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1.

Background

We evaluated a series of oligometastatic colorectal cancer (CRC) patients treated with stereotactic ablative body radiotherapy (SABR) delivered in all active lung metastases.

Patients and Methods

Forty-four patients with 69 lung metastases were treated with SABR. Eleven patients presented with other sites of metastases before stereotactic body radiotherapy (SBRT), even though they had controlled/cured systemic disease.

Results

The median follow-up was 36 months. The median overall survival (OS) was 38 months and 2 years, 3-year OS rates were 67.7% and 50.8%, respectively. The median progression-free survival (PFS) was 10 months and 2 years, 3-year PFS rates were 20.3% and 16.2%, respectively. Local recurrence occurred in 16 patients (36%).The first site of failure was local only in 22%, distant only in 35%, and local and distant in 14% of the patients. The 1-year, 2-year, and 3-year local PFS (LPFS) were 68.8%, 60.2%, and 54.2%, respectively. No Grade ≥ 3 toxicities were recorded in the univariate analysis; multiple lung metastases and synchronous oligometastatic disease were significantly associated with worse PFS (P = .04, and P < .001, respectively) and worse metastases-free survival (MFS; P = .04, and P < .001, respectively). The type of response was identified as a significant prognostic factor for OS (P = .014), PFS (P = .006), and LPFS (P < .001). In multivariate analysis single lung metastases treated with SBRT was associated with better MFS (P = .015). Metachronous oligometastatic disease and type of response were associated with significantly better PFS.

Conclusion

Stereotactic body radiotherapy is a valid therapy in the treatment of lung metastases for oligometastatic CRC patients presenting long survival. The rate of local control remains lower compared with other primaries. Further prospective cohorts would better evaluate effective fractionation for patients with oligometastatic CRC.  相似文献   

2.

Background

The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC.

Materials and Methods

We identified 1877 patients with metastatic CRC with available histologic findings and molecular profiling and summarized the baseline clinical and pathologic characteristics and overall survival (OS) stratified by the histologic type. The data from separate cohorts with consensus molecular subtype (CMS) and CpG island methylator information were also summarized.

Results

The mucinous histologic type was found in 277 of the 1877 patients (14.8%) and was associated with an increased prevalence of microsatellite instability (P < .001) and a right-sided primary (P < .001). An increased frequency of CMS1 (microsatellite instability immune) and lower rates of CMS2 (canonical) were identified, with mucinous compared with nonmucinous adenocarcinoma (P < .0001). Mutations in SMAD4 (P < .001), GNAS (P < .001), ERBB2 (P = .02), BRAF (P < .001), and KRAS (P < .001) occurred at greater frequencies in the mucinous CRC cases, and TP53 (P < .001), APC (P < .001), and NRAS mutations (P = .03) were less common. Univariate (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; P < .001) and multivariate analysis (HR, 1.36; 95% CI, 1.12-1.64; P = .002) demonstrated that the mucinous histologic type is associated with worse OS. The features associated with the mucinous histologic subtype were independent predictors for shorter OS, including BRAF (HR, 1.74; 95% CI, 1.35-2.25; P < .001) and KRAS (HR, 1.42; 95% CI, 1.22-1.65; P < .001) mutations, right-sided location (HR, 1.20; 95% CI, 1.04-1.39; P = .01), and synchronous metastases (HR, 2.92; 95% CI, 2.49-3.42; P < .001).

Conclusion

Compared with nonmucinous adenocarcinoma, the mucinous histologic type is associated with a worse prognosis, even when controlling for known prognostic features. This unique biologic behavior should be considered in the treatment and prognostic assessment of patients with CRC.  相似文献   

3.

Background

We assessed the role of N-cadherin as a prognostic biomarker in patients with invasive bladder cancer (BCa) who had undergone radical cystectomy (RC).

Patients and Methods

The present retrospective single-center study included 433 BCa patients who had undergone RC and bilateral lymph node dissection. Formalin-fixed paraffin tissue microarrays were stained with an anti–N-cadherin monoclonal mouse antibody. N-cadherin expression was considered positive if any immunoreactivity was detected. Multivariable Cox regression models were created to evaluate the prognostic effect of N-cadherin on survival.

