Predictive Marker Of Survival Research Articles

Role of Hematological Markers in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Treated With Pembrolizumab.

The predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear. We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response. Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab.

TP53 and EGFR amplification are negative predictors of overall survival in patients diagnosed with non-small cell lung cancer with brain metastases

BackgroundThe discovery of driver genes such as EGFR, KRAS, and ALK, has dramatically shifted treatment patterns in patients harboring these oncogenes. However, dissemination into the central nervous system (CNS) is a severe complication. In addition, the particular anatomical structure of the CNS has made it difficult to obtain tissue specimens from brain metastases (BM) to generate a gene map, as such, potential predictive markers for survival in patients with non-small cell lung cancer (NSCLC) and BM (NSCLC-BM) remain unclear. MethodsData from 28 patients diagnosed with NSCLC-BM between June 2019 and May 2021 at Guangdong Sanjiu Brain Hospital (Guangzhou, China), were reviewed. Targeted next-generation sequencing (NGS) of a 168 cancer-related gene panel was available for surgically resected brain tissues from all patients. In addition, molecular characteristics and overall survival (OS) were analyzed to determine potential predictive markers. ResultsAmong patients with NSCLC-BM, NGS revealed that TP53 was the most frequent mutation (61 %), with a detection rate of 39 %, closely by EGFR amplification. Additionally, CDKN2A, MYC, LRP1B, and RNF43 were frequently observed (18 %). The median OS was significantly shorter in the TP53 mutation group than in the wildtype group (14 versus undefined months, p = 0.014). Similar results were also found in the genetic alteration of EGFR amplification, suggesting that EGFR amplification was associated with worse OS (14 vs. 24 months, p = 0.039). Interestingly, NGS revealed that gene alternations such as TP53, EGFR amplification, and CDKN2A, tended to coexist and such a co-alteration panel indicated worse clinical outcomes (median OS, 5 months). In addition, the detection rate of negative survival genes, including TP53 or EGFR amplification, was much higher in tumor tissues than in plasma samples, indicating the limited predictive value of matched PLA samples. ConclusionsGene signatures, such as TP53 or EGFR amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.

Elevation of C-reactive protein during concurrent chemoradiotherapy is a poor predictive factor for head and neck cancer

ObjectiveThe prognostic role of pretreatment C-reactive protein (CRP) has been reported for head and neck cancer. However, little is known about the relationship between the changes in CRP levels during treatment and prognosis. This study aimed to investigate the correlation between CRP elevation during concurrent chemoradiotherapy (CCRT) and survival outcomes. MethodsThe medical records of patients with oropharyngeal, hypopharyngeal, and laryngeal cancer treated with CCRT at the University of Tsukuba Hospital and National Hospital Organization Mito Medical Center from April 2014 to December 2019 were retrospectively reviewed. Patients were divided into normal (<0.3 mg/dl) and elevated (≥0.3 mg/dl) CRP groups according to the CRP level after the first cycle of cisplatin. The primary endpoint was progression-free survival (PFS). ResultsA total of 74 patients were enrolled, of whom 36 (49%) showed elevated CRP levels after the first cycle of cisplatin. The 3-year PFS was 83.3% and 61.0% in the normal and elevated CRP groups, respectively, showing significant differences between the two groups. ConclusionElevated CRP levels after the first cycle of cisplatin is an objective predictive marker for survival in patient with head and neck squamous cell carcinoma treated with CCRT.

The Significance of the D-Dimer Level as a Prognostic Marker for Survival and Treatment Outcomes in Patients With Stage IV Colorectal Cancer.

Predictive markers for survival and therapeutic efficacy in stage IV colorectal cancer have not been established. As described in our previous report, D-dimer levels may have potential utility as an indicator of cancer activity. The present study evaluated the significance of the D-dimer level as a marker for the survival and treatment outcomes in patients with stage IV colorectal cancer. A total of 34 patients who underwent surgery for stage IV colorectal cancer between February 2017 and October 2019 were enrolled. The D-dimer level was measured using a blood sample obtained at the first visit to our hospital. The median preoperative D-dimer level was 1.2 μg/ml (range=0.5-41.0 μg/ml). We divided patients into two groups using a D-dimer level of 2.0 μg/ml as the cut-off value based on receiver operating characteristic curve analysis. The group with a high-D-dimer-level had a significantly shorter overall survival than that with a low D-dimer level. Progression-free survival after first-line chemotherapy tended to be better in those with a low D-dimer level group than in the high-D-dimer-level group. The preoperative D-dimer level may be a useful indicator for survival and chemotherapeutic outcome in patients with stage IV colorectal cancer.

Clinicopathological and immunohistochemical characterization of gastrointestinal stromal tumour at four tertiary health centers in Nigeria using CD117, DOG1, and human epidermal growth factor receptor-2 biomarkers.

Gastrointestinal stromal tumors (GISTs) are neoplastic lesions that primarily affect the digestive tract and develop from interstitial cells of Cajal. These lesions require histopathological and immunohistochemical characterization due to their malignant potential and personalized treatment. In this investigation, the sex, age, lesional sites of origin, histopathological types, the prevalence of human epidermal growth factor receptors (HER-2) expression, prognostic indices (based on tumor size and mitotic figures), expression of CD117 and DOG1, and characteristics of patients with GIST were all characterized. This was a retrospective cross-sectional analysis of GIST cases seen at four tertiary health-care centers in Nigeria over a 10-year period (2008-2017) and investigated utilizing histopathological and immunohistochemical (CD117, DOG1, and HER-2) methods. In this investigation, there were twenty GIST cases. Notably, the majority (40%) of the cases had tumors with sizes between 7.0 and 8.0 cm; the stomach was the most frequent site (70%) and the spindle cell type of GIST was the most prevalent (80%) histopathological type. In addition, the stomach was significantly associated with GIST as an origin site (with a P = 0.001), and 100% and 50% of these tumors were immunoreactive with CD117 and DOG1, respectively. In our study, GISTs most frequently develop in the stomach, and CD117 and DOG1 are essential for correctly diagnosing these tumors. However, HER-2 immunoreactivity is a predictive marker of survival for personalized care.

Randomized phase II study of neoadjuvant checkpoint blockade for surgically resectable undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS): Survival results after 2 years of follow-up and intratumoral B-cell receptor (BCR) correlates.

LBA11501 Background: We conducted a randomized, phase II non-comparative trial evaluating the efficacy of neoadjuvant ICB [nivolumab or ipilimumab/nivolumab] in patients (pts) with surgically resectable retroperitoneal DDLPS or extremity/truncal UPS treated with concurrent neoadjuvant radiation therapy (XRT, UPS only). Methods: As of February 28 2022, all pts have a minimum follow-up of 2 years from the start of ICB treatment. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan Meier method. The association of pathologic response (percent hyalinization and viable tumor at surgery) with PFS and OS was assessed using Cox univariate models. Comparison of survival curves was done by log-rank method. The intratumoral BCR repertoire was evaluated by bulk tumor RNA sequencing with TRUST4 algorithm, on biopsy specimens collected at baseline. Description of the intratumoral BCR repertoire included diversity by inverse Simpson index, and clonal distribution by Gini coefficient. High and low categories were defined by median values. Results: At a median follow-up of 31 months (interquartile range [IQR]=27-43) since start of ICB treatment, the median PFS was not reached (NR) in UPS (IQR=19-NR) and 18 months for DDLPS (IQR=8-NR), with 13 pts experiencing relapse (2 UPS, 11 DDLPS) and 2 pts who had progressive metastatic disease on treatment (1 UPS, 1 DDLPS). Five pts died of disease relapse (1 UPS, 4 DDLPS) and the median OS was NR. There was no association between percent hyalinization at surgery and PFS (Hazard Ratio [HR]=0.98, p=0.12) or OS (HR=0.99, p=0.60) nor between percent viable tumor at surgery and PFS (HR=1.00, p=0.62) or OS (HR=1.00, p=0.67). There was no association between RECIST response and PFS (p=0.67) or OS (p=0.67). The median BCR heavy chain (IgH) clonal counts detected at baseline was 2,536 per sample (IQR=82-7,680), and the median BCR light chain (IgL) clonal count was 8,870 per sample (IQR=306-30,214). Pts with higher intratumoral BCR clonality and diversity at baseline tended to have longer PFS (Table). High BCR IgH clonality was significantly associated with OS (p=0.02) with consistent trends in each histotype (DDLPS: p=0.06; UPS: p=0.25). Conclusions: Survival results demonstrate efficacy of ICB with XRT in UPS but there is a crucial need to define better predictive markers of survival after neoadjuvant therapy. Further characterization of the BCR repertoire is ongoing and will be presented at the meeting. Clinical trial information: NCT03307616. [Table: see text]

Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups.

Simple SummaryImmune checkpoint inhibitors (ICIs) and radiotherapy (RT) are widely used for patients with brain metastasis (BM). To evaluate markers for treatment response and find a treatment concept which has the best outcome effects, we analyzed data of 93 patients with BM from different cancer types. Predictive markers for survival were good performance status, melanoma as cancer type, low metastasis volume, normal inflammatory blood parameters, and a stereotactic radiotherapy concept with high doses. We found that the best survival outcome can be achieved with the concurrent use of RT and ICI. Concurrent treatment was particularly beneficial in patients with low inflammatory status and more and larger metastases, and when high doses cannot be administered. In concurrently treated patients, therapeutic response was often delayed compared to sequential treatment. Specific immune responses such as pseudoprogression and abscopal effects were induced by concurrent treatment and associated with prolonged survival.While immune checkpoint inhibitors (ICIs) in combination with radiotherapy (RT) are widely used for patients with brain metastasis (BM), markers that predict treatment response for combined RT and ICI (RT-ICI) and their optimal dosing and sequence for the best immunogenic effects are still under investigation. The aim of this study was to evaluate prognostic factors for therapeutic outcome and to compare effects of concurrent and non-concurrent RT-ICI. We retrospectively analyzed data of 93 patients with 319 BMs of different cancer types who received PD-1 inhibitors and RT at the University Hospital Cologne between September/2014 and November/2020. Primary study endpoints were overall survival (OS), progression-free survival (PFS), and local control (LC). We included 66.7% melanoma, 22.8% lung, and 5.5% other cancer types with a mean follow-up time of 23.8 months. Median OS time was 12.19 months. LC at 6 months was 95.3% (concurrent) vs. 69.2% (non-concurrent; p = 0.008). Univariate Cox regression analysis detected following prognostic factors for OS: neutrophil-to-lymphocyte ratio NLR favoring <3 (low; HR 2.037 (1.184–3.506), p = 0.010), lactate dehydrogenase (LDH) favoring ≤ULN (HR 1.853 (1.059–3.241), p = 0.031), absence of neurological symptoms (HR 2.114 (1.285–3.478), p = 0.003), RT concept favoring SRS (HR 1.985 (1.112–3.543), p = 0.019), RT dose favoring ≥60 Gy (HR 0.519 (0.309–0.871), p = 0.013), and prior anti-CTLA4 treatment (HR 0.498 (0.271–0.914), p = 0.024). Independent prognostic factors for OS were concurrent RT-ICI application (HR 0.539 (0.299–0.971), p = 0.024) with a median OS of 17.61 vs. 6.83 months (non-concurrent), ECOG performance status favoring 0 (HR 7.756 (1.253–6.061), p = 0.012), cancer type favoring melanoma (HR 0.516 (0.288–0.926), p = 0.026), BM volume (PTV) favoring ≤3 cm3 (HR 1.947 (1.007–3.763), p = 0.048). Subgroups with the following factors showed significantly longer OS when being treated concurrently: RT dose <60 Gy (p = 0.014), PTV > 3 cm3 (p = 0.007), other cancer types than melanoma (p = 0.006), anti-CTLA4-naïve patients (p < 0.001), low NLR (p = 0.039), steroid intake ≤4 mg (p = 0.042). Specific immune responses, such as abscopal effects (AbEs), pseudoprogression (PsP), or immune-related adverse events (IrAEs), occurred more frequently with concurrent RT-ICI and resulted in better OS. Other toxicities, including radionecrosis, were not statistically different in both groups. The concurrent application of RT and ICI, the ECOG-PS, cancer type, and PTV had an independently prognostic impact on OS. In concurrently treated patients, treatment response (LC) was delayed and specific immune responses (AbE, PsP, IrAE) occurred more frequently with longer OS rates. Our results suggest that concurrent RT-ICI application is more beneficial than sequential treatment in patients with low pretreatment inflammatory status, more and larger BMs, and with other cancer types than melanoma.

Systemic Inflammation Status Relates to Anti–inflammatory Drug Benefit and Survival in Rectal Cancer

BackgroundSystemic inflammation status has been recognized as a sensitive marker associated with survival in cancers and anti–inflammatory treatment outcomes in inflammation-derived diseases. This study aimed to investigate the role of systemic inflammation status as a predictive marker for survival and anti–inflammatory treatment benefit in rectal cancer patients. MethodsA total of 475 patients with stage I-III rectal cancer receiving curative resection were prospectively enrolled. The platelet-neutrophils to lymphocytes ratio (PNLR) that integrates neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios was applied to enable a comprehensive evaluation of systemic inflammation status and investigate its association with survival and nonsteroidal anti–inflammatory drugs (NSAIDs) benefit. Patients were grouped according to baseline PNLR and perioperative use of NSAIDs. ResultsThe high-PNLR group had worse 5-y disease-free survival (DFS) compared with the low-PNLR group (61.2% versus 70.9%, P = 0.014). Multivariate analyses confirmed that PNLR was an independent predictor for DFS (hazard ratio [HR] 1.42, 95% CI: 1.03-1.97, P = 0.031). A nomogram including PNLR and other independent prognostic factors was developed and validated to predict DFS. In the high-PNLR subset, NSAIDs group had a 21.3% lower risk of recurrence than non–NSAIDs group (P = 0.009), and multivariate analysis confirmed the independently significant association of perioperative NSAIDs use with better DFS (hazard ratio 0.36, 95% CI 0.16-0.78, P = 0.010). However, this association was not significant in the low-PLR subset. ConclusionsBaseline PNLR could be used to predict DFS and NSAIDs benefit in rectal cancer patients. This study highlights the potential survival benefit from the anti–inflammatory treatment in the patients with elevated systemic inflammation status in cancer patients.

Temporalis muscle thickness as an indicator of sarcopenia predicts progression-free survival in head and neck squamous cell carcinoma

Temporalis muscle thickness (TMT) on brain magnetic resonance imaging (MRI) is correlated with sarcopenia and can be a predictive marker for survival in patients with brain tumors, but the association of TMT on head and neck computed tomography (CT) with survival in head and neck squamous cell carcinoma (HNSCC) remains unclear. We investigated whether TMT on CT could predict progression-free survival (PFS) in patients with HNSCC. A total of 106 patients with newly diagnosed HNSCC were included in this retrospective study. The patients underwent baseline head and neck CT and/or MRI between July, 2008 and August, 2018. The correlation between TMT on CT and MRI was tested using intraclass correlation coefficient (ICC). The cut-off value of TMT on CT for determining tumor progression was identified using receiver-operating characteristic curve analysis. Uni- and consecutive multi-variable Cox regression models were used to verify the association between TMT and PFS. TMT on CT and MRI showed excellent correlation (ICC, 0.894). After a mean follow-up of 37 months, 49 out of 106 patients showed locoregional recurrence and/or distant metastasis. The cut-off TMT of 6.47 mm showed good performance in predicting tumor progression (area under the curve, 0.779). The Cox regression model showed that TMT ≤ 6.24 mm (median value in study population) was a significant contributing factor for predicting shorter PFS (hazard ratio 0.399; 95% confidence interval 0.209–0.763; P = .005). TMT may be used as a surrogate parameter for pre-treatment sarcopenia and could help predict PFS in patients with HNSCC.

Identification of mRNA Prognostic Markers for TGCT by Integration of Co-Expression and CeRNA Network.

Testicular germ cell tumor (TGCT) is the most common malignant tumor in young men and is associated with poor prognosis. We assessed the RNA expression profiles of 13 TGCT tissues and 4 adjacent normal tissues by transcriptome sequencing to identify novel prognostic biomarkers. We detected several differentially expressed mRNAs in TGCT that were functionally annotated by GO and KEGG enrichment analyses to tumorigenesis-related processes such as immunity and chemotherapeutic resistance. An mRNA-lncRNA-miRNA regulatory network was constructed using RNA-Seq data and public databases, and integrated with TCGA database to develop a prediction model for metastasis and recurrence. Finally, GRK4, PCYT2 and RGSL1 were identified as predictive markers of survival and therapeutic response. In conclusion, we found several potential predictors for TGCT prognosis and immunotherapeutic response by ceRNA network analysis.

Dynamic Changes in Absolute Lymphocyte Counts During Eribulin Therapy Are Associated With Survival Benefit.

We investigated the usefulness of dynamic changes in absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) during eribulin therapy as predictive markers for survival benefit including post-progression survival (PPS). We retrospectively investigated 94 advanced breast cancer (ABC) patients who underwent eribulin therapy between July 2011 and June 2020. The multivariate analysis showed that high baseline ALC and low NLR were independent predictive markers for overall survival (OS) (p=0.007 and p=0.011, respectively) and PPS (p=0.005 and p=0.007, respectively). Dynamic changes in ALC were also associated with OS and PPS (p=0.015, and p=0.026, respectively) and were an independent predictive marker for PPS (p=0.021). Baseline ALC and NLR and dynamic changes in ALC during eribulin therapy were significantly associated with survival benefit including PPS for patients with ABC.

Predictive impact of the prognostic nutritional index in early-staged hepatocellular carcinoma after operative microwave ablation

BackgroundThe prognostic nutritional index (PNI) is used to assess immune and nutritional status, and is a prognostic factor for several malignant tumors. However, little evidence exists regarding the predictive impact of prognostic nutritional index (PNI) after local ablation therapy for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the value of PNI to predict recurrence and survival after operative microwave ablation in patients with early-stage HCC. MethodsThis retrospective study included 341 patients who underwent operative microwave ablation for HCC in Barcelona Clinic Liver Cancer (BCLC) stage 0-A at our institute between 2007 and 2015. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis in multivariate Cox regression analyses. ResultsThe OS rates at 1, 3, 5, and 10 years after microwave ablation were 100%, 92.7%, 85.1%, and 57.5% in patients with high-PNI levels, and 96.5%, 78.2%, 59.7%, and 20.7% in patients with low-PNI levels, respectively (P < 0.001). The RFS rates at 1, 3, 5, and 10 years after microwave ablation were 96.3%, 75.2%, 55.4%, and 30.4% in patients with high-PNI levels, and 94.4%, 48.8%, 36.4%, and 13.1% in patients with low-PNI levels, respectively (P < 0.001). In multivariate analyses, preoperative PNI level was an independent prognostic factor for both OS and RFS. ConclusionOur results revealed the preoperative PNI level was a simple and novel predictive marker of survival and recurrence after microwave ablation in patients with early-stage HCC.

Meta-analysis of cardiac markers for predictive factors on severity and mortality of COVID-19

ObjectivesPrevious observational studies have suggested that increased cardiac markers are commonly found in COVID-19. This study aimed to determine the relationship between several cardiac markers and the severity/mortality of COVID-19 patients. MethodsSeveral cardiac markers were analysed in this meta-analysis. RevMan 5.4 was used to provide pooled estimates for standardised mean difference (SMD) with 95% confidence intervals. ResultsTwenty-nine clinical studies were included in this meta-analysis. Significantly higher CK-MB (0.64, 95% CI = 0.19–1.09), PCT (0.47, 95% CI = 0.26−0.68), NT-proBNP (1.90, 95% CI = 1.63–2.17), BNP (1.86, 95% CI = 1.63−2.09), and d-dimer (1.30, 95% CI = 0.91−1.69) were found in severe compared with non-severe COVID-19. Significantly higher CK-MB (3.84, 95% CI = 0.62−7.05), PCT (1.49, 95% CI = 0.86−2.13), NT-proBNP (4.66, 95% CI = 2.42−6.91), BNP (1.96, 95% CI = 0.78−3.14), troponin (1.64 (95% CI = 0.83−2.45), and d-dimer (2.72, 95% CI = 2.14−3.29) were found in those who died from compared with survivors of COVID-19. ConclusionsHigh CK-MB, PCT, NT-proBNP, BNP, and d-dimer could be predictive markers for severity of COVID-19, while high CK-MB, PCT, NT-proBNP, BNP, troponin, and d-dimer could be predictive markers for survival of COVID-19 patients.

A balance score between immune stimulatory and suppressive microenvironments identifies mediators of tumour immunity and predicts pan-cancer survival

BackgroundThe balance between immune-stimulatory and immune-suppressive mechanisms in the tumour microenvironment is associated with tumour rejection and can predict the efficacy of immune checkpoint-inhibition therapies.MethodsWe consider the observed differences between the transcriptional programmes associated with cancer types where the levels of immune infiltration predict a favourable prognosis versus those in which the immune infiltration predicts an unfavourable prognosis and defined a score named Mediators of Immune Response Against Cancer in soLid microEnvironments (MIRACLE). MIRACLE deconvolves T cell infiltration, from inhibitory mechanisms, such as TGFβ, EMT and PI3Kγ signatures.ResultsOur score outperforms current state-of-the-art immune signatures as a predictive marker of survival in TCGA (n = 9305, HR: 0.043, p value: 6.7 × 10−36). In a validation cohort (n = 7623), MIRACLE predicts better survival compared to other immune metrics (HR: 0.1985, p value: 2.73 × 10−38). MIRACLE also predicts response to checkpoint-inhibitor therapies (n = 333). The tumour-intrinsic factors inversely associated with the reported score such as EGFR, PRKAR1A and MAP3K1 are frequently associated with immune-suppressive phenotypes.ConclusionsThe association of cancer outcome with the level of infiltrating immune cells is mediated by the balance of activatory and suppressive factors. MIRACLE accounts for this balance and predicts favourable cancer outcomes.

Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer.

BackgroundGastric cancer (GC) is a heterogeneous disease, and is a leading cause of cancer deaths in Eastern Asia. Genomic analysis, such as whole-exome sequencing (WES), can help identify key genetic alterations leading to the malignancy and diversity of GC, and may help identify new drug targets.MethodsWe identified genomic alterations in a cohort of 38 GC patients, including 26 metastatic and 12 non-metastatic patients. We analyzed the association between novel gene mutations and copy number variations (CNVs) with tumor metastasis and patient survival.ResultsA number of significantly mutated genes in somatic and germline cells were identified. Among them, ATAD3B somatic mutation, a potential biomarker of immunotherapy in stomach cancers, was associated with better patient survival (P=0.0939) and metastasis (P=0.074). POLE germline variation was correlated with shorter overall survival (OS; P=0.0100). Novel CNVs were also identified and can potentially be used as biomarkers. These included 9p24.1 deletion (P=0.0376) and 16p11.2 amplification (P=0.0066), which were both associated with shorter OS. CNVs of several genes including MMP9, PTPN1, and SS18L1 were found to be significantly related to metastasis (P<0.05).ConclusionsWe characterized the mutational landscape of 38 GC patients and discovered several potential new predictive markers of survival and metastasis in GC.

The Prognostic Model of Pre-Treatment Complete Blood Count (CBC) for Recurrence in Early Cervical Cancer

The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC profiles of the patients from nine tertiary medical centers in South Korea who were treated surgically for early stage cervical cancer were reviewed. Statistical models by the Akaike’s information criterion (AIC) were developed using CBC profiles to calculate individuals’ risk scores for clinical outcomes. A total of 1443 patients were included in the study and the median follow-up was 63.7 months with a range of 3–183 months. Univariate analyses identified the components of CBC that were significantly related to clinical outcomes including white blood cell (WBC), hemoglobin, neutrophil, and platelet levels. The models developed using CBC profiles and the conventional clinical predictive factors provided individuals’ risk scores that were significantly better in predicting clinical outcomes than the models using the conventional clinical predictive factors alone. Pre-treatment CBC profiles including WBC, hemoglobin, neutrophil, lymphocyte, and platelet levels were found to be a potential biomarker for survival prognosis in early cervical cancer.

Serum copper, zinc and metallothionein serve as potential biomarkers for hepatocellular carcinoma.

BackgroundCopper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib.MethodsWe enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy.ResultsThe serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival.ConclusionsThe Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.

Prognostic Value of Changes in Preoperative and Postoperative Serum CA19-9 Levels in Gastric Cancer.

Objective: The prognostic significance of serum CA19-9 levels in gastric cancer patients remains a matter debate. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative serum CA19-9 levels in patients with gastric cancer.Methods: A total of 1,046 gastric cancer patients who underwent curative gastrectomy in West China Hospital of Sichuan University from January 2011 to December 2016 were analyzed retrospectively. Patients were categorized by minimum P-value using X-tile, while the baseline confounders for CA19-9 changes were balanced through propensity score matching (PSM). The relationships between CA19-9 changes and other clinicopathologic features were measured. Univariate and multivariate analysis were performed to explore the risk factors associated with survival outcomes.Results: We included 653 patients. Changes in CA19-9 levels significantly correlated with age, tumor size, macroscopic type, histological grade, T stage and TNM stage. Kaplan–Meier curves revealed that patients with CA19-9 changes <20% had significant better overall survival than those with changes more than 20% (p < 0.001); Cox regression analysis revealed the CA19-9 change (p = 0.010), gender (p = 0.031), histological grade (p = 0.036) and TNM stage (p < 0.001) were independent risk factors for survival after PSM. Stratification analysis indicated that patients with CA19-9 change more than 20% had worse prognosis that those with CA19-9 change no more than 20% in male (p = 0.002), poorly differentiated or undifferentiated type (p = 0.031) and TNM stage III (p = 0.006).Conclusion: Changes in preoperative and postoperative serum CA19-9 levels were closely associated with clinicopathological traits and was an independent prognostic factor in gastric cancer patients. This parameter may be a reliable marker for prediction of survival.

Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients.

BackgroundThere is increasing evidence that immunotherapy with nivolumab, an anti‐programmed death 1 monoclonal antibody, is effective in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the predictive role of hematological inflammatory markers such as neutrophil‐to‐lymphocyte ratio (NLR) and the modified Glasgow prognostic score (mGPS) in patients with R/M SCCHN treated with nivolumab remains unclear.MethodsWe conducted a multi‐institutional cohort study to evaluate the impact of pretreatment NLR and mGPS on overall survival (OS) and progression‐free survival (PFS) in patients with R/M SCCHN treated with nivolumab in Japan. From 2012 to 2013, 102 patients were eligible, of whom 88 were finally included in the analysis. mGPS was calculated as follows: mGPS of 0, C‐reactive protein (CRP) ≤1.0 mg/dL; 1, CRP > 1.0 mg/dL; and 2, CRP > 1.0 mg/dL and albumin < 3.5 mg/dL. Optimal cutoff point of dichotomized NLR was calculated using the area under the receiver operating characteristic curve (AUROC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models adjusted by potential confounders.ResultsHigher NLR was significantly associated with worse survival (1‐year OS: 45.3% vs 16.3%, log‐rank P‐value < .001, adjusted HR: 4.40 (95% CIs: 1.78‐10.88); one‐year PFS: 39.1% vs 9.0%, P‐value = .001, adjusted HR: 3.37 (95% CI: 1.64‐6.92)). In addition, high mGPS (=2) was significantly associated with worse survival compared to low mGPS (=0) (1‐year OS: 37.4% vs 26.1%, P‐value = .004, adjusted HR: 4.20 (95% CI:1.54‐11.49); 1‐year PFS: 41.5% vs 24.8%, P‐value = .007, adjusted HR: 2.01 (95% CI: 0.87‐4.68)). These associations were consistent with subgroup analyses stratified by potential confounders.ConclusionsPretreatment NLR and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with nivolumab.

Does body mass index really predict the response to systemic therapies in metastatic melanoma: A multicenter study from the MelBase French National Cohort?

10031 Background: Obesity is an established risk factor for several cancers and higher body mass index (BMI) is associated with poor prognosis. These data are still debated in melanoma. Furthermore, recently the concept of “obesity paradox” has emerged. In a large cohort published by McQuade JL et al, higher BMI was associated with better survival in patients with metastatic melanoma (MM) especially for those treated with targeted therapy (TT) and immune checkpoint inhibitors (ICI). We studied the association between BMI and progression-free survival (PFS) and overall survival (OS) in patients with MM treated with systemic therapies. Methods: This study was conducted from the prospective MelBase cohort (NCT02828202). Patients with MM treated with first-line ICI, TT, or CT were included. BMI was categorized by WHO criteria. Underweight patients were excluded. The co-primary outcomes were the associations between BMI and PFS or OS, stratified by treatment, sex and age. Multivariate analyses were performed. Results: A total of 1214 patients were analyzed. The majority of them were treated with ICI, followed by TT. Obese patients represented 22% of cohort (Table). Median follow-up was 13.5 months. The patients who were overweight or obese did not have different PFS (p = 0.88) or OS (p = 0.25) than patients with normal BMI. Stratifying this cohort by treatment received, age, sex and others parameters (such as LDH, number of metastatic site) did not revealed any difference. Multivariate analysis did not change the results. Conclusions: BMI was not associated with clinical outcomes in our cohort, especially in ICI and TT groups. Thus, we did not confirm the results presented by McQuade Jl et al. with a cohort quite similar in term of size. Because BMI is too simplistic and then an imperfect measure of body composition, the published data are not reproducible. We caution the oncologists, about BMI as valuable predictive marker of survival for melanoma patients. [Table: see text]