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1.

Background

The rate of noninterventional treatment (NIT) in prostate cancer (PCa) active surveillance (AS) candidates is on the rise. However, contemporary data are unavailable. We described community-based NIT rates within 16 Surveillance Epidemiology and End Results (SEER) registries between 2010 and 2014.

Patients and Methods

We identified 23,360 PCa patients who fulfilled the University of California San Francisco AS criteria (prostate-specific antigen [PSA] < 10 ng/mL, clinical T stage ≤ T2a, Gleason score ≤ 6, and positive cores < 33%). Annual NIT rates as well as patient distribution according to PSA, age, number of positive cores, and clinical T stage were studied. Multivariable logistic regression analysis tested NIT predictors.

Results

Between 2010 and 2014, the NIT rate increased from 30.2% to 57.5% (P = .004). Within 16 SEER registries, NIT rates ranged from 25.9% to 62%. NIT rate increased uniformly within all examined registries. Of patient and tumor characteristics (PSA > 4 ng/mL, cT2a and > 1 positive core) only the proportion of NIT patients aged < 65 years increased over time from 47.3% to 53.2% (P = .03). By multivariable logistic regression analysis predicting NIT rate, older age (odd ratio [OR] = 1.05), more contemporary year of diagnosis (OR = 1.41), and being unmarried (OR = 1.45) and uninsured (OR = 2.41) were independent predictors.

Conclusion

The NIT rate has markedly increased across all examined SEER registries. Nonetheless, important differences distinguish those who received high-end NIT from low-end NIT. PCa characteristics of NIT patients remained unchanged over time. However, in addition to geographical differences in NIT rates, patient characteristics such as age, marital status, and insurance status represent potential NIT access barriers.  相似文献   

2.

Introduction

Mosaic loss of chromosome Y (mLOY) is the most commonly detectable mosaic chromosomal event in cancers; however, its underlying relationship with tumorigenesis is still unclear.

Methods

We conducted a mendelian randomization study to systematically investigate the effect of mLOY on lung cancer based on a published genome-wide association study and inferred the causal relationship between mLOY and lung cancer. Kaplan-Meier and Cox regression analyses were used to evaluate the effect of mLOY on lung cancer prognosis.

Results

We discovered that genetically defined mLOY was a protective factor against lung cancer development in nonsmokers but not in smokers (lifelong nonsmokers: OR = 0.80, 95% confidence interval [CI]: 0.69–0.93, p = 4.03×10–3; smokers: OR = 0.96, 95% CI: 0.89–1.04, p =2.90 × 10–1, pHeterogeneity = 3.83 × 10–2). A U-shaped curve between the copy number level of chromosome Y and lung cancer risk was fitted (p for linearity Wald = 8.81 × 10–10) to support the idea that heavy mLOY caused by acquired damaging environmental factors may have effects on lung cancer that are different from those of genetically defined mLOY, whereas genetically predicted mLOY was linearly associated with a decreased lung cancer risk (p for linearity Wald = 0.15). In addition, increased genetically defined mLOY was also significantly associated with a better outcome of lung cancer (HR = 0.86, 95% CI: 0.75–0.98, p = 2.03 × 10–2).

Conclusions

In summary, we propose a "two-sides" model: “natural” mLOY reduces the risk and ensures a better prognosis of lung cancer, although the effect can be abolished by an aberrant loss of chromosome Y caused by environmental risk factors. Our results reveal a complex relationship between mLOY and lung cancer and provide important implications for the prevention of lung cancer.  相似文献   

3.

Introduction

The clinicopathologic features and prognostic predictors of radiological part-solid lung adenocarcinomas were unclear.

Methods

We retrospectively compared the clinicopathologic features and survival times of part-solid tumors with those of pure ground glass nodules (pGGNs) and pure solid tumors treated with surgery at Fudan University Shanghai Cancer Center and evaluated the prognostic implications of consolidation-to-tumor ratio (CTR), solid component size, and tumor size for part-solid lung adenocarcinomas.

