorer long-term survival, and may benefit only marginally from surgical treatment.Trial registration:ChiCTR2500102958 (Medical Research).

Introduction. Glioblastoma is the most aggressive primary brain tumor, characterized by rapid progression and a median survival of no more than 12–18 months. Fluorescence-guided surgery should be of critical importance, as it allows visualization of the tumor and facilitates its complete removal, which is essential for increasing survival. Purpose of the study. Comparative analysis of remote treatment results in patients with glioblastoma using fluorescent surgery and white light surgery without fluorophores. Material and methods. A single-center, retrospective study included 54 patients with newly diagnosed glioblastoma (24 patients in the main group with fluorescent surgery; 30 patients in the control group with white light surgery without fluorophores). In the main group, 11 patients used 5 ALA (20 mg/kg) orally, and 13 patients received Photoditazine (1 mg/kg) intravenously. Preoperative magnetic resonance imaging (MRI) data allowed complete resection of contrast-positive tumor areas, according to the operating surgeon, in all patients. The groups were representative in terms of gender, age, tumor size, preoperative Karnofsky index, tumor resection radicality, and volume of postoperative adjuvant therapy. All patients underwent surgery using an operating microscope. Control of resection radicality was assessed based on contrast-enhanced MRI data performed within 24 hours after surgery. Remote treatment results were assessed based on overall and relapse-free survival data, taking into account stratification by MGMT promoter status as a predictive biomarker of response to adjuvant therapy. Results. The GTR97 % index in the fluorescent surgery group was 91.70 %, while in the control group it was only 60 %. The median free-progression survival in the fluorescence-guided surgery group was 10.1±1.1 months, in the control group (with white light surgery, without fluorescence-guided surgery) was 6.3±1.3 months (p=0.049). The median overall survival in the fluorescence-guided surgery group was 19.2±1.5 months, in the control group (with white light surgery, without fluorescence-guided surgery) was 13.6±1.4 months (p=0.075). The MGMT promoter status in patients was the main predictive independent prognostic factor (p>0.05), influencing the median overall and recurrence-free survival in both groups. The median overall survival in patients with a methylated MGMT promoter (MGMT+) in the fluorescent surgery group was 25.3±1.3 months, in the control group (with white light surgery, without fluorescent surgery) 16.8±1.1 months (p=0.068). For patients with an unmethylated MGMT promoter (MGMT-), the median overall survival in the fluorescent surgery group was 17.1±1.4 months, in the control group 11.0±1.9 months (p=0.083). Conclusion. Fluorescence-guided surgery not only increases the radicality of the surgical intervention, ensuring more accurate detection of the tumor and its resection, but also increases the median overall and relapse-free survival in patients with glioblastoma.

Cytoreductive surgery is the cornerstone of ovarian cancer treatment. However, a substantial proportion of patients do not undergo surgery, and, for this clinically relevant sub,-group, survival outcomes are not well defined and treatment strategies differ considerably. This study evaluates overall survival in women with non-surgically treated ovarian cancer and provides a comprehensive overview of their further treatment. Studies reporting survival in non-surgically treated patients with ovarian cancer were included. Those lacking relevant data, involving successful surgery only or other malignancies were excluded. Risk of bias was assessed with the ROBINS-I tool. Survival and treatment data were extracted and pooled to evaluate overall survival and compare treatment strategies. This systematic review followed the PRISMA guidelines and was registered in PROSPERO. Of 5759 records screened, 15 observational studies were included. Most studies had moderate to serious risk of bias; 4 were excluded from quantitative analysis due to critical bias. Reasons for non-surgical management included poor performance status, disease progression, and patient preference. The median overall survival for patients treated with chemotherapy alone ranged from 7.8 to 19.5 months, with a pooled survival of 13.18 months (95% confidence interval 4.83 to 21.53, I2 = 87.2%). For patients who did not receive systemic therapy, the median overall survival ranged from 1.2 to 5.0 months. Hazard ratios comparing chemotherapy alone to chemotherapy plus cytoreductive surgery yielded a pooled hazard rate of 1.95 (95% confidence interval 1.67 to 2.27, I2 = 58.9%). Treatment regimens varied widely but mainly included platinum-based chemotherapy with paclitaxel. Only 2 studies analyzed treatment regimens in relation to overall survival, showing inconsistent results. Patients with advanced ovarian cancer who do not undergo cytoreductive surgery had better survival when they received chemotherapy, although outcomes remain poorer than chemotherapy with surgery. Serious risk of bias and heterogeneity underscore the need for focused, prospective research in this population.