Results

N-cadherin expression was observed in 189 patients (43.7%). It was associated with advanced pathologic stage (P = .001) and lymph node metastasis (P < .001). During a median follow-up period of 10.6 years, N-cadherin expression was associated with worse recurrence-free survival, overall survival, and cancer-specific survival (P < .001, P = .001, and P < .001, respectively). On multivariable analysis adjusted for the effects of standard clinicopathologic features, N-cadherin expression retained its association with worse recurrence-free survival (hazard ratio, 1.41; 95% confidence interval, 1.02-1.92; P = .032) but not cancer-specific survival (P = .07) and overall survival (P = .3).

Conclusion

N-cadherin was expressed in approximately 40% of patients with invasive BCa. Its expression was associated with features of biologically and pathologically adverse disease and worse recurrence-free survival. N-cadherin could be a part of a marker panel to help clinical decision-making and therapy for BCa.  相似文献   

4.

Background

To investigate the superiority of breast-conserving surgery (BCS) plus radiotherapy (RT) compared with mastectomy alone for patients with stage I breast cancer in a real-world setting.

Patients and Methods

The data from patients with histologically confirmed stage I breast cancer treated from 1999 to 2014 were retrospectively reviewed. The association of outcomes with the choice of treatment (BCS plus RT vs. mastectomy) was evaluated using multivariable proportional hazards regression and further confirmed using propensity score matching methods.

Results

Of 6137 eligible patients in the present study, 1296 underwent BCS plus RT and 4841 underwent mastectomy plus axillary lymph node dissection without RT (mastectomy group). Multivariate analysis revealed that BCS plus RT was related to similar locoregional recurrence-free survival but greater distant metastasis-free survival (P = .003) and overall survival (P = .036) compared with mastectomy. For the 1252 pairs of patients matched using propensity score matching, the BCS plus RT groups enjoyed significantly greater 5-year overall survival (99.1% vs. 96.1%; P = .001), distant metastasis-free survival (97.0% vs. 92.2%; P < .001), and disease-free survival (95.3% vs. 90.2%; P = .001) compared with the mastectomy group.

Conclusion

BCS plus RT provided better outcomes than mastectomy for eligible patients with stage I breast cancer and should be offered as a preferred treatment option.  相似文献   

5.

Background

Adjuvant chemotherapy is controversial in patients with locally advanced rectal cancer after preoperative chemoradiation. Valentini et al developed 3 nomograms (VN) to predict outcomes in these patients. The neoadjuvant rectal score (NAR) was developed after VN to predict survival. We aimed to validate these tools in a retrospective cohort at an academic institution.

Patients and Methods

VN and the NAR were applied to 158 consecutive patients with locally advanced rectal cancer treated with chemoradiation followed by surgery. According to the score, they were divided into low, intermediate, or high risk of relapse or death. For statistical analysis, we performed Kaplan-Meier curves, log-rank tests, and Cox regression analysis.

Results

Five-year overall survival was 83%, 77%, and 67% for low-, intermediate-, and high-risk groups, respectively (P = .023), according to VN, and 84%, 71%, and 59% for low-, intermediate-, and high-risk groups, respectively (P = .004), according to NAR. When the score was considered as a continuous variable, a significant association with the risk of death was observed (NAR: hazard ratio, 1.04; P < .001; VN: hazard ratio, 1.10; P < .001).

Conclusion

We confirmed the value of these scores to stratify patients according to their individual risk when designing new trials.  相似文献   

6.

Introduction

We examined the value of tumor location in predicting the clinicopathologic features, survival, and metastases of pulmonary adenocarcinoma.

Patients and Methods

A total of 417 cases of pulmonary adenocarcinoma were included in the present study. The tumors with invasion of the segmental and/or lobar bronchus were classified as central adenocarcinoma and those without as peripheral adenocarcinoma. Histologic grade, cytologic features, and adenocarcinoma type (terminal respiratory unit [TRU] type vs. non-TRU type) were compared between the 2 groups. The prognostic factors for disease-free survival (DFS) were analyzed using univariate and multivariate analyses.

