Chinese clinical oncology最新文献

Background: The long-term survival rate of female adolescent and young adults (AYAs) with acute leukemia (AL) is improving. Thus, preserving the possibility of pregnancy has gained priority among this population. However, the data on the reproductive outcomes among AYA AL survivors are limited. Our study aimed to identify the incidence of long-term menstruation status and natural pregnancy among AYA AL survivors receiving chemotherapy regimens with or without hematopoietic stem cell transplantation (HSCT).

Methods: We retrospectively assessed the pregnancy and live birth rate of patients with AL admitted to The First Affiliated Hospital, Zhejiang University School of Medicine, from December 1, 2013, and August 25, 2019. A total of 150 patients aged 15-35 years were included. The patient group consisted of 78 patients with AL with a median age of 25.9 years [interquantile range (IQR), 15.6-34.5 years], while the control group consisted of 72 patients with acute promyelocytic leukemia (APML) with a median age of 25.1 years (IQR, 15.8-34.7 years).

Results: The number of pregnancies (3 vs. 16) and live births (2 vs. 17) was higher in the control group than in the AL group. Among the patient group, 60 (76.9%) experienced acute ovarian failure (AOF), and 8 patients (10.3%) reported oligomenorrhea. Moreover, in the AOF subgroup, 57 patients underwent HSCT, and 3 underwent chemotherapy only. A cyclophosphamide equivalent dose (CED) ≥3,410 mg/m2 was found to be closely associated with AOF.

Conclusions: Our study provides a more comprehensive fertility profile for AYA patients with AL and evidence-based support for fertility preservation consultation in this patient group.

Background and objective: Liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM) initially showed no clear survival advantage in early attempts, leading to waning enthusiasm. Interest was revived in 2013 following the prospective, non-randomized Norwegian Secondary Cancer (SECA) I study, which reported a 5-year overall survival (OS) of 60%-far surpassing outcomes with systemic therapy alone. More recently, the TransMet randomized controlled trial demonstrated a 5-year OS of 73% in the LT-plus-chemotherapy arm vs. 9% with chemotherapy alone, a result comparable to outcomes for established LT indications. This review aims to summarize recent advances and discuss key considerations for implementing LT for uCRLM in clinical practice-particularly patient selection and standardization of protocols.

Methods: In this narrative review of currently available reports on the outcomes of LT for uCRLM, we identified eight studies [2017-2025] from European and North American centers.

Key content and findings: Four were prospective (including one randomized trial) and three were multicenter. Their protocols varied considerably, especially regarding donor sources (living vs. deceased) and inclusion criteria for factors such as primary tumor laterality, kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status, and metabolic tumor volume. Overall, 3-year OS ranged from 62% to 100%. Recurrence-free survival (RFS) also showed wide variability, with 3-year RFS between 38% and 68.6%. Centers that employed consistent selection protocols typically reported better survival outcomes, underscoring the importance of standardization. Donor availability emerged as a key factor, with living donor LT offering an alternative in regions where deceased donor access is limited-such as North America and parts of Asia. Extended observation periods and stratification by KRAS status or tumor location (right- vs. left-sided) might help refine patient selection.

Conclusions: Although LT for uCRLM is no longer considered purely exploratory, questions remain about the best use of adjuvant chemotherapy. Moving forward, multicenter collaborations, standardized protocols, incorporation of tumor biology insights from resectable CRLM literature, and decision-support strategies (including artificial intelligence) may help optimize patient selection and improve outcomes in this advancing field.

Background: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy, ranking as the second most aggressive endocrine tumor after anaplastic thyroid cancer. ACC typically presents symptoms caused by the tumor mass and less often with signs of excess hormones. Due to its rarity, the diagnosis and management of ACC pose significant challenges, with limited clinical guidelines, a lack of large-scale randomized studies, and a paucity of treatment experience.

Case description: This report highlights the case of a 51-year-old male patient who presented with a giant intra-abdominal mass, which raised suspicion for ACC. He initially reported a history of abdominal discomfort associated with a large palpable abdominal mass. However, by the time of his presentation to our department, he was asymptomatic. After thorough imaging, a large tumor was resected, and histopathological examination confirmed the diagnosis of ACC. The tumor, measuring 31 cm in diameter and weighing 4.7 kg, is one of the largest reported cases of ACC.

Conclusions: This case is significant as it underscores the critical role of early detection and surgical intervention in potentially improving patient outcomes. Additionally, it highlights the need for continued research to better understand the pathophysiology, diagnosis, and therapeutic approaches to this rare and aggressive malignancy, which remains a considerable clinical challenge.

