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1.
Oncologist ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543577

RESUMO

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

2.
Radiat Oncol ; 16(1): 16, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468176

RESUMO

BACKGROUND: The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who have achieved a clinical complete response (cCR) after chemoradiotherapy. This study aimed to investigate the long-term clinical outcomes of this strategy in comparation to surgical resection. METHODS: Stage II/III rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy and achieved a cCR were selected from the databases of three centers. cCR was evaluated by findings from digital rectal examination, colonoscopy, and radiographic images. Patients in whom the watch-and-wait strategy was adopted were matched with patients who underwent radical resection through 1:1 propensity score matching analyses. Survival was calculated and compared in the two groups using the Kaplan-Meier method with the log rank test. RESULTS: A total of 117 patients in whom the watch-and-wait strategy was adopted were matched with 354 patients who underwent radical resection. After matching, there were 94 patients in each group, and no significant differences in term of age, sex, T stage, N stage or tumor location were observed between the two groups. The median follow-up time was 38.2 months. Patients in whom the watch-and-wait strategy was adopted exhibited a higher rate of local recurrences (14.9% vs. 1.1%), but most (85.7%) were salvageable. Three-year non-regrowth local recurrence-free survival was comparable between the two groups (98% vs. 98%, P = 0.506), but the watch-and-wait group presented an obvious advantage in terms of sphincter preservation, especially in patients with a tumor located within 3 cm of the anal verge (89.7% vs. 41.2%, P < 0.001). Three-year distant metastasis-free survival (88% in the watch-and-wait group vs. 89% in the surgical group, P = 0.874), 3-year disease-specific survival (99% vs. 96%, P = 0.643) and overall survival (99% vs. 96%, P = 0.905) were also comparable between the two groups, although a higher rate (35.7%) of distant metastases was observed in patients who exhibited local regrowth in the watch-and-wait group. CONCLUSION: The watch-and-wait strategy was safe, with similar survival outcomes but a superior sphincter preservation rate as compared to surgery in rectal cancer patients achieving a cCR after neoadjuvant chemoradiotherapy, and could be offered as a promising conservative alternative to invasive radical surgery.

3.
Cancer Med ; 10(2): 659-674, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33314798

RESUMO

BACKGROUND: To estimate the adjusted conditional overall survival (COS) in patients with esophageal cancer after receiving various treatment modalities via a national population-based database, and to investigate the possible time-dependent effects. MATERIALS AND METHODS: Eligible patients diagnosed with esophageal cancer between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. The Kaplan-Meier method was used to calculate conventional survival time. The inverse probability of treatment weighting method was used to estimate the adjusted COS in patients receiving different treatment modalities. Landmark analysis was employed to investigate the possible time-dependent effects of different treatment modalities in patients who had survived a certain period of time. RESULTS: A total of 25,232 patients were included in the final analysis. The conventional 5-year overall survival was 19.3%. The 5-year adjusted COS increased most for the first 3 years, and increased slightly afterwards. In patients with regional esophageal or gastroesophageal junction cancer, stage-specific analysis showed that surgery only and preoperative radiation therapy benefited most for patients with localized disease, preoperative radiation therapy plus surgery benefited regional, and preoperative radiation therapy plus surgery benefited distant disease, with the 5-year adjusted COS given patients had survived 3 years being 67.0% (95% CI 65.2%-68.7%), 59.9% (95% CI 58.3%-61.5%), 58.4% (95% CI 56.3%-60.5%), and 61.8% (95% CI 59.5%-64.1%), respectively. In time-dependent analysis, the benefits of surgery only in localized cases were prominent within 48 months after diagnosis. Preoperative radiation therapy showed long-lasting benefits in patients with regional disease. In patients with distant disease, all treatment modalities showed similar and short-term effects. CONCLUSIONS: The adjusted COS in patients with esophageal cancer increased as time accrued after receiving various treatment modalities. The time-dependent effects in specific tumor stage provided a dynamic view on optimization of treatment strategies.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33348033

