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Background: Noninvasive biomarkers for the assessment of response to chemotherapy in advanced breast cancer (BCa) are essential for optimized therapeutic decision-making. We evaluated the potential of soluble Periostin (POSTN) in circulation as a novel biomarker for chemotherapy efficacy monitoring. Methods: Two hundred and thirty-one patients with different stages of BCa were included. Of those patients, 58 patients with inoperable metastatic disease receiving HER2-targeted or non-targeted chemotherapy were enrolled to assess the performances of markers in recapitulating the chemotherapy efficacy assessed by imaging. POSTN, together with CA153 or CEA at different time points (C0, C2, and C4) were determined. Results: POSTN levels were significantly associated with tumor volume (P < 0.0001) and TNM stages (P < 0.0001) of BCa. For early monitoring, dynamics of POSTN could recapitulate the chemotherapy efficacy among all molecular subtypes (Cohen's weighted kappa = 0.638, P < 0.0001), much better than that of carcinoembryonic antigen (CEA) and cancer antigen 153 (CA15-3). For early partial response, superior performance of POSTN was observed (Cohen's weighted kappa = 0.827, P < 0.0001) in cases with baseline levels above 17.19 ng/mL. For long-term monitoring, the POSTN response was observed to be strongly consistent with the course of the disease. Moreover, progression free survival analysis showed that patients experienced a significant early decrease of POSTN tended to obtain more benefits from the treatments. Conclusions: The current study suggests that soluble POSTN is an informative serum biomarker to complement the current clinical approaches for early and long-term chemotherapy efficacy monitoring in advanced BCa. [ABSTRACT FROM AUTHOR]

Background: The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis. Methods: The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively. Results: By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3. Conclusions: CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen. [ABSTRACT FROM AUTHOR]

Purpose. We aimed to identify new predictive biomarkers for cetuximab in first-line treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). Methods. The study included patients with KRAS wild-type unresectable liver-limited mCRC treated with chemotherapy with or without cetuximab. Next-generation sequencing was done for single nucleotide polymorphism according to custom panel. Potential predictive biomarkers were identified and integrated into a predictive model within a training cohort. The model was validated in a validation cohort. Results. Thirty-one of 247(12.6%) patients harbored RAS mutations. In training cohort (N=93), six potential predictive genes, namely, ATP6V1B1, CUL9, ERBB2, LY6G6D, PTCH1, and RBMXL3, were identified. According to predictive model, patients were divided into responsive group (n=66) or refractory group (n=27). In responsive group, efficacy outcomes were significantly improved by addition of cetuximab to chemotherapy. In refractory group, no benefit was observed. Interaction test was significant across all endpoints. In validation cohort (N=123), similar results were also observed. Conclusions. In the first-line treatment of mCRC, the predictive model integrating six new predictive mutations divided patients well, indicating a promising approach to further refine patient selection for cetuximab on the basis of RAS mutations. [ABSTRACT FROM AUTHOR]

The addition of bevacizumab to chemotherapy has demonstrated efficacy as a first-line treatment for non-small cell lung cancer (NSCLC). Whether this combination is effective as a salvage treatment for patients with NSCLC remains unclear. The present retrospective study was designed to compare the efficacy and safety of chemotherapy plus bevacizumab with chemotherapy alone as a third-line, or continuing, treatment for patients with NSCLC. Between January 2011 and June 2016, a total of 38 patients with stage IV NSCLC who had received chemotherapy plus bevacizumab subsequent to failure of =2 prior regimens were matched with 38 patients who had received chemotherapy alone using propensity score matching from a dataset of 165 patients. The variables that were analyzed included age, sex, smoking history, histology, epithelial growth factor receptor mutation status, number of prior regimens and type of chemotherapy regimen. Univariate and multivariate analyses were used to evaluate the prognostic factors for survival outcomes and tumor response, and toxicity analyses were performed. The objective response rate (ORR) and disease control rate (DCR) were improved in patients who underwent chemotherapy-bevacizumab treatment compared with chemotherapy alone (ORR, 23.7 vs. 5.3%, P<0.001; DCR, 65.8 vs. 31.6%, P<0.001). Progression-free survival was prolonged in the chemotherapy-bevacizumab group compared with the chemotherapy-alone group (median, 3.9 vs. 2.2 months; HR, 0.54; 95% CI, 0.32-0.89, P=0.014). Incidence of =grade 3 adverse events was low and similar across the groups. The combination of chemotherapy and bevacizumab is a potentially effective and safe alternative salvage treatment for patients with NSCLC who have not received bevacizumab treatment previously. [ABSTRACT FROM AUTHOR]

