Oncology最新文献

Introduction: There remain controversies about the role of surgery for N3 stage non-small cell lung cancer (NSCLC) patients.

Methods: N3 stage NSCLC patients were identified from the US National Cancer Institute Surveillance, Epidemiology, and End Results database (2010-2020). Survival analysis and multivariate regression models were used to adjust covariates and analyze factors associated with survival. Propensity score matching was used to balance selection bias.

Results: Of 6,473 included patients, 121 received treatment that included lobectomy with mediastinal lymph node dissection. Overall survival (OS) was significantly prolonged in the lobectomy group than in the nonsurgery group (median survival time [MST]: 57 vs. 16 months; log-rank p < 0.001). A total of 403 patients were matched, and OS was significant longer in the lobectomy group (MST: 51 vs. 16 months; log-rank p < 0.001). Multivariate regression analyses indicated that lobectomy was independently associated with improved OS (hazard ratio [HR] 0.398, 95% confidence interval [CI] 0.302-0.526; p < 0.001) and lung cancer-specific death (LCSD) (subhazard ratio [SHR] 0.343, 95% CI: 0.249-0.474; p < 0.001).

Conclusion: Compared with nonsurgical treatment modalities, lobectomy with lymph node dissection was associated with improved OS and LCSD in selected N3 stage NSCLC patients.

Introduction: In the USA, endometrial cancer incidence rose by 4.5% annually from 1999 to 2015, reaching 18 per 100,000 women, with a disproportionate impact on African American women. Despite advancements in endometrial cancer research, racial disparities in mortality rates persist. Our retrospective cohort study aimed to investigate the mortality trends and disparities among patients with endometrial cancer in the USA.

Methods: Patients with endometrial cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were compared across different races and geographical regions.

Results: From 1999 to 2020, endometrial cancer accounted for 90,145 deaths in the USA. Overall, the AAMRs of endometrial cancer increased significantly from 2.50 (95% CI, 2.41-2.58) in 1999 to 3.94 (95% CI, 3.85-4.04) per 100,000 individuals in 2020, with an AAPC of +2.23 (95% CI, 1.39-3.07). The highest AAMR was observed among African Americans (2.69 [95% CI, 2.65-2.74]), followed by whites (1.44 [95% CI, 1.43-1.45]), Hispanics (1.16 [95% CI, 1.13-1.20]), Asians (1.00 [95% CI, 0.96-1.04]), and American Indians (0.99 [95% CI, 0.88-1.10]). The highest AAMR from endometrial cancer was recorded in the Northeast region (1.73 [95% CI, 1.71-1.76]).

Conclusion: There was an increasing trend of mortality rates from endometrial cancer in the last 2 decades, which disproportionately affected African Americans. Targeted interventions are warranted to address the mortality disparities among patients with endometrial cancer.

Introduction: Next-generation sequencing (NGS) of tumor DNA can detect actionable drivers and help guide therapy for patients with advanced-stage cancers. While tissue-based genotyping is considered a standard of care, blood-based genotyping is emerging as a valid alternative. Tumor genomic profiles may vary by region, and data from the Middle East and North Africa (MENA) are not widely available. This study elucidates the genomic landscape of advanced solid cancers in patients from the MENA region by retrospectively analyzing results from NGS circulating tumor DNA (ctDNA) testing.

Methods: In routine clinical practice, 926 plasma samples from 767 patients with advanced cancers from the MENA region were profiled using a comprehensive NGS assay (Guardant360®). We conducted a pan-cancer analysis and sub-analyses focusing on lung, breast, and colorectal cancers.

Results: In the pan-cancer group, TP53 (58.5%), EGFR (20.4%), and KRAS (18.9%) were the most frequently mutated genes. EGFR (10.2%), FGFR1 (4.9%), and PIK3CA (4.9%) showed the most amplifications, while fusions were observed in 2.7% of patients, including ALK, FGFR2, and RET. For lung adenocarcinoma, EGFR (30.5%), KRAS (19.3%), and ERBB2 (4.6%) were the most frequently identified alterations among the genes recommended for evaluation by the National Comprehensive Cancer Network (NCCN). In patients with breast cancer, PIK3CA (35.3%), ESR1 (21.7%), and BRCA1/2 (13.3%) had the most prevalent alterations among NCCN-recommended genes. In colorectal cancer, KRAS (39.0%), NRAS (8.0%), and BRAF (V600E, 4.0%) were the most observed mutations among genes recommended by the NCCN. Comparing this cohort to publicly available Western and Eastern datasets also indicated similarities (including PIK3CA in breast cancer) and variances (including EGFR in lung adenocarcinoma) in key genes of interest in the analyzed cancer types.

Conclusion: Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions.

Introduction: The incidence of neuroendocrine tumors (NETs) is rising. Our objective was to assess trends in gastroenteropancreatic (GEP)-NETs diagnosis (June 2010 to June 2021) at TOHCC and to explore whether early COVID-19 pandemic data impacted these trends.

Methods: This was a single-center retrospective chart review of data collected from June 2010 to June 2021. We searched all databases, including OACIS/EPIC, PACS, and OPIS and found 647 GEP-NET patients. Descriptive analyses were performed using frequencies and related percentages.

Results: Of 647 patients with GEP-NETs, the small bowel was the most common primary location (n = 210, 32.4%), followed by the pancreas (n = 118, 18.2%), and unknown primary location (n = 99, 15.3%). Most of the cases were classified as metastatic or locally advanced at the initial presentation. There has been no significant variation in the frequency distribution of these cases over the last decade. Stages 1 and 2 were found in 158 cases (23.8%), and lower gastrointestinal (GI) tumors were the most common disease among them (n = 88, 55.7%). There were 5 lower GI cases in 2010-2011 and average number per registration year was 5.5 until 2016-2017, after which time the number of cases increased to 10, 15, 11, and 13 during the last 4 years. Regarding early-stage pancreatic and upper GI NETs, the total number of cases was 52 (32.9%) and 18 (11.4%), respectively. The average number of cases per registration year for pancreatic tumors was 4.7, while that for upper GI tumors was 1.6 over the last decade.

Discussion: At our center, most GEP-NETs presented in an advanced setting. Small bowel is the most common location overall. The incidence of early-stage disease has increased. Disease detection for all GEP-NETs was consistent throughout the last decade, except for the lower GI cases that have increased since mid-2017, perhaps reflecting the adoption of Ontario FIT testing. Despite endoscopy closures and disruption of some diagnostic services during the pandemic, cases of GEP-NETs for all stages did not decrease.

Introduction: Skin cancer (SC) is common in fair skin (FS) at a 1:5 lifetime incidence for nonmelanoma skin cancer. In order to assist clinicians' decisions, a risk intervention technology was developed, which combines a dual-mode machine learning of visual and sonified (pixel to sound) data. The addition of an audio technology enhances malignant features of lesions, increases sensitivity and was previously validated under a prospective clinical setting in FS. In dark skin (DS), although rare by a 10-30 factor, skin cancer is diagnosed at more advanced stages resulting in a delayed diagnosis and affecting life quality and expectancy. It is known as well that SC diagnostic accuracy by machine learning in DS is decreased as compared to FS. The present study tests the use of sonification aided by artificial intelligence algorithms to compare diagnostics of different skin tones.

Methodology: Biopsy-validated smartphone images were diagnosed in a retrospective study by a dual audio-visual convoluted neural network. A total of 60 Fitzpatrick I-III were compared to 72 Fitzpatrick IV-VI. A dichotomous diagnostic output, either malignant or benign, was assessed for sensitivity, specificity and area under the curves (AUCs) for the receiver operating characteristic (ROC) curve.

Results: ROC curve analytics indicated an AUC of 0.858 (95% CI: 0.795-0.921) and 0.856 (95% CI: 0.759-0.953) for fair and DS (p = NS). Sensitivity of Fitzpatrick I-III skin and Fitzpatrick IV-VI were 84.4% (71.8-96.9) and 79.6% (63.4-93.8), respectively (p = NS). Specificity of Fitzpatrick I-III skin and Fitzpatrick IV-VI were 84.2% (72.6-95.8) and 85.3% (73.4-97.2), respectively (p = NS). The positive predictive and negative predictive values as well as accuracy (0.817 vs. 0.847) were all within the same range (p = NS).

Conclusions: The results demonstrate that the dual-modality classifier identifies skin cancer of FS and DS similarly well. Sonification of malignant signs of a skin lesion demonstrates promising results, even with smartphone images, which should be considered as a tool to achieve more effective and accessible healthcare.

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract, the treatment of which represents a significant breakthrough in targeted cancer therapy. Given its overall rare nature, genomic differences and clinical implications between demographic groups have not been previously investigated.

Methods: Anonymized demographic, clinical, and genomic data from 1,559 GIST patients in the American Association for Cancer Research Project GENIE database were analyzed using cBioPortal and custom Python scripts. Data on patient demographics, genomic alterations, and co-occurrence genetic alerations were collected and classified according to clinical implications using the OncoKB database. χ2 tests for differences in genomic alterations were used across various demographic factors and mutual exclusivity analysis was employed to identify co-mutation patterns.

Results: Male patients demonstrated higher incidence of PDGFRA mutation (14.56% vs. 8.05%; p < 0.001), while female patients had higher likelihood of NF1 mutations (7.46% vs. 3.23%; p = 0.001). Asian patients had higher alteration rates at KIT (85.59%; p = 0.002). Co-occurrence analysis revealed KIT alterations frequently co-occurred with CDKN2A (q < 0.001), MTAP (q = 0.045), and PTEN (q = 0.056), while there was mutual exclusivity with PDGFRA (q < 0.001), NF1 (q < 0.001), and BRAF (q = 0.015). CDKN2A alterations co-occurred with MTAP (q < 0.001) and PIK3CA (q = 0.015), while being mutually exclusive with TP53 (q = 0.002) and NF1 (q = 0.007). Trends were similar among patients who had received no prior medical treatment. Imatinib-resistant mutations were more common among male patients (25.6% vs. 18.9%; p = 0.0056) and individuals under 55 (27.3% vs. 20.9%; p = 0.0228). Among patients with imatinib-resistant mutations, 77.78% had sunitinib resistance, while 70.25% maintained sensitivity to ripretinib.

Conclusion: Sex and race/ethnic differences in genomic alterations, as well as co-mutations, were prevalent among patients with GIST. Variations in mutational profiles highlight the importance of distinct genetic drivers that may be targeted to treat different patient populations.

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: Tongue squamous cell carcinoma (TSCC) is a common malignant tumour type with aggressive invasion and a poor prognosis. To date, invasion-related gene expression signatures for the prognostic stratification of TSCC patients are unavailable in clinical practice. This study aimed to assess the impact of invasion-related genes on the prognosis of TSCC patients.

Methods: We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis.

Results: A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line.

Conclusion: This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.

Introduction: This study aimed to evaluate the clinical value of iodine-131 combined with levothyroxine sodium in the treatment of patients with differentiated thyroid cancer (DTC) after surgery.

Methods: Prospective randomized controlled studies were conducted. A total of 374 DTC patients who underwent total or near-total thyroidectomy in the Department of Thyroid Surgery, Tianjin Union Medical Center and Tianjin Medical University General Hospital, from January 2019 to February 2022 were selected and divided into control group (187 cases) and observation group (187 cases) according to random number table method. The control group was treated with levothyroxine sodium after surgery, and the observation group was treated with iodine-131 on the basis of the control group. Gender, age, course of disease, tumor diameter, pathological type, TNM classification, treatment effect, thyroglobulin (Tg) levels before and after treatment, SF-36 health status questionnaires (SF-36), occurrence of adverse reactions after treatment, and recurrence rate of 1-year follow-up were compared and analyzed between the two groups.

Results: There was no significant difference in baseline data between the two groups. After treatment, the effective rate of the observation group increased by 11.23% compared to the control group, with a statistically significant difference (91.98% vs. 80.75%, p < 0.05). There was no significant difference in Tg level and scores of SF-36 evaluation including physical functioning, physical problems, vitality, pain, mental health, emotional problems, social functioning, and general health perception between the two groups before surgery (p > 0.05), Tg levels and scores of SF-36 evaluation in all dimensions were significantly improved in both groups after treatment (p < 0.05), and the levels of Tg and scores of SF-36 in all dimensions in observation group were significantly better than those in control group after treatment (p < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). The recurrence rate in the observation group was 5.89% lower than that in the control group 1 year after treatment, with a statistically significant difference (2.67% vs. 8.56%, p < 0.05).

Conclusions: The combination of iodine-131 and levothyroxine sodium in the postoperative treatment of DTC can improve the therapeutic effect and reduce the postoperative recurrence rate without increasing adverse reactions, which is worthy of clinical reference and promotion.

Background: Preoperative diagnosis of parathyroid cancer (PC) where possible allows for en-bloc resection of the tumour, which is associated with excellent prognosis. The rule of >3 (size of tumour larger than 3 cm; corrected calcium more than 3 mmol/L) as proposed by Schulte and Talat has a specificity of 95% in predicting malignancy in parathyroid neoplasms. We looked at the impact of rule of 3 in predicting malignancy and outcomes on intervention in a South Asian cohort.

Methods: Patients who underwent parathyroid surgery between 2010 and 2023 at two tertiary referral centres were assessed. Patients with PC were selected and their clinicopathological parameters, treatment modalities, and outcomes were analysed.

Results: Thirteen of 336 (3.8%) patients with a mean age of 61.8 (±17.5) years were diagnosed with PC during the study period. The highest mean preoperative values were PTH (92.4 ± 66.27 pmol/L), highest corrected calcium (3.21 ± 0.28 mmol/L), and alkaline phosphatase (419 IU/mL). Nine patients underwent en-bloc excision while the other had focussed parathyroidectomy. Recurrences were recorded in 2 (28.5%) patients over a mean follow-up period of 69 (±48.6) months. One patient with lung metastasis underwent video-assisted thoracic surgery. There was no disease specific mortality in this cohort during the study period.

Conclusions: In our experience, the predictive rule of 3 has low sensitivity to suspect PC preoperatively, resulting in limited usefulness in clinical practice. Outcomes appear to be less favourable with higher recurrence rates in cases where less than en-bloc resection is performed.