Results

Central adenocarcinoma was associated with lymphatic and/or vascular invasion (P = .011), necrosis (P < .001), high histologic grade (P = .004), and advanced stage (P < .001). For lung adenocarcinoma 1 to 4 cm in size, central adenocarcinoma was linked to a greater rate of nodal metastasis than peripheral adenocarcinoma. However, for lung adenocarcinoma of other sizes, central and peripheral adenocarcinoma had no differences in the rates of nodal metastasis. For nuclear features, central adenocarcinoma showed high mitotic counts, advanced nuclear atypia, and larger nuclei (P < .001, P < .001, P < .001, respectively). More peripheral adenocarcinomas than central adenocarcinomas were TRU type (229 of 281 [81.5%] vs. 58 of 136 [42.6%]; P < .001). Multivariate survival analyses of DFS showed that tumor location (central vs. peripheral, hazard ratio, 1.744; P < .001) was a stage-independent prognostic factor.

Conclusion

Central adenocarcinoma is associated with a high potential for regional lymph node metastases, even at a small size. The results of our study showed that tumor location is an important factor for choosing treatment strategies and predicting DFS.  相似文献   

7.

Introduction

The purpose of this study was to determine the impact of radiation dose to substructures of the heart in lung stereotactic body radiotherapy (SBRT) patients on non–cancer-related deaths.

Methods

Patients treated with lung SBRT at a single institution from 2005 to 2013 were included. The heart and its substructures were contoured, and dose was calculated including mean, max, and max 10 cc dose. Clinical variables including stage, histology, age, gender, Charlson comorbidity index (CCI), preexisting cardiac disease, pulmonary function (forced expiratory volume in 1 second, diffusion capacity), and smoking status were explored for association with non–cancer-related deaths in univariable (UVA) and multivariable (MVA) analyses. Heart dosimetric parameters were correlated with the risk of radiation pneumonitis (RP) using UVA and MVA.

Results

A total of 189 patients were included with median age of 76 years (range, 48-93 years). Of these patients, 45.5% were female, 27.5% were T2, 16.9% were current smokers, 64% had preexisting cardiac risk factors, and 34.5% had CCI score of ≥ 3. Mean lung dose ± SD was 456 ± 231 cGy. Heart max, mean, and 10 cc doses were 1867 ± 1712 cGy, 265 ± 269 cGy, and 1150 ± 1075 cGy, respectively. There were 14 (7.4%) ≥ Grade 2 RP and 3 (1.6%) were ≥ Grade 3. The median overall survival was 37.3 months (95% confidence interval, 29.8-45.3 months). On UVA, female gender (P < .01), higher Eastern Cooperative Oncology Group (P = .01), cardiac risk (P < .01), CCI (P < .01), and bilateral ventricles max dose (P = .02) were associated with non–cancer-related deaths; on MVA, bilateral ventricles max dose was significant (P = .05). No heart parameters were associated with RP.

Conclusions

Higher bilateral ventricles max dose is associated with poorer survival. Heart dose parameters should be considered when planning patients for SBRT.  相似文献   

8.

Background

Inflammation plays a crucial role in cancer development. In this study, we evaluate the prognostic values of systemic inflammation markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) for the progression-free survival and overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

Materials and Methods

PubMed and the Cochrane Library databases were searched for published studies on the effect of NLR, PLR, and CRP in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

Results

In the meta-analysis, NLR (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.27-3.18; P = .003) and PLR (HR, 6.96; 95% CI, 5.04-9.62; P < .001) had a significant influence on progression-free survival, whereas all considered proinflammatory markers had a significant impact on overall survival: NLR (HR, 2.14; 95% CI, 1.67-2.73; P < .001), PLR (HR, 14.67; 95% CI, 11.10-19.57; P < .001), and CRP (HR, 1.96; 95% CI, 1.26-3.05; P = .003).

Conclusions

Inflammation markers such as NLR, PLR, and CRP are predictors of clinical outcome and could provide additional information to individualize treatment.  相似文献   

9.

Background

Current evidence-based guideline-concordant care (GCC) for locally advanced non–small-cell lung cancer (NSCLC) patients with good performance status is concurrent chemoradiation. In this study we evaluated factors associated with lack of GCC and its effects on overall survival (OS).

Patients and Methods

Unresectable stage III NSCLC patients, diagnosed from 2005 to 2013 with a Charlson–Deyo score of 0, were identified from the National Cancer Database. Primary outcomes were receipt of GCC, defined as concurrent chemoradiation (thoracic radiotherapy, starting within 2 weeks of chemotherapy, to at least 60 Gy), and OS. Multivariable logistic regression modeling identified variables associated with non-GCC. Cox proportional hazard modeling was used to examine OS.