Radiation therapy (RT) plays a critical role in the management of intracranial malignancies, offering a potent and targeted approach to tumor control. The benefits of RT have been recognized for decades, and it is commonly employed in the management of both primary brain tumors and, especially, brain metastases. Through the induction of DNA damage and disruption of cellular integrity, RT promotes apoptosis and inhibits the proliferative capacity of cancer cells. Advances in imaging, dose planning, and delivery techniques have significantly enhanced the precision of RT, allowing for effective tumor eradication while minimizing harm to surrounding healthy tissue. As a result, RT improves local disease control and contributes to prolonged survival in patients with brain tumors. Nonetheless, intracranial RT may inadvertently damage surrounding healthy brain structures. The effects of RT can manifest as both acute and delayed toxicities, potentially compromising patient quality of life and long-term outcomes. For treating clinicians, a thorough understanding of these complications is necessary to design radiation treatment plans that properly balance the therapeutic efficacy of therapy with the risks of adverse treatment-related outcomes. In this review, we explore the distinct pathophysiological mechanisms, symptoms, and management strategies associated with acute, early delayed (one to six months), and late delayed radiation-induced brain toxicities. In particular, we discuss the risks of somnolence syndrome, peri-ictal pseudoprogression, radiation necrosis, vascular disorders, cognitive impairment, cranial neuropathies, endocrine dysfunction, the development of secondary malignancies, stroke-like migraine attacks after radiation therapy (SMART) syndrome, and acute late-onset encephalopathy after radiation therapy (ALERT) syndrome after brain RT.

Background: The association between infection and gastrointestinal cancers (GICs) were indicated by pervious studies, but the direct causal link between infection and GIC remains largely unknown. We performed multivariable mendelian randomization (MR) analyses in order to investigate the causal relationship between genetically predicted infection and the GIC risk.

Methods: Instrumental variables (IVs) for several common pathogens including Helicobacter pylori (H. pylori), human papillomavirus (HPV) and herpesvirus were retrieved from different genome-wide association studies (GWAS), respectively. The summary-level statistics of GIC were obtained from the European heritage. The inverse-variance weighted MR was conducted as the main approach followed by multiple sensitivity analyses. Twenty datasets of seropositivity and antigen antibody levels against infectious pathogens were utilized as IVs. Four GWAS datasets of GIC were retrieved.

Results: It is notable that no evidence demonstrated the causal relationship of H. pylori with gastric cancer (GC) in European ancestry. Several infectious agents were proposed as protective factors for GIC in European population. MR results showed that anti-Epstein-Barr virus (EBV) immunoglobulin G (IgG) seropositivity [odds ratio (OR) =0.32, 95% confidence interval (CI): 0.11-0.95] and EBV ZEBRA antibody levels (OR =0.74, 95% CI: 0.58-0.94) was negatively correlated with the risk of GC. Genetical predisposition of herpes simplex virus (HSV) infection showed a negative correlation with the risk of colon cancer. Similarly, increased levels of H. pylori GroEL antibody also exhibited as a protective factor for colorectal cancer (CRC; OR =0.80, 95% CI: 0.69-0.93).

Conclusions: The results reflected differential patterns of geographically distribution and pathogenic role of infectious pathogens among diverse population. Human and infection pathogens co-evolution shape the risk of cancers.

Background: Poor prognosis brings great physical suffering and financial burden to patients with renal cell carcinoma (RCC) after nephrectomy. This study aims to explore the application of machine learning for feature selection in predicting survivability and construct a well-performed prognostic model for identifying and managing the high-risk patients.

Methods: We retrospectively analyzed 737 patients with RCC after nephrectomy. Important features were respectively selected by least absolute shrinkage and selection operator (LASSO) regression and random survival forest (RSF), and the LASSO-Cox model and RSF-Cox model were constructed in conjunction with Cox regression. And their predictive performance were evaluated and compared by the C-index, calibration curve, decision curve analysis (DCA), area under the curve (AUC) of the receiver operating characteristic (ROC), and Kaplan-Meier curve. Besides, a Cox model was constructed using all clinical variables and compared with the C-index and AUC of the two models described above to demonstrate the necessity of feature selection.

Results: A total of 725 cases fitted this study ultimately, of which 48 died during the period of follow-up. The shared variables for the two models were tumor size, preoperative plasma fibrinogen content, N stage, and Fuhrman grade. In the training set, the C-index of the Cox, LASSO-Cox and RSF-Cox was 0.863, 0.893 and 0.874, and the 5-year AUC was 0.816, 0.880 and 0.837. And in the validation set, the C-index was 0.837, 0.856 and 0.821, and the 5-year AUC was 0.790, 0.855 and 0.852. The calibration and DCA curves suggested that the LASSO-Cox model outperformed the RSF-Cox model in survival prediction and net benefit. Significant survival differences were observed between the low and high-risk groups.

Conclusions: The LASSO-Cox model we constructed has been simplified and obtained higher efficiency, which can help to inform early intervention and clinical decision-making.

Background: The introduction of immune checkpoint inhibitors (ICIs) has enabled long-term survival for non-small cell lung cancer (NSCLC) patients. However, the proportion of patients achieving this is still low compared to patients with melanoma. Many NSCLC patients experience early progression (primary resistance) following ICI treatment, or relapse after initial responses (acquired resistance). While chemotherapy regimens, typically involving cytotoxic agents, are commonly used after ICI resistance, little evidence has been accumulated regarding the efficacy of ICI rechallenge. The aim of this study was to evaluate the efficacy of ICI rechallenge in patients who experienced failure of primary treatment with ICI-containing regimens. Additionally, we assessed whether the administration of local therapy prior to rechallenge influenced the efficacy of ICI rechallenge.