Objective: Exploring the therapeutic value of ovarianectomy in patients with colorectal cancer accompanied by ovarian metastasis and simultaneous multiple organ distant metastasis. Methods: A retrospective analysis was conducted on the clinical pathological data of 125 patients with colorectal cancer and ovarian metastasis accompanied by multiple organ distant metastasis, who were treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to December 2023. Based on whether ovarianectomy was performed, patients were divided into a surgical group (95 cases, 76.0%) and a non-surgical group (30 cases, 24.0%). The effectiveness of systemic treatment and overall survival (OS) were compared between the two groups. Results: Among the 95 patients in the surgical group, 8 patients (8.4%) experienced minor postoperative complications, with no instances of systemic treatment being affected by postoperative complications. Within the surgical group, 11 patients (11.6%) underwent preoperative neoadjuvant therapy. Postoperative pathological reports from these patients revealed that ovarian metastases exhibited the poorest treatment response compared to tumor foci in other sites, all demonstrating only mild therapeutic effects. All 95 patients in the surgical group received postoperative systemic treatment (chemotherapy±targeted therapy), and the efficacy was assessed. Among them, 16 patients (16.8%) had partial remission (PR), 57 patients (60.0%) had stable disease (SD), 3 patients (3.2%) had disease progression (PD), and 19 patients (20.0%) could not be evaluated. In the non-surgical group of 30 patients, 7 (23.3%) had SD and 23 (76.7%) had PD. The difference in efficacy between the two groups was statistically significant (P＜0.001). The median OS for all patients was 28 months (95% CI: 21.5-34.5), with 1-, 3-, and 5-year survival rates of 84.5%, 40.7%, and 23.9%, respectively. The median OS for patients in the surgical group was 35 months (95% CI: 23.9-46.1), with 1-, 3-, and 5-year survival rates of 87.1%, 45.0%, and 26.4%, respectively. The median OS for patients in the non-surgical group was 23 months (95% CI: 16.6-29.4), with 1-, 3-, and 5-year survival rates of 76.2%, 27.8%, and 13.9%, respectively. The prognosis of patients in the surgical group was significantly better than that in the non-surgical group (P=0.034). Conclusion: Performing ovarianectomy in patients with colorectal cancer and ovarian metastases accompanied by multiple organ distant metastases can prolong survival, improve the efficacy of systemic treatment, and enhance quality of life, resulting in significant overall clinical benefits.

Outcomes for upper gastrointestinal (UGI) cancers are poor except for those patients whose cancers are diagnosed at a very early stage. Unique socioeconomic factors may result in worse outcomes in the safety-net setting given that these patients often seek care later in the disease course. This study aims to understand the survival outcomes of patients with UGI cancers in a safety-net health care (SNH) setting. Patients diagnosed with esophageal squamous (ES), esophageal adenocarcinoma (EA), and gastric carcinomas (G) at JPS Health Network in Fort Worth, Texas from January 1, 2018, to December 31, 2022, were identified in the tumor registry database. The electronic health record was queried for clinical characteristics, pathology variables, and management outcomes. Kaplan-Meier curve was used to illustrate the difference in survival time across cancer stages from an index date of diagnosis with censoring at date of last contact. A total of 171 patients were included: the median age was 57 years, but 15 patients were under 40 years. By ethnicity, 40% were Hispanic. The majority were male (71%) and uninsured (65%). G was the most common primary site (n = 92, 54%), followed by EA (n = 58, 34%) and ES (n = 21, 12%). Of the 125 stage 4B patients, 69 (55%) did not receive any treatment, 6 received only palliative radiation, and the remainder received systemic therapy. In patients with stage 4B, the median overall survival for patients with systemic treatment was 7.9 months (95% CI: 6.7-11), compared with 2.1 months (95% CI: 1.5-3.0) without treatment. In an urban safety-net population with a high percentage of Hispanic population, most patients with advanced UGI cancers did not receive systemic therapy. Interventions to improve outcomes must consider the unique socioeconomic needs of this vulnerable population to translate clinical trial results into improved outcomes.

