Oncology最新文献

Background: Chronic lymphocytic leukemia (CLL) is a rare hematologic malignancy to occur in pregnancy, with an estimated incidence of 1 in 75,000 pregnancies. Pregnant women with CLL face increased susceptibility to infections, due to a weakened immune system. Higher risks of fetal malformations and death are associated with CLL treatment during pregnancy, emphasizing the need for careful consideration and management in these cases.

Summary: This review aimed to summarize the current evidence regarding the diagnosis, prognosis, and treatment of CLL in pregnant cases. A comprehensive search strategy was employed across multiple databases, yielding 14 case reports for inclusion. The cases were divided based on CLL diagnosis onset, either before or during pregnancy. Our results showed that patients diagnosed during pregnancy (n = 5) were mostly asymptomatic at diagnosis, with management ranging from supportive care to leukapheresis and transfusions. Postpartum treatment varied, with some patients requiring no additional therapy and others receiving chemotherapy. Pregnancy outcomes were generally favorable, with most neonates born healthy at term. However, one case of Richter transformation resulted in maternal death despite treatment. Among patients with pre-existing CLL (n = 9), the majority experienced an indolent course during pregnancy, with only supportive care required. A few cases necessitated treatment due to progressive disease or complications, including chemotherapy, leukapheresis, and splenectomy.

Key messages: This review highlights the heterogeneous nature of CLL in pregnancy and the importance of individualized management based on disease severity, gestational age, and maternal-fetal risks. Close monitoring, supportive care, and a multidisciplinary approach are essential for optimizing outcomes in this rare and complex clinical scenario.

Introduction: Locoregional gastric cancer is a still serious problem and perioperative treatments may improve the success of management. Different regimens were examined. The present study purposed to compare the efficacy of fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) and docetaxel-cisplatin-fluorouracil (DCF) regimens.

Methods: A retrospective multicenter study assessed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared.

Results: Demographic features were similar between the two groups, but the time period was different. The FLOT group had 7.8% pathological complete response, while the DCF group did not. Disease-free survival was longer in the FLOT than in the DCF group (median not reached - 13.94 months, respectively). Median overall survival was similar (30.9 vs. 37.8 months), but median follow-up affected the analysis. Survival for 36 months was 63% for the FLOT group and 40% for the DCF group (log-rank; p = 0.015).

Conclusion: FLOT regimen was superior to DCF regimen for response and survival rates. DCF is a historical approach. Long-term follow-up period is needed for FLOT treatment.

Introduction: Atezolizumab plus bevacizumab (AB) therapy was the effective immune checkpoint inhibitor (ICI) for unresectable hepatocellular carcinoma (u-HCC). However, immune-related adverse events (irAEs) are common in patients receiving ICI therapies. Our research aimed to explore the risk factors for irAE development, with attention to interleukin-7 (IL-7) risk alleles, lymphocyte counts, and autoantibodies.

Methods: Seventy-six patients receiving AB therapy for u-HCC were recruited. Single nucleotide polymorphism genotyping was done for the analysis of rs16906115 polymorphism near IL-7-expressing genes using 20 μL of stored buffy coat at baseline. The association between IL-7 risk alleles, lymphocyte counts, autoantibodies, and irAE development was investigated.

Results: irAEs were found in 14 (18%) patients. The incidence of irAEs did not differ significantly between the groups showing IL-7 AG/AA and the GG group (p = 0.72). The incidence in the group with a lymphocyte count of 1,130/µL or more at baseline was higher than in that with a value below 1,130/µL (p = 0.0093). The group showing IL-7 AG/AA or lymphocyte count >1,130/μL had a higher irAE prevalence rate than the others (p = 0.019). IL-7 AG/AA or lymphocyte count >1,130/μL and positivity for autoantibodies at baseline were the prognostic factors for irAE development. irAE incidence could be stratified using a combination of IL-7 AG/AA or lymphocyte counts ≥1,130/µL and positive autoantibodies (p = 0.016).

Conclusion: Patients with IL-7 risk alleles, high lymphocyte counts, and autoantibodies at baseline may require careful monitoring for irAE development.

Introduction: Cisplatin (CDDP) often causes acute kidney injury (AKI), and magnesium supplementation has been suggested to be important in preventing CDDP-induced AKI. Sodium bicarbonate Ringer's solution (BRS) is a crystalloid solution composed of various electrolytes, including Mg2+, and can be generally used to supplement missing extracellular fluid and correct metabolic acidosis; however, the clinical outcomes of hydration with BRS for CDDP-induced AKI remain unclear. In this study, we retrospectively compared the effects of BRS and normal saline for hydration in patients undergoing CDDP treatment.