Methods: We retrospectively reviewed the records of advanced NSCLC patients for whom response was evaluated as progressive disease (PD) after receiving an ICI-containing regimen as first-line therapy and underwent rechallenge with an ICI in Funabashi Municipal Medical Center between January 2020 and March 2024. We analyzed progression-free survival (PFS) and overall survival (OS) based on whether local therapy (including beyond PD with local therapy) was performed. PFS was compared using the Kaplan-Meier method, with statistical significance set at P<0.05 using log-rank testing.

Results: The study included 20 patients, with 10 patients in the local therapy group and 10 in the no-local therapy group. No significant differences in patient characteristics were apparent between groups, although the no-local therapy group tended to show a higher number of organs with residual metastases at the time of rechallenge. When ICI rechallenge was administered after local therapy, median PFS was significantly longer in the local therapy group (9.0 months) than in the no-local therapy group (1.6 months, P=0.02), particularly in cases where radiation therapy was applied to the primary lesion just before rechallenge. However, no significant difference in OS was evident between the local treatment group (21.4 months) and the no-local treatment group (18.8 months; P=0.12).

Conclusions: Rechallenge with ICI following local therapy in NSCLC patients who developed resistance to ICIs may extend PFS, suggesting potential value as a therapeutic option.

Background and objective: Pulsed reduced dose rate (PRDR) radiotherapy, also known as pulsed low dose rate (PLDR) radiotherapy, involves delivering radiation at significantly lower dose rates in a pulsed manner (0.1-0.2 Gy/minute for a 3-minute interval resulting in a time-averaged, effective dose rate of 0.0667 Gy/min). This approach enhances tumor sensitivity while minimizing normal tissue damage, presenting a promising strategy for recurrent tumor treatment. This comprehensive review aims to consolidate the biological rationale, clinical applications, and prospects of PRDR radiotherapy across several disease sites.

Methods: We conducted a comprehensive literature search on the Medline database, ClinicalTrials.gov, and Google Scholar using various word combinations in the "title" field, including "PRDR", "Pulsed reduced dose rate", "Pulsed low dose rate", "PLDR" and various types of cancers. There were no limitations on the publication year. All obtained publications were reviewed, and their key references were cross-checked to ensure a balanced and high-quality review.

Key content and findings: PRDR has multiple radiobiologic advantages, including reoxygenation, redistribution, and immune regulation. These factors collectively contribute to PRDR's efficacy and reduced toxicity. PRDR has shown feasibility across multiple treatment modalities, including both intensity-modulated radiotherapy (IMRT) and pencil beam scanning (PBS) proton therapy, demonstrating significant potential in treating a variety of recurrent tumors. Clinical evidence supports its efficacy in central nervous system (CNS) tumors (i.e., glioma, meningioma, ependymoma, and brain metastases), recurrent breast cancer, head and neck cancers, gastrointestinal cancers, and cervical cancers.

Conclusions: PRDR radiotherapy shows promising efficacy and safety across various malignancies, especially in the re-irradiation setting. It is particularly effective for CNS tumors with manageable toxicity and shows potential in recurrent breast, head and neck, and gastrointestinal cancers. Treatment doses typically range from 40 to 66 Gy, depending on tumor type and clinical context. These findings position PRDR as a viable option for patients being considered for re-irradiation above traditional palliative doses. Large-scale clinical trials will likely further validate its efficacy and safety, along with studies aimed at understanding the underlying molecular mechanisms driving its unique therapeutic benefits. The role of PRDR is expected to expand, potentially offering new hope for patients with challenging cancer diagnoses.

Melanoma is one of the most common types of skin cancer and is the most lethal type of skin cancer presently. Despite the presence of various drugs for the treatment of melanomas, increasing resistance to the existing treatment is a major concern. Due to the involvement of complex mechanisms including genetic mutations, the presence of neoantigens, tumor microenvironment, and cellular plasticity, the tumor cell develops the ability to evade the effects of current therapies including targeted drugs and immunotherapy limiting the treatment efficacy. This leads to difficulties in achieving long-term control in patients with advanced melanoma. It is important to understand the molecular mechanisms underlying chemoresistance to overcome this resistance and develop potential therapeutic strategies. In this article, we will discuss the most common drugs used to fight skin cancer and their mechanisms of fighting cancer, followed by a discussion of intrinsic resistance and extrinsic resistance. We will address molecular mechanisms of chemoresistance including the alteration in apoptosis and lipid metabolism, the role of tumor microenvironments, genetic and epigenetic mutations, phenotypic switching of cells, and the presence of neoantigens. Next, the strategies to overcome drug resistance including blocking alternative pathways that cancer cells use to avoid treatment, using combination therapies that target multiple signaling pathways, and personalizing treatment regimens to account for a patient's genetic and immunologic characteristics have been discussed. Lastly, the need for advanced techniques including transcriptomic, metabolomics, and proteomics in identifying novel targets and therapies to treat hard-to-treat melanoma or skin cancers has been discussed.