Background. Due to increasing life expectancy, the incidence of metastatic renal cell carcinoma (mRCC) in patients aged ≥75 years is growing. Further studies are needed to determine additional prognostic factors in elderly patients with mRCC and indications for systemic therapy. Aim. To determine the impact of prognostic factors and systemic therapy on survival rates in patients aged ≥75 years and 75 years with mRCC. Materials and methods. A retrospective study included 172 patients with mRCC, including 77 patients aged ≥75 years, who received systemic therapy at the Moscow City Oncology Hospital No. 62 (Moscow) and the City Clinical Oncological Dispensary (Saint Petersburg) between 2006 and 2020. Clinical data from the medical records were obtained and analyzed retrospectively, all patients underwent clinical, laboratory, and pathomorphological examination. Survival rates were evaluated using statistical survival analysis with calculation of descriptive characteristics of lifespans in the form of a life table and construction of Kaplan–Meier curves. Results and conclusion. In the study, elderly patients were less likely to be in the IMDC (International Metastatic RCC Database Consortium) favorable prognosis group (20.8 % vs 29.5 %). In patients ≥75 years of age, solitary metastases (6.5 % vs 15.8 %), liver (7.8 % vs 23.2 %) and lymph node metastases (27.3 % vs 41.1 %) were less frequent, but metastatic bone involvement was more frequently observed (33.8 % vs 26.3 %). In patients ≥75 years of age, metastasectomy was significantly less frequently performed (14.3 % vs 34.7 %). Only liver (p = 0.0066) and lymph node (p = 0.0037) metastases were statistically significantly less frequent in elderly RCC patients, as well as metastasectomy (p = 0.01). The 3- and 5-year overall survival rates in mRCC patients 75 years and ≥75 years were 54.4 % and 35.8 %, 39.7 % and 21.2 % (p = 0.03), respectively. Median overall survival in patients 75 (n = 95) and ≥75 years (n = 77) of age with mRCC was 43.8 months (95 % confidence interval 31.9–52.3) and 32.4 months, respectively (95 % confidence interval 28.9–38.6). Multivariate analysis of patients ≥75 years of age, showed independent negative effect of gender (p 0.001), tumor histologic subtype (p = 0.043), number of metastases (p = 0.049), metastases to bone (p 0.001) and lymph nodes (p = 0.026), IMDC prognosis (p = 0.01), and radiation therapy (p = 0.002) and nephrectomy (p 0.001) on overall survival rates. Multivariate analysis of patients 75 years of age confirmed independent negative effect of tumor histologic subtype (p 0.001) and bone metastases (p = 0.034) on overall survival rates. Older patients with mRCC showed better response to first- and second-line systemic therapy: 57.1 % and 40 %, 65.1 % and 48.5 %, respectively. It is necessary to expand the indications for active treatment in senile mRCC patients in order to increase survival rates.

Background:JAK/STAT interferon signaling interacts with the PI3K/AKT/mTOR pathway to drive hepatocellular carcinoma (HCC) progression and metastasis. RSAD2, an interferon-inducible gene, is upregulated by the PI3K/AKT/mTOR pathway and serves as a key factor for metabolic reprogramming to promote stem-like properties of cancer stem cells and tumor proliferation. In patients with resected HCC, RSAD2 upregulation showed an association with microvascular invasion, which is a proven risk factor for developing HCC metastasis. This clinical observation was compatible with preclinical findings. On the other hand, RSAD2 upregulation has been reported to confer poor prognosis in breast and gastric cancers. However, further clinical study of RSAD2 in HCC is lacking. As a result, we investigated the clinical implications of RSAD2 gene expression in HCC patients, in terms of its associations with survival, the presence of extra-hepatic metastasis, and other clinical manifestations. Methods: We studied 309 treatment-naïve HCC patients, as well as data from the TCGA and GTEx databases. Results:RSAD2 gene expression was differentially upregulated in HCC tumors when compared to normal liver tissues (p < 0.01). Elevated RSAD2 mRNA levels in the blood and the presence of extra-hepatic metastasis were independent prognostic factors for poor overall survival (OS) (p < 0.01). The median OS of patients with high RSAD2 expression vs. low expression were 5.4 vs. 14.2 months, respectively (p < 0.01). A high RSAD2 mRNA level was significantly correlated with the presence of extra-hepatic metastasis, nutritional disturbance, and functional impairment after controlling for confounding clinical factors (p < 0.05). Conclusions: High RSAD2 gene expression is associated with poorer OS, the presence of extra-hepatic metastasis, and quality-of-life disturbances in HCC patients.

