Bevacizumab improves survival in metastatic colorectal cancer patients with primary tumor resection: A meta-analysis.
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ABSTRACT:
SUBMITTER: Cao D
PROVIDER: S-EPMC6937309 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Bevacizumab improves survival in metastatic colorectal cancer patients with primary tumor resection: A meta-analysis.
Cao Dedong D Zheng Yongfa Y Xu Huilin H Ge Wei W Xu Ximing X
Scientific reports 20191230 1
It is not well determined whether primary tumor resection is associated with better outcomes in metastatic colorectal cancer (mCRC) patients treated with bevacizumab. In this meta-analysis, we aimed to assess the prognostic role of primary tumor resection in mCRC treated with bevacizumab. Electronic databases including the Cochrane library, Embase, and Pubmed were searched until April 2018. Clinical studies assessing the influence of primary tumor resection on the efficacy of bevacizumab in pati ...[more]
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Project description:PurposeBevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis.MethodsWe performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients.ResultsIn the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60-1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55-0.92, P = 0.009). Similar results were observed in the validation cohort.ConclusionsAddition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC.
| S-EPMC3975091 | biostudies-literature
Project description:BackgroundColorectal cancer is one of the leading causes of cancer deaths in both sexes in the world. Improvement of existing therapy modalities and implementing new ones in order to improve survival of patients with colorectal cancer represents a great challenge for medicine. The aim of this paper was to assess the impact that adding bevacizumab to chemotherapy has on survival in patients with metastatic colorectal cancer, compared to the use of chemotherapy alone.MethodsHazard ratios (HRs) with their 95% confidence intervals (CI) were determined from the studies and pooled. Two-sided p values were reported and considered to indicate statistical significance if less than 0.05.ResultsA total of 12 studies that meet the inclusion criteria were identified in the literature search, 3 phase II studies and 9 phase III studies. Based on the random effects meta-analysis, a statistically significant improvement was identified for both overall survival (HR = 0.84; 95% CI: 0.74-0.94; p = 0.003) and progression free survival (HR = 0.64; 95% CI: 0.55-0.73; p<0.00001) in patients with metastatic colorectal cancer when bevacizumab was added to chemotherapy, compared to chemotherapy treatment alone.ConclusionThe findings of this meta analysis confirm the benefit of adding bevacizumab to chemotherapy in terms of survival and progression free survival, but the magnitude of this effect is not consistent throughout the included studies. This suggests the need for further research of interaction of bevacizumab with chemotherapeutic agents as well as recognition of patients' characteristics important for the treatment selection criteria.
| S-EPMC5006969 | biostudies-literature
Project description:The emerging debate between primary tumor location and clinical outcome of bevacizumab treated metastatic colorectal cancer (mCRC) continues. The aim of the present study is to investigate the association between the primary tumor location and clinical outcome of 115 mCRC patients receiving bevacizumab based treatment. A meta-analysis including 21 studies was carried out to confirm the conclusion. In our prospective study, we found that right-sided mCRC commonly occurred in older cases (p = 0.03) with multiple-site metastasis (p = 0.03). Progression-free survival (PFS) of the left-sided patients undergoing bevacizumab plus a FOLFIRI regimen was superior to the right-sided cases (p = 0.03, crude HR = 0.31, 95%CI = 0.11–0.87; adjusted HR = 0.21, 95%CI = 0.06–0.66). The meta-analysis confirmed that efficacy of bevacizumab-based treatment in left-sided mCRC patients was better than the right-sided cases in the overall population (Ph = 0.24, combined OR = 1.36, 95%CI = 1.07–1.72), RAS/BRAF wild-type (Ph = 0.19, combined OR = 1.66, 95%CI = 1.17–2.34), clinical trial (Ph = 0.23, combined OR = 1.42, 95%CI = 1.07–1.88), Caucasian population (Ph = 0.18, combined OR = 1.37, 95%CI = 1.02–1.85) and first-line (Ph = 0.19, combined OR = 1.48, 95%CI = 1.13–1.96) subgroups. Improved survival of bevacizumab plus chemotherapy treated left-sided mCRC patients was observed in the overall population [Ph < 0.01, combined MSR = 1.09, 95%CI = 1.00–1.18 for PFS; Ph < 0.01, combined MSR = 1.24, 95%CI = 1.13–1.36 for overall survival (OS)], especially in the RAS/BRAF wild-type (Ph = 0.09, combined MSR = 1.10, 95%CI = 1.03–1.19 for PFS; Ph = 0.02, combined MSR = 1.34, 95%CI = 1.21–1.49 for OS). These findings indicate that primary tumor sidedness can predict clinical outcome of bevacizumab-treated RAS/BRAF wild-type mCRC patients and the left-sided patients may benefit more from bevacizumab plus FOLFIRI.
