Cancer Medicine最新文献

Background: The level of measurable residual disease (MRD) is one of the most important features correlating depths of response and long-term outcomes in multiple myeloma (MM) and MRD evaluation is currently the gold standard tool for assessing treatment response. Nevertheless, reproducibility across laboratories is a major concern, as discrepancies among results make comparability impractical.

Aims: herein, we report preliminary results from the "Italian MM-MRD network" project.

Patients & methods: MRD in bone marrow (BM) samples have been measured from newly diagnosed MM patients using next-generation flow-cytometry (NGF) or next-generation sequencing (NGS) approaches in different laboratories.

Results: The NGF workgroup (7 laboratories) implemented the Euro-Flow Standard-Operating-Protocol to reach minimum 1 × 10^-5 sensitivity. The inter-operator retrospective study (Stage 1) showed high inter-center concordance in monoclonal plasma cells detection (ICC = 0.90, p < 0.001), whereas moderate concordance was observed in the inter-laboratory correlation (Stage 2) in in-vivo samples (ICC = 0.63, p < 0.001), reaching a median limit-of-detection (LOD) and limit-of-quantification (LOQ) of 8 × 10-6 and 2 × 10^-5, respectively. Greater variability was also observed in the analysis of other BM cell populations. The NGS workgroup (4 laboratories) employed a targeted amplicon-based approach to detect clonotypic IGH/IGK gene rearrangements in diagnostic samples, subsequently used to track MRD in mock samples. The experimental design was divided into three quality-control (QC) rounds, focused on finding a shared strategy for clonotype identification (QC1: 100% concordance among centers), or quantifying MRD in mock samples (concordance: 81% [QC2]; 91% [QC3]). The 10^-5-sensitivity level was successfully reached in most of tested dilutions (QC2: 19/20 = 95%; QC3: 19/23 = 83%).

Conclusion: Overall, this pilot study provided preliminary data for MRD harmonization across Italian centers, paving the way for an expanded network, aiming at reducing variability, improving comparability, and enabling broader use of MRD-monitoring in clinical practice.

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes across several cancers, yet many patients do not respond, highlighting the need for robust predictive biomarkers. Tertiary lymphoid structures (TLS), ectopic lymphoid aggregates that support local antigen presentation and adaptive immune activation, have emerged as potential indicators of favourable prognosis and immunotherapy responsiveness.

Methods: This review summarises current clinical and translational evidence examining the prognostic and predictive value of TLS in solid malignancies. Studies assessing TLS presence, organisation, and biological function were identified through searches of major scientific databases and evaluated with respect to their association with patient outcomes and responses to ICIs.

Results: Across multiple tumour types, TLS correlate with improved survival and enhanced anti‑tumour immune activity. TLS‑rich tumours typically show increased infiltration of effector immune cells and more inflamed tumour microenvironments. Several studies also indicate that TLS maturity, particularly the presence of germinal‑centre‑like features, strengthens their predictive value for ICI benefit. However, substantial variation exists in TLS assessment methods and definitions, limiting comparability and hindering translation into routine clinical use.

Conclusions: TLS represent a promising biomarker for prognosis and immunotherapy response. Standardised evaluation methods and prospective clinical validation are essential to enable their integration into personalised treatment strategies.

Background: Immune-related hepatitis (ir-hepatitis) is an immune-related adverse event that can be resistant to systemic steroid therapy. Mycophenolate mofetil (MMF) is recommended for steroid-refractory cases; however, evidence supporting its efficacy remains unclear. We aimed to evaluate the efficacy of MMF in patients with solid tumors, the optimal timing for administration, and its effect on cumulative steroid dosage.

Methods: A retrospective cohort analysis was conducted between January 2015 and August 2023. We obtained data from eligible consecutive patients who developed ir-hepatitis with grade ≥ 2 alanine aminotransferase (ALT) elevation requiring systemic steroids. Participants were divided into three groups: MMF-early combination, MMF-late combination, and systemic steroid-only. ALT improvement rate was used to assess the efficacy of MMF based on the Common Terminology Criteria for Adverse Events version 5.0.