Background: This study compared the differences between the estimated glomerular filtration rate (eGFR) calculated by several equations based on serum creatinine (Scr) and cystatin C (CysC) concentrations for monitoring renal function in patients with small-cell lung cancer (SCLC) during chemotherapy.Methods: Seventy-one patients with SCLC were retrospectively analyzed. The eGFR before and after each chemotherapy cycle was calculated by the following equations: the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, the modification of diet in renal disease (MDRD) equation, the Cockcroft-Gault (CG) equation, and five CysC-based equations. The patients were compared among the different eGFR groups.Results: The mean decreases in eGFRCKD-EPI (−2.25 ± 9.89 ml/min/1.73 m2) between each treatment cycle were more significant than the decreases in eGFRCG (−0.46 ± 10.17 ml/min/1.73 m2), eGFRMDRD (−0.48 ± 9.79 ml/min/1.73 m2), and five calculated eGFRCysC (p < 0.05). Single-/multiparameter analyses showed that patients with a higher body mass index (BMI >23) and receiving more treatment cycles (>3) were at increased risk for developing renal impairment with an eGFR less than 60 ml/min/1.73 m2 during chemotherapy.Conclusions: The eGFR calculated by the CKD-EPI equation changed more significantly between each chemotherapy cycle than did the eGFR from the other equations based on Scr or CysC in patients with SCLC. Oncologists should pay more attention to the renal function of specific patient groups during treatment. [ABSTRACT FROM AUTHOR]

Background: Whether patients with resectable colorectal liver metastases (CRLM) receive survival benefit from neoadjuvant chemotherapy remains controversial. Methods: We retrospectively analyzed 466 patients with resectable CRLM between 2000 and 2010. Patient characteristics and survival data were recorded. Results: The patients were divided into one group with neoadjuvant chemotherapy (group NC, n = 121) and another without (group WN, n = 345). There was no difference in 5-year survival (52% vs. 48%) between the two groups. No significant differences were identified between the two groups in terms of 30-day mortality (1.7% vs. 1.2%) or morbidity (33.9% vs. 25.8%). A primary tumor at stage T4, ≥4 liver metastases, the largest liver metastasis ≥5 cm in diameter, and a serum CEA level ≥5 ng/ml were independent prognostic factors. By assigning one point to each, the patients were divided into a low-risk group (0–2) and a high-risk (3–4). The patients in the low-risk group received no survival benefit from neoadjuvant chemotherapy, whereas those in the high-risk group received survival benefit (5-year survival, 39% vs. 33%, P = 0.028). Conclusions: Preoperative neoadjuvant chemotherapy did not increase mortality or complications. Not all resectable patients, only those with >2 independent risk factors, received survival benefit from neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Primary tumour resection (PTR) is still a selection for patients with low tumour burden and good condition, especially with conversion therapy purpose for colorectal liver-limited metastases (CRLMs). The objective was to evaluate whether pre-PTR chemotherapy could improve progression-free survival (PFS) for patients with asymptomatic synchronous unresectable CRLMs. Patients with asymptomatic synchronous unresectable CRLMs were randomly assigned to receive pre-PTR chemotherapy (arm A) or upfront PTR (arm B). Chemotherapy regimens of mFOLFOX6 plus cetuximab, mFOLFOX6 plus bevacizumab or mFOLFOX6 alone were chosen according to the RAS genotype. The primary end-point was PFS; secondary end-points included overall survival (OS), tumour response, disease control rate (DCR), liver metastases resection rate, surgical complications and chemotherapy toxicity. Three hundred and twenty patients were randomly assigned to arm A (160 patients) and arm B (160 patients). Patients in arm A had significantly improved the median PFS compared with arm B (10.5 versus 9.1 months; P = 0.013). Patients in arm A also had significantly better DCR (84.4% versus 75.0%; P = 0.037). The median OS (29.4 versus 27.2 months; P = 0.058), objective response rate (ORR) (53.1% versus 45.0%; P = 0.146) and liver metastases resection rate (21.9% versus 18.1%; P = 0.402) were not significantly different. The Clavien–Dindo 3–4 complications post PTR (4.5% versus 3.8%, P = 0.759) and the incidence of grade 3/4 chemotherapy events (42.2% versus 40.4%, P = 0.744) reached no statistical significance. For asymptomatic synchronous unresectable CRLMs, Pre-PTR chemotherapy improved the PFS compared with upfront PTR. • It was the first RCT to evaluate the PFS of pre-PTR chemotherapy for CRLMs. • Pre-PTR chemotherapy improved the PFS compared with upfront PTR. • This trial provided evidence to confirm the advantages of pre-PTR chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non–small-cell lung cancer (NSCLC) with N2 lymph node involvement. Methods and Materials: This study included 183 patients from four centers in southwest China who underwent radical section of Stage III-N2 NSCLC without any preoperative therapy. One hundred and four were treated with POCRT and 79 with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 48 and 54 Gy), whereas the cycles of platinum-based chemotherapy ranged from two to six with a median of four. Results: The median duration of follow-up was 72 months. The 5-year overall survival rate (OS) was 30.5% in the POCRT group, and 14.4% in the POCT group (p = 0.007). The 5-year disease-free survival rate (DFS) was 22.2% in POCRT group and 9.3% in POCT group (p = 0.003). In a multivariate analysis, N1 nodal involvement (N1+/N2+) was associated with significantly worse OS (HR = 1.454, 95% CI, 1.012–2.087, p = 0.043) and DFS (HR = 1.685, 95% CI, 1.196–2.372, p = 0.003). Absence of radiotherapy and treatment with fewer than three cycles of chemotherapy both were poor prognostic factors for both OS and DFS. Conclusions: As compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected Stage III–N2 nodal disease in NSCLC. Future study of treatment modality with radiotherapy and chemotherapy is warranted, especially focusing on both N1 and N2 nodal status. [Copyright &y& Elsevier]