Lung cancer after lung transplantation: Early detection and curative surgery drive long-term survival.

Proton Beam Therapy for Intrahepatic and Perihilar Cholangiocarcinoma: A Multicenter Prospective Registry Study: Potential Candidates for High-Dose Proton Beam Therapy.

Primary cardiac sarcomas (PCSs) are uncommon malignant tumors with a poor prognosis. This study aims to present the clinical characteristics and treatment outcomes for PCS observed in our centers. We retrospectively gathered records of patients diagnosed with PCS at Peking University Cancer Hospital and Zhejiang Cancer Hospital between 2016 and 2023. Clinicopathological data, treatments, and outcomes were included in the analysis. Between January 2016 and October 2023, a total of 26 patients with primary cardiac sarcoma were included in this study, with a majority being female (57.7%). The median age of the patients was 38.5 years, ranging from 15 to 82 years. The median overall survival (OS) for all patients was 18.7 months (95% CI: 16.2-25.4). Patients with normal baseline LDH levels had a significantly longer median OS of 25.4 months compared to 12.9 months for those with elevated LDH levels (p < 0.01). The median OS for patients who underwent R0 resection was 23.7 months, while it was 16.9 months for those who underwent R1/R2 resection, and 11.6 months for those who did not undergo surgery. Patients who received anthracycline-based chemotherapy seem to have better survival outcomes compared to those who received paclitaxel-based chemotherapy (mOS for chemotherapy 11.3 vs. 8.97 months, p = 0.25), but there was no statistical difference. First-line treatment with antiangiogenic agents or immunotherapy may enhance survival, with statistical significance observed. PCS presents a complex management challenge. Complete surgical resection remains the primary treatment option when feasible. Systemic treatment options, including chemotherapy, targeted therapy, and immunotherapy, may also improve survival outcomes.

The aim of this study was to assess the efficacy and safety of pimitespib in real-world clinical settings for tyrosine kinase inhibitor-resistant GISTs. We retrospectively analyzed 15 patients at Osaka University Hospital. Patients treated with pimitespib as a fourth- or later-line treatment for unresectable or recurrent GISTs were included. Patient background, pimitespib dose, number of courses, adverse events, best response, progression-free survival, and overall survival were analyzed. The median overall survival of patients treated with pimitespib was 24.4months（95% confidence interval [CI] 7.2-not reached) and the one-year overall survival rate was 70.9%. The median progression-free survival was 4.6months (95%CI 1.8-7.4), and the one-year progression-free survival rate was 15.2%. A partial response was observed in 0 patients, stable disease lasting for ≥ 12weeks in 7 (46.7%), progressive disease in 7 (40.0%), and a non-evaluable state in 2 (13.3%). The disease control rate was 40%. Treatment-related adverse events were reported in all patients, with the most common being diarrhea (87%), followed by anorexia (27%), nausea (27%), and increased blood creatinine levels (27%). None of the patients discontinued the treatment because of adverse events. Pimitespib may offer a tolerable and effective treatment option for patients with unresectable or recurrent GISTs in clinical practice.