Results: Among 4405 patients treated with immune checkpoint inhibitors, 151 (3.4%) developed ir-hepatitis requiring systemic steroids, of whom 123 had grade ≥ 2 ALT elevation. The median patient age was 62 years (interquartile range: 54-72), and 42 patients (34%) received MMF. Forty-one patients were evaluable for MMF timing. The ALT improvement rate on day 7 was significantly higher in the MMF-early combination group (n = 10) than in the MMF-late combination group (n = 31) (78.5% vs. 41.6%, p < 0.01). Among 40 patients evaluable for steroid dosage, cumulative systemic steroid dosage was significantly lower in the MMF-early combination group (n = 8) than in the MMF-late combination group (n = 32) (2121 mg vs. 3745 mg, p = 0.03). These effects were comparable even for the MMF-early combination and systemic steroid-only groups.

Conclusions: Despite the small sample size, early combination therapy with MMF and systemic steroids rapidly improved ir-hepatitis, consequently reducing the cumulative systemic steroid dosage.

Background: Over half of esophageal cancer (EC) cases occur in China, where paclitaxel and platinum agents have become the preferred chemotherapeutic regimen for EC patients. However, there is a clinical need for a non-platinum-based therapeutic option.

Methods: Cases were collected from Sun Yat-sen University Cancer Center between January 2019 and November 2023. Patients with metastatic or locally advanced EC received 4-6 cycles of chemo-immunotherapy, including nab-paclitaxel, capecitabine, and a programmed death receptor 1 (PD-1) inhibitor, with or without subsequent surgery, radiotherapy, or maintenance therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), pathological complete response (pCR), complete (R0) resection rate, and major pathologic response (MPR) were assessed.

Results: Among the 72 patients retrospectively analyzed, the median PFS was 24.7 months (95% confidence interval: 7.0-42.3 months). 75% of patients were regarded as responders, with an ORR of 66.7% in 42 patients with measurable lesions. The 6-month, 1-year, and 2-year PFS rates (DCRs) were 100%, 96.2%, and 67.9%, respectively. In total, 9 patients underwent surgery, and 29 patients received radiotherapy following the regimen. The R0 resection rate was 77.8%, while both pCR and MPR were 66.7%. The most common adverse events were myelosuppression (27.8%) and liver dysfunction (25.0%).

Conclusion: Our study demonstrated that the combination of nab-paclitaxel, capecitabine, and a PD-1 inhibitor was an effective and tolerable strategy for EC patients and a promising first-line or neoadjuvant treatment option.

Background: This study evaluated the long-term survival outcomes of concurrent chemoradiation (CCRT) for high-risk salivary gland carcinomas (SGCs).

Method: Postoperative patients with high-risk SGCs, other than adenoid cystic carcinoma (ACC), with T3-4/N1-3M0 disease were enrolled. This study included a cohort of 55 patients who received CCRT, derived from a prospective phase II trial, and a retrospective cohort of 61 patients treated with RT alone.

Results: The median follow-up for survivors was 54.1 months. In the subgroup analysis, patients without ENE treated with CCRT showed significantly better 5-year OS (83.4% vs. 69.0%, p = 0.032), with a numerically higher 5-year DFS (57.3% vs. 41.6%, p = 0.062). In the subgroup of patients with N0-1 disease, those treated with CCRT showed a numerically higher 5-year DFS (69.1% vs. 44.9%, p = 0.073) and OS (90.7% vs. 76.2%, p = 0.057). On multivariate analyses, CCRT significantly predicted superior DFS (p = 0.021) and OS (p = 0.004) for patients without ENE and superior DFS (p = 0.027) for patients with N0-1 disease.

Conclusion: For postoperative high-risk non-ACC SGCs, CCRT was associated with improved long-term survival outcomes in patients without ENE or with N0-1 disease, which need further evaluation in randomized trials. However, for patients with ENE or N2-3 disease, they may need alternative treatment strategies to enhance their prognosis.

Trial registration: The prospective cohort analyzed in this study originated from the non-ACC group enrolled in a phase 2 clinical trial (NCT02776163).

Context: Limited information is available on the symptom burden and symptom clusters in cancer survivors.