| S-EPMC6702298 | biostudies-other
Project description:BackgroundThe impact of primary tumor resection (PTR) on the prognosis of unresectable metastatic colorectal cancer (mCRC) patients remains debatable. We aimed to develop several prognostic nomograms which could be useful in predicting whether patients might benefit from PTR or not.MethodsPatients diagnosed as mCRC without resected metastasis were identified from the Surveillance Epidemiology and End Results database and randomly assigned into two groups: a training cohort (6369 patients) and a validation cohort (2774 patients). Univariate and multivariable Cox analyses were performed to identify the independent predictors and construct nomograms that could independently predict the overall survival (OS) of unresectable mCRC patients in PTR and non-PTR groups, respectively. The performance of these nomograms was assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA).ResultsBased on the result of univariate and multivariable Cox analyses, two nomograms were respectively constructed to predict the 1-year OS rates of unresectable mCRC patients when receiving PTR and not. The first one included age, gender, tumor grade, proximal colon, N stage, CEA, chemotherapy, radiotherapy, histology type, brain metastasis, liver metastasis, lung metastasis, and bone metastasis. The second nomogram included age, race, tumor grade, primary site, CEA, chemotherapy, brain metastasis, and bone metastasis. These nomograms showed favorable sensitivity with the C-index range of 0.700-0.725. The calibration curves and DCAs also exhibited adequate fit and ideal net benefits in prognosis prediction and clinical application.ConclusionsThese practical prognosis nomograms could assist clinicians in making appropriate treatment decisions to effectively manage the disease.
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Project description:BackgroundPatients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection (PTR) is still controversial in a metastatic, non resectable setting.AimTo explore the survival impact of PTR in patients with metastatic colorectal cancer (mCRC) depending on PTL.MethodsWe retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts.ResultsFour hundred and sixty-six patients were included. A total of 153 (32.8%) patients had unresected synchronous mCRC and 313 (67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174 (37.3%), 203 (43.6%) and 89 (19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score.ConclusionIn mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.
| S-EPMC7667454 | biostudies-literature
Project description:Background: Surgery has been the primary treatment in patients with localized gastrointestinal stromal tumors (GISTs) for many decades, whereas it remains controversial regarding the efficacy of primary tumor resection for metastatic GISTs treated with chemotherapy, and likewise it is unclear who would benefit from the surgical resection. Methods: GISTs patients with distant metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of surgery on survival. Results: In total, of 455 patients with metastatic GISTs, 235 patients (51.6%) underwent primary tumor resection and 220 patients (48.4%) did not. Median survival of patients in resection group was 72 (95% CI: 62.90-81.10) months vs. 40 (95% CI: 29.53-50.47) months for those in non-resection group (p < 0.001). Similarly, surgery in conjunction with chemotherapy led to a favorable impact on survival than chemotherapy alone (OS: 72 vs. 40 months, p < 0.001; CSS: 74 vs. 44 months, p < 0.001). Multivariable analysis showed that both OS (HR: 0.581, 95% CI: 0.386-0.874, p = 0.009) and CSS (HR: 0.663, 95% CI: 0.439-0.912, p = 0.042] were dramatically improved in patients with surgical removal of primary site, as well as primary tumor size between 5 and 10 cm, while increasing age was predictive of poorer survival. Stratified analysis revealed that patients with tumor locations in the stomach demonstrated a prolonged survival after surgery, with no significant differential surgical effect between the stomach and small intestine. Conclusions: Our study preliminarily suggests that carefully selected patients with metastatic GISTs might prolong survival after treatment of surgery, especially those with a primary tumor between 5 and 10 cm and a tumor located in the stomach.
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Project description:BackgroundThe role of primary tumor resection in occult M1a lung adenocarcinoma remains unclear, especially for patients receiving targeted therapy. The purpose of this study is to assess the effect of primary tumor resection on overall survival (OS) in lung adenocarcinoma patients with occult pleural disseminations receiving targeted therapy.MethodsLung adenocarcinoma patients with intraoperatively-confirmed occult pleural dissemination (M1a), who hospitalized in the Department of Thoracic Surgery in Fudan Shanghai Cancer Center from May 2008 to December 2017 and received EGFR-TKIs therapy, were enrolled. Log-rank tests were used to compare the survival differences between groups.Results34 patients receiving EGFR-TKIs were enrolled. The majority of them were never smokers (29/34, 85.3%). Among the enrolled patients, 20 (58.8%) patients underwent primary tumor resection, while 14 (41.2%) patients not. There was no distributional difference of baselines between patients undergoing and not undergoing primary tumor resection. Further analyses demonstrated that the patients undergoing primary tumor resection had a prolonged OS compared with those not (log-rank P= 0.042). The 2-year and 5-year OS for patients receiving primary tumor resection and EGFR-TKIs was 90.0% and 60.1%.ConclusionsPrimary tumor resection was associated with improved survival in patients with occult intraoperatively-confirmed M1a adenocarcinoma receiving EGFR-TKIs.
