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In attempt to improve long-term disease control outcomes for high-risk prostate cancer, numerous clinical trials have tested the addition of chemotherapy (CTX)—either adjuvant or neoadjuvant—to definitive local therapy, either radical prostatectomy (RP) or radiation therapy (RT).Neoadjuvant trials generally confirm safety, feasibility, and pre-RP PSA reduction, but rates of pathologic complete response are rare, and no indications for neoadjuvant CTX have been firmly established. Adjuvant regimens have included CTX alone or in combination with androgen deprivation therapy (ADT).Here we provide a review of the relevant literature, and also quantify utilization of CTX in the definitive management of localized high-risk prostate cancer by querying the National Cancer Data Base. Between 2004 and 2013, 177 patients (of 29,659 total) treated with definitive RT, and 995 (of 367,570 total) treated with RP had CTX incorporated into their treatment regimens. Low numbers of RT?+?CTX patients precluded further analysis of this population, but we investigated the impact of CTX on overall survival (OS) for patients treated with RP +/? CTX. Disease-free survival or biochemical-recurrence-free survival are not available through the National Cancer Data Base. Propensity-score matching was conducted as patients treated with CTX were a higher-risk group. For nonmatched groups, OS at 5-years was 89.6% for the CTX group vs. 95.6%, for the no-CTX group (P < 0.01). The difference in OS between CTX and no-CTX groups did not persist after propensity-score matching, with 5-year OS 89.6% vs. 90.9%, respectively (Hazard ratio 0.99; P?=?0.88).In summary, CTX was not shown to improve OS in this retrospective study. Multimodal regimens—such as RP followed by ADT, RT, and CTX; or RT in conjunction with ADT followed by CTX—have shown promise, but long-term follow-up of randomized data is required.  相似文献   

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Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Methods

Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.

Results

In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.

Conclusions

Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection.  相似文献   

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Objectives

There are 2 main treatment paradigms recognized by the National Comprehensive Cancer Network for resectable malignant pleural mesothelioma (MPM): induction chemotherapy followed by resection (IC/R), and up-front resection with postoperative chemotherapy (R/PC). These paradigms are being compared in an accruing randomized phase II trial. In the absence of such completed trials, in this study we evaluated overall survival (OS) and postoperative outcomes of IC/R and R/PC.

Methods

The National Cancer Database was queried for newly diagnosed epithelioid/biphasic MPM. Metastatic, node-positive, and/or cT4 disease was excluded, along with nondefinitive surgery and lack of chemotherapy. Multivariable logistic regression ascertained factors independently associated with induction chemotherapy delivery. Kaplan–Meier analysis was used to evaluate OS between cohorts; multivariable Cox proportional hazards modeling was used to assess factors associated with OS. Survival was also evaluated between propensity-matched populations. Last, postoperative outcomes were assessed between groups.

Results

Overall, 361 patients (182 IC/R, 179 R/PC) were analyzed. Temporal trends revealed that IC/R is decreasing over time. Survival of the IC/R cohort was similar to that of R/PC patients (20.9 vs 21.7 months; P = .500); this persisted after propensity matching (20.8 vs 22.0 months; P = .270). However, patients who underwent IC/R experienced longer postoperative hospitalization (median 7 days vs 6 days; P = .001) and higher 30-day mortality (3.3% vs 0%; P = .020).

Conclusions

To our knowledge, this is the only comparative investigation of the 2 major management paradigms of operable MPM. IC/R regimens are decreasing over time in the United States. Although associated with survival similar to R/PC, IC/R might be associated with worse postoperative outcomes. Careful induction chemotherapy patient selection is thus highly recommended.  相似文献   

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BackgroundThe role of postmastectomy radiotherapy (PMRT) for women with pT3N0M0 breast cancer is controversial. We sought to determine the benefit of PMRT in this cohort using the National Cancer Database (NCDB).MethodsWe analyzed women with pT3N0M0 breast cancer who received mastectomy with or without PMRT between 2004 and 2012. We excluded men, women ≤18 years, neoadjuvant or unknown radiation or chemotherapy status, unknown estrogen or progesterone receptor status, unknown surgical margin status, histology other than invasive ductal or lobular carcinoma, and if death occurred <3 months after diagnosis. A total of 4291 patients was included for analysis. Chi-squared analysis was used to compare patient characteristics. Univariate (UVA) and multivariate (MVA) Cox proportional hazards modeling was used to identify factors associated with survival. Propensity score matching was performed to address confounding variables. Survival analysis was performed using Kaplan-Meier and shared frailty models.ResultsOf the 4291 women analyzed, 2030 (47%) received PMRT. On MVA, PMRT (HR 0.72, p < 0.001), chemotherapy (HR 0.51, p < 0.001), and hormone therapy (HR 0.63, p < 0.001) were associated with improved overall survival (OS). After propensity score matching, a matched cohort of 2800 women was analyzed. At 5 years, OS was 83.7% and 79.8% with and without PMRT, respectively (p < 0.001). This difference in OS benefit increased with time. At 10 years, OS was 67.4% and 59.2% with and without PMRT, respectively.ConclusionsPMRT was associated with improved OS in women with pT3N0M0 breast cancer, which strongly suggests PMRT may provide a survival advantage and should be considered.  相似文献   

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AimThere lacks a predictive model for overall survival (OS) of node-negative perihilar cholangiocarcinoma (PHC). This study aimed at developing and validating a prognostic nomogram to predict OS of node-negative PHC after resection.MethodsWe established a nomogram via multivariate regression analysis by using the design cohort (n = 410, obtained from Surveillance, Epidemiology, and End Results database), and its external verification was done in the validation cohort (n = 100, the First Affiliated Hospital of Sun Yat-sen University). Predictive accuracy of the nomogram was assessed by concordance-index (C-index), calibration curves, and decision curve analysis (DCA). Performance of the nomogram was compared with the American Joint Committee on Cancer (AJCC) staging system.ResultsMultivariate regression analysis revealed that age, tumor grade, and the count of examined lymph nodes were independent prognostic factors for OS of node-negative PHC. The nomogram had a C-index of 0.603 and 0.626 in design cohort and validation cohort, respectively, which was better than that of AJCC staging system (both p < 0.05). The calibration curves showed good consistency between actual and nomogram-predicted OS probabilities. DCA showed that nomogram had better clinical usefulness. Furthermore, the nomogram-predicted scores could stratify the patients into three risk groups, and patients in higher risk group had worse prognosis than those in lower risk group (all p < 0.05).ConclusionThe proposed nomogram had a better prognostic accuracy than the AJCC staging system in predicting postoperative OS of node-negative PHC. It was helpful to guide the adjuvant therapeutic strategies for node-negative PHC.  相似文献   

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Background

Inhibition of the receptor activator of NF-κB ligand (RANKL) has become a standard of care supportive treatment to prevent skeletal related events in cancer patients. Moreover, RANKL inhibition has been implicated with better survival outcome in lung cancer, while RANKL expression induces tumor progression and metastatic spread in vivo in breast cancer. Whether RANK/RANKL may have an impact on the pathogenesis of clear cell renal cell carcinoma (ccRCC) is currently unknown.

Patients and Methods

A retrospective tissue micro array (TMA)-study was carried out determining the expression of RANK/RANKL in primary tumors of 306 ccRCC patients. Additionally, 24 ccRCC cell lines were employed for in vitro analyses of the RANK/RANKL axis including cell proliferation, migration and anchorage independent growth.

Results

RANK (+) vs. RANK (?) tumors had both worse cancer specific survival (CSS) (6.3 vs. 1.3 years; p < 0.001) and recurrence free survival (RFS) (9.9 vs. 5.8 years; p < 0.001). RANK (+) (HR 2.21; p < 0.001) was an independent prognostic factor for CSS and RFS (HR 4.98; p < 0.001). RANKL treatment resulted in increased proliferation, soft agar growth, and colony formation of RANK (+) RCC cell lines, which could be reversed by treatment with an NF-κB inhibitor and with a combination of osteoprotegrin and RANKL in vitro.

Conclusions

RANK is expressed in ccRCC tissue, correlates with clinicopathological features, survival outcome, and when stimulated with RANKL can induce ccRCC progression in vitro. Consequently, RANKL inhibition combined with standard of care treatment may be a promising approach to improve ccRCC patient's survival.  相似文献   

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PurposeTo use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).Patients and methodsWe enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.ResultsAfter multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P < 0.0001) and 0.58 (0.47–0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2–4 (ypT3–4) and postchemotherapy pathologic nodal stages N2–3 (ypN2–3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38–0.69, P < 0.0001), 0.60 (0.40–0.88, P = 0.0096), and 0.64 (0.48–0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0–4, ypN0–3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.ConclusionFor patients with breast cancer ypT3–4, ypN2–3, or pathologic stages IIIA–IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.  相似文献   

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