Objectives: Describe the occurrence, severity, and distress of 44 symptoms; determine risk factors associated with a higher symptom burden; and evaluate for symptom clusters using symptom occurrence rates.

Methods: Survivors (n = 1147) were recruited using an online survey. Symptom burden and symptom clusters were assessed using the Memorial Symptom Assessment Scale that included 44 symptoms and evaluated occurrence, severity, and distress. Simultaneous multivariable linear regression analysis was performed to determine risk factors associated with a higher symptom burden. Exploratory factor analysis was used to identify symptom clusters using ratings of symptom occurrence.

Results: Survivors reported an average ten concurrent symptoms. Survivors who are younger, female, with a higher comorbidity burden, evidence of metastatic disease, and a poorer functional status were at increased risk for a higher symptom burden. Six symptom clusters were identified (i.e., psychological cluster, cancer and treatment-related cluster, respiratory cluster, pain cluster, weight loss cluster, epithelial cluster).

Conclusion: Additional research is warranted to confirm the prevalence rates for the various symptoms and symptom clusters; identify additional risk factors for a higher symptom burden; and determine the underlying mechanisms for the symptom clusters. Future studies need to develop and test targeted interventions for each of the symptom clusters within and across various types of cancer.

Purpose: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) effectively treats high-risk acute lymphoblastic leukemia (ALL), yet challenges persist due to post-transplant relapse and conditioning regimen toxicities. The determination of an appropriate preconditioning regimen is critical to improving patient outcomes. In our transplant center, we have modified the traditional busulfan (Bu)/cyclophosphamide (Cy)/etoposide (Vp16) protocol by adding fludarabine (Flu) and cytarabine (Ara-C), while reducing the dosage of Cy. This novel modification seeks to enhance transplantation outcomes for ALL patients.

Methods: This study retrospectively collected clinical data from 88 high-risk ALL patients who received transplantation from June 2018 to December 2023. Among these patients, 40 received the novel modified Bu/Cy/Vp16/Flu/Ara-C conditioning protocol, while 48 received the traditional Bu/Cy/Vp16 regimen and served as a control group.

Results: This study demonstrated a notably reduced incidence of cardiac toxicity in patients treated with the modified Bu/Cy/Vp16/Flu/Ara-C conditioning compared to those on the traditional Bu/Cy/Vp16 regimen. Furthermore, other types of conditioning-related toxicities were within acceptable limits in the modified regimen group. Regarding efficacy, the Bu/Cy/Vp16/Flu/Ara-C protocol significantly reduced the cumulative two-year relapse rate in high-risk ALL patients compared to the Bu/Cy/Vp16 scheme (38.7% (20.9%-52.5%) vs. 11.8% (0.2%-22.1%), p = 0.017). The modified regimen showed significant improvements in 2-year overall survival at 71.6% (57.1%-89.6%) compared to 50.6% (38%-67.3%) (p = 0.048), and in two-year disease-free survival at 66.7% (51.9%-85.6%) compared to 45.3% (33.1%-62.1%) (p = 0.015). Transplant-related mortality was comparable between the two groups. A subgroup analysis based on disease status (CR1 and ≥ CR2) revealed that high-risk ALL patients on the modified regimen had lower relapse rates and significantly better OS and DFS than those on the Bu/Cy/Vp16 scheme.

Conclusions: The novel modified Bu/Cy/Vp16/Flu/Ara-C conditioning significantly enhances the prognosis of high-risk ALL patients receiving transplantation, especially those in CR1.

Objective: Lymph node metastasis (LNM) is an important factor leading to poor prognosis of tumors. This study aims to predict the risk probability of LNM in neuroendocrine carcinoma of cervix (NECC).

Methods: 202 and 92 patients were included as the training cohort and the validation cohort respectively. Logistics regression analysis was conducted to determine the risk factors related to LNM in the training cohort. The validity of the model was evaluated by the calibration curve and the consistency index. The receiver operating characteristic curve was used to determine the optimal threshold for predicting the risk of LNM. Then, it compared the predictive ability of the different models and their ability to identify low-risk patients.