Results

A total of 911 patients and 988 pulmonary nodules (including 329 part-solid nodules [PSNs], 501 pGGNs, and 158 pure solid nodules) were analyzed. More female patients (p = 0.015) and nonsmokers (p = 0.003) were seen with PSNs than with pure solid nodules. The prevalence of lymphatic metastasis was lower in patients with PSNs than in those with pure solid tumors (2.2% versus 27% [p < 0.001]). The 5-year lung cancer–specific (LCS) recurrence-free survival and LCS overall survival of patients with PSNs were worse than those of patients with pGGNs (p < 0.001 and p = .042, respectively) but better than those of patients with pure solid tumors ([p < 0.001 and p < 0.0001, respectively]). CTR (OR = 12.90; 95% confidence interval [CI]: 1.85–90.04), solid component size (OR = 1.45; 95% CI: 1.28–1.64), and tumor size (OR = 1.23; 95% CI: 1.15–1.31) could predict pathologic invasive adenocarcinoma for patients with PSNs. None of them could predict the prognosis. Patients receiving sublobar resection had prognoses comparable to those of patients receiving lobectomy (p = .178 for 5-year LCS recurrence-free survival and p = .319 for 5-year LCS overall survival). The prognostic differences between patients with systemic lymph node dissection and those without systemic lymph node dissection were statistically insignificant.

Conclusions

Part-solid lung adenocarcinoma showed clinicopathologic features different from those of pure solid tumor. CTR, solid component size, and tumor size could not predict the prognosis. Part-solid lung adenocarcinomas define one special clinical subtype.  相似文献   

4.

Objective

Concurrent chemoradiotherapy (CRT) was the standard treatment for locally advanced NSCLC (LA-NSCLC). This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on adverse events (AEs).

Methods

We collected individual patient data from 3600 patients with LA-NSCLC who participated in 16 cooperative group trials of concurrent CRT. The TRT parameters examined included field design strategy (elective nodal irradiation [ENI] versus involved-field [IF] TRT [IF-TRT]) and TRT dose (60 Gy versus ≥60 Gy). The primary end point of this analysis was the occurrence of AEs. ORs for AEs were calculated with univariable and multivariable logistic models.

Results

TRT doses ranged from 60 to 74 Gy. ENI was not associated with more grade 3 or higher AEs than IF-TRT was (multivariable OR = 0.77, 95% confidence interval [CI]: 0.543–1.102, p = 0.1545). Doses higher than 60 Gy (high-dose TRT) were associated with significantly more grade 3 or higher AEs (multivariable OR = 1.82, 95% CI: 1.501–2.203, p < 0.0001). In contrast, ENI was associated with significantly more grade 4 or higher AEs (multivariable OR = 1.33, 95% CI: 1.035–1.709, p = 0.0258). Doses higher than 60 Gy were also associated with more grade 4 or higher AEs (multivariate OR = 1.42, 95% CI: 1.191–1.700, p = 0.0001). Grade 5 AEs plus treatment-related deaths were more frequent with higher-dose TRT (p = 0.0012) but not ENI (p = 0.099).

Conclusions

For patients with LA-NSCLC treated with concurrent CRT, IF-TRT was not associated with the overall risk of grade 3 or higher AEs but was associated with significantly fewer grade 4 or higher AEs than ENI TRT. This is likely the result of irradiation of a lesser amount of adjacent critical normal tissue. Higher TRT doses were associated significantly with grade 3 or higher and grade 4 or higher AEs. On the basis of these findings and our prior report on survival, CRT using IF-TRT and 60 Gy (conventionally fractionated) were associated with more favorable patient survival and less toxicity than was the use of ENI or higher radiotherapy doses.  相似文献   

5.

Aims

Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment.

Material and methods

Men with mCRPC from 20 UK cancer centres starting various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months.

Results

In total, 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate [FACT-P] mean = –3.89, 95% confidence interval –6.7 to –1.05, P = 0.007; Trial Outcome Index [TOI] analysis mean = –3.10, 95% confidence interval –5.34 to –0.83, P = 0.007). Those who came off novel therapy and remained on luteinising hormone-releasing hormone agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale mean difference = –4.45, 95% confidence interval –7.06 to –1.83, P = 0.001; TOI mean difference = –5.62, 95% confidence interval –10.97 to –0.26, P = 0.040). At 3 and 6 months, men who reported pain at baseline improved (43%, 40%), but for others pain levels remained the same (45%, 42%) or worsened (13%, 18%). Information regarding supportive care was lacking throughout the period of time on the study.

Conclusion

Most mCRPC treated patients experience reduced QoL and inadequate pain control. More help with pain management and better information provision regarding supportive care is warranted.  相似文献   

6.

Background

Radical cystectomy (RC) may occasionally be performed in individuals with metastatic urothelial carcinoma of the bladder (mUCB). However, the role of lymph node dissection (LND) for such cases is unknown. Thus, we tested the effect of RC on cancer-specific mortality (CSM) and overall mortality in mUCB patients and the effect of LND and its extent on CSM.

Patients and Methods

Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013), we identified patients with mUCB who underwent RC with or without LND or non-RC management. Kaplan-Meier analyses and multivariable Cox regression models (CRMs) were used, after propensity score matching. The number of removed nodes best predicting CSM was identified using cubic splines and then was tested in multivariable CRMs.

Results

Of 2314 patients, 319 (13.8%) underwent RC. After 2:1 propensity score matching, CSM-free survival was 14 versus 8 months (P < .001), and overall mortality–free survival was 12 versus 7 months (P < .001) for, respectively, RC and non-RC patients. In multivariable CRMs, lower CSM (hazard ratio = 0.48; P < .001) and lower overall mortality (hazard ratio = 0.49; P < .001) rates were recorded in RC patients. LND status did not affect CSM-free survival (13 vs. 10 months; P = .1). Cubic splines-derived cutoff of ≥ 13 number of removed nodes showed better CSM-free survival (20 vs. 11 months; P = .02) and reduced CSM in CRMs (hazard ratio = 0.67; P = .02).

Conclusion

Our study validates the survival benefit of RC in mUCB and highlights the importance of more extensive LND. These findings may corroborate the hypothesis of potential cytoreductive effect of surgery in the context of metastatic disease.  相似文献   

7.

Background

Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.

Patients and Methods

Surgical specimens were recruited from 129 patients with sporadic ccRCC and 26 patients with VHL-associated hereditary ccRCC. The PD-L1 expression level was assessed using immunohistochemistry. Correlations between PD-L1 expression and clinicopathological features were analyzed.

Results

In sporadic ccRCC, the positive expression rate of PD-L1 was 47.3% (61/129). Positive PD-L1 expression was correlated with advanced tumor T stage (P = .011), higher Fuhrman nuclear grade (P = .022), poor disease-free survival (P = .037), and sex (P = .025). In the VHL-associated hereditary ccRCC, positive PD-L1 expression rate was 34.6% (9/26), lower than that in sporadic ccRCC. Positive PD-L1 was correlated with higher Fuhrman nuclear grade (P = .008), but not with sex, age, tumor stage, or the onset age of VHL-associated tumors.

Conclusion

Positive PD-L1 expression was correlated with the aggressive clinicopathological features in sporadic and VHL-associated hereditary ccRCC. Whether PD-L1 expression level in ccRCC is related to the effectiveness of programmed death-1/PD-L1 checkpoint inhibitor immunotherapy needs to be further investigated.  相似文献   

8.

Introduction

Despite the risk of morbidity and mortality associated with autologous hematopoietic cell transplantation (ASCT), there are no clear guidelines as to how to screen for these risks. This study sought to determine the utility of pulmonary function tests (PFTs) prior to ASCT on predicting posttransplant clinical outcomes.

Patients and Methods

Patients undergoing ASCT between 2010 and 2012 at the Ottawa Hospital (n = 172) were reviewed. PFT results prior to ASCT were retrieved. The primary outcomes were incidence of intensive care unit (ICU) admission, Seattle Criteria for pulmonary toxicities, and transplant-related mortality (TRM).

Results

PFTs were performed for 91 (53%) patients prior to ASCT. There were more smokers in the PFT cohort than the non-PFT cohort (41.8% vs. 19.8%, respectively; P < .0001). Pulmonary toxicity as measured by the Seattle Criteria did not correlate with PFT results (normal vs. abnormal, 8.1% and 6.1%, respectively; P = 1.00). There were no differences in incidence of ICU admission by PFT result (normal vs. abnormal, 2.7% vs. 8.2%, respectively; P = .61) and no difference in TRM by PFT result (normal vs. abnormal, 0% vs. 2.0%, respectively; P = 1.00).

Conclusion

Despite testing patients deemed higher risk for pulmonary toxicity, abnormal PFTs did not predict for an increased risk of pulmonary toxicity, ICU admission, or TRM at our center.  相似文献   

9.

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Patients and Methods

We conducted a multicenter retrospective analysis in the Triveneto region of Italy.

Results

One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.

Conclusion

This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined.  相似文献   

10.

