Independent Predictor Of Shorter Overall Survival Research Articles

Evaluation of CD56 and CD117 Double-positive as a Predictor of Poor Prognosis in Multiple Myeloma Patients: A Retrospective Analysis.

Despite advancements in treatment, multiple myeloma (MM) remains a challenging hematologic malignancy. It is crucial to stratify risk and perform prognostic assessment through various markers, including the cluster of differentiation 56 (CD56) and thecluster of differentiation 117 (CD117) expression. However, the relationship of these markers with MM-related survival remains unclear. In this context, the objective of this study isto investigate the prognostic implications of CD56 and CD117 expression and associated clinical features in MM patients. The population of this retrospective single-center study consisted of adult MM patients whose CD56 and CD117 expressionswere analyzed. Patients were divided into four groups according to their immunophenotypes: CD56+ CD117-, CD56-CD117+, CD56+CD117+, and CD56-CD117-.These groups were compared in terms of demographic and clinical characteristics, response to treatment, and survival outcomes. Of the 168 MM patients included in the study, CD56 positive, CD117 positive,CD56, and CD117 double-positive and double negative were observed in 57.1%, 38.1%, 21.4%, and 26.2%, respectively. Patients with double positivehad significantly higher cytogenetic risk and significantly lower overall response rate (ORR) compared toother patients(p<0.001 for both cases). ORR and overall survival (OS) were significantly lower in CD56 positivepatients than those CD56 negative (p=0.017 and p=0.004, respectively). Mortality rates were significantly higher in CD56 positive patients and CD117 positive than in those with double negative(p<0.001 and p=0.002). Double negative patients had significantly lower ORR and OS and higher mortality than others (p=0.001, p=0.002, and p<0.001, respectively). The high cytogenetic risk was found to bean independent predictor of shorter OS (p>0.001). The study's findings revealed that CD56 and CD117 double- positive MM patients had poorer prognosis, lower ORR, shorter OS, and higher mortality.

Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy

ObjectivesAccurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, MYC copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value. Materials and MethodsMYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation. ResultsNine (11 %) of 82 cases had MYC CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. MYC CNG was significantly associated with STK11 mutation (P=0.023), whereas positive MYC IHC was significantly associated with KRAS mutation (P=0.0076) and current/former smoking (P=0.0007). MYC CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1–6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15–0.72, P=0.0055). MYC IHC positive/PD-L1 < 1 % cases had the shortest OS (median 230 versus 918 days, P=0.00069) and PFS (median 84 versus 254 days, P=0.0087). MYC CNG was not associated with OS or PFS. ConclusionWe find that positive MYC IHC is an independent predictor of shorter OS after immunotherapy treatment, with MYC positive/PD-L1 < 1 % status predictive of particularly poor immunotherapy response. We identify positive MYC IHC as a feature of possible relevance to NSCLC treatment selection and of interest for future therapy development.

Prognostic value of preoperative prealbumin levels in patients with unresectable hepatocellular carcinoma undergoing transcatheter arterial chemoembolisation

BackgroundThis retrospective study analyzed the prognostic value of preoperative prealbumin (PAB) levels in patients with unresectable hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolisation (TACE). MethodsFour hundred and two patients diagnosed with unresectable HCC were included in this retrospective study. All patients underwent their first TACE procedure. Based on PAB levels before the first TACE, 402 patients were classified as having low PAB levels and high PAB levels. Potential confounding factors between the two groups were eliminated using. Propensity Score Matching (PSM) analysis. The time to progression (TTP) and overall survival (OS) of the two groups were compared using Kaplan-Meier curves before and after PSM. Risk factors for poor prognosis were determined using univariate and multivariate Cox proportional hazards models. ResultsBefore PSM, the high PAB level group had a significantly longer median TTP and OS than the low PAB level group (all P values < 0.0001). After PSM, the high PAB level group still had a significantly longer median TTP and OS than the low PAB level group (all P values < 0.05). After PSM, low PAB level was found to be an independent predictor of shorter OS (HR = 0.656; 95% CI:0.448–0.961; P = 0.03). The subgroup analysis before PSM showed that low PAB levels increased the risk of poor prognosis in most subgroups. ConclusionsLow preoperative PAB levels are associated with poor prognosis in patients with unresectable HCC after TACE.