Results: Multivariate logistic regression analysis confirmed that the depth of stromal invasion (p = 0.029), parametrium invasion (p = 0.046), lymphovascular space invasion (p = 0.011), cervical-uterine junction invasion (p = 0.046), and positive CD56 (p = 0.008) were the independent risk factors for LNM, which were included in the construction of the nomogram model. Both the internal and external calibration curves showed that the model fits well. The C-index of the training cohort and the validation cohort in this developed model (0.894 and 0.92, respectively) was superior to other models. The optimal threshold of risk probability of LNM predicted by the model was 0.20. Based on this threshold, this model showed a good recognition ability to identify low-risk patients.

Conclusion: The nomogram model constructed by combining clinical parameters with neuroendocrine markers could effectively predict the risk probability of LNM in NECC and identify the low-risk population.

Background: Hepatocellular carcinoma (HCC) survival in the United States varies sharply by neighborhood disadvantage.

Aim: To determine whether residence in persistently impoverished or low-SES census tracts is independently associated with lower all-cause and HCC-specific survival.

Methods: We identified 51,323 adults with HCC using a population-based retrospective cohort from the Surveillance, Epidemiology, and End Results Research Plus Specialized Database (2006-2020). Two census tract-level socioeconomic exposures were defined: persistent poverty (≥ 20% living below the poverty line for approximately 30 years) and low SES (Yost Index first quintile). Overlap Propensity Score Weighting, combined with marginal structural models, estimated the 1-, 5-, 10-, and 15-year risks of all-cause and HCC-specific mortality.

Results: The median follow-up was 16 months, 6058 (11.8%) lived in persistently impoverished tracts, and 9863 (19.5%) lived in low-SES tracts. After weighting, residents of persistently impoverished areas had a 1-year all-cause mortality risk of 46.0% vs. 40.3% (RD, 5.6%; 95% CI, 4.4% to 6.9%; RR, 1.14; 95% CI, 1.11 to 1.17) and an HCC-specific mortality risk of 33.3% vs. 28.6% (RD, 4.8%; 95% CI, 3.2% to 6.3%; RR, 1.17; 95% CI, 1.11 to 1.22). Living in low-SES tracts raised 1-year all-cause mortality risk to 32.5% vs. 30.1% (RD, 4.8%; 95% CI, 3.6% to 6.0%; RR, 1.12; 95% CI, 1.09 to 1.15) and HCC-specific mortality risk to 32.5% vs. 30.1% (RD, 2.5%; 95% CI, 1.4% to 3.5%; RR, 1.08; 95% CI, 1.05 to 1.12).

Conclusions: Both persistent neighborhood poverty and contemporary low SES independently contribute to significant increases in mortality risk after HCC diagnosis.

Introduction: Exercise interventions improve quality of life and survival for individuals living with and beyond cancer (ILWBC), yet equitable access remains limited. Evidence on characteristics of who enrolls in exercise oncology programs is scarce, leaving gaps for equity-focused recruitment and scale-up, particularly in rural and underserved settings. The EXercise for Cancer to Enhance Living Well (EXCEL) study offers a unique opportunity to examine these issues across a Canada-wide cohort.

Methods: EXCEL is an 8-12-week tailored exercise intervention delivered primarily to ILWBC in rural/remote communities, with additional enrollment of urban participants lacking exercise oncology resources. Adults with any cancer type or stage were eligible if pre-treatment, receiving treatment, or within 3 years post-treatment. This analysis describes baseline demographic, lifestyle, medical, and fitness factors by rural versus urban residence using descriptive statistics.

Results: Of 1495 participants enrolled in the EXCEL program (rural n = 1085; urban n = 400), baseline characteristics differed modestly by geography. Age did not differ significantly between rural and urban participants. Rural participants were more often male, had lower educational attainment, and demonstrated higher BMI than urban participants. Urban participants exhibited greater ethnic diversity and higher levels of education. Physical activity levels were similar with 78% classified as physically active at baseline.

Conclusion: This Canada-wide baseline analysis reveals rural-urban variations in age, treatment status, disease burden, education, and lifestyle, yet comparable physical activity and functional capacity levels. These findings provide descriptive evidence to inform recruitment strategies and considerations for exercise oncology program delivery across geographic settings.