Oncology最新文献

Introduction: Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC).

Methods: A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed.

Results: We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p < 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines.

Conclusions: Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future.

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: The prognostic nutritional index (PNI) and D-dimer level are two useful measures for gastric cancer prognosis. As they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a PNI-D score - which combines the PNI and D-dimer level - and validate its usefulness as a prognostic marker.

Methods: We collected data from 1,218 patients with gastric cancer who had undergone radical gastrectomy (R0) between January 2004 and December 2015. Patients were divided into three PNI-D score groups based on the following criteria: score 2, low-PNI (≤46) and high D-dimer levels (>1.0 µg/mL); score 1, either low-PNI or high D-dimer levels; and score 0, no abnormality. We defined the PNI-D score as low (score 0 or 1) and high (score 2), respectively.

Results: The PNI-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank p < 0.0001). The 5-year overall survival rates of patients with PNI-D scores of low and high were 88.1% and 64.7%, respectively; their 5-year recurrence-free survival rates were 86.7% and 61.3%, respectively; and their 5-year disease-specific survival rates were 99.3% and 76.5%, respectively. Cox multivariate analysis revealed that a high-PNI-D score was an independent, statistically significant prognostic factor for poor overall (p = 0.01) survival in patients with gastric cancer.

Conclusions: The PNI-D is an independent prognostic factor for patients with gastric cancer.

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.

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, is an adapter 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 was to assess the prognostic implications of the IRS-1 expression in HNSCC from evidence-based results.

Methods: A systematic literature search was done to identify articles describing IRS-1 and HNSCC 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 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 who 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: Immune checkpoint inhibitor-related pneumonitis (ICI-P) is a life-threatening complication, limiting immune checkpoint inhibitors (ICIs) clinical application in non-small cell lung cancer (NSCLC). But risk factors for developing ICI-P have not been well defined.

Methods: This study employed a retrospective analysis method. Following approval from the Ethics Committee of Chinese PLA General Hospital, we retrieved patient information on NSCLC registered in the hospital's PRIDE workstation, selecting patients who received treatment with ICIs from January 1, 2018, to September 30, 2023. Complete medical records of patients were collected and verified. Logistic regression analysis was used to identify independent high-risk factors for the occurrence of ICI-P.

Results: A total of 753 patients with NSCLC who received treatment with ICIs were included, with a mean age of (63 ± 9.5) years. A total of 102 patients diagnosed with ICI-P were identified, resulting in an incidence rate of 13.5%. Development of ICI-P was independently associated with history of interstitial lung disease (ILD) (OR, 3.85; CI, 1.99-7.46; p < 0.001), prior thoracic radiotherapy (OR, 2.65; CI, 1.56-4.48; p < 0.001), concurrent thoracic radiotherapy (OR, 3.56; CI, 1.69-7.47; p < 0.001) and treatment with programmed cell death 1 (PD-1) inhibitors compared with programmed death-ligand 1 (PD-L1) inhibitors (OR, 3.54; CI, 1.05-11.98; p = 0.04).

Conclusion: Independent risk factors for ICI-P occurrence included the history of ILD, previous chest radiotherapy, concurrent chest radiotherapy, and the use of PD-1 inhibitors (compared to non-PD-1 inhibitors). Specialty assessment of ILD before treatment and cautious use of ICIs in radiotherapy patients, represent feasible strategies to prevent the occurrence of ICI-P.

Introduction: The effectiveness and tolerability of triple therapy, which combines regorafenib, a programmed death 1 (PD-1) inhibitor, and transarterial chemoembolization (TACE), were compared to dual therapy consisting of regorafenib and a PD-1 inhibitor in patients with advanced hepatocellular carcinoma (HCC).

Methods: A retrospective analysis was conducted on patients with advanced HCC who underwent second-line therapy from March 2019 to June 2022 at multiple centers. Patients were stratified into two groups: dual therapy (comprising regorafenib and a PD-1 inhibitor) and triple therapy (consisting of regorafenib, a PD-1 inhibitor, and TACE). Propensity score matching (PSM) was used to control for potential confounding variables.

Results: After PSM, 112 eligible patients were included, with 56 in the triple therapy group and 56 in the dual therapy group. Median overall survival (OS) was significantly longer in the triple therapy group (15.4 vs. 8.9 months, p < 0.001), as was median progression-free survival (6.8 vs. 3.3 months, p < 0.001). The objective response rate (37.5% vs. 5.4%, p < 0.001) and disease control rate (73.2% vs. 44.6%, p = 0.002) were significantly higher in the triple therapy group compared to the dual therapy group. The incidence and severity of adverse events were similar between the two groups.