| S-EPMC8092396 | biostudies-literature
Project description:BackgroundSurgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC.Patients and methodsPatients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy.ResultsFifty-three patients were enrolled. The median age was 52 years (range 23-74), 29 (55%) were males, ECOG PS 0-1 was 13 (66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22 (42%) had a single metastatic site, and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1-20] and the median OS was 28.2 months (95% CI 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6-not reached) compared to 9.6 months (95% CI 7.0-18.3) for the non-surgical group, log-rank p = 0.0165. The median OS for both groups was not reached (95% CI 53.3-not reached) and 23.2 months (95% CI 17.0-28.4) respectively, log-rank p = 0.0006. Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively.ConclusionsPatients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible.Trial registrationClinicaltrials.gov , NCT01311050 , registered March 6, 2011, retrospectively registered.
| S-EPMC7346377 | biostudies-literature
Project description:ImportanceBiologic therapy (BT) (eg, bevacizumab or cetuximab) is increasingly used to treat metastatic colorectal cancer (mCRC). Recent investigations have suggested that right- or left-sided primary tumor origin affects survival and response to BT.ObjectiveTo evaluate the association of tumor origin with mortality in a diverse population-based data set of patients receiving systemic chemotherapy (SC) and bevacizumab or cetuximab for mCRC.Design, setting, and participantsThis population-based nonconcurrent cohort study of statewide California Cancer Registry data included all patients aged 40 to 85 years diagnosed with mCRC and treated with SC only or SC plus bevacizumab or cetuximab from January 1, 2004, through December 31, 2014. Patients were stratified by tumor origin in the left vs right sides.InterventionsTreatment with SC or SC plus bevacizumab or cetuximab.Main outcomes and measuresMortality hazards by tumor origin (right vs left sides) were assessed for patients receiving SC alone or SC plus bevacizumab or cetuximab. Subgroup analysis for patients with wild-type KRAS tumors was also performed.ResultsA total of 11 905 patients with mCRC (6713 men [56.4%] and 5192 women [43.6%]; mean [SD] age, 60.0 [10.9] years) were eligible for the study. Among these, 4632 patients received SC and BT. Compared with SC alone, SC plus bevacizumab reduced mortality among patients with right- and left-sided mCRC, whereas SC plus cetuximab reduced mortality only among patients with left-sided tumors and was associated with significantly higher mortality for right-sided tumors (hazard ratio [HR], 1.31; 95% CI, 1.14-1.51; P < .001). Among patients treated with SC plus BT, right-sided tumor origin was associated with higher mortality among patients receiving bevacizumab (HR, 1.31; 95% CI, 1.25-1.36; P < .001) and cetuximab (HR, 1.88; 95% CI, 1.68-2.12; P < .001) BT, compared with left-sided tumor origin. In patients with wild-type KRAS tumors (n = 668), cetuximab was associated with reduced mortality among only patients with left-sided mCRC compared with bevacizumab (HR, 0.75; 95% CI, 0.63-0.90; P = .002), whereas patients with right-sided mCRC had more than double the mortality compared with those with left-sided mCRC (HR, 2.44; 95% CI, 1.83-3.25, P < .001).Conclusions and relevancePrimary tumor site is associated with response to BT in mCRC. Right-sided primary tumor location is associated with higher mortality regardless of BT type. In patients with wild-type KRAS tumors, treatment with cetuximab benefited only those with left-sided mCRC and was associated with significantly poorer survival among those with right-sided mCRC. Our results underscore the importance of stratification by tumor site for current treatment guidelines and future clinical trials.
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Project description:This study investigates survival of patients diagnosed with pancreatic neuroendocrine tumor with liver metastases based on local treatment on the primary tumor. Patients diagnosed with stage IV PNET between 2010 and 2014 were identified from the Surveillance Epidemiology and End Results database. Cancer-Specific Survival and Overall Survival were examined. A total of 191 patients with pancreatic neuroendocrine tumor with liver metastases were included in this analysis. There were 47 patients (24.6%) who received surgical resection and 144 (75.4%) who did not. Patients with N1 stage was more likely to be treated with surgical resection. The results showed that surgical resection of primary tumor was associated with Cancer-Specific Survival (p = 0.028) and Overall Survival (p = 0.025) benefit. Not receiving surgery, being unmarried and N1 stage are factors associated with poor survival. This study reveals that local treatment on the primary benefits both Cancer-Specific Survival and Overall Survival in PNET patients with LM. This may be suggestive for the management on this patient population.
| S-EPMC5668092 | biostudies-other