RESUMO

OBJECTIVES: The objective of this study was to identify the nutrition impact symptom (NIS) clusters in patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT) and explore their relationships with the weight loss rate (WLR). METHODS: This longitudinal study included 169 patients. At baseline (T1), the demographics, clinical information, and weight before radiotherapy (RT) were recorded. At the third week (T2) and the end of RT (T3), we assessed the weight, prevalence, severity, and interference of the NIS with the Head and Neck Patient Symptom Checklist. The mean scores of the severity of NIS at T2 and T3 were used as a whole to perform the exploratory factor analysis and identify the symptom clusters. Cronbach's α coefficient was used to evaluate the internal consistency of the symptom clusters. Generalized estimating equations were used to analyze the relationships between clusters and the WLR. RESULTS: We extracted three clusters from 14 NISs: the RT-specific symptom cluster including pain, difficulty swallowing, oral mucositis, thick saliva, difficulty chewing, and dry mouth (Cronbach's α = 0.820); the gastrointestinal symptom cluster including nausea, loss of appetite, feeling full, vomiting, and taste change (Cronbach's α = 0.592); the psychological status cluster including depressed, anxious, and lack of energy (Cronbach's α = 0.710). The multivariable model showed that participants with more serious RT-specific symptom cluster (ß = 1.020, 95% CI: 0.570-1.471, P < 0.001) had higher WLR. CONCLUSIONS: The NIS had close internal connections with each other, so the strategies applied by healthcare professionals should focus on multiple related symptoms, especially to manage the RT-specific symptom cluster.

5.
Cancer Res ; 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323378

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly diseases. In our previous comprehensive genomic study, we found that FAM135B was a novel cancer-related gene, yet its biological functions and molecular mechanisms remain unclear. In this study, we demonstrate that the protein levels of FAM135B are significantly higher in ESCC tissues than in precancerous tissues, and high expression of FAM135B correlates with poorer clinical prognosis. Ectopic expression of FAM135B promoted ESCC cell proliferation in vitro and in vivo, likely through its direct interaction with growth factor GRN, thus forming a feedforward loop with AKT/mTOR signaling. ESCC patients with overexpression of both FAM135B and GRN had worse prognosis; multivariate Cox model analysis indicated that high expression of both FAM135B and GRN was an independent prognostic factor for ESCC patients. FAM135B transgenic mice bore heavier tumor burden than wild-type mice and survived a relatively shorter lifespan after 4-NQO treatment. Additionally, serum level of GRN in transgenic mice was higher than in wild-type mice, suggesting that serum GRN levels might provide diagnostic discrimination for ESCC patients. These findings suggest that the interaction between FAM135B and GRN plays critical roles in the regulation of ESCC progression and both FAM135B and GRN might be potential therapeutic targets and prognostic factors in ESCC.

6.
Chin J Cancer Res ; 32(5): 645-653, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33223759

RESUMO

Objective: A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma (HCC) after narrow-margin hepatectomy (<1 cm). This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy. Methods: Patients with central HCC after narrow-margin hepatectomy (<1 cm) were prospectively assigned to adjuvant radiotherapy group and control group. Patients' outcome, adverse events, long-term recurrence and survival rates were investigated. Results: The 1-, 5-, and 10-year recurrence-free survival (RFS) rates were 81.0%, 43.9%, and 38.7%, respectively in adjuvant radiotherapy group and 71.7%, 35.8%, and 24.2%, respectively in control group (log-rank test, P=0.09). The 1-, 5-, and 10-year overall survival (OS) rates were 96.6%, 54.7%, and 42.8%, respectively in adjuvant radiotherapy group and 90.2%, 55.1%, and 30.0%, respectively in control group (log-rank test, P=0.20). The 1-, 5-, and 10-year RFS rates for patients with small HCC (≤5 cm) were 91.1%, 51.6%, and 48.4%, respectively in adjuvant radiotherapy group and 80.0%, 36.6%, and 26.6%, respectively in control group (log-rank test, P=0.03). Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group (log-rank test, P=0.05). Conclusions: Our updated results showed a sustained clinical benefit on reducing recurrence, improving long-term survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy. Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.

7.
BMC Cancer ; 20(1): 1132, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228588

RESUMO

BACKGROUND: Previous studies have revealed that nearly 15-20% of selected high-risk T1-2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1-2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT). METHODS: Female patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event. RESULTS: A total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1-222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1-2, and 3-4 risk factors (p < 0.001). CONCLUSIONS: Risk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1-2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3-4 risk factors.

8.
Gynecol Oncol ; 159(2): 365-372, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32933759

RESUMO

OBJECTIVE: High-dose-rate (HDR) afterloading brachytherapy using Iridium-192 source involves large radiation activity varieties due to fast decay. It was unknown but clinically desirable to evaluate its impacts on patient outcomes to support more informed decisions. METHODS: Data of 510 cervical carcinoma (CC) patients were retrospectively included. High-radioactive (HR) and low-radioactive (LR) groups were statistically defined per patient-specific average mean-dose-rate (MDR) of all fractions. The cutoffs were calculated using R-3.6.1 packages based on significance of correlation with binary outcome or survival time. Categorized 1-month and 3-month follow-up results were analyzed as short-term outcomes. Long-term outcomes were evaluated using local recurrence-free survival (LRFS) and metastatic recurrence-free survival (MRFS). Propensity-score-matched (PSM) pairs were generated to reduce bias. RESULTS: The median follow-up time was 47.1 months (interquartile range: 33.9 months-66.4 months), involving MDR varieties of up to 9 folds ranging from 6059.99 cGy/h to 54013.66 cGy/h due to 17 source replacements at intervals ranging from 93 days-199 days. Both short-term (1-month: p = 0.22; 3-month: p = 0.79) and long-term (LRFS: p = 0.10; MRFS: p = 0.46) outcomes showed no significant difference between HR and LR. Subgroup analysis displayed significantly better results in LR for stage I-II (3-month, p = 0.02) and stage II (LRFS, p = 0.04) patients. Both LRFS and MRFS of LR were significantly non-inferior to HR (p ≤ 0.02). CONCLUSIONS: LR is clinically non-inferior or partially superior to HR for CC treatment using HDR, which dispels concerns of potentially undermined patient outcomes when source replacement is delayed.

9.
Cancer Manag Res ; 12: 5293-5299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753948

RESUMO

Purpose: This study aimed to retrospectively analyze the failure patterns and clinical outcomes in patients with locally advanced cervical esophageal carcinoma (CEC) after definitive radiotherapy (RT), and illustrate the mapping of regional failures. Patients and Methods: We reviewed 82 patients with CEC confirmed as squamous cell carcinoma who had completed definitive RT from August 2008 to December 2017. Data on clinical characteristics were collected from the medical records system. Patterns of treatment failures and the survival follow-up were analyzed. Results: The median age was 58 (38-78) years. In 37 patients, the lesions were limited to the cervical esophagus, while in the remaining 45 patients, the disease got beyond the cervical esophagus (pharynx or thoracic esophagus involved). While 10 patients had stage Ⅱ disease, 72 had stage III disease. The completed median dose for 95% PGTV and 95% PTV was 66 Gy and 58 Gy. While the median follow-up was 27.6 months, the median progression-free survival (PFS) and overall survival (OS) was 16.1 and 28.3 months, respectively. The 3-year PFS and OS was 30.3% and 45.3%, respectively. Treatment failures were reported in 55 patients, of which 22, 8, 7, 9, 2, 3, and 4 patients had developed local, regional, distant, local-regional, regional-distant, local-distant and local-regional-distant failure, respectively. Of the 41 relapsed nodal sites, 28 were located "in-field" whereas 1 was "marginal" and 12 were "out-field". The most frequent regional relapses were at level VIb, IV and the upper-middle mediastinum. Conclusion: Regional recurrences focused on lower neck and upper-middle mediastinum, and mainly "in-field", after definitive RT in patients with CEC.

10.
J Clin Oncol ; 38(31): 3604-3614, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32780661

RESUMO

PURPOSE: No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China. PATIENTS AND METHODS: Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority. RESULTS: Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group (P = .019). CONCLUSION: CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.

11.
BMC Cancer ; 20(1): 614, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611327

RESUMO

BACKGROUND: Microvascular invasion (MVI) is considered to be one of the important prognostic factors that affect postoperative recurrence in patients with hepatocellular carcinoma (HCC) with variable results across their treatment options. This study was carried out to investigate efficacy of postoperative adjuvant RT in HCC patients with MVI. METHODS: This was single center, prospective study carried out in HCC patients with MVI, aged 35-72 years. All patients were non-randomly allocated to receive standard postoperative treatment of HBV/HCV and nutritional therapy or RT in addition to standard postoperative treatment (1:1). The primary endpoints assessed were relapse-free survival and overall survival. The prognostic factors associated with survival outcomes were also analyzed. The safety events were graded according to NCI-CTCAE v4.03 criteria. RESULTS: Of the 115 patients eligible for study, 59 patients were included in analysis. Univariate analysis revealed that MVI classification (P = 0.009), post-operative treatment strategies (P = 0.009) were prognostic factors for worst RFS; tumor size (P = 0.011), MVI classification (P = 0.005) and post-operative treatment (P = 0.015) were associated for OS. The 1-, 2-, 3-year RFS rates were 86.2, 70.5 and 63.4% for patients in RT group, and 46.4, 36.1, and 36.1% in control group. For OS, corresponding rates were 96.6, 80.7, and 80.7% for patients in RT group and 79.7, 58.3, and 50.0% in control group. Subgroup classification of HCC patients according to low risk MVI showed significantly longer RFS (P = 0.035) and OS (P = 0.004) in RT group than control group, while for high risk MVI, RT depicted longer OS than control group with no significance (P = 0.106). Toxicities were usually observed in acute stage with no grade 4 toxicities. CONCLUSION: Postoperative adjuvant RT following hepatectomy offers better RFS for HCC patients with MVI than with standard postoperative therapy. Also, it will be useful to control microscopic lesions in both M1 (low risk) and M2 (high risk) subgroups of HCC patients with MVI. TRIAL REGISTRATION: Trial Registration number: ChiCTR1800017371 . Date of Registration: 2018-07-26. Registration Status: Retrospectively registered.

12.
Int J Gynecol Cancer ; 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474447

RESUMO

OBJECTIVE: The benefit of adjuvant chemotherapy after definitive chemoradiotherapy in patients with pelvic lymph node-positive cervical cancer has been poorly studied. This study aimed to test the hypothesis that the addition of adjuvant chemotherapy to definitive radiotherapy or concurrent chemoradiotherapy improves survival in patients with pelvic lymph node-positive cervical squamous cell carcinoma. METHODS: This retrospective study enrolled patients with stage IB-IVA pelvic lymph node-positive cervical squamous cell carcinoma, without para-aortic lymph node metastases and initially treated with definitive radiotherapy or concurrent chemoradiotherapy between March 2007 and February 2018. Patients were classified into the adjuvant chemotherapy (5-fluorouracil or paclitaxel, plus cisplatin) and no-adjuvant chemotherapy groups. Treatment outcomes were compared between the two groups before and after 1:1 ratio propensity score matching. RESULTS: Medical records of 951 patients were reviewed and 792 patients were excluded. Finally, 159 patients were enrolled for analysis. Of these, 42 patients received a median of two cycles (range, 1-6) of adjuvant chemotherapy and 117 patients under observation after primary treatment. The median follow-up period was 33.8 months (range, 2.9-113.0). Before propensity score matching, no significant difference was observed in survivals between the two groups (P>0.05). After propensity score matching, 37 pairs of patients were selected. The 3-year rates of progression-free survival, overall survival, local control, and distant metastasis-free survival in the adjuvant chemotherapy and no-adjuvant chemotherapy groups were 80.2% and 60.4% (P=0.07), 83.0% and 63.7% (P=0.17), 94.0% and 81.9% (P=0.12), and 85.9% and 60.1% (P=0.04), respectively. The incidences of grade 3-4 acute and late toxicities were comparable between the two groups (P>0.05). DISCUSSION: Adjuvant chemotherapy significantly improved 3-year distant metastasis-free survival in patients with pelvic lymph node-positive cervical squamous cell carcinoma. Further prospective studies are needed to provide supportive evidence for the therapeutic efficacy of adjuvant chemotherapy.

13.
Biomed Pharmacother ; 128: 110284, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32480224

RESUMO

BACKGROUND: Liver cancer is a devastating disease that has second highest cancer mortality rate worldwide. Although surgical resection or liver transplantation sometimes cures early stage liver cancer, few therapeutic options are available for advanced-stage liver cancer, highlighting the importance of a better understanding of the disease to find novel therapeutic targets. METHODS: Firstly, clinical features of EPS8L3 on liver cancer RNA-seq dataset of The Cancer Genome Atlas (TCGA) database was analyzed, including gene expression levels in tumor tissues in comparison with the normal tissues as well as the patients' OS. To confirm the candidate genes, we used short hairpin RNA (shRNA) to knock down the gene and quantify the cell proliferation, apoptosis, and migration. Then micro-array analysis was did to investigate the intracellular mechanisms of EPS8L3. Moreover, to gain further insights into the translational value of the findings, we treated the liver cancer cells with Sorafenib after knocking down the candidate gene, in order to interrogate the combinatorial inhibitory effects on cell metabolism. RESULTS: As a result, by comparing gene expression profiles of normal liver and cancerous tissues, we find that epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8L3), a gene with unknown function, is upregulated in liver cancer, and is associated with poor prognosis. Further gene set analyses on liver cancer cells revealed that EPS8L3 is pertinent to cell division and proliferation. Indeed, knocking down EPS8L3 inhibits cell proliferation and migration, and triggers apoptosis in vitro. Additionally, when inoculated into mice, EPS8L3 knocked down cells exhibit slower growth rate. Moreover, EPS8L3 expression can substantially increase the efficacy of low dosage of Sorafenib treatment. Furthermore, the results of immunohistochemical staining of 90 paired liver cancer and adjacent normal samples demonstrated high expression of EPS8L3 yields poor prognosis in Chinese liver cancer patients. CONCLUSIONS: Collectively, our results suggest that EPS8L3 has pivotal oncogenic functions in liver cancer and we propose that EPS8L3 could be a potential therapeutic target to treat liver cancer.

14.
Front Oncol ; 10: 731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477949

RESUMO

Background: To identify multiparametric magnetic resonance imaging (mp-MRI)-based radiomics features as prognostic factors in patients with localized prostate cancer after radiotherapy. Methods:From 2011 to 2016, a total of 91 consecutive patients with T1-4N0M0 prostate cancer were identified and divided into two cohorts for an adaptive boosting (Adaboost) model (training cohort: n = 73; test cohort: n = 18). All patients were treated with neoadjuvant endocrine therapy followed by radiotherapy. The optimal feature set, identified through an Inception-Resnet v2 network, consisted of a combination of T1, T2, and diffusion-weighted imaging (DWI) MR series. Through a Wilcoxon sign rank test, a total of 45 distinct signatures were extracted from 1,536 radiomics features and used in our Adaboost model. Results:Among 91 patients, 29 (32%) were classified as biochemical recurrence (BCR) and 62 (68%) as non-BCR. Once trained, the model demonstrated a predictive classification accuracy of 50.0 and 86.1% respectively for BCR and non-BCR groups on our test samples. The overall classification accuracy of the test cohort was 74.1%. The highest classification accuracy was 77.8% between three-fold cross-validation. The areas under the curve (AUC) of receiver operating characteristic curve (ROC) indices for the training and test cohorts were 0.99 and 0.73, respectively. Conclusion:The potential of multiparametric MRI-based radiomics to predict the BCR of localized prostate cancer patients was demonstrated in this manuscript. This analysis provided additional prognostic factors based on routine MR images and holds the potential to contribute to precision medicine and inform treatment management.

15.
Int J Radiat Oncol Biol Phys ; 108(4): 1030-1039, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32585337

RESUMO

PURPOSE: The present study aimed to evaluate the effect of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy in patients with node-positive stage II to III (cT1-4N1-2M0) breast cancer. METHODS AND MATERIALS: A total of 1813 patients from 12 institutions were retrospectively reviewed. Patients were classified into 1 of 3 groups based on the pathologic lymph node status after neoadjuvant chemotherapy: ypN0, ypN1, and ypN2-3. The role of PMRT was separately evaluated in each group. Locoregional control, disease-free survival, and overall survival (OS) were estimated using the Kaplan-Meier method. The effect of PMRT was assessed by propensity score-matched analyses and multivariate Cox analyses. RESULTS: With a median follow-up of 72.9 months, 5-year locoregional control, disease-free survival, and OS rates were 86.3%, 68.4%, and 83.1% for the entire cohort, respectively. There were 490 (27.0%), 567 (31.3%), and 756 (41.7%) patients in the ypN0, ypN1, and ypN2-3 groups, respectively. PMRT significantly improved 5-year OS in the ypN2-3 group (74.2% vs 55.9%; P < .001) but had no effect on 5-year OS in the ypN0 group (93.1% vs 95.5%; P = .517) and ypN1 group (88.4% vs 87.8%; P = .549). CONCLUSIONS: With modern systemic therapy, PMRT significantly improved OS in the ypN2-3 group but not in the ypN0 and ypN1 groups. Whether PMRT can be safely omitted in the ypN0 and ypN1 groups should be addressed prospectively.

16.
Theranostics ; 10(7): 3035-3048, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194853

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC), one of the leading causes of cancer mortality worldwide, is a heterogeneous cancer with diverse clinical manifestations. However, little is known about the epigenetic heterogeneity and its clinical relevance for this prevalent cancer. Methods: We generated 7.56 Tb single-base resolution whole-genome bisulfite sequencing data for 84 ESCC and paired paraneoplastic tissues. The analysis identified inter- and intratumor DNA methylation (DNAm) heterogeneity, epigenome-wide DNAm alterations together with the functional regulators involved in the hyper- or hypomethylated regions, and their association with clinical features. We then validated the correlation between the methylation level of specific regions and clinical outcomes of 96 ESCC patients in an independent cohort. Results: ESCC manifested substantial inter- and intratumor DNAm heterogeneity. The high intratumor DNAm heterogeneity was associated with lymph node metastasis and worse overall survival. Interestingly, hypermethylated regions in ESCC were enriched in promoters of numerous transcription factors, and demethylated noncoding regions related to RXR transcription factor binding appeared to contribute to the development of ESCC. Furthermore, we identified numerous DNAm alterations associated with carcinogenesis and lymph node metastasis of ESCC. We also validated three novel prognostic markers for ESCC, including one each in the promoter of CLK1, the 3' untranslated region of ZEB2, and the intergenic locus surrounded by several lncRNAs. Conclusions: This study presents the first population-level resource for dissecting base-resolution DNAm variation in ESCC and provides novel insights into the ESCC pathogenesis and progression, which might facilitate diagnosis and prognosis for this prevalent malignancy.

17.
Int J Radiat Oncol Biol Phys ; 108(1): 277-285, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32147519

RESUMO

PURPOSE: The aim of this study was to determine whether radiation-induced lymphopenia affects the survival of patients with breast cancer. METHODS AND MATERIALS: Post hoc analysis was conducted on data from 598 patients with breast cancer from a randomized controlled trial comparing postmastectomy hypofractionated radiation therapy (HFRT; 43.5 Gy in 15 fractions over 3 weeks) with conventional fractionated radiation therapy (CFRT; 50 Gy in 25 fractions over 5 weeks). Mean peripheral lymphocyte count (PLC) at different time points in the 2 groups was compared by the t test. Disease-free survival and overall survival were analyzed by the Kaplan-Meier method and compared between groups by the log-rank test. RESULTS: Baseline PLC (pre-PLC) was comparable between HFRT and CFRT patients (1.60 ± 0.57 × 109/L vs 1.56 ± 0.52 × 109/L; P = .33). In both groups, the PLC declined steadily during the course of radiation therapy but started to recover at 1 month after radiation therapy. Incidence of lymphopenia was significantly lower in HFRT patients (45.4% vs 55.7%; P = .01). Nadir-PLC was significantly higher in HFRT patients (1.08 ± 0.37 × 109/L vs 0.97 ± 0.31× 109/L; P < .001), as was the nadir-PLC/pre-PLC ratio (0.72 ± 0.28 vs 0.67 ± 0.28; P = .02). Median follow-up was 57.6 months (interquartile range, 38.5-81.4). The 5-year disease-free survival was significantly lower in patients with a nadir-PLC/pre-PLC ratio <0.8 than in those with a ratio ≥0.8 (71.8% vs 82.6%; P = .01); however, overall survival was comparable between the groups (85.8% vs 90.6%; P = .24). CONCLUSIONS: The risk of radiation-induced lymphopenia in patients with breast cancer is lower with HFRT than with CFRT. A low nadir-PLC/pre-PLC ratio may predict poor prognosis.

