Oncology最新文献

Introduction: Head and neck squamous cell carcinoma (HNSCC) is the most common mucosal neoplasm that affects the head and neck region. It is the 6th most common cancer globally, most commonly seen in South Asian countries. Insulin receptor substrate 1 (IRS-1) like Insulin Receptor (IR) is an adaptor protein that integrates multiple transmembrane signals from growth factors and hormones, to regulate cell growth, survival, differentiation, and metabolism. Evidence suggests that IRS 1 plays a vital role in cancer progression and nodal metastasis. The aim is to assess the prognostic implications of the insulin receptor substrate 1 expression in head and neck squamous cell carcinoma from evidence-based results.

Methods: A systematic literature search was done to identify articles describing Insulin receptor substrate 1 (IRS 1) and head and neck squamous cell carcinoma carried out for Pubmed, Cochrane, and Google Scholar, using MeSH terms.

Results: A total of 486 cases of HNSCC were included in this systematic review. Out of 3 studies, increased/high expression of IRS 1 was 67%. 64% of the cases in Stage I and Stage II (TNM staging) showed higher expression of IRS 1, whereas 70% of the Stage III and Stage IV cases showed upregulation of IRS 1. IRS 1 was equally upregulated in cases with lymph node metastasis as well as in cases without any lymph node metastasis. 74% of the patients that showed high expression of IRS 1 showed high mortality during the follow-up period of 13 months.

Conclusion: This review concluded that elevated levels of IRS 1 expression were associated with poor prognosis and increased lymph node metastasis.

Introduction: Gastrointestinal varices rupture is considered to be prone to occur during atezolizumab and bevacizumab (Atez/Bev) treatment. This study aimed to investigate predictive factors affecting the increase in spleen volume (SpV) and the association of SpV variation with the clinical outcomes of Atez/Bev.

Methods: A total of 164 HCC patients were included in this retrospective multicenter study. We measured SpV based on CT scans obtained before treatment and at evaluations. We used the inverse probability of treatment weight to address the imbalance between patient characteristics.

Results: The median pretreatment SpV was 184 (130-257) cm3 and the median SpV variation was 27 (9-60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. There were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients with SpV variation <25 cm3 and those with SpV variation ≥25 cm3 in the crude (p=0.3 and 0.7) and IPTW-weighted cohorts (p = 0.08 and 0.8, respectively). Regarding pretreatment SpV, there were no significant differences in PFS or OS between patients with and without pretreatment spleen enlargement in the crude (both p = 0.3) and IPTW-weighted cohort (p = 0.6 and 0.3, respectively).

Conclusion: Caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or patients with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy.

Introduction: In 2018, we reported the results of a study to assess the feasibility of applying the ACOSOG Z0011 criteria to Japanese patients with early-stage breast cancer (median follow-up, 3 years). Their results over the longer term can now be presented. Risk factors for axillary and locoregional recurrence in Z0011-eligible patients are unknown.

Methods: Long-term survival outcomes were investigated by analyzing data from patients enrolled in the feasibility study. Data from the feasibility study patients, and from patients eligible for the Z0011 strategy after its introduction into clinical practice, were subjected to multivariate logistic regression analysis to identify risk factors for axillary and locoregional recurrence.

Results: Regarding long-term outcomes for the feasibility study patients (n = 189), distant disease-free survival rates at 5 and 7 years were 90.4 ± 2.1% and 85.9 ± 2.6%, respectively, and overall survival rates at 5 and 7 years were 97.3 ± 1.2% and 95.3 ± 1.7%, respectively. Analysis of data from these patients plus the 93 who received Z0011 in clinical practice (total, n = 282) identified the following independent risk factors for axillary recurrence: absence of high axillary tangential irradiation (OR, 5.87 [95% CI, 1.09-31.35], p = 0.04) and number of positive sentinel lymph nodes (OR, 4.65 [95% CI, 1.11-19.48], p = 0.04). Only high Ki67 labeling index (OR, 5.92 [95% CI, 1.31-26.70], p = 0.02) was identified as an independent risk factor for locoregional recurrence.

Conclusion: Long-term survival outcome results of the feasibility study show that the Z0011 strategy can be used to treat Japanese patients with early-stage breast cancer. Our findings regarding risk factors suggest that high axillary tangent irradiation is necessary for prevention of axillary recurrence, and that irradiation, including of the regional lymph nodes, should be considered, especially in patients with high Ki67 index values.

Neuroendocrine differentiation is often found in colorectal cancer but its impact on prognosis remains controversial. This study explored the association between neuroendocrine differentiation and prognosis in stage II/III colorectal cancer patients.

Methods: Between 2012 and 2018, a total of 3,441 stage II/III colorectal cancer patients were included for analysis. To verify neuroendocrine differentiation, immunohistochemistry was performed to explore the expression of chromogranin A and synaptophysin in colorectal cancer. In addition, the difference in overall survival between groups was analyzed. A Kaplan-Meier analysis was used to determine the clinicopathological characteristics significantly correlated with survival, and a Cox proportional hazards analysis was used to identify factors independently affecting overall survival prognosis. Furthermore, the findings were validated by the Gene Expression Omnibus database.