Purpose: We aimed to study the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) in the treatment of unresectable hepatocellular carcinoma (HCC) with extrahepatic spread (EHS). Materials and Methods: A total of 323 patients with unresectable HCC received HAIC plus lipiodol microvascular embolization. HAIC was performed via puncture of the left subclavian artery with a temporary 4-French angio-catheter placed in the common/proper hepatic artery. The HAIC regimen consisted of a daily infusion of cisplatin (10 mg/m2), mitomycin-C (2 mg/m2), and leucovorin (15 mg/m2), administered over a period of 20–30 min, and then a 5-fluorouracil (5-FU, 100 mg/m2) infusion for the remaining of 22 h of each day, for five consecutive days. Before the temporary catheter was removed, 10 mL of ethiodized oil (Lipiodol, Guerbet, France) was injected to obtain a synergistic effect of chemoinfusion and lipiodol microvascular embolization. Treatment responses were evaluated based on mRECIST criteria. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients with EHS were compared to those without. Subgroup analyses of patients with and without major portal vein tumor thrombosis (PVTT) were performed both before and after propensity score matching (PSM). The survival analyses were conducted with the Kaplan–Meier method and compared using the log-rank test. All the statistical analyses were performed by SPSS (version 26.0). Result: The overall ORR was 59.1%. The median OS of the initial cohort and patients positive and negative for EHS were 16.3, 12.0, and 18.0 months, respectively (p = 0.002). In the subgroup analysis, there was no statistical difference in survival in patients with major PVTT between the with-EHS and without-EHS groups (13.0 vs. 15.0 months, p = 0.407). However, the median OS in patients with EHS was significantly shorter than those without EHS (11.4 vs. 19.4 months, p < 0.001) in the subgroup of non-major PVTT patients. After PSM, there were no significant survival differences between the EHS and non-EHS groups in any patient cohort or sub-cohort analysis. Conclusions: For unresectable HCC, controlling intrahepatic tumor progression through HAIC is more important than controlling extrahepatic tumor growth, especially in patients with major PVTT. Personalized locoregional HAIC can be performed in patients with EHS.

Background:Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate uesd for the treatment of HER2- positive (HER2+)breast cancer. This systematic review aimed to evaluate the efficacy and safety of T-DXd in advanced HER2-positive breast cancer.Methods:PubMed, Web of Science and Embase databases were searched for literature on trastuzumab deruxtecan treatment for HER2-positive or low-expression breast cancer before December 30, 2024. The outcome measures were progression-free survival (PFS), overall survival (OS), objective response rates, and adverse events of any grade and grade ≥ 3. Meta-analysis of the relevant data was performed using Stata 14.0.Results:A total of 2995 patients from 7 studies were included. The median PFS and median overall survival of patients in the T-DXd group were significantly longer than those of patients in the control group (mPFS HR = 0.43;95% CI:0.31–0.62, p<0.05; mOS HR = 0.72; 95% CI:0.64–0.82, p<0.05). Further subgroup analyses based on differences in hormone receptor expression, occurrence of brain metastases, visceral basal conditions, and previous lines of treatment showed that all patients in the T-DXd group had significantly longer mPFS than those in the control group (P < .05). The objective remission rate of patients in the T-DXd group was significantly higher than that of patients in the control group (RR = 2.31; 95%CI: 1.88–2.85, P<0.05). In addition, the T-DXd also increased the incidence of adverse events such as anemia, nausea, vomiting, constipation and interstitial lung disease, but the incidence of neutropenia, diarrhea, and alopecia was not significantly different between the 2 groups. No significant publication bias was observed in this study. The results of the sensitivity analysis showed high heterogeneity in mPFS, but the results obtained after excluding the DESTINY-Breast04 studies were all more robust.Conclusion:T-DXd has significant long-term and near-term efficacy in prolonging median overall survival, median PFS, and increasing the objective remission rate in patients with HER2-positive or low-expression breast cancer; however, the treatment is associated with notable adverse events, and physicians should be alert to the occurrence of serious adverse events when using this drug.

This study aimed to provide evidence regarding the treatment of patients with unresectable pancreatic cancer. We conducted a prospective single-arm phase II trial using the FOLFIRINOX regimen. After completing 4–8 cycles, patients underwent surgical resection when feasible. The primary endpoint was R0 resection rate. Fifteen patients were enrolled in this study. A median of six courses of FOLFIRINOX chemotherapy was administered, and a partial response or R0 resection was achieved in 26.7% and 33% of the patients, respectively. Severe adverse events due to chemotherapy and major surgical complications were observed in 33.3% and 6.7% of patients, respectively. The median overall survival of patients who underwent R0 resection or with R1 or unresectable disease was 47.8 months (95% confidence interval (CI), 22.5–73.1) or 14.5 months (95% CI, 11.8–17.2), respectively (P = 0.031). Well-selected patients with unresectable locally advanced pancreatic cancer treated with FOLFIRINOX achieved relatively high R0 resection rates and prolonged survival. Therefore, induction with FOLFIRINOX is feasible and well tolerated for locally advanced, initially unresectable pancreatic cancer and may be effective in facilitating R0 resection and prolonging survival.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-23608-5.