Cytoplasmic poly(A)-binding protein 1 (PABPC1) is a prognostic biomarker to predict survival in nasopharyngeal carcinoma regardless of chemoradiotherapy

BackgroundNasopharyngeal carcinoma (NPC), especially the nonkeratinizing type, is a malignant tumor primarily occurring in southern China and Southeast Asia. Chemotherapy (CT) and combined radiotherapy (RT) is used to treat NPC. However, the mortality rate is high in recurrent and metastatic NPC. We developed a molecular marker, analyzed its correlation with clinical characteristics, and assessed the prognostic value among NPC patients with or without chemoradiotherapy.MethodsA total of 157 NPC patients were included in this study, with 120 undergoing treatment and 37 without treatment. EBER1/2 expression was investigated using in situ hybridization (ISH). Expression of PABPC1, Ki-67, and p53 was detected with immunohistochemistry. The correlations of EBER1/2 and the expression of the three proteins having clinical features and prognosis were evaluated.ResultsThe expression of PABPC1 was associated with age, recurrence, and treatment but not with gender, TNM classification, or the expression of Ki-67, p53, or EBER. High expression of PABPC1 was associated with poor overall survival (OS) and disease-free survival (DFS) and was an independent predictor depending on multivariate analysis. Comparatively, no significant correlation was observed between the expression of p53, Ki-67, and EBER and survival. In this study, 120 patients received treatments and revealed significantly better OS and DFS than the untreated 37 patients. PABPC1 high expression was an independent predictor of shorter OS in the treated (HR = 4.012 (1.238–13.522), 95% CI, p = 0.021) and the untreated groups (HR = 5.473 (1.051–28.508), 95% CI, p = 0.044). However, it was not an independent predictor of shorter DFS in either the treated or the untreated groups. No significant survival difference was observed between patients with docetaxel-based induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) and those with paclitaxel-based IC + CCRT. However, when combined with treatment and PABPC1 expression, patients with paclitaxel-added chemoradiotherapy plus PABPC1 low expression had significantly better OS than those who underwent chemoradiotherapy (p = 0.036).ConclusionsHigh expression of PABPC1 is associated with poorer OS and DFS among NPC patients. Patients with PABPC1 having low expression revealed good survival irrespective of the treatment received, indicating that PABPC1 could be a potential biomarker for triaging NPC patients.

Natural Course and Prognosis of Primary Spinal Glioblastoma: A Nationwide Study.

Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited. PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected. Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5-23.7), and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0-1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02-0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05-7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32-12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D-E) (HR 0.38, 95% CI 0.07-1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118-1.05; p = 0.06) was at the limit of significance. Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.

Clinical impact of MAPK pathway alterations in advanced biliary tract cancer (BTC): SCRUM-Japan GOZILA and COLOMATE international collaboration.

4086 Background: Abnormalities in the MAPK pathway are potential therapeutic targets in various cancers. However, the clinical impact of alterations in the MAPK pathway in BTC have not been elucidated, especially outside of canonical mutations in KRAS and BRAF. We investigated the clinical outcomes of advanced BTC with MAPK pathway alterations treated with chemotherapy in Japan and the United States. Methods: Patients with advanced BTC who received gemcitabine plus cisplatin as first-line therapy were included from the GOZILA study in Japan and Duke Molecular Registry of Tumors in the US. Genetic abnormalities were detected by Guardant360, a cell-free DNA assay, in Japan and by blood or tissue-based next-generation sequencing (NGS) at Duke University. Two hundred and seven patients with BTC from Japan were included in an exploratory cohort to evaluate the association of MAPK alterations with overall survival (OS) according to MAPK alteration status. One hundred and ten patients with BTC from both Japan and the US harboring oncogenic alterations in the MAPK pathway were included in a biomarker selected cohort to assess the association of specific MAPK alterations with OS. Multivariate analysis was performed using a Cox regression model based on a univariate p-value &lt; 0.2. Results: MAPK pathway-related oncogenic alterations detected in each cohort are shown in the table below. In the exploratory cohort, median OS was shorter for patients with MAPK alterations vs. no MAPK alteration (15.9 m vs. 24.9 m, log-rank p = 0.001). Based on univariate analysis, the following covariates were selected for multivariate analyses: age, prior resection, and MAPK pathway alteration in the exploratory cohort; country, the timing of NGS, distant metastasis, KRAS amplification, and BRAF class 2 mutation in the biomarker selected cohort. In the exploratory cohort, multivariate analysis identified MAPK pathway alterations as an independent predictor of shorter OS with a HR of 1.92 (95% CI = 1.28-2.87, p = 0.001). In the biomarker selected cohort, multivariate analysis identified BRAF class 2 mutations and KRAS amplification as independent predictors of shorter OS with a HR of 16.2 (95% CI = 3.26-80.8, p = 0.001) and 5.97 (95% CI = 1.74-19.3, p = 0.002) respectively. Conclusions: MAPK pathway alterations, especially BRAF class 2 mutation and KRAS amplification, had a significant negative impact on clinical outcomes in BTC receiving first-line chemotherapy. These results are newly confirmed in BTC. [Table: see text]

Impact of a personal history of cutaneous squamous cell carcinoma in the overall survival of cutaneous melanoma patients

AbstractBackgroundThere have been previous studies on the association between cutaneous squamous cell carcinoma (cSCC) and cutaneous melanoma (CM) survival, and also the association between skin cancers and relative telomere length (RTL). In this study we analysed the overall survival (OS) of patients with CM and a positive history of cSCC to evaluate the impact of this history on survival and any possible association with RTL.Materials and MethodsA retrospective cohort study on 1613 patients with CM diagnosed between 1 January 2000 and 31 December 2015 at the Instituto Valenciano de Oncología. Contingency tables were used to analyze the association between a positive history of cSCC and other covariates. OS was evaluated using Kaplan–Meier curves and log‐rank test. Cox regression was used to determine the prognostic role of each covariate.ResultsPatients with a positive history of cSCC had a shorter OS (p &lt; 0.001), but this was not significant at multivariate analysis. The covariates that resulted in independent predictors of shorter OS were gender, localisation, and lymphovascular invasion. Age and Breslow thickness were independent predictors only after 15 months of follow‐up; mitotic rate only between 15 and 65 months; disease stage only below 65 months, and RTL only after 65 months of follow‐up. A positive history of cSCC was not associated with RTL.ConclusionsOur results suggest that CM patients with a positive history of cSCC have a worse OS because it is related to other independent prognostic factors such as male gender and older age.

Exosome Component 4 Promotes Epithelial Ovarian Cancer Cell Proliferation, Migration, and Invasion via the Wnt Pathway.

BackgroundOf gynecologic malignancies, ovarian cancer is the leading cause of death, mainly due to the lack of sensitive tumor markers, which means it almost always presents at an advanced stage. Exosome Component 4 (EXOSC4) is involved in RNA degradation, but its role in epithelial ovarian cancer (EOC) is unclear.MethodsThe expression levels of EXOSC4 in EOC and normal ovarian tissue specimens were determined by immunohistochemical staining. The overall survival (OS) and progression-free survival (PFS) of patients with EOC were evaluated after patients were classified into high and low EXOSC4 expression groups, and the Cox regression model was established to identify independent predictors of patient prognosis. The effects of EXOSC4 on proliferation, colony formation, migration, and invasion were examined in the SKOV-3 and HO8910 cell lines by lentivirus-mediated shRNA knockdown. Flow cytometry was used to detect cell cycle changes. The mRNA levels of cyclin D1, CDK4, and c-myc were detected by RT-PCR. The protein expression levels of β-catenin, cyclin D1, CDK4, c-myc, vimentin, N-cadherin, and E-cadherin were assessed by western blot. Wnt/β-catenin activation was measured by TCF/LEF reporter assay.ResultsEXOSC4 was significantly elevated in EOC tissues and cell lines. High EXOSC4 expression was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and pathological grade, and identified as an independent predictor of shorter OS and PFS. EXOSC4 knockdown suppressed proliferation, migration, and invasion in EOC cell lines. Cells were arrested at G0/G1 phase after EXOSC4 knockdown. The mRNA levels of cyclin D1, CDK4, and c-myc were decreased. β-catenin, cyclin D1, CDK4, c-myc, vimentin, and N-cadherin protein expression levels were reduced, while those of E-cadherin was increased. Wnt/β-catenin activity was suppressed after the EXOSC4 knockdown.ConclusionsEXOSC4 is involved in EOC. Knockdown of EXOSC4 can inhibit the proliferation, migration, and invasion ability of EOC by suppressing the Wnt pathway. EXOSC4 is expected to be a novel biomarker and molecular target in EOC.

Prognostic Impact of Indicators of Systemic Inflammation and the Nutritional Status of Patients with Resected Carcinoma of the Ampulla of Vater: A Single-Center Retrospective Study.

Several indicators of systemic inflammation and nutritional status were recently shown to serve as novel prognostic factors for certain cancers. Here, we aimed to investigate the prognostic impact of preoperative indicators of systemic inflammation and nutritional status associated with the survival of patients with resected ampulla of Vater carcinoma (AC). We retrospectively analyzed the records of 91 patients who underwent pancreatoduodenectomy (PD) for AC from January 2002 through December 2018. Indices for systemic inflammation and nutritional status (Systemic immune-inflammation index [SII], Prognostic nutritional index [PNI], modified Glasgow prognostic score [mGPS], and Controlling nutritional status score [CONUT]) were determined using preoperative blood tests. Clinicopathological factors and these indices were analyzed to identify predictors of overall survival (OS). The median preoperative SII and PNI values were 456.7 and 47.5, respectively, and their optimal cut-off values were 670.0 and 50.0, respectively. Univariate analysis revealed that high SII, low PNI, mGPS ≥ 1, and malnutrition, assessed using the CONUT, were significant predictors of shorter OS. Multivariate analysis revealed that high SII (HR = 2.71, p = 0.023) and malnutrition assessed using the CONUT (hazard ratio = 3.98, p = 0.006) were independent predictors of shorter OS. SII and the CONUT predicted the survival of patients with AC after radical resection. These indicators are easily calculated using preoperative blood tests and may contribute to the development of improved strategies to treat AC.

Role of Resin Microsphere Y90 Dosimetry in Predicting Objective Tumor Response, Survival and Treatment Related Toxicity in Surgically Unresectable Colorectal Liver Metastasis: A Retrospective Single Institution Study.

Simple SummaryColorectal liver metastases are difficult to treat, with only a minority of patients eligible for surgical resection. Yttrium-90 selective internal radiation therapy is an alternative treatment currently used for patients who have progressed on chemotherapy. A technique called dosimetry allows clinicians to analyze how much radiation was delivered to target lesions post-treatment. The aim of this study is to evaluate the relationship of various dosimetric parameters with objective tumor response, overall survival, and treatment related toxicity with the potential goal of optimizing Yttrium-90 treatment in this patient population. Additionally, other potential predictors of survival outcomes, including clinical and demographic factors, were also evaluated. We found that delivering a mean tumor dose ≥100 Gy when using resin microspheres was significantly associated with objective tumor response and prolonged overall survival. In this study, no mean non-tumoral liver dose threshold was found to predict treatment related toxicity.Purpose: To Evaluate the correlation between tumor dosimetric parameters with objective tumor response (OR) and overall survival (OS) in patients with surgically unresectable colorectal liver metastasis (CRLM) undergoing resin-based Ytrrium-90 selective internal radiation therapy (Y90 SIRT). Materials and Methods: 45 consecutive patients with CRLM underwent resin-based Y90 SIRT in one or both hepatic lobes (66 treated lobes total). Dose volume histograms were created with MIM Sureplan® v.6.9 using post-treatment SPECT/CT. Dosimetry analyses were based on the cumulative volume of the five largest tumors in each treatment session and non-tumoral liver (NTL) dose. Receiver operating characteristic (ROC) curve was used to evaluate tumor dosimetric factors in predicting OR by Response Evaluation Criteria for Solid Tumors at 3 months post-Y90. Additionally, ROC curve was used to evaluate non-tumoral liver dose as a predictor of grade ≥ 3 liver toxicity and radioembolization induced liver disease (REILD) 3 months post Y90. To minimize for potential confounding demographic and clinical factors, univariate and multivariate analysis of survival with mean tumor dose as one of the factors were also performed. Kaplan-Meier estimation was used for OS analysis from initial Y90 SIRT. Results: 26 out of 45 patients had OR with a median OS of 17.2 months versus 6.8 months for patients without OR (p < 0.001). Mean tumor dose (TD) of the five largest tumors was the strongest predictor of OR with an area under the curve of 0.73 (p < 0.001). Minimum TD, and TD to 30%, 50%, and 70% of tumor volume also predicted OR (p’s < 0.05). Mean TD ≥ 100 Gy predicted a significantly prolonged median OS of 19 vs. 11 months for those receiving TD < 100 Gy (p = 0.016). On univariate analysis, mean TD < 100 Gy, presence of any genomic mutation, presence of MAPK pathway mutation, bilobar hepatic metastases and diffuse metastatic disease (>10 lesions per liver lobe) were found to be predictors of shorter median OS. On multivariate analysis, mean TD < 100 Gy, presence of any genomic mutation, and diffuse hepatic metastatic disease were found to be independent predictors of shorter OS. Overall, six (13.3%) patients developed grade ≥ 3 liver toxicity post Y90 of whom two (4.4%) patients developed REILD. No dose threshold predicting grade ≥ 3 liver toxicity or REILD was identified. Conclusions: Mean TD ≥ 100 Gy in patients with unresectable CRLM undergoing resin-based Y90 SIRT predicts OR and prolonged OS.

Clinical relevance of circulating activin A and follistatin in small cell lung cancer

ObjectivesCirculating levels of activin A (ActA) and follistatin (FST) have been investigated in various disorders including malignancies. However, to date, their diagnostic and prognostic relevance is largely unknown in small cell lung cancer (SCLC). Our aim was to evaluate circulating ActA and FST levels as potential biomarkers in this devastating disease. MethodsSeventy-nine Caucasian SCLC patients and 67 age- and sex-matched healthy volunteers were included in this study. Circulating ActA and FST concentrations were measured by ELISA and correlated with clinicopathological parameters and long-term outcomes. ResultsPlasma ActA and FST concentrations were significantly elevated in SCLC patients when compared to healthy volunteers (p < 0.0001). Furthermore, extensive-stage SCLC patients had significantly higher circulating ActA levels than those with limited-stage disease (p = 0.0179). Circulating FST concentration was not associated with disease stage (p = 0.6859). Notably, patients with high (≥548.8 pg/ml) plasma ActA concentration exhibited significantly worse median overall survival (OS) compared to those with low (<548.8 pg/ml) ActA levels (p = 0.0009). Moreover, Cox regression analysis adjusted for clinicopathological parameters revealed that high ActA concentration is an independent predictor of shorter OS (HR: 1.932; p = 0.023). No significant differences in OS have been observed with regards to plasma FST levels (p = 0.1218). ConclusionBlood ActA levels are elevated and correlate with disease stage in SCLC patients. Measurement of circulating ActA levels might help in the estimