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1.

Introduction

Breast cancer (BC) is the most common cancer in women, and the incidence of brain metastasis (BM) from BC ranges from 20% to 30%, with a median survival of 10 to 15 months. Previous reports have shown that the presence of obesity or diabetes negatively impacts survival. The present study investigates the association between obesity or diabetes mellitus (DM) and overall survival of patients with BC with BM.

Materials and Methods

A database from 2 referral centers for the period of July 2014 to February 2018 was analyzed. The inclusion criteria were as follows: patients who had a confirmed diagnosis of BC with BM were followed and treated at these centers. Demographic data, body weight and height, clinical and oncologic history, functional status, prognostic scales, and prognoses were examined.

Results

A total of 228 patients were included. The median age at BM was 50 years; the median survival after diagnosis was 12.1 months; 108 patients had a body mass index (BMI) ≥ 25, and 40 (17%) patients had DM. The association between survival and the presence of BMI > 25 exhibited a P value of 0.3.

Discussion

We found no association between overweight, obesity, or DM and survival in patients with BC with BM. The role of obesity in cancer is a robust research topic, as there are many questions to be answered.

Conclusion

Obesity as a prognostic indicator should be further studied, because we found no association between overall survival and either patients with BM from BC with a BMI > 25 or those with normal weight.  相似文献   

2.

Background

Metastases to the brain occur in 10%-16% of patients with breast cancer, with incidence reportedly increasing. Historically, brain metastases (BM) have been treated with whole-brain radiation therapy (WBRT), but stereotactic radiosurgery (SRS) is an increasingly favored treatment option. In this study we used a population-level database to compare patterns of care and survival between WBRT and SRS for BM from breast cancer.

Materials and Methods

The National Cancer Database was used to select patients treated with radiation for BM from primary breast cancer. Groups were classified on the basis of the modality of radiation delivered to the brain and compared across several demographic factors. A Kaplan–Meier survival curve and Cox multivariate analysis were used to compare overall survival. A matched analysis using propensity scores was used to further reduce confounders and compare survival.

Results

The treatment groups were significantly different across several socioeconomic variables including income, insurance status, and treatment setting. The percentage of patients who received SRS increased dramatically in the second half of the analyzed time period (P < .001). Unadjusted median survival was significantly longer for patients who received SRS versus those who received WBRT (P < .001). This finding persisted after propensity score-matching.

Conclusion

Receipt of SRS was associated with different socioeconomic variables and longer overall survival compared with WBRT, highlighting the need for less toxic treatment for patients who are now living longer. The results revealed important socioeconomic differences between patients selected for SRS versus WBRT and emphasizes disparities in access to modern radiation techniques across the United States.  相似文献   

3.

Purpose

To assess the pharmacologic costs of second-line treatments for metastatic renal-cell cancer (mRCC).

Methods

The present evaluation was restricted to pivotal phase 3 randomized controlled trials in second-line for mRCC. We calculated the pharmacologic costs necessary to get the benefit in progression-free survival and overall survival (OS) for each trial. The costs of drugs are at the pharmacy of our hospital and are expressed in euros.

Results

Our analysis evaluated 5 phase 3 randomized controlled trials including 3112 patients. The lowest cost per month of progression-free survival and OS gained was associated with the use of cabozantinib (€2006 and €1473, respectively), while everolimus had the highest cost per month of OS gained (€28,590).

Conclusion

Combining pharmacologic costs of drugs with the measure of efficacy represented by OS, cabozantinib is a cost-effective second-line treatments for patients with mRCC.  相似文献   

4.

Background

The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.

Patients and Methods

Within the PLCO (Prostate, Lung, Colorectal, and Ovary) trial, patients who were diagnosed with clinically localized prostate cancer and subsequently received treatment with prostatectomy or radiation therapy (with or without hormonal treatment) were included. Univariate and multivariate Cox regression analyses were then performed to determine factors affecting overall and prostate cancer-specific survival. Factors with P < .05 in univariate analysis were included in the multivariate analysis.

Results

A total of 3953 patients were included in the current analysis. These included 2044 patients treated with prostatectomy and 1909 patients treated with radiation therapy with or without hormonal treatment. In an adjusted multivariate analysis for factors affecting overall survival, prostatectomy was associated with better overall survival compared with radiation therapy (hazard ratio, 0.548; 95% confidence interval [CI], 0.440- 681; P < .001). Likewise, in an adjusted multivariate analysis for factors affecting prostate cancer-specific survival, prostatectomy was associated with better prostate cancer-specific survival compared with radiation therapy (hazard ratio, 0.485; 95% CI, 0.286- 0.822; P = .007). Similar findings were found with propensity score matching and repeating the same analyses on the post-matching cohort.

Conclusion

Prostatectomy seems to predict better overall and prostate cancer-specific survival compared with radiation therapy among patients with clinically localized prostate cancer diagnosed within the PLCO trial.  相似文献   

5.

Background

There are no previous reports directly evaluating immunologic conditions in tumor microenvironment including both bladder cancer (BCa) and upper urinary tract carcinoma (UTUC). In this study, we aimed to clarify the difference of immunity status and its clinical significance depending on the tumor site in urothelial carcinoma.

Patients and Methods

Tumor tissue–infiltrating lymphocytes were extracted from 70 urothelial cancer patients who underwent surgical resection (52 cases of BCa and 18 cases of UTUC). The immunologic classification was established by unsupervised clustering analysis according to the expression ratio of 9 extracellular surface markers measured by flow cytometry, and we examined the relationship between immunologic classification and clinical importance such as pathologic status and prognosis (progression-free survival and cancer-specific survival).

Results

The immunologic condition was classified into 2 groups. Group 1 (n = 41) comprised the CD4 T-cell–dominant group and group 2 (n = 29) the immunologically activated group. This immunologic classification was significantly correlated with tumor grade (P = .020) but not tumor location in multivariate analysis. In invasive BCa patients (n = 33), progression-free survival and cancer-specific survival of group 2 were significantly worse than those of group 1 (P = .021 and P = .022, respectively), while there was no significant difference between groups 1 and 2 in patients with invasive UTUC (n = 17).

Conclusion

Although there was no difference in the local immunologic condition of urothelial carcinoma between BCa and UTUC, its significance as a prognostic predictor might vary depending on tumor site.  相似文献   

6.

Introduction

Colorectal cancer is a major public health issue, with incidences continuing to rise owing to the growing and aging world population. Current screening strategies for colorectal cancer diagnosis suffer from various limitations, including invasiveness and poor uptake. Consequently, there is an unmet clinical need for a minimally invasive, sensitive, and specific method for detecting the presence of colorectal cancer and pre-malignant lesions.

Patients and Methods

An indirect enzyme-linked immunosorbent assay was used to measure the primary (IgM) and secondary (IgG) adaptive humoral immune responses to a panel of previously identified cancer antigens in the sera of normal and adenoma samples, and sera from patients with colorectal cancer.

Results

An optimal panel of 7 biomarkers capable of identifying patients with colorectal cancer as distinct from both normal and adenoma samples is identified. The cumulative sensitivity and specificity of the assay are 70.8% and 86.5%, respectively. The positive and negative predictive values of the cohort are 77.3% and 82.1%. This assay was not able to accurately discriminate between normal and adenoma samples. Patients whose serum was positive for the presence of anti-ICLN IgM autoantibodies had a significantly poorer 5-year survival than patients whose serum was negative (P = .004).

Conclusion

This study describes a novel minimally invasive enzyme-linked immunosorbent assay-based method, capable of identifying patients with colorectal cancer as distinct from both normal and adenoma samples. Patients are likely to be far more amenable to a blood-based test such as the one described herein, rather than a fecal-based test, likely leading to increased patient uptake.  相似文献   

7.

Purpose

To report outcomes from high-dose chemotherapy (HDCT) and autologous stem-cell transplantation (ASCT) for metastatic germ-cell cancer in Scotland.

Patients and Methods

All patients who underwent this treatment between the years 2001 and 2016 at the Beatson West of Scotland Cancer Centre in Glasgow were identified. Information regarding baseline patient and tumor characteristics, prognostic features, HDCT delivery, and survival outcomes were obtained retrospectively from patients’ medical records.

Results

Eighteen patients (15 male and 3 female subjects) received HDCT and ASCT in the salvage setting. Of the 14 male patients who had relapsed disease, 8 (57%) were high or very high risk according to the International Prognostic Factor Study Group (IPFSG) risk categorization. The mean time interval between HDCT cycles was 8.6 weeks, which is longer than the specified 3 to 4 weeks in the literature. A total of 67% of patients had no biochemical or radiologic evidence of disease after salvage treatment, including surgery. Progression-free survival and overall survival rates at 2 years were 67% and 72%, respectively. However, 12 patients (67%) and 6 patients (39%) had long-term neurotoxicity and ototoxicity, respectively.

Conclusion

Delivery of HDCT and ASCT as salvage treatment for metastatic germ-cell cancer is feasible within a tertiary cancer center with survival outcomes comparable to published literature, although maintaining dose intensity is a challenge. We hope to recruit subjects to the international TIGER trial (ClinicalTrials.gov, NCT02375204), which will attempt to clarify if HDCT is superior to conventional-dose chemotherapy in the salvage setting.  相似文献   

8.

Background

Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Their real-life evaluation is insufficient, especially in elderly and frail patients. The aim was to describe use, safety, and effectiveness of targeted therapies in first-line mCRC treatment according to age.

Patients and Methods

Two field cohorts of patients initiating bevacizumab or cetuximab for first-line mCRC were pooled. Patients characteristics, use, and safety were compared between younger and elderly patients (<75 vs. ≥75 years). Two-year overall survival (OS) and progression-free survival (PFS) were estimated in both age groups using the Kaplan–Meier method adjusted on factors associated with death or progression identified with Cox multivariate modeling.

Results

Eight hundred patients (n = 411, 51.4% bevacizumab) were included: 498 (62.3%) male, median age 64 years, 118 (14.8%) Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. Elderly patients (n = 126, 15.8%) were more often treated with 5-fluorouracil alone than younger. Severe adverse events were equivalent across age groups. ECOG-PS ≥1, abnormal hemoglobin, and abnormal alkaline phosphatases were associated with a higher risk of death; OS adjusted on these factors was similar between elderly and younger patients. ECOG-PS ≥1, lung metastases, abnormal hemoglobin, and abnormal creatinine clearance were associated with a higher risk of progression or death; PFS adjusted on these factors was similar across groups.

Conclusion

Despite treatment adaptations, elderly patients could benefit from targeted therapies as younger without safety warning.  相似文献   

9.

Aims

To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series.

Materials and methods

Six centres submitted data extracted from historical records on patients aged 18 years or younger, diagnosed between 1964 and 2017. The univariate and multivariable Cox proportional hazard model was used to identify potential predictors of progression-free survival, using national data as a control.

Results

Data on 166 patients were available for analysis. Females (74%) were predominant, and the age ranged from 3 to 19 years at diagnosis, mean 14.1 years. Nodal metastases were present in 51%; 12% had distant metastases. After surgery, 95% received radioactive iodine (39% on more than one occasion) and 4% received external beam radiotherapy. With a median follow-up duration of 5 years, 69% are alive with no evidence of disease; 20% are alive with a raised thyroglobulin level as the only evidence of residual disease; 6% have residual structural disease detectable on imaging; 2% have died, from cerebral metastases.

Conclusion

Despite most patients having advanced disease at presentation, outcomes are very good. A national prospective registry should allow systematic collection of good-quality data and may facilitate research to further improve outcomes.  相似文献   

10.

Background

The prognostic value of tumor sidedness in metastatic colorectal cancer (CRC) has been established, but its impact on nonmetastatic disease remains unclear. Our study aimed to explore the prognostic effect of tumor sidedness by subgroup survival analyses, according to histology and tumor grade in stage I-IV CRCs.

Methods

A retrospective population-based study was conducted based on Surveillance, Epidemiology and End Results (SEER) data. Population data in the SEER 9 registry (1975-2014) were used to determine survival trends of CRCs, and associated population data in the SEER 18 registry (2000 to 2014) were used to assess the prognostic impact of tumor sidedness on CRCs.

Results

The 5-year cause-specific survival for all subgroups of CRCs improved from 1975 to 2014. Of 238,826 patients, 44.2% had right-sided cancer. Patients with right-sided cancer were more likely to be older, to be women, to have disease of mucinous or signet-ring cell histology, to have more poorly differentiated tumors, and to be diagnosed with a more advanced disease stage. Multivariate Cox regression showed stage I-II right-sided cancers had better cause-specific survival than the left-sided cancers (left colon: hazard ratio [HR] = 1.091, 95% confidence interval [CI], 1.052-1.132; rectum: HR = 1.363; 95% CI, 1.304-1.425; P < .001), while stage III and IV right-sided cancers had worse cause-specific survival. In subgroup analyses by histology and tumor grade within stage III CRCs, right-sided poorly differentiated mucinous adenocarcinoma showed significantly better survival (left colon: HR = 1.352; 95% CI, 1.145-1.596; rectum: HR = 1.125; 95% CI, 0.916-1.381; P = .002).

Conclusion

The relationship between sidedness and prognosis in CRCs depends on stage and histopathologic characteristics, especially for stage III disease.  相似文献   

11.

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM2.5) levels on LC in Taiwan, in relation to contrasting PM2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

Methods

We reviewed 371,084 patients with LC to assess smoking prevalence and correlations between the incidence of adenocarcinoma lung cancer (AdLC) and non-AdLC. Two subsets were selected to assess different AdLC stage trends and the effect of PM2.5 on survival of patients with AdLC.

Results

From 1995 to 2015, the proportion of male adult ever-smokers decreased from 59.4% to 29.9% whereas the female smoking rate remained low (3.2% to 5.3%). AdLC incidence in males and females increased from 9.06 to 23.25 and 7.05 to 24.22 per 100,000 population, respectively. Since 1993, atmospheric visibility in NT improved (from 7.6 to 11.5 km), but deteriorated in ST (from 16.3 to 4.2 km). The annual percent change in AdLC stages IB to IV was 0.3% since 2009 (95% confidence interval [CI]: -1.9%–2.6%) in NT, and 4.6% since 2007 (95% CI: 3.3%–5.8%) in ST; 53% patients with LC had never smoked. Five-year survival rates for never-smokers, those with EGFR wild-type genes, and female patients with AdLC were 12.6% in NT and 4.5% in ST (hazard ratio: 0.79, 95% CI: 0.70–0.90).

Conclusions

In Taiwan, greater than 50% of patients with LC had never smoked. PM2.5 level changes can affect AdLC incidence and patient survival.  相似文献   

12.

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Materials and methods

The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.

Results

In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).

Conclusions

We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.  相似文献   

13.

Introduction

The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in controlling immune suppression by down-regulating T effector cell activities, enabling tumor cells to escape from the host’s antitumor immunsurveillance. While only a small part of colon cancer cells express PD-L1, we sought to evaluate the differential impact of stromal and epithelial PD-L1 expression of primary tumors and liver metastasis on overall survival (OS) in colon cancer patients.

Patients and Methods

Using a next-generation tissue microarray approach, we assessed both epithelial and stromal PD-L1 expression levels in primary tumors (n = 279) and corresponding liver metastases (n = 14) of colon cancer patients. PD-L1 positivity was graded according to the percentage (0.1%-1%, > 1%, > 5%, > 50%) of tumor cells with membranous PD-L1 expression or as the percentage of positive stroma cells and associated inflammatory infiltrates. We also assessed the interplay between stromal PD-1/PD-L1 and both intratumoral and stromal CD8 count and their impact on outcome. The primary end point was OS.

Results

Stromal PD-L1 and PD-1 expression were both associated with less aggressive tumor behavior in colon cancer patients, which translated into better OS and disease-free survival, respectively. Conversely, PD-L1 staining in the tumor cells was less frequent than stromal staining and was associated with features of aggressive tumor biology, although without impact on outcome. Interestingly, the PD-L1 staining pattern remained similar between primary tumors and corresponding liver metastases. Stromal PD-1 expression correlated significantly with stromal PD-L1 staining and both intratumoral and stromal CD8 expression.

Conclusion

Stromal PD-1/PD-L1 expression might serve as a prognostic marker in colon cancer patients.  相似文献   

14.

Aims

Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.

Materials and methods

One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan–Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.

Results

In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.

Conclusion

Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.  相似文献   

15.

Background

Breast cancer is one of the most relevant malignancies among women. Molecular abnormalities in promotor region of survivin gene may account for overexpression of survivin and increased breast cancer risk. This study aimed to explore the potential association between survivin promotor gene -31G/C single nucleotide polymorphism (rs9904341) and its serum level alteration on one hand, and the risk of breast cancer in Egyptian patients on the other hand. It also aimed to assess the usefulness of survivin as an early noninvasive diagnostic biomarker and in breast cancer staging.

Patients and Methods

A total of 135 patients with physically and pathologically confirmed breast cancer and 40 unrelated control subjects as well as 40 patients with benign breast mass were recruited from the early detection unit at National Cancer Institute, Cairo University. Genotyping was performed using allelic discrimination probes by real-time quantitative PCR and serum survivin by enzyme-linked immunosorbent assay.

Results

The minor allele C of -31G/C survivin single nucleotide polymorphism was more frequent in breast cancer patients (19.3%) compared to the control group (7.5%). Furthermore, subjects with the GC + CC genotype were at increased risk of breast cancer compared to the GG genotype of the control group and also the benign group. Moreover, those patients exhibited higher serum levels of survivin compared to GG genotype. There was also significant elevation of serum survivin in different breast cancer stages.

Conclusion

Genetic variation in -31G/C of the survivin gene may contribute to the disposition of breast cancer in the Egyptian population. Serum survivin alteration played a pivotal role in the pathogenesis of breast cancer.  相似文献   

16.

Introduction

Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC.

Methods

The main databases were searched for trials and cohort studies without restrictions to publication status or language. Two independent researchers performed the screening and selection of eligible studies. Outcomes were overall survival, cancer-specific survival, and disease-free survival. The inverse variance method and the random effects method for meta-analysis were used to assess pooled survival estimates.

Results

A total of 11,195 nonduplicate records were identified by the original search strategy. After screening by title and abstract, 1051 potentially eligible records were identified. A total of 43 articles were included. The comparative studies showed lower 3-year overall survival and lower 2-year and 5-year cancer-specific survival for biopsy-proven disease compared to clinical disease. However, 5-year overall survival was the same for both groups. For the pooled estimates, 3-year disease-free survival and 2-year cancer-specific survival were lower for biopsied disease.

Conclusions

Results of this systematic review and meta-analysis show a discrepancy in oncological outcomes for patients undergoing SBRT for suspected early-stage NSCLC in whom there is pathologic conformation of malignancy and those who there is only a clinical diagnose of NSCLC. These results emphasize the importance of obtaining pathologic proof of malignancy.  相似文献   

17.

Background

Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being diagnosed with rectal and colon cancers at our institutions.

Patients and Methods

This study included 3381 rectal and colon cancer patients from the Mayo Clinic cancer registry from 1972 to 2017 who were diagnosed with rectal or colon cancer and who were < 50 years old. Patient and cancer characteristics are described. The Cochran-Armitage trend test was used to see if the change in percentage diagnosed at age < 50 years had a significant trend over the years. A linear regression model was fit to estimate the percentage change per year when the trend was approximately linear.

Results

The percentage of patients diagnosed with rectal or colon cancer in different age categories over the years showed a rising trend for individuals aged < 50. Most of these tumors were distal (rectum, left-sided colon, and right-sided colon were 49.8%, 28.8%, and 21.4%, respectively). This was more so for patients < 50 diagnosed with rectal cancer, which showed a linear increase at a rate of 0.26% per year (P < .001).

Conclusion

Our study affirms the rising proportion of colorectal cancers found in young individuals, with a linear ongoing rise of rectal cancers in particular. This may have implications for the current screening recommendations for colorectal cancers, which are already being revised.  相似文献   

18.

Aims

Chemoradiotherapy (CRT) is established as a superior treatment option to definitive radiotherapy in the non-surgical management of oesophageal cancer. For patients precluded from CRT through choice or comorbidity there is little evidence to guide delivery of single-modality radiotherapy. In this study we outline outcomes for patients unfit for CRT who received a hypofractionated radiotherapy (HRT) regimen.

Materials and methods

A retrospective UK single-centre analysis of 61 consecutive patients with lower- or middle-third adenocarcinoma (OAC; 61%) or squamous cell carcinoma of the oesophagus managed using HRT with radical intent between April 2009 and 2014. Treatment consisted of 50 Gy in 16 fractions (n = 49, 80.3%) or 50–52.5 Gy in 20 fractions (n = 12, 19.7%). Outcomes were referenced against a contemporaneous comparator cohort of 80 (54% OAC) consecutive patients managed with conventionally fractionated CRT within the same centre.

Results

Three-year and median overall survival were, respectively, 56.9% and 29 months with HRT compared with 55.5% and 26 months for CRT; adjusted hazard ratio 0.79 (95% confidence interval 0.48–1.28). Grade 3 and 4 toxicity rates were low at 16.4% (n = 10) for those receiving HRT and 40.2% (n = 32) for the CRT group. In patients with OAC, CRT delivered superior overall survival (hazard ratio 0.46; 95% confidence interval 0.25–0.85) and progression-free survival (hazard ratio 0.45; 95% confidence interval 0.23–0.88) when compared with HRT.

Conclusions

The HRT regimen described here was safe and tolerable in patients unable to receive CRT, and delivered promising survival outcomes. The use of HRT for the treatment of oesophageal cancer, both alone and as a sequential or concurrent treatment with chemotherapy, requires further study. New precision radiotherapy technologies may provide additional scope for improving outcomes in oesophageal cancer using HRT-based approaches and should be evaluated.  相似文献   

19.

Background

The conventional chemotherapy of colorectal cancer with irinotecan, 5-fluorouracil, and oxaliplatin remains one of the front-line treatments worldwide. However, its efficacy is quite low. Recently studies of the epithelial–mesenchymal transition (EMT) have become the focus of investigations into the cause of chemoresistance in several types of cancer, including colorectal cancer. The data about the role of EMT in chemosensitivity are controversial.

Materials and Methods

Human colon adenocarcinoma cell lines HT29 and HCT116 and 14 primary short-term cultures established from patient tumors were used. The chemosensitivity to irinotecan, 5-fluorouracil, and oxaliplatin was assessed using the (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Immunocytochemistry, immunohistochemistry, and Western blot test were used to investigate the E-cadherin expression, the loss of which is a major hallmark of EMT.

Results

Elevated chemosensitivity of the cell line with EMT phenotype, HCT116, was demonstrated. Increased chemosensitivity was revealed in HT29 cell line upon EMT induction. E-cadherin–positive short-term cultures were more resistant to all the drugs tested, whereas each of E-cadherin–negative cultures showed sensitivity to at least one drug. The statistically significant dependency of cells viability on the E-cadherin expression (P < .04) was demonstrated on the short-term cultures using 2 concentrations of each drug.

Conclusion

The data obtained may serve as a basis for the analysis of colon cancer chemosensitivity using short-term cultures and the assay of E-cadherin expression.  相似文献   

20.

Background

Based on estrogen active substances, many women consume soy foods in the belief that it could prevent breast cancer (BC). Women with different molecular subtypes would be likely to have diverse reactions to soy foods, especially those with the estrogen-receptor-positive (ER+) subtype. The aim of the current study is to identify the differentially expressed genes (DEGs) on soy foods in premenopausal patients with Lumina A subtype of BC (LABC) after soy food treatment, and to further investigate the critical molecule change.

Materials and Methods

GSE58792 retrieved from Gene Expression Omnibus was analyzed to obtain DEGs using GEO2R. Gene Ontology and pathway enrichment analysis were performed using FunRich and GeneMINIA. Overall survival of critical genes was performed by the Kaplan-Meier plotter online tool.

Results

A total of 108 DEGs were obtained from the dataset, among which 35 were up-regulated and 73 down-regulated. Soy foods significantly reduced the expression of TFF3, TFF1, GATA3, and ESR1, which were related to the activity of the ER-related pathway and the sensitivity of tamoxifen. Furthermore, the lower expressions of TOX3, FSIP1, ESR1, and CLGN were related to prolonged survival time of patients with BC. The most significant signaling pathways were epithelial-to-mesenchymal transition in up-regulated DEGs, mesenchymal-to-epithelial transition, and mammary gland alveolus development in down-regulated DEGs, which were all related to the development and prognosis of BC.

Conclusions

Soy foods could dramatically alter the ER-related gene profile in LABC. Particularly, down-regulated DEGs of TFF3, TFF1, GATA3, and ESR1 might weaken the sensitivity of tamoxifen and increase the efficacy of neoadjuvant chemotherapy in premenopausal patients with LABC.  相似文献   

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