Methods: We analyzed the incidence rate of AKI (grade ≥ 1), the severity of AKI, the serum magnesium level, and the incidence rate of grade ≥ 3 hematological toxicities (leukopenia, neutropenia, anemia, or thrombocytopenia) following CDDP and fluorouracil (5-FU) administration in 131 in-patients who received CDDP and 5-FU for the first time to treat esophageal cancer.

Results: Fifty-six patients (43%) received saline alone, while 75 patients (57%) received BRS for hydration. The incidence rate of AKI (grade ≥ 1) was significantly lower in the BRS group (11%) than that in the saline group (39%, p < 0.001). Moreover, severe AKI (grade ≥ 2) was significantly less common in the BRS group than in the saline group. Although the serum magnesium levels before CDDP administration were not significantly different between the two groups (p = 0.939), the serum magnesium levels on days 2-3 after CDDP administration in the BRS group were significantly higher than those in the saline group (p < 0.001). In contrast, there were no significant differences in the incidence rates of hematological toxicity between the two groups. Multivariate analysis revealed that BRS use was an independent factor that significantly contributed to AKI prevention (odds ratio = 0.061, p < 0.001).

Conclusion: Hydration with BRS could prevent CDDP-induced AKI in patients with esophageal cancer.

Background: Clinical decision-making in oncology is a complex process influenced by numerous disease-related factors, patient demographics, and logistical considerations. With the advent of Artificial Intelligence (AI), precision medicine is undergoing a shift towards more precise and personalized care. Wearable device technology complements this paradigm shift by offering continuous monitoring of patient vitals, facilitating early intervention, and improving treatment adherence. The integration of these technologies promises to enhance the quality of oncological care, making it more responsive and tailored to individual patient needs, thereby enabling wider implementation of such applications in the clinical setting.

Summary: This review article addresses the integration of wearable devices and AI in oncology, exploring their role in patient monitoring, treatment optimization, and research advancement along with an overview of completed clinical trials and utility in different aspects. The vast applications have been exemplified using several studies and all the clinical trials completed till date have been summarized in table 2. Additionally, we discuss challenges in implementation, regulatory considerations, and future perspectives for leveraging these technologies to enhance cancer care and radically changing the global health sector.

Key messages: AI is transforming cancer care by enhancing diagnostic, prognostic, and treatment planning tools, thus making precision medicine more effective. Wearable technology facilitates continuous, non-invasive monitoring, improving patient engagement and adherence to treatment protocols. The combined use of AI and wearables aids in monitoring patient activity, assessing frailty, predicting chemotherapy tolerance, detecting biomarkers, and managing treatment adherence. Despite these advancements, challenges, such as data security, privacy, and the need for standardized devices persist. In the foreseeable future, wearable technology can hold significant potential to revolutionize personalized oncology care, empowering clinicians to deliver comprehensive and tailored treatments alongside standard therapy.

Introduction: Cell-free DNA (cfDNA) is expected to contribute to the decision for treatment and prediction of effects with minimally invasion. We investigated the correlation between gene mutations before and after lenvatinib (LEN) treatment and its effectiveness, in order to find advanced hepatocellular carcinoma (HCC) patients who would benefit greatly from the therapy.

Methods: We analyzed cfDNA before and 6-8 weeks after the start of treatment in 20 advanced HCC patients who started LEN. A next-generation sequencer was used for CTNNB1 and TP53. Concerning TERT promoter, -124C>T and -146C>T mutations are researched using digital PCR. In addition, we examined liver tumor biopsy tissues by the same method. Computerized tomography evaluation was performed at 6-8 weeks and 3-4 months to assess the efficacy.

Results: Frequencies of TERT promoter, CTNNB1, and TP53 mutations in pretreatment cfDNA were 45%, 65%, and 65%, but 53%, 41%, and 47% in HCC tissues, respectively. There were no clear correlations between these gene mutations and the disease-suppressing effect or progression-free survival. Overall, there were many cases showing a decrease in mutations after LEN treatment. Integrating the reduction of CTNNB1 and TP53 genetic mutations increased the potential for disease suppression.

Conclusion: This study suggests that analysis of cfDNA in advanced HCC patients may be useful for identifying LEN responders and determining therapeutic efficacy. Furthermore, it has potential for selecting responders for other molecular-targeted drugs.

Introduction: As the primary members of the deubiquitinase family, ubiquitin-specific proteases can regulate the efficacy of immunotherapy and mediate immune evasion. However, further research is needed to explore the influence of USP52 on the prognosis of colorectal cancer (CRC), the tumor immune microenvironment, and therapeutic response.

Methods: The differential expression of USP52 between CRC and normal tissues was analyzed using multiple public databases. The relationship between USP52 with the prognosis and clinicopathological characteristics of CRC patients was evaluated, and a nomogram was constructed to predict patient survival based on USP52 expression. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP52 in CRC. The impact of USP52 on the tumor microenvironment (TME) was estimated. Moreover, the effect of USP52 on the response to immunotherapy and chemotherapeutic drugs in CRC was investigated. Finally, the correlation between tumor mutation burden (TMB)/microsatellite instability (MSI) status and USP52 was explored.

Results: The expression of USP52 was markedly upregulated in CRC, correlating with a poor prognosis in patients. GSVA uncovered a strong association between high USP52 and immune suppression. Furthermore, high USP52 was found to be correlated with a non-inflamed TME, resulting in reduced immune cell infiltration levels. Additionally, it was observed that patients with high USP52 exhibited low sensitivity to both immunotherapy and chemotherapeutic drugs. Lastly, high USP52 was negatively associated with high TMB and MSI.

Conclusion: This study revealed the significance of USP52 in TME, efficacy of therapy, and clinical prognosis in CRC, offering novel insights for the therapeutic advancements in CRC.

Introduction: Our study delves into the intricate interplay of risk factors and the strategic selection of adjuvant therapy, scrutinizing their influence on recurrence and survival outcomes in stage IIA (T3N0M0) colon cancer patients.

Materials and methods: The study examined the medical records of patients who underwent surgery for stage IIA colon cancer. Identification of stage IIA (pT3N0M0) colon cancer involved a comprehensive review of postoperative clinical records and histological reports. Parameters such as demographic data, tumor characteristics, microsatellite instability status, tumor locations, recurrence risk factors, preoperative carcinoembryonic antigen levels, and adjuvant treatments were systematically evaluated.

Results: In our study involving 220 patients, 138 were male (62.7%), with a median age of 62 years and a median body mass index of 25.1 kg/m2. In the patient group without risk factors, no statistically significant difference was detected in disease-free survival (DFS) rates between those who received treatment and those who did not (p = 0.546). DFS rates of patients with >1 risk factor were statistically significantly lower than those with a single risk factor (p = 0.017). In patients with >1 risk factor, the DFS of those who did not receive adjuvant treatment was significantly lower than those who received adjuvant treatment (p < 0.001). In the patient group with recurrence, when adjuvant treatments were considered, recurrence was significantly higher in the group receiving capecitabine (p = 0.01).

Conclusion: The decision for adjuvant chemotherapy in stage IIA colon cancer patients involves careful consideration of various parameters and risk factors. The evolving landscape of research may refine recommendations, ensuring optimal treatment outcomes while minimizing unnecessary toxicity.

Introduction: In silico tools capable of predicting the functional consequences of genomic differences between individuals, many of which are AI-driven, have been the most effective over the past two decades for non-synonymous single nucleotide variants (nsSNVs). When appropriately selected for the purpose of the study, a high predictive performance can be expected. In this feasibility study, we investigate the distribution of nsSNVs with an allele frequency below 5%. To classify the putative functional consequence, a tier-based filtration led by AI-driven predictors and scoring system was implemented to the overall decision-making process, resulting in a list of prioritised genes.

Methods: The study has been conducted on breast cancer patients of homogeneous ethnicity. Germline rare variants have been sequenced in genes that influence pharmacokinetic parameters of anticancer drugs or molecular signalling pathways in cancer. After AI-driven functional pathogenicity classification and data mining in pharmacogenomic (PGx) databases, variants were collapsed to the gene level and ranked according to their putative deleterious role.

Results: In breast cancer patients, seven of the twelve genes prioritised based on the predictions were found to be associated with response to oncotherapy, histological grade, and tumour subtype. Most importantly, we showed that the group of patients with at least one rare nsSNVs in cystic fibrosis transmembrane conductance regulator (CFTR) had significantly reduced disease-free (log rank, p = 0.002) and overall survival (log rank, p = 0.006).

Conclusion: AI-driven in silico analysis with PGx data mining provided an effective approach navigating for functional consequences across germline genetic background, which can be easily integrated into the overall decision-making process for future studies. The study revealed a statistically significant association with numerous clinicopathological parameters, including treatment response. Our study indicates that CFTR may be involved in the processes influencing the effectiveness of oncotherapy or in the malignant progression of the disease itself.

Introduction: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients.

Methods: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated.

Results: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis.

Conclusion: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable.