Friend Leukemia Virus Integration 1 Expression Has Prognostic Significance in Nasopharyngeal Carcinoma

This study aimed to investigate the expression pattern and prognostic value of friend leukemia virus integration 1 (FLI-1) in nasopharyngeal carcinoma (NPC). Immunohistochemistry (IHC) staining of FLI-1 was performed in specimens from 198 untreated NPC patients. Ninety-nine patients were randomly assigned to the training set to analyze the prognostic value of FLI-1 and other clinicopathological characteristics, while the others were assigned to the testing set for validation. Clinicopathological data were compared using the Pearson chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards model to test independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI). Cytoplasmic FLI-1 expression positively correlated with N stage, distant metastasis and death (P< 0.05) and also predicted poorer overall survival (OS) (P= 0.014), distant metastasis-free survival (DMFS) (P= 0.010), progression-free survival (PFS) (P= 0.031). In multivariate analysis, FLI-1 expression and clinical stage were both independent prognostic factors of poor OS and DMFS. Prognoses of patients in the training set, the testing set, and the entire set were clearly divided into four risk subgroups by supplementing FLI-1 with clinical stage. These results indicate that FLI-1 expression is an independent prognostic factor for NPC patients and suggest that supplementing FLI-1 with clinical stage could be helpful for more accurate risk definition.     

Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease

ObjectivesTo evaluate long-term outcomes of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and adjuvant chemotherapy (AC) in nasopharyngeal carcinoma (NPC) patients with N3 disease.Materials and methodsFrom September 2005 to August 2016, 143 patients confirmed NPC with the 8th AJCC/UICC staging criteria N3 were reviewed. All patients received IC followed by IMRT and AC.ResultsAfter a median follow-up of 67 months, the 5-year and 10-year overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) were 75.7% and 61.6%, 61.2% and 53.4%, 73.1% and 72.1%, 92.4% and 87%, 88.9% and 81.8%, respectively. Multivariate analyses indicated that T stage (P = 0.001) appeared to be prognostic factors for OS. T stage (P = 0.001 and P = 0.002) and neck lymph node necrosis (P = 0.015 and P = 0.045) were independent predictors of PFS and DMFS. The acute toxicities were mainly grade 1/2 hematologic toxicities in patients treated with IC+IMRT+AC, and severe toxicities were uncommon.ConclusionsIC followed by IMRT and AC achieved satisfactory long-term survival outcomes in NPC patients with N3 disease. Neck lymph node necrosis and late T stage served as predictors of poor prognosis for patients.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease

ObjectivesTo evaluate long-term outcomes of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and adjuvant chemotherapy (AC) in nasopharyngeal carcinoma (NPC) patients with N3 disease.Materials and methodsFrom September 2005 to August 2016, 143 patients confirmed NPC with the 8th AJCC/UICC staging criteria N3 were reviewed. All patients received IC followed by IMRT and AC.ResultsAfter a median follow-up of 67 months, the 5-year and 10-year overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) were 75.7% and 61.6%, 61.2% and 53.4%, 73.1% and 72.1%, 92.4% and 87%, 88.9% and 81.8%, respectively. Multivariate analyses indicated that T stage (P = 0.001) appeared to be prognostic factors for OS. T stage (P = 0.001 and P = 0.002) and neck lymph node necrosis (P = 0.015 and P = 0.045) were independent predictors of PFS and DMFS. The acute toxicities were mainly grade 1/2 hematologic toxicities in patients treated with IC+IMRT+AC, and severe toxicities were uncommon.ConclusionsIC followed by IMRT and AC achieved satisfactory long-term survival outcomes in NPC patients with N3 disease. Neck lymph node necrosis and late T stage served as predictors of poor prognosis for patients.     

Socioeconomic status,human papillomavirus,and overall survival in head and neck squamous cell carcinomas in Toronto,Canada

BackgroundDespite universal healthcare in some countries, lower socioeconomic status (SES) has been associated with worse cancer survival. The influence of SES on head and neck cancer (HNC) survival is of immense interest, since SES is associated with the risk and prognostic factors associated with this disease.Patients and methodsNewly diagnosed HNC patients from 2003 to 2010 (n = 2124) were identified at Toronto’s Princess Margaret Cancer Centre. Principal component analysis was used to calculate a composite score using neighbourhood-level SES variables obtained from the 2006 Canada Census. Associations of SES with overall survival were evaluated in HNC subsets and by p16 status (surrogate for human papillomavirus).ResultsSES score was higher for oral cavity (n = 423) and p16-positive oropharyngeal cancer (OPC, n = 404) patients compared with other disease sites. Lower SES was associated with worse survival [HR 1.14 (1.06–1.22), p = 0.0002], larger tumor staging (p < 0.001), current smoking (p < 0.0001), heavier alcohol consumption (p < 0.0001), and greater comorbidity (p < 0.0002), but not with treatment regimen (p > 0.20). After adjusting for age, sex, and stage, the lowest SES quintile was associated with the worst survival only for OPC patients [HR 1.66 (1.09–2.53), n = 832], primarily in the p16-negative subset [HR 1.63 (0.96–2.79)]. The predictive ability of the prognostic models improved when smoking/alcohol was added to the model (c-index 0.71 vs. 0.69), but addition of SES did not (c-index 0.69).ConclusionSES was associated with survival, but this effect was lost after accounting for other factors (age, sex, TNM stage, smoking/alcohol). Lower SES was associated with greater smoking, alcohol consumption, comorbidity, and stage.     

Prognostic value of Ki-67 in nasopharyngeal carcinoma: a meta-analysis

The prognostic value of Ki-67 in nasopharyngeal carcinoma (NPC) was controversial according to previous studies. We aimed to clarify the association between K-67 expression and survival in NPC through meta-analysis. We conducted a meta-analysis to explore the potential prognostic effect of Ki-67 on overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) in NPC. A total of 13 studies comprising 1314 NPC patients were included. High Ki-67 expression was associated with poor OS (hazard ratio [HR]= 2.70, 95% confidence interval [CI]= 1.97–3.71, P<0.001), DFS (HR = 1.93, 95% CI = 1.49–2.50, P<0.001), and LRFS (HR = 1.86, 95% CI = 1.11–3.12, P=0.019). However, there was no significant association between Ki-67 and DMFS (HR = 1.37, 95% CI = 0.78–2.38, P=0.270). Furthermore, the prognostic role of Ki-67 was maintained throughout different sample sizes, analyses of HR, and study designs for OS and DFS in various subgroups. Elevated Ki-67 expression is a reliable prognostic factor for poorer survival outcomes in NPC.     

Low baseline vitamin D levels increase the risk of bone metastases among females with breast cancer − Hospital based cohort study

BackgroundSerum vitamin D (Vit-D) has been linked to the development of breast cancer (BC); however, their effect on pathological features and outcomes is undetermined. The purpose of this study was to examine the prognostic significance of baseline Vit-D levels and their effect on clinical outcomes.MethodsWe evaluated baseline serum Vit-D levels and baseline clinic-pathological features of female patients with non-metastatic BC between October 2018 and December 2019. A low Vit-D level was described as less than 30 nanogram per liter (ng/l). Patients were observed for a median of 24 months. To evaluate relationships between qualitative variables, the chi-square test was used. The Kaplan-Meier technique was used for survival analysis, and the log-rank test was used to compare the two survival curves. Correlation analysis was also used to examine the link between Vit-D levels and clinical outcomes.ResultsThe eligibility criteria were fulfilled by 221 patients. The median age of onset was (50.7). The median Vit-D level was (23.1 ng/l) with a range of (4–46 ng/l). Approximately half of the patients (56.5%) had Vit-D levels < 30 ng/l, with HER2 positive and triple negative (TNBC) patients having a greater proportion of low Vit-D levels (p = <0.001). Patients with low baseline Vit-D levels had a larger tumor size, more positive lymph nodes, and were diagnosed at a later stage. Following follow-up, Vit-D deficiency was associated with a significantly increased risk of bone metastases (HR 3.37, 95% CI 1.32–8.59, p = 0.006), and Vit-D levels were significantly correlated with disease-free survival (DFS) and overall survival (OS) (r = 0.850, r = 0.573, p < 0.00, p < 0.001, respectively).ConclusionsLow serum Vit-D is associated with advanced stage and adverse characteristics. It is more prevalent in HER-2 positive and TNBC patients; it increases the chance of bone metastases, and has a significant correlation with DFS and OS.     

The ADCY9 genetic variants are associated with glioma susceptibility and patient prognosis

PurposeGenetic factor is a risk factor in glioma occurrence. This study was designed to detect the effect of ADCY9 polymorphisms on glioma risk and prognosis.MethodsWe performed a case-control study of 1080 participants (584 cases and 496 controls) to assess the relationship of ADCY9 polymorphisms with the risk and prognosis of glioma among the Chinses Han population. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the relationship between ADCY9 variants and glioma risk. The correlation of SNPs with survival was analyzed by the Cox regression model.ResultsOur study showed that rs2230742 and rs2531992 polymorphisms played protective roles in glioma susceptibility (OR 0.65, p = 0.001; OR 0.73, p = 0.038, respectively). While rs2230742 significantly increased the susceptibility of III-V grade glioma patients (OR 1.50, p = 0.036). Haplotype analysis revealed that C_rs879620A_rs2230742A_rs2230741 haplotype was related to a significantly decreased glioma risk (OR 0.65, p = 0.002). Notably, rs2531995 and rs879620 polymorphisms significantly enhanced death risk in high-grade glioma patients (hazard ratio [HR] 1.36, p = 0.041; HR 1.37, p = 0.042; respectively). For rs2230742 and rs2531992 SNPs, glioma patients had a worse prognosis (HR 2.30, p = 0.021; HR 2.30, p = 0.021; respectively). We further observed that age, chemotherapy, and surgical scope can affect the glioma prognosis.ConclusionWe firstly studied the association of ADCY9 variants with glioma risk and prognosis, which might give scientific evidence for exploring the molecular mechanism of glioma.     

The prognostic value of circulating tumor DNA in patients with melanoma: A systematic review and meta-analysis

BackgroundCirculating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma patients, yet results remain inconclusive. The purpose of this study was to illustrate the prognostic value of ctDNA in melanoma.ObjectivesTo describe the clinical prognostic value of ctDNA for melanoma patients.MethodsSearched for eligible articles from Pubmed, Web of Science and Embase. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ctDNA at baseline or during treatment and overall survival (OS) and progression-free survival (PFS).ResultsA total of 9 articles were obtained, involving 617 melanoma patients. The pooled HRs revealed that compared with baseline undetectable ctDNA patients, detectable ctDNA was highly correlated with poor OS (HR 2.91, 95% CI: 2.22–3.82; p < 0.001) and PFS (HR 2.75, 95% CI: 1.98–3.83; p < 0.001). A meta-analysis of these adjusted HRs was performed and confirmed that ctDNA collected at baseline was associated with poorer OS/PFS (OS: HR 3.00, 95% CI 2.19–4.11, p < 0.001/PFS: HR 2.68, 95% CI 1.77–4.06, p < 0.001). During treatment, a significant association was shown between ctDNA and poorer OS/PFS (OS: HR 6.26, 95% CI 2.48–15.80, p < 0.001; PFS: HR 4.93, 95% CI 2.36–10.33, p < 0.001).ConclusionInvestigation and application of ctDNA will improve "liquid biopsy" and play a role in early prediction, monitoring disease progression and precise adjusting treatment strategies in melanoma patients.     

Clinical significance of ALDH1A1 expression and its association with E-cadherin and N-cadherin in resected large cell neuroendocrine carcinoma

BackgroundThe roles of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) in solid tumors are well established. However, the interaction between CSCs and EMT in pulmonary large cell neuroendocrine carcinoma (LCNEC) remains unknown. The aim of this study was to investigate the expression and clinical significance of a CSC marker (ALDH1A1) and its correlation with Epithelial-like phenotype marker (E-cadherin) and Mesenchymal-like phenotype marker (N-cadherin) in LCNEC patients.MethodsImmunohistochemistry (IHC) for ALDH1A1, E-cadherin and N-cadherin expression was conducted on tissue microarrays made from 79 resected LCNEC patient samples. ALDH1A1 protein expression was evaluated by the IHC score, and its correlations with the expression of E-cadherin, N-cadherin and clinicopathological features were determined based on IHC data. Survival analyses were also performed.ResultsALDH1A1 was positively expressed in 75.9% (60/79 cases) of LCNEC patients. No significant difference in clinicopathological variables was observed between the ALDH1A1-negative and ALDH1A1-positive groups. However, ALDH1A1 expression was positively correlated with E-cadherin (Spearman's rho = 0.229, p-value = 0.007), which represents the epithelial-like phenotype, but not with N-cadherin. Patients with expression of ALDH1A1 had significantly longer disease-free survival (DFS) and overall survival (OS) than those who were ALDH1A1 negative (median DFS: 52 vs 12 months, p = 0.028; median OS: not reached; p = 0.027). Multivariate analysis showed that ALDH1A1 was an independent favorable prognostic factor for DFS (p = 0.032, HR: 0.438, 95% CI: 0.206–0.932) and OS (p = 0.025, HR: 0.279, 95% CI: 0.091–0.852) in LCNEC patients.ConclusionThis study suggests that ALDH1A1 can act as a favorable independent prognostic factor for LCNEC, which related to the epithelioid phenotype in EMT, and its internal mechanism needs further study.     

Preoperative red blood cell distribution width as an independent prognostic factor in metastatic renal cell carcinoma

ObjectiveThis study aimed to explore the prognostic value of preoperative red blood cell distribution width (RDW) in patients with metastatic renal cell carcinoma (mRCC).MethodsClinicopathological data of 230 patients with mRCC treated at the First Affiliated Hospital of Chongqing Medical University and the Chinese PLA General Hospital from January 2008 to December 2018 were retrospectively analyzed. Patients were stratified according to the optimal cut-off value of RDW calculated using X-tile software. The prognostic value of RDW was analyzed using the Kaplan-Meier curve with log-rank test and univariate and multivariate Cox proportional hazards models.ResultsA total of 230 patients were included. The optimal cut-off value of RDW obtained using X-tile software was 13.1%. The median Progression-free survival (PFS) and Overall survival (OS) of all populations were 12.06 months (IQR: 4.73–36.9) and 32.20 months (IQR: 13.73–69.46), respectively. Kaplan–Meier curves showed that patients with high RDW had worse PFS and OS than those with low RDW (median PFS of 9.7 months vs. 17.9 months, P = 0.002, and median OS of 27.8 months vs. 45.1 months, P = 0.012, respectively). Multivariate analysis showed that RDW was an independent risk factor for PFS (HR: 1.505; 95% CI: 1.111–2.037; P = 0.008) and OS (HR: 1.626; 95% CI: 1.164–2.272; P = 0.004) in mRCC after cytoreductive nephrectomy.ConclusionPreoperative RDW was independently associated with PFS and OS in patients with mRCC and may be a potential predictor of survival outcomes in mRCC.     

Survival of hepatocellular carcinoma patients is significantly improving: a population-based study from southern Switzerland

BackgroundDuring the last 20 years, relevant diagnostic procedures and advanced treatments have been progressively introduced in the management of hepatocellular carcinoma (HCC).The aim of the present study was to assess up-to-date survival trends for HCC in southern Switzerland, a region with one of the highest incidence rates in the country.MethodsHCCs diagnosed in 1996–2009 were selected by the Ticino Cancer Registry. Cancer-specific survival (CSS) analysis was performed using the Kaplan–Meier method by calendar period: 1996–2000, 2001–2005 and 2006–2009. The log-rank test was used to detect differences in survival curves. Simultaneous assessment of prognostic factors was performed by a multivariate analysis using the Cox proportional-hazards regression model.Results619 HCCs were analysed. There was a significant increase of patients undergoing transarterial chemoembolisation (TACE), whereas patients undergoing curative or palliative supportive treatments remained unchanged (p < 0.0001). No shift to earlier stages was detected. Significant differences in CCS were observed by age-group (p < 0.0001), diagnosis period (p < 0.0001), diagnosis technique (p = 0.0035), Barcelona-Clinic liver cancer stage (p < 0.0001), treatment (p < 0.0001). Multivariate analysis confirmed the independent impact on CSS of factors above mentioned, not including the diagnosis technique. Death risk was higher for patients diagnosed in 1996–2000 (HR: 1.32; 95% CI: 1.03; 1.68) and 2001–2005 (HR: 1.33; 95% CI: 1.05; 1.67) in comparison with 2006–2009 (reference group).ConclusionsThe current population-based report describes a major increase in HCC survival. Simultaneously an increased use of TACE has been detected, probable cofactor of the observed survival increase. Possibly additional efforts could be made to decrease the HCC stage at diagnosis through active surveillance of cirrhotic patients to allow an increase in curative treatments. For sure efforts should be made to comply with a standardised staging system for HCC, particularly for comparative population-based issues.     

Image-guided brachytherapy in cervical cancer: Experience in the Complejo Hospitalario de Navarra

PurposeTo evaluate dosimetric and clinical findings of MRI-guided HDR brachytherapy (HDR-B) for cervical carcinoma.Material and methodsAll patients had a CT, MRI and pelvic-paraaortic lymphadenectomy. Treatment: pelvic (+/−)para-aortic3D/IMRT radiotherapy (45 Gy), weekly cisplatin and HDR-B and pelvic node/parametrial boost 60 Gy until interstitial brachytherapy was done. Two implants: 2008–2011: 5 fractions of 6 Gy, 2011: 2016, 4 fractions of 7 Gy. MRI/TAC were done in each implant. The following were defined: GTV, CTH-HR, CTV-IR; OAR: rectum, bladder and sigmoid.ResultsFrom 2007 to 2016: 57 patients. Patients: T1b2-T2a: 4p, T2b 41p, T3a: 2p; T3B 8p T4a: 2p; N0: 32p, N1 21p, no lymphadenectomy: 4p. Median follow up: 74.6 m (16–122 m), recurrence: 5p local, 6p node, 9p metastasis and 37p without recurrence.Local control 5 years: 90.1%; Ib2-IIB: 94.8%, III-IVa: 72.2%. (p:0.01). RDFS 5y was 92.5%; IB2-IIB: 93%, III: 85% (p:0.024); for pN0: 100%; pN+ iliac-paraaortic: 71.4% (p: 0.007). MFS 5y was 84.1%. Overall survival (OS) at 5y: 66.6% and the cancer specific survival (CEOS) was 74%. Univariate analysis survival: stage Ib2-II 83% vs. III-IVa 41% (p = 0.001); histology: squamous 78%, adenocarcinoma 59.7% (p: ns); lymph node: N0 85% vs. PA+P− 72%, and PA+P+ 35% (p = 0.010). In relation with: HR-CTV dose > 85 Gy, CEOS: 82.5% vs. 77%, and volume CTV-HR < 30 cc: 81.8% and >30 cc: 67%; p: ns. Acute grade 2–3 toxicity: rectal 15.7%, intestinal 15.7% and vesical 15.5%.ConclusionUse of interstitial HDR-BQ guided by RM increased CTV-HR dose and local control, like EMBRACE results. Nodal boost improves RDFS and perhaps OS.     

Myoepithelial carcinoma of major salivary glands: Analysis of population-based clinicopathologic and prognostic features

BackgroundThis study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients.MethodsThe Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses.ResultsIn total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03–7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%.ConclusionsHistological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.     

Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors

OBJECTIVES: The full potential of stereotactic body radiation therapy (SBRT), in the treatment of unresectable intrahepatic malignancies, has yet to be realized as our experience is still limited. Thus, we evaluated SBRT outcomes for primary and metastatic liver tumors, with the goal of identifying factors that may aid in optimization of therapy. METHODS: From2005 to 2010, 62 patients with 106 primary and metastatic liver tumors were treated with SBRT to a median biologic effective dose (BED) of 100 Gy (42.6-180). The majority of patients received either three (47%) or five fractions (48%). Median gross tumor volume (GTV) was 8.8 cm³ (0.2-222.4). RESULTS: With a median followup of 18 months (0.46-46.8), freedom from local progression (FFLP) was observed in 97 of 106 treated tumors, with 1- and 2-year FFLP rates of 93% and 82%. Median overall survival (OS) for all patients was 25.2 months, with 1- and 2-year OS of 81%and 52%. Neither BED nor GTV significantly predicted for FFLP. Local failure was associated with a higher risk of death [hazard ratio (HR) = 5.1, P = .0007]. One Child-Pugh Class B patient developed radiationinduced liver disease. There were no other significant toxicities. CONCLUSIONS: SBRT provides excellent local control for both primary and metastatic liver lesions with minimal toxicity. Future studies should focus on appropriate selection of patients and on careful assessment of liver function to maximize both the safety and efficacy of treatment.     

Prognostic impact of the simple L-index and absolute lymphocyte count early after allogeneic hematopoietic stem cell transplantation

Background aimsThe L-index, designed as a quantitative parameter to simultaneously assess the duration and severity of lymphopenia, and absolute lymphocyte count (ALC) have a prognostic impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, discrepancies have been reported in the impact of ALC, and limited information is currently available on the L-index.MethodsTo search for a better clinical tool, the authors retrospectively compared the simple L-index at 30 days (sL-index(30)), which aims to make the original L-index more compact, and ALC at 30 days (ALC(30)) after allo-HSCT in 217 patients who underwent allo-HSCT at the authors’ institutions.ResultsMedian sL-index(30) was 11 712 (range, 4419–18 511) and median ALC(30) was 404 (range, 0–3754). In a multivariate analysis, higher sL-index(30) was associated with a significantly higher cumulative incidence of relapse (CIR) (hazard ratio [HR], 1.01, 95% confidence interval [CI], 1.00–1.02, P = 0.02 for every increase of 100 in sL-index(30)) as well as non-relapse mortality (NRM) (HR, 1.02, 95% CI, 1.00–1.03, P = 0.01 for every increase of 100 in sL-index(30)). Although higher ALC(30) was associated with significantly lower CIR (HR, 0.94, 95% CI, 0.89–1.00, P = 0.04 for every increase of 100/μL in ALC(30)), it was not extracted as an independent risk factor for NRM (HR, 0.96, 95% CI, 0.88–1.05, P = 0.39). Higher sL-index(30) was associated with a slightly higher rate of grade 3–4 acute graft-versus-host disease (GVHD) (HR, 1.02, 95% CI, 1.00–1.04, P = 0.12 for every increase of 100 in sL-index(30)) but not chronic GVHD (HR, 1.00, 95% CI, 0.99–1.01, P = 0.63). ALC(30) was not associated with rates of grade 3–4 acute GVHD (HR, 1.02, 95% CI, 0.88–1.17, P = 0.81) or chronic GVHD (HR, 1.02, 95% CI, 0.98–1.06, P = 0.34). In a receiver operating characteristic curve, the cutoff values of sL-index(30) and ALC(30) for CIR were 9000 and 500, respectively, and the cutoff value of sL-index(30) for NRM was 12 000.ConclusionssL-index(30) is a promising tool that may be applied to various survival outcomes. A large-scale prospective study is needed to clarify whether medical interventions based on sL-index(30) values will improve the clinical prognosis of patients.     

Kanglaite injection plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer: A meta-analysis of 27 RCTs

BackgroundKanglaite injection (KLT) is a broad-spectrum anti-tumor drug, which is extracted from the seeds of the Chinese medicinal herb Coix lacryma-jobi, and has been widely used for the treatment of advanced lung cancer.PurposeTo evaluate the combined effects of Kanglaite injection plus platinum-based chemotherapy (PBC) on patients with stage III/IV non-small cell lung cancer (NSCLC).Study designA systematic review and meta-analysis of randomized clinical trials (RCTs).Materials and methodsTwelve databases were searched from their inceptions until July 05, 2019. All the RCTs comparing the efficacy and safety of Kanglaite injection plus PBC versus PBC alone were selected. Analyses were performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis (TSA). Disease control rate (DCR) was defined as the primary endpoint, objective response rate (ORR), survival rate, quality of life (QOL), cellular immunity function, and toxicities were defined as the secondary endpoints.ResultsTwenty-seven RCTs recruiting 2,243 patients with stage III/IV NSCLC were included. The results showed that, compared with PBC alone, Kanglaite injection plus PBC improved DCR (RR = 1.20, 95% CI 1.15–1.26, p < 0.00001), ORR (RR = 1.45, 95% CI 1.31–1.60, p < 0.00001), 1-year survival rate (RR = 1.20, 95% CI 1.02–1.43, p = 0.03), QOL (RR = 1.32, 95% CI 1.25–1.40, p < 0.00001), CD4⁺ T cells (WMD = 4.86, 95% CI 4.00–5.73, p < 0.00001), CD4⁺/CD8⁺ ratio (WMD = 0.19, 95% CI 0.07–0.31, p < 0.002), and reduced severe toxicities by 59% (RR = 0.41, 95% CI 0.33–0.51, p < 0.00001). Most results were robust and the quality of evidence was from moderate to low.ConclusionsKanglaite injection in combination with PBC showed significantly higher efficacy than PBC alone in the treatment of stage III/IV NSCLC. Moreover, the combination therapy can improve cellular immunity and attenuate the severe toxicities caused by chemotherapy. However, high-quality RCTs are warranted to further assess the effects of the combined therapy.     

Luminal (Her2 negative) prognostic index and survival of breast cancer patients

PurposeThe group of luminal (Her2 negative) is distinguished from other subtypes of breast cancer. We aimed to produce a prognostic index specific for luminal (Her2 negative) subtype breast cancer that could assist clinical treatment.MethodsThe test set comprised 406 consecutive luminal (Her2 negative) breast cancer patients. The relationship of 11 clinicopathologic factors including survivin with the 5-year disease-free survival was analyzed.ResultsIn univariate analysis, TNM stage, surgery, tumor size, lymph node involvement, and survivin expression were prognostic factors. In multivariate analysis, tumor size [HR (95% CI): 1.98 (1.12–3.49), p = 0.019], the number of lymph node metastasis [HR (95% CI): 1.75 (1.33–2.29), p < 0.0001] and the expression of progesterone receptor [HR (95% CI): 0.58 (0.36–0.95), p = 0.029] can independently predict prognosis. Prognostic index (PI) was calculated as 0.68 × tumor size + 0.56 × the number of lymph node metastasis − 0.54 × PR. According to the PI, patients were categorized into three groups: low, middle, and high risk group with the 5-year disease-free survival rates of 91.91%, 84.97% and 70.47%, respectively (P < 0.001). In the validation set, the luminal prognostic index (LPI) remained significant.ConclusionThe LPI may be a useful tool for evaluating the outcome of patients with luminal (Her-2 negative) breast cancer.     

Neoadjuvant chemotherapy with or without oxaliplatin after short-course radiotherapy in high-risk rectal cancer: A subgroup analysis from a prospective study

AimTo evaluate the role of oxaliplatin in neoadjuvant chemotherapy delivered after short-course irradiation.BackgroundUsing oxaliplatin in the above setting is uncertain.Patients and methodsA subgroup of 136 patients managed by short-course radiotherapy and 3 cycles of consolidation chemotherapy within the framework of a randomised study was included in this post-hoc analysis. Sixty-seven patients received FOLFOX4 (oxaliplatin group) while oxaliplatin was omitted in the second period of accrual in 69 patients because of protocol amendment (fluorouracil-only group).ResultsGrade 3+ acute toxicity from neoadjuvant treatment was observed in 30% of patients in the oxaliplatin group vs. 16% in the fluorouracil-only group (p = 0.053). The corresponding proportions of patients having radical surgery or achieving complete pathological response were 72% vs. 77% (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.39–1.98; p = 0.75) and 15% vs. 7% (OR = 2.25; 95% CI: 0.83–6.94; p = 0.16), respectively. The long-term outcomes were similar in the two groups. Overall and disease-free survival rates at 5 years were 63% vs. 56% (p = 0.78) and 49% vs. 44% (p = 0.59), respectively. The corresponding numbers for cumulative incidence of local failure or distant metastases were 33% vs. 38% (hazard ratio [HR] = 0.89; 95% CI: 0.52–1.52; p = 0.68) and 33% vs. 33% (HR = 0.78; 95% CI: 0.43–1.40; p = 0.41), respectively.ConclusionOur findings do not support adding oxaliplatin to three cycles of chemotherapy delivered after short-course irradiation.