18.
Br J Cancer ; 122(7): 978-985, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31937925

RESUMO

BACKGROUND: Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. METHODS: A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. RESULTS: Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. CONCLUSIONS: This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

19.
Front Oncol ; 9: 1065, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681599

RESUMO

The safety and efficacy of transcatheter arterial chemoembolization (TACE) plus intensity-modulated radiotherapy (IMRT) combined with sorafenib in hepatocellular carcinoma (HCC) showing macrovascular invasion (MVI) remain controversial. The records of 63 patients with HCC showing MVI, who underwent IMRT plus TACE combined with (28 participants; Group A) or without (35 participants; Group B) sorafenib from 2015 to 2018, were retrospectively reviewed to assess the progression-free survival (PFS), overall survival (OS), and treatment-associated toxicity. The median PFS was longer in Group A (13.6 months) than in Group B (9.2 months), and still significant after propensity score matching (PSM). However, the median OS was similar in the two groups (19.0 vs. 15.2 months, P = 0.094 before PSM; P = 0.204 after PSM). The grade 3 hematologic and hepatic toxicity was present in 10 (15.9%) and 7 (11.1%) patients, respectively. The incidence of skin reaction, hand-foot syndrome, and diarrhea, all grade 1-2 adverse events, was significantly higher in Group A than in Group B. No patient experienced grade 4 or 5 toxicity, and radiation-induced liver disease was also not observed. TACE plus IMRT combined with sorafenib showed a good safety profile and clinical benefit in patients with HCC having MVI.

20.
Front Oncol ; 9: 1080, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681609

RESUMO

Purpose: To analyze the prognostic factors and optimal response interval for stereotactic body radiotherapy (SBRT) in patients with lung oligometastases (OM) or oligoprogression (OP) from colorectal cancer (CRC). Method: Patients with lung OM or OP from CRC treated by SBRT at our hospital were included in this retrospective review. The local control (LC), response to SBRT in different evaluation interval and regional metastases (RM) was analyzed. The risk factor for LC and RM was calculated using the Kaplan-Meier method and compared using the Log-rank test. Multivariate analysis with a Cox proportional hazards model was used to test independent significance. Results: A total of 53 patients with 105 lung metastases lesions treated from 2012 to 2018 were involved in this retrospective study. The median biologically effective dose (BED) for these patients was 100 Gy (range: 75-131.2 Gy). Complete response (CR) increased from 27 (25.7%) to 46 (43.8%) lesions at 1.8 and 5.3 months following SBRT, and at the last follow-up, 52 (49.5%) lesions achieved CR. The median follow-up duration for all patients was 14 months (range: 5-63 months), and 1-year LC was 90.4%. During the follow-up, 10 lesions suffered local relapse after SBRT (9 of them occurred within 8 months after SBRT). The univariate analysis shows BED ≥ 100 Gy (P = 0.003) and gross tumor volume (GTV) < 1.6 cm3 (P = 0.011) were better predictors for 1-year LC. The patients with lung oligoprogression had higher 1-year RM when compared with patients with lung oligometastases (hazard ratio 2.78; 95% confidence interval [CI] 1.04-7.48, P = 0.042). Until the last follow up, 4 (7.5%) patients suffered grade 2 radiation pneumonitis, and no grade 3-4 toxicity was observed. Conclusions: SBRT provides favorable LC in CRC patients with lung OM or OP, and the GTV and BED can affect the LC. Radiology examinations nearly 5-6 months following SBRT appear to represent the final local effect of SBRT, and the patients with oligoprogression has higher RM.

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