Conclusion: Triple therapy demonstrated superior survival benefits compared to dual therapy in patients with advanced HCC. Additionally, the safety profiles of the two treatment regimens were comparable.

Introduction: Cisplatin-based highly emetogenic chemotherapy is recommended in combination with neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3-receptor antagonist (5HT3RA), dexamethasone (DEX), and olanzapine. However, olanzapine is contraindicated in patients with preexisting diabetes mellitus (DM). This study compared the efficacy of a triplet antiemetic regimen (NK1RA, 5HT3RA, and DEX) in patients with and without preexisting DM treated with cisplatin-based chemotherapy.

Methods: This retrospective study enrolled patients with esophageal cancer with and without preexisting DM who received fluorouracil and cisplatin (FP) combination chemotherapy as initial therapy with a triplet antiemetic regimen for antiemetic prophylaxis. These data were compared using propensity score matching (PSM). The primary endpoint was the complete response (CR) rate during the first cycle, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120 h). The CR rate was analyzed using univariate and multivariate logistic regression, including previously reported risk factors. The significance level was set at 5%.

Results: Out of 210 eligible patients, 39 and 39 were patients with DM and non-DM patients after PSM, respectively. The CR rate measured by multivariate analysis during the overall period with DM and non-DM was 56.4% and 41.0% (adjusted odds ratio of 0.566 [95% confidence intervals: 0.209-1.536], p = 0.264), respectively. The CR rate during the delayed period (24-120 h) with DM and non-DM patients was 84.6% and 46.2% (p = 0.002), respectively.

Conclusions: A triplet antiemetic regimen in patients with esophageal cancer with preexisting DM might be more effective in delayed period compared to non-DM patients.

Introduction: Durvalumab plus tremelimumab combination therapy (STRIDE regimen) is a new first-line option for unresectable hepatocellular carcinoma (uHCC), but little real-world data are available to determine which patients are most likely to respond.

Methods: This study retrospectively evaluated patients with uHCC who were treated with the STRIDE regimen as the 1st line at our hospital. The primary endpoint of the study was the objective response rate (ORR). We focused on identifying factors associated with cases that had a favorable response.

Results: Twenty-one patients were included. In best response, there were 11 partial response cases, with an ORR of 52.4%. Median progression-free survival was 6.8 months, and overall survival did not reach the median time. A high tumor-to-liver ratio of the maximum value of the standardized uptake value (TLR) on baseline fluorodeoxyglucose positron emission tomography (FDG-PET) was associated with response, while TLRs were significantly higher in poorly differentiated uHCC.

Conclusion: The STRIDE regimen may be beneficial for systemic therapy-naive uHCC patients. High TLR on baseline FDG-PET could be a potentially useful biomarker for response.

Introduction: The relationship between preoperative peak oxygen uptake/weight (VO₂/W) and postoperative pulmonary complications (PPC) in lobectomies, including video-assisted thoracoscopic surgery, remains unclear. Traditional pulmonary function tests are often unreliable in this group, necessitating alternative predictive methods. Therefore, this study aimed to clarify the predictive value of preoperative peak VO₂/W for PPC and explore factors related to PPC in lung cancer patients with chronic obstructive pulmonary disease (COPD).

Methods: This single-center retrospective cohort study included 40 patients with lung cancer complicated by COPD who underwent a preoperative cardiopulmonary exercise test between January 2017 and March 2024. Patients were divided into those with and without PPC (PPC and non-PPC groups, respectively). Clinical parameters such as surgical approach, pulmonary function, low attenuation area, and peak VO₂/W were compared between the groups. The association between these parameters and PPC was analyzed using multivariate logistic regression.

Results: The preoperative % diffusing capacity of the lung for carbon monoxide (%DLCO) and peak VO₂/W were significantly lower in the PPC group than in the non-PPC group (p < 0.01 and p < 0.001, respectively), while the ventilatory equivalent/ventilatory carbon dioxide (VE/VCO₂) slope was significantly higher in the PPC group than in the non-PPC group (p < 0.05). In the multivariate logistic analysis including the %DLCO, peak VO₂/W, VE/VCO_{2 slope}, and forced expiratory volume in 1 s, only peak VO₂/W was identified as a significant independent factor for predicting PPC. The area under the receiver operating characteristic curve of peak VO₂/W to predict PPC was 0.93, with a cutoff value of 14.6 mL/min/kg, sensitivity of 78%, and specificity of 95%.

Conclusions: This study revealed that peak VO₂/W was the most important parameter for predicting PPC in lung cancer patients with COPD. Incorporating cardiopulmonary exercise tests into preoperative assessments could improve risk stratification and perioperative management, potentially reducing the incidence of PPC in this high-risk population.