Introduction

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis classification system (TNM) staging manual has been updated and provides more specified stage grouping for prostate cancer (PCa). We aimed to validate the updated AJCC stage groups for PCa using a radical prostatectomy (RP) cohort.

Patients and Methods

We analyzed the data of 3032 patients previously treated with RP for localized PCa. We stratified patients into stage groups according to the 8th edition of the AJCC manual and compared biochemical recurrence (BCR)-free survival using Kaplan-Meier analyses.

Results

There were 217 patients in stage group I, 33 in IIA, 1101 in IIB, 535 in IIC, 129 in IIIA, 781 in IIIB, and 236 in IIIC. There were no significant differences in BCR-free survival between stage groups IIC and IIIA (P = .875). Subsequently, the low–Gleason score (GS) IIIA subgroup (GS ≤ 3 + 4, P = .025) showed superior BCR-free survival than the IIC group, and the high-GS IIIA subgroups (GS ≥ 4 + 3, P = .004) showed a poorer BCR-free survival than the IIC group. Furthermore, there were no significant differences between groups I and IIA (P = 330) and between groups IIA and IIB (P = .942). Our new staging system provided a better ability to discriminate the prognosis of each group. However, our study has several limitations, such as retrospective design, relatively short follow-up period, and need for further validation.

Conclusion

The current AJCC prognostic groups show some contradictory results, particularly concerning prognosis of the IIC and IIIA groups. We suggest that GS be given more weight than serum prostate-specific antigen level in stage group stratification.  相似文献   

11.
12.

Background

The purpose of the study was to compare cancer detection rates between 12-core transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and multiparametric magnetic resonance imaging (mpMRI)-guided target prostate biopsy (MRI-TBx) according to prostate-specific antigen (PSA) level in biopsy-naive patients.

Patients and Methods

A retrospective study was conducted in 2009 biopsy-naive patients with suspected prostate cancer (PSA ≤20 ng/mL). Patients underwent TRUS-Bx (n = 1786) or MRI-guided target prostate biopsy (MRI-TBx; n = 223) from September 2013 to March 2017 and were stratified according to each of 4 PSA cutoffs. MRI-TBx was performed on lesions with Prostate Imaging Reporting and Data System (PI-RADS) scores of 3 to 5 on mpMRI. Clinically significant prostate cancer (csPCa) was defined as Gleason ≥7. Propensity score matching was performed using the prebiopsy variables, which included age, PSA, prostate volume, and PSA density.

Results

Propensity score matching resulted in 222 patients in each group. There were significant differences between the TRUS-Bx and MRI-TBx groups in the overall detection rates of prostate cancer (41.4% vs. 55.4%; P = .003) and csPCa (30.1% vs. 42.8%; P = .005). However, across PSA cutoffs, MRI-TBx detected more prostate cancer than TRUS-Bx at PSA levels of 2.5 to <4 (29.5% vs. 56.6%; P < .001). The csPCa detection rates of TRUS-Bx and MRI-TBx did not differ significantly within the PSA cutoffs. There was a significantly higher detection rate of prostate cancer and csPCa in lesions with PI-RADS scores 4 and 5 than in those with a score of 3.

Conclusion

Prebiopsy mpMRI and subsequent targeted biopsy had a higher detection rate than TRUS-Bx in patients with prostate cancer and csPCa.  相似文献   

13.

Background

Given the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status.

Patients and Methods

We analyzed 261 patients who received NAC followed by BCS and adjuvant radiotherapy in 13 institutions of the Korean Radiation Oncology Group from 2005 to 2011. The tumors were classified into one of 3 subtypes: luminal (estrogen receptor positive or progesterone receptor positive and HER2 negative), HER2 (HER2 positive), or triple negative (estrogen receptor, progesterone receptor, and HER2 negative). We compared locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) according to ENI in different subgroups generated by the subtype and pCR statuses.

Results

In all patients, the 5-year LRC, DFS, and OS rates were 96.0%, 91.0%, and 96.8%, respectively. In all patients, axillary lymph node dissection was found to be the only favorable factor for LRC (P = .023) and DFS (P = .001). Age ≥ 50 years (P = .027), negative resection margin (P = .002), and axillary lymph node dissection (P = .002) were all favorable factors for OS. ENI did not affect LRC, DFS, or OS. Subgroup analysis by tumor subtype and pCR showed that ENI was not associated with greater LRC or DFS in any subgroups.

Conclusion

In ypN0 patients after NAC and BCS, ENI did not improve LRC or survival, regardless of subtype or primary tumor response. This result should be verified through larger prospective trials.  相似文献   

14.

Aims

Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question.

Materials and methods

Multiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment.

Results

Multiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10?6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10?6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up.

Conclusion

Multiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment.  相似文献   

15.

Introduction

Intrathecal chemoprophylaxis is often administered to patients with diffuse large B-cell lymphoma (DLBCL) to lower the rates of central nervous system (CNS) relapse, although its benefit has not been well-described. Prognostic models, including the CNS-International Prognostic Index (IPI), have been developed to aid in identifying patients at highest risk for CNS relapse.

Patients and Methods

We evaluated 112 patients diagnosed with DLBCL from 2009 to 2016 at Emory Healthcare and classified them as high (n = 44) or low risk (n = 68) for CNS relapse and compared CNS prophylaxis rates and relapse rates between groups. The primary outcome was to compare the CNS relapse rate in high-risk patients who received intrathecal prophylaxis with patients who did not.

Results

Twenty-six patients (14 high-risk and 12 low-risk) received intrathecal prophylaxis. Only 4 of 112 patients experienced a CNS relapse, including 1 in the high-risk group and 3 in the low-risk group. Among 14 high-risk patients who received intrathecal prophylaxis, no patient experienced CNS relapse compared with 1 of 30 high-risk patients without prophylaxis (P = 1.0).

Conclusion

Given the low rates of CNS relapse in this series, it is difficult to discern the impact of current risk stratification combined with intrathecal prophylaxis on outcomes. Our observation that many high-risk patients did not receive prophylaxis, whereas many low-risk patients received prophylaxis emphasizes the need for a standardized approach.  相似文献   

16.

Background

The effectiveness of prophylactic central neck dissection (pCND) following total thyroidectomy (TT) in patients with clinical node-negative (cN0) papillary thyroid carcinoma (PTC) is still controversial. The aim of this meta-analysis is to evaluate the outcome of pCND and to provide quantitative evidence.

Method

A detailed literature search of PubMed, EMBASE, ClinicalTrails.gov and Cochrane Library electronic databases for articles published up to October 2016 was carried out. This meta-analysis was performed by the random method (Mantel–Haenszel) model. Locoregional recurrence (LRR) and surgical complications were analyzed.

Results

Twenty-two studies comparing pCND + TT (combined) and TT alone in cN0 PTC patients were analyzed. A total of 6930 cases were enrolled, including 2381 cases in the combined group and 4009 cases in the TT-alone group. Compared with TT alone, patients in the combined group showed a significantly lower rate of overall LRR (OR = 0.66, 95% CI = 0.48–0.89) and central compartment recurrence (OR = 0.40, 95% CI = 0.22–0.73). There was no statistical difference in the rate of lateral compartment recurrence. However, the combined group showed a significantly higher rate of temporary and permanent hypoparathyroidism (OR = 2.28, 95% CI = 1.92–2.27/OR = 1.84, 95% CI = 1.15–2.95) and temporary recurrent laryngeal nerve injury (LNR) (OR = 1.53, 95% CI = 1.08–2.16). There was no statistical difference in the rate of permanent LNR, hematoma, hemorrhage or wound infection.

Conclusions

This meta-analysis revealed that pCND with TT was a significantly efficient way to reduce the risk of LRR. However, pCND + TT increased the incidence rate of temporary and permanent hypoparathyroidism and temporary LNR.  相似文献   

17.

Background

First-line adjuvant chemotherapy options for early-stage colorectal cancer (CRC) include CapeOx (capecitabine, intravenous oxaliplatin) and FOLFOX (intravenous 5-fluorouracil, leucovorin, oxaliplatin). Capecitabine is an oral prodrug analog of 5-fluorouracil, and recent studies have suggested that proton pump inhibitors (PPIs) may detrimentally affect capecitabine efficacy. Conversely, some literature suggests that PPIs may negatively affect CRC itself. To gain insight into the nature of PPIs’ effect on capecitabine and CRC, we investigated their effects on effectiveness of CapeOx versus FOLFOX chemotherapy.

Patients and Methods

We conducted a retrospective chart review of 389 patients with stage II-III CRC who received adjuvant CapeOx or FOLFOX from 2004 to 2013. Information regarding PPI receipt, chemotherapy, and patient outcomes from medical records was analyzed.

Results

Three-year recurrence-free survival was significantly lower in CapeOx-treated PPI recipients than non-PPI recipients (69.5 vs. 82.6%; P = .029). Unadjusted analysis showed that CapeOx-treated PPI recipients were twice as likely to experience cancer recurrence or death as CapeOx-treated non-PPI recipients (hazard ratio = 2.03; 95% confidence interval, 1.06-3.88; P = .033). FOLFOX-treated PPI recipients had a non–statistically significant difference in 3-year recurrence-free survival versus non-PPI recipients (82.9 vs. 61.7%; P = .066) and a non–statistically significant difference in recurrence/death (hazard ratio = 0.51; 95% confidence interval, 0.25-1.06; P = .071). No significant differences were seen in overall survival between groups.

Conclusion

Our results suggest PPIs negatively affected recurrence-free survival in CapeOx-treated CRC patients and yielded no significant effects among FOLFOX-treated patients, potentially implicating a pharmacokinetic interaction between PPIs and capecitabine. No overall survival effects were seen. Given PPIs’ widespread use, further studies are required to corroborate our findings.  相似文献   

18.

Aims

Women treated with pelvic radiation therapy (PRT) for gynaecological or anorectal cancer report a high number of sexual problems and unmet post-treatment psychosexual information needs. Currently, there is suboptimal adherence to recommended rehabilitation aids, such as vaginal dilators, and a paucity of resources to facilitate post-radiation rehabilitation and reduce distress in this population. This randomised controlled trial aimed to evaluate the effectiveness of a study-developed psychosexual rehabilitation booklet in this setting.

Materials and methods

Eighty-two women scheduled for PRT to treat gynaecological/anorectal cancer were randomised to receive the intervention booklet (n = 44) or standard information materials (n = 38). Self-report questionnaires administered at pre-treatment baseline and at 3, 6 and 12 months post-treatment assessed adherence with rehabilitation aids, booklet knowledge, anxiety, depression and sexual functioning/satisfaction.

Results

Dilator adherence and booklet knowledge were significantly higher in the intervention group than in the control group (averaged over time points), with scores significantly increasing over time. Younger age and gynaecological cancer were significant predictors of greater dilator adherence. No significant group differences were found on psychological and sexual measures.

Conclusions

The psychosexual rehabilitation booklet was effective in educating women with gynaecological and anorectal cancers about PRT-related psychosexual side-effects and rehabilitation options, as well as promoting uptake of vaginal dilator use. Future research should elucidate the effectiveness of this booklet in women with greater psychological and sexual functioning needs.  相似文献   

19.

Background

In order to determine the optimal combination of perioperative chemotherapy and chemoradiotherapy for Western patients with advanced resectable gastric cancer, the international multicentre CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated. In this trial, patients with resectable gastric cancer were randomised before start of treatment between adjuvant chemotherapy or adjuvant chemoradiotherapy following neoadjuvant chemotherapy plus gastric cancer resection. The purpose of this study was to report on surgical morbidity and mortality in this trial, and to identify factors associated with surgical morbidity.

Methods

Patients who underwent a gastrectomy with curative intent were selected. Logistic regression analyses were used to assess risk factors for developing postoperative complications.

Results

Between 2007 and 2015, 788 patients were included in the CRITICS trial, of whom 636 patients were eligible for current analyses. Complications occurred in 296 patients (47%). Postoperative mortality was 2.2% (n = 14). Complications due to anastomotic leakage was cause of death in 5 patients. Failure to complete preoperative chemotherapy (OR = 2.09, P = 0.004), splenectomy (OR = 2.82, P = 0.012), and male sex (OR = 1.55, P = 0.020) were associated with a greater risk for postoperative complications. Total gastrectomy and oesophago-cardia resection were associated with greater risk for morbidity compared with subtotal gastrectomy (OR = 1.88, P = 0.001 and OR = 1.89, P = 0.038).

Conclusion

Compared to other Western studies, surgical morbidity in the CRITICS trial was slightly higher whereas mortality was low. Complications following anastomotic leakage was the most important factor for postoperative mortality. Important proxies for developing postoperative complications were failure to complete preoperative chemotherapy, splenectomy, male sex, total gastrectomy, and oesophago-cardia resection.  相似文献   

20.

Background

Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non–small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients.

Patients and Methods

All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression.

Results

A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes.

Conclusions

SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities.  相似文献   

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