Results

Twenty-three percent of patients (n = 10,476) received GCC. Uninsured patients were more likely to receive non-GCC (odds ratio [OR], 1.54; P < .001) compared with privately insured patients. Other groups with greater odds of receiving non-GCC included: patients treated in the western, southern, or northeastern United States (ORs, 1.39, 1.37, and 1.19, respectively; all Ps < .001) compared with the Midwest; adenocarcinoma histology (OR, 1.48; P < .001) compared with squamous cell carcinoma; and women (OR, 1.08; P = .002). Those who received non-GCC had higher death rates compared with those who received GCC (hazard ratio [HR], 1.42; P < .001). The uninsured (HR, 1.53; P < .001), patients treated in the western, southern, or northeastern United States (HRs, 1.56, 1.41, and 1.34, respectively; P < .001), adenocarcinomas (HR, 1.39; P < .001), and women (HR, 1.44; P < .001) also all had lower OS for non-GCC versus GCC.

Conclusion

Socioeconomic factors, including lack of insurance and geography, are associated with non-GCC. Patient- and disease-specific factors, including increasing adenocarcinoma histology and sex, are also associated with non-GCC. Non-GCC diminishes OS.  相似文献   

10.

Introduction

To investigate the relationship between malnutrition and the severity of radiation pneumonitis (RP) in patients with lung cancer with normal baseline pulmonary function and lungs' V20 < 35% treated by intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy.

Materials and Methods

A total of 150 patients with lung cancer who received definitive IMRT (≥ 60 Gy) and concurrent chemotherapy were enrolled. In the condition of normal baseline pulmonary function and strict constraints of the irradiation dose to normal lung tissues, we recorded Eastern Cooperative Oncology Group score; concurrent chemotherapy; clinical stage; the level of albumin (ALB), hemoglobin, and C-reactive protein; Subjective Global Assessment (SGA) scores; radiation esophagitis grade; V20 of lungs; and mean lung dose. These factors were correlated with RP using univariate and multivariate regression analyses.

Results

Of 150 patients, 12 patients (8.0%) developed Grade 3 to 5 RP, 37 (24.6%) patients developed grade 3 to 5 esophageal toxicity. In univariate analysis, ALB level (P = .002), radiation esophagitis (P < .001), and SGA score (P < .001) were significantly associated with RP. Multivariate analysis revealed that SGA (P < .001) was the independent predictor of RP.

Conclusions

SGA could be a predictor for RP in patients with lung cancer treated with definitive IMRT and concurrent chemotherapy.  相似文献   

11.

Introduction

Lysosomal-associated membrane protein 1 (LAMP1) is a lysosomal and plasma membrane protein that contributes to tumor metastatic potential and differentiation.

Patients and Methods

We performed immunohistochemical staining to investigate LAMP1 protein expression levels in 122 diffuse large B-cell lymphoma (DLBCL) tumor samples and 45 reactive hyperplasia tissues. Correlations between LAMP1 expression, various clinicopathologic features, and patient prognosis were evaluated by univariate and multivariate analyses.

Results

LAMP1 expression was greater in the DLBCL tissues than in the reactive hyperplasia tissues. High LAMP1 expression was significantly associated with a high international prognostic index (score, 3-5; P = .023) and elevated lactate dehydrogenase level (P = .028). Moreover, high LAMP1 expression (P = .026), elevated serum lactate dehydrogenase level (P = .011), and high international prognostic index (P < .001) were independently associated with worse overall survival and progression-free survival.

Conclusion

These data provide the first evidence that LAMP1 expression is associated with a poor prognosis in patients with DLBCL.  相似文献   

12.

Background

It has been reported that some patients with breast cancer may refuse cancer-directed surgery, but the incidence in the United States is not currently known. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with refusal of recommended breast cancer–directed surgery.

Patients

A retrospective review of the Surveillance Epidemiology and End Results (SEER) database between 2004 and 2013 was performed. Patients who underwent cancer-directed surgery were compared with patients in whom cancer-directed surgery was refused, even though it was recommended.

Results

Of 531,700 patients identified, 3389 (0.64%) refused surgery. An increasing trend was observed from 2004 to 2013 (P = .009). Older age (50-69: odds ratio [OR] 4.96; 95% confidence interval, 1.23-19.96; P = .024, ≥ 70 years: OR 17.27; 95% CI, 4.29-69.54; P < .001), ethnicity (P < .001), marital status (single: OR 2.28; 95% CI, 1.98-2.62; P < .001, separated/divorced/widowed: OR 2.26; 95% CI, 2.01-2.53; P < .001), higher stage (II: OR 2.05; 95% CI, 1.83-2.3; P < .001, III: OR 2.2; 95% CI, 1.87-2.6; P < .001, IV: OR 13.3; 95% CI, 11.67-15.16; P < .001), and lack of medical insurance (OR 2.11; 95% CI, 1.59-2.8; P < .001) were identified as risk factors associated with refusal of surgery. Survival analysis showed a 2.42 higher risk of mortality in these patients.

Conclusion

There has been an increasing rate of patients refusing recommended surgery, which significantly affects survival. Age, ethnicity, marital status, disease stage, and lack of insurance are associated with higher risk of refusal of surgery.  相似文献   

13.

Purpose

To examine the clinicopathologic characteristics and survival outcomes of different histologic types of triple-negative breast cancer (TNBC).

Methods

We used the SEER database to identify patients with TNBC diagnosed between 2010 and 2014. Our analysis focused on the seven most prevalent histologic types. Differences were compared between invasive carcinoma of no special type (NST) and the other six types.

Results

Significant differences were observed in age at diagnosis, tumor grade, size, nodal status and treatment. As tumor size increased, the number of positive lymph nodes increased markedly in invasive lobular carcinoma (ILC) and mixed NST and lobular carcinoma (NST-ILC), while in metaplastic carcinoma the number only increased slightly. In multivariate survival analyses, compared with patients with invasive carcinoma NST, breast cancer-specific survival (BCSS) and overall survival (OS) were worse for those with NST-ILC (BCSS: hazard ratio [HR] 1.81, P < .001; OS: HR 1.56, P = .005) or metaplastic carcinoma (BCSS: HR 1.95, P < .001; OS: HR 1.73, P < .001). By contrast, patients with medullary (HR 0.40, P = .010) or apocrine carcinoma (HR 0.27, P = .008) showed better BCSS. Time-dependent receiver operating characteristic (ROC) analyses indicated that T category in ILC and N category in metaplastic carcinoma were of less prognostic value.

Conclusions

According to the histologic classification of TNBC, this heterogeneous disease can be divided into several entities with different clinicopathologic features and prognoses. In the era of molecular subtyping of breast cancer, the histologic classification of TNBC is still of considerable clinical significance.  相似文献   

14.

Background

The current study aimed to comprehensively investigate the impact of various clinicopathologic features on the efficacy of programmed cell death-1 (PD-1) and ligand (PD-L1) inhibitors in patients with previously treated non–small-cell lung cancer (NSCLC).

Patients and Methods

Randomized controlled trials that compared PD-1/PD-L1-inhibitor monotherapy with chemotherapy or placebo in patients with previously treated NSCLC were included.

Results

Five trials were included (n = 3025). For all studies, PD-1/PD-L1 inhibitors significantly prolonged overall survival (OS) (hazard ratio [HR], 0.70; P < .001) and progression-free survival (PFS) versus chemotherapy (HR, 0.86; P = .020). Subgroup analysis showed that anti-PD-1/PD-L1 monotherapy could markedly improve OS in elderly patients (HR, 0.69; P < .001), female patients (HR, 0.70; P < .001), never-smoking patients (HR, 0.73; P = .001), and patients with a histology of squamous cell carcinoma (HR, 0.67; P < .001), but not PFS in the elderly and female patient groups. Notably, PD-1/PD-L1 inhibitors cannot prolong both OS (HR, 0.76; P = .390) and PFS (HR, 0.74; P = .210) in patients with central nervous system (CNS) metastasis, whereas patients without CNS metastasis could benefit from anti-PD-1/PD-L1 monotherapy on OS (HR, 0.71; P < .001).

Conclusion

PD-1/PD-L1-inhibitor monotherapy could significantly prolong both OS and PFS in patients with previously treated NSCLC. Subgroup analyses showed that most patients including elderly, females, never-smokers, and patients with squamous cell carcinomas do benefit. However, whether patients with CNS metastasis could benefit from anti-PD-1/PD-L1 monotherapy requires further validation.  相似文献   

15.

Background

Surgical resection is an established therapeutic strategy for colorectal cancer (CRC) metastasis. However, controversies exist when CRC liver and lung metastases (CLLMs) are found concomitantly or when recurrence develops after either liver or lung resection. No predictive score model is available to risk stratify these patients in preparation for surgery, and cure has not yet been reported.

Patients and Methods

All consecutive patients who had undergone surgery for CLLMs at our institution during a 20-year period were reviewed. Our policy was to propose sequential surgery of both sites with perioperative chemotherapy, if the strategy was potentially curative. Overall survival, disease-free survival, and cure were evaluated.

Results

Sequential resection was performed in 150 patients with CLLMs. The median number of liver and lung metastases resected was 3 and 1, respectively. The median follow-up period was 59 months (range, 7-274 months). The median, 5-year, and 10-year overall survival was 76 months, 60%, and 35% respectively. CRC that was metastatic at the initial diagnosis (P = .012), a prelung resection carcinoembryonic antigen level > 100 ng/mL (P = .014), a prelung resection cancer antigen 19-9 level > 37 U/mL (P = .034), and an interval between liver and lung resection of < 24 months (P = .024) were independent poor prognostic factors for survival. The 5-year survival was significantly different for patients with ≤ 2 and ≥ 3 risk factors (77.3% vs. 26.5%). Of 75 patients with ≥ 5 years of follow-up data available from the first metastasis resection, 15 (20%) with disease-free survival ≥ 5 years were considered cured. The use of targeted therapy was the only independent predictor of cure.

Conclusion

Curative-intent surgery provides good long-term survival and offers a chance of cure in select patients. Patients with ≤ 2 risk factors are good candidates for sequential resection.  相似文献   

16.

Background

TP53 mutation (TP53mut) and a complex karyotype (CK) were shown to be predictors of poor outcome in mantle-cell lymphoma (MCL). In this study we examined the combined effect of both of these risk factors.

Patients and Methods

Patients diagnosed with MCL between January 2000 and December 2014 (n = 74) were evaluated. Forty-eight of them had available material for TP53 and cytogenetic examination. We analyzed the prognostic effect of combined TP53mut and CK in the cohort of patients treated with rituximab-containing therapy.

Results

Three-year (3-y) overall survival (OS) and 3-y progression-free survival (PFS) in CK patients were shorter compared with non-CK (P = .001 for OS; P = .02 for PFS). TP53mut was a predictor of shorter survival compared with TP53 wild type (OS and PFS; P < .001). The incidence of TP53mut was not significantly associated with CK (P = .240). CK and TP53mut were predictors of inferior PFS and OS independent of age and Mantle-Cell Lymphoma International Prognostic Index, with hazard ratios of 2.35 (P = .024), 4.50 (P < .001) for PFS and 4.31 (P < .001), 5.46 (P < .001) for OS analysis in the CK and TP53mut groups, respectively. The combination of TP53mut and CK status stratified the patients into 3 prognostic groups (P < .001) with the worst outcome in patients with CK and TP53mut.

Conclusion

TP53 mutation and CK occurred independently and patients harboring both had a dismal prognosis. The study suggests the importance of molecular cytogenetics and examination of the TP53mut status to be performed simultaneously before treatment.  相似文献   

17.
18.

Background

First-line nab-paclitaxel/carboplatin was associated with a significantly improved overall response rate (primary endpoint) versus paclitaxel/carboplatin in a phase III trial of advanced non–small-cell lung cancer (NSCLC). We report the results of an analysis evaluating the correlation of response and the time to response with survival and quality-adjusted outcomes.

Patients and Methods

Using a landmark approach, progression-free survival (PFS), overall survival (OS), and quality-adjusted time without symptoms or toxicity (Q-TWiST) were compared between patients with a confirmed partial or complete response at or before 6 weeks (≤ 6-week responders) and those without (≤ 6-week nonresponders). The outcomes were also analyzed in two 12-week landmark analyses: ≤ 12-week responders versus ≤ 12-week nonresponders and early responders (≤ 6 weeks) versus late responders (6-12 weeks) versus ≤ 12-week nonresponders.

Results

The median OS and PFS for the ≤ 6-week responders versus ≤ 6-week nonresponders were 14.5 versus 10.3 months (P < .001) and 5.5 versus 4.5 months (P = .002), respectively. The ≤ 6-week responders gained 2.1 months of mean Q-TWiST. The median OS and PFS for the ≤ 12-week responders versus ≤ 12-week nonresponders were 16.3 versus 8.4 months and 5.3 versus 2.8 months (both P < .001), respectively, and the ≤ 12-week responders gained 3.2 months of mean Q-TWiST. The median OS was 13.1, 16.6, and 8.4 months (P < .001), the median PFS was 4.1, 6.7, and 2.8 months (P < .001), and the mean Q-TWiST was 10.2, 11.7, and 7.8 months for the early responders, late responders, and ≤ 12-week nonresponders, respectively. Both early and late responders had significantly longer Q-TWiST compared with the ≤ 12-week nonresponders (difference, +2.4 and +3.9 months, respectively; P < .05).

Conclusion

These results underscore response as an important surrogate for assessment of long-term treatment outcomes in advanced NSCLC.  相似文献   

19.

Background

Studies of various prostate cancer patient cohorts found men receiving external-beam radiotherapy (EBRT) had higher mortality than men undergoing radical prostatectomy (RP). Conversely, a recent clinical trial showed no survival differences between treatment groups. We used the National Cancer Data Base (NCDB) to evaluate overall survival in intermediate-risk (T2b-T2c or Gleason 7 [grade group II or III] or prostate-specific antigen 10-20 ng/mL) prostate cancer patients undergoing EBRT with or without androgen deprivation therapy (ADT), RP, or no initial treatment.

Patients and Methods

We analyzed 268,378 men with intermediate-risk prostate cancer from 2004 to 2012. Kaplan-Meier estimates and multivariable Cox proportional hazards models were used to compare survival between treatments.

Results

After adjusting for patient and facility covariables, men receiving no initial treatment averaged greater adjusted mortality risk than men receiving EBRT (hazard ratio [HR], 1.71; 95% confidence interval [CI] 1.62-1.80; P < .001), EBRT + ADT (HR, 1.73; 95% CI 1.64-1.81; P < .001), or RP (HR, 4.18; 95% CI 3.94-4.43; P < .001). Men undergoing RP had significantly lower adjusted mortality risk than men receiving either EBRT (HR, 0.41; 95% CI 0.39-0.43; P < .001) or EBRT + ADT (HR, 0.41; 95% CI 0.39-0.43; P < .001). No difference was observed between men receiving EBRT or EBRT + ADT (HR, 1.01; 95% CI 0.97-1.05; P = .624).

Conclusion

Men treated with RP experienced significantly lower overall mortality risk than EBRT with or without ADT and no treatment patients, regardless of patient, demographic, or facility characteristics. The results are limited by the lack of cancer-specific mortality in this database.  相似文献   

20.

Background

The significance of FMS-like tyrosine kinase 3 (FLT3)-ITD mutation in acute myeloid leukemia (AML) prognosis has been well established. The aims of this study were to investigate the prognostic impact of the FLT3 protein (CD135) expression and its association with FLT3-ITD mutation, and to identify its role in minimal residual disease.

Patients and Methods

CD135 was measured by flow cytometry on leukemic blasts of 257 adults with de novo AML. High expression of CD135 ≥ 20% was correlated with clinical, laboratory, and other prognostic factors that influenced treatment outcome. FLT3-ITD mutation was tested by PCR.

Results

The frequency of CD135 expression was 138 (53.7%) of 257. FLT3-ITD was detected in (21.4%). Positive CD135 expression was associated with high total leukocyte count (P = .006), platelet count (P = .003), monocytic leukemia (P < .001), and CD34 (P = .008) and CD117 (P = .006) expression. CD135 expression ≥ 25% was a predictor of FLT3-ITD mutation (P = .03). CD135 overexpression was a negative predictor of complete remission and of postinduction minimal residual disease at days 14 and 28 (P < .001). CD135 had an adverse impact on overall and disease-free survival (68.5% vs. 15%, P = .002). Multivariate analysis indicated CD135 was the sole independent prognostic factor for overall survival (hazard ratio = 2.49; 95% confidence interval, 1.855-3.345; P < .001).

Conclusion

CD135 is emerging as a prognostic factor, a new marker for minimal residual disease, and a potential novel therapeutic target of AML.  相似文献   

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