Results: Among the 3441 stage II/III colorectal cancer patients, in comparison to patients with neuroendocrine differentiation (+), patients with neuroendocrine differentiation (+) had a poorer prognosis (P = 0.001). Furthermore, multivariate survival analysis of stage II cases revealed that tumor differentiation (P = 0.018), nerve invasion (P < 0.001) and neuroendocrine differentiation (+) (P = 0.002) were independent prognostic factors. Moreover, the prognosis of patients with neuroendocrine differentiation (+) was similar to that of patients with high-risk factors in stage II cases (P = 0.639). High chromogranin A expression was correlated with poor prognosis in stage II colorectal cancer patients in the Gene Expression Omnibus database (P < 0.001).

Conclusion: The prognosis of colorectal cancer with neuroendocrine differentiation (+) was poor, especially in stage II colorectal cancer patients. neuroendocrine differentiation might be another high-risk factor for the prognosis of stage II colorectal cancer patients.

Introduction: Pulmonary adenocarcinoma with enteric differentiation (PAED) without thyroid transcription factor-1 (TTF-1)- expression is an extremely rare variant of lung cancer. Due to its rarity, few clinicopathological and molecular studies have been performed on PAED, particularly in Caucasian patients. Therefore, it is necessary to obtain clinicopathological data of Caucasian PAED patients without TTF-1 expression, their systemic therapy options and the efficacy of their systemic treatment.

Methods: We examined the clinicopathological features of 121 cases of TTF-1 negative pulmonary adenocarcinoma at a certified German lung cancer center including 79 cases without a PAED and 42 cases with a PAED, compared these subgroups and investigated patients` response to chemotherapy and immunotherapy as first-line treatment. By using endoscopy and/or a PET-CT, a primary adenocarcinoma of the digestive tract was excluded in all PAED patients.

Results: A comparison of clinicopathological data of TTF-1- negative PAED and non-PAED patients revealed a significantly lower frequency of high Programmed Death receptor Ligand 1 (PD-L1) expression in PAED resulting in the lack of single-agent immunotherapy (p=0.032) in this subgroup. Frequencies of an activating Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation were high in both groups (46.7 % and 50.0% ), but G12C gene mutations were seldomly noted (in 6.7% and 18.5% of patients with evaluable data). Median overall survival (OS) was poor in both groups (10 and 12 months). The majority of PAED patients received platinum-based and taxane-containing chemotherapy or chemo-/immunotherapy with an objective response rate (ORR) of 31.6 % and a disease control rate (DCR) of 57.9%. Median progression-free survival (PFS) and OS of PAED patients with systemic therapy was very poor (3.9 months and 5.9 months).

Conclusions: Caucasian patients with TTF-1 negative PAED have a poor prognosis with a reduced ORR to standard first-line systemic therapy and short survival times (PFS and OS).

Introduction: Androgen receptor pathway inhibitors (ARPIs) that significantly improve the prognosis of patients with prostate cancer include abiraterone acetate (androgen synthesis inhibitor) and enzalutamide (androgen receptor inhibitor). A recent analysis of ARPI and cardiovascular events using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) has been reported; however, the evidence on cardiovascular events for abiraterone acetate and enzalutamide in real-world clinical practice is insufficient. Using a large Japanese database of medical institutions, the Japanese Medical Data Center (JMDC) medical institution database (JMDC Inc., Tokyo, Japan), this study tested the hypothesis that the risk of cardiovascular events with enzalutamide is lower than that with abiraterone acetate.

Method: Using the JMDC medical institution database, patients with new use of abiraterone acetate or enzalutamide who had not experienced a major cardiovascular event between October 2014 and February 2022 were included. After adjusting for age, comorbidities, and concomitant medications using propensity score matching, cumulative incidence rates were compared for cardiovascular death and all cardiovascular events as the primary endpoints, and major cardiovascular events, myocardial infarction, heart failure, and stroke as secondary endpoints.

Result: A total of 3,033 patients in the enzalutamide group and 2,021 in the abiraterone group met the eligibility criteria. After propensity score matching, the cohort included 1,940 patients in the enzalutamide group and 1,940 patients in the abiraterone group. Enzalutamide was associated with significantly lower cumulative rates of cardiovascular death (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.10-0.93), all cardiovascular events (HR: 0.79, 95% CI: 0.64-0.98), major cardiovascular events (HR: 0.79, 95% CI: 0.64-0.97), and myocardial infarction (HR: 0.62, 95% CI: 0.46-0.84) compared to abiraterone.

Conclusion: In a national sample of males with prostate cancer, those newly treated with enzalutamide had a lower risk of adverse cardiovascular events than those treated with abiraterone acetate.

Introduction: The objective response rate to immunotherapy is limited in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients, whose prognosis is still dismal. Few prognostic factors are clinically available, mostly related to patient or disease characteristics. Gene expression signatures offer better prognostic abilities but are mainly used in research. One such GE model classifies HNSCC into 6 clusters with different prognoses. Claudin-1 (CLDN1), which influences tumor microenvironment and immune cell infiltration, has emerged as a potential target, especially in cancers like HNSCC with high CLDN1 expression.

Methods: A single-center cohort of 100 loco-regionally advanced HNSCC patients from the BD2Decide observational study was analyzed. Patients were selected to balance long-term survivors and deceased patients, including HPV-negative and HPV-positive cases. Primary tumor specimens underwent GE analysis using Affymetrix ClariomD chips. Primary endpoint was overall survival (OS).

Results: The cohort comprised 100 HNSCC patients with a median age of 60 years, predominantly men (76%). Median OS and disease-free survival (DFS) were 94.24 and 42.79 months, respectively. CLDN1 expression varied significantly among primary sites, being highest in hypopharynx cancers. Differences in expression were not significant when stratified by HPV status or clinical stage. CLDN1 expression differed across the 6 transcriptomic clusters, with the highest levels in clusters associated with mesenchymal and hypoxic features. Higher CLDN1 expression correlated with shorter OS (hazard ratio [HR]: 3, p = 0.0023) and DFS (HR: 2.14, p = 0.02).

Conclusion: CLDN1 expression is heterogeneous in HNSCC and carries prognostic significance. It is highest in tumors with HPV-like biology and hypoxic environments, and lowest in immune-sensitive clusters. High CLDN1 is a negative prognostic factor and a promising therapeutic target. Anti-CLDN1 treatments could improve outcomes of CLDN1+ HNSCC patients, and combination therapies with ICIs might overcome resistance in CLDN1- cases. These findings support the need for clinical studies on anti-CLDN1 therapies.

Introduction: β-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC.

Methods: A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue.

Results: Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer.

Conclusion: In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location.

Introduction: Recent reports have described the usefulness of carbon ion radiotherapy (CIRT) for inoperable sacral chordomas. However, its long-term local control rate needs to be improved. The present study identified the risk factors that affect the local relapse of sacral chordomas and the appropriate margins from the tumors.

Methods: Forty-nine patients with sacral chordoma treated with CIRT between 2011 and 2022 were retrospectively analyzed. Factors predicting the risk of local recurrence were evaluated, including age, sex, tumor size, muscle invaded with tumor, and surgery before CIRT. To determine the appropriate margin, the distance between the clinical target volume (CTV) and the out-field recurrent lesions was analyzed.

Results: The patients included 37 males and 12 females with a mean age of 67.1 years. A multivariate analysis showed that a tumor size >8 cm and invasion into the gluteus maximus muscle were significant risk factors with hazard ratios of 5.56 and 15.20 (p = 0.02 and 0.01), respectively. Out-field recurrence occurred in 13 cases, with 6, 3, and 4 relapses occurring in the muscle, bone, and both, respectively. The tumor occurred within 20 mm from the CTV in 60% of relapses in the muscles.

Conclusion: The current study presented novel findings on CIRT for sacral chordomas, although there were several limitations, such as a short follow-up period to investigate slow-growth tumors and a small number of tumor specimens owing to inoperative cases. A tumor size >8 cm and invasion into the gluteus maximus muscle were shown to be risk factors for recurrence in the treatment of sacral chordoma with CIRT. Our findings further suggest that an additional 2-cm margin from the CTV in the muscle fiber direction is recommended during CIRT.

Introduction: Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer, with around 60% of patients being diagnosed at an advanced stage. Recently, cancer-derived sialylated immunoglobulin G (SIA-IgG) has been suggested to play a role in the progression of various epithelial tumors, but its significance in LSCC remains unknown. This study aims to investigate the clinical significance of SIA-IgG as a novel biomarker in relation to the initiation, progression, and prognostication of LSCC.

Methods: Immunohistochemistry (IHC) were utilized to assess SIA-IgG expression in tumor samples from 75 LSCC patients, aiming to investigate its correlation with clinical prognosis. Vitro functional experiments were conducted to explore the impact of SIA-IgG expression on the proliferative and migratory abilities of laryngocarcinoma cells.

Results: High expression of SIA-IgG was associated with pT stage, pN stage, TNM stage, and recurrence during follow-up, and was correlated with poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox analysis demonstrated that SIA-IgG served as an independent risk factor for OS and DFS. Knocking down SIA-IgG significantly weakened laryngocarcinoma cells' proliferation, clonogenesis, and migration abilities.

Conclusions: The frequent expression of SIA-IgG in LSCC is significantly associated with poor prognosis. High levels of SIA-IgG can enhance proliferation and migration in laryngocarcinoma cells. These findings suggest that SIA-IgG has potential as a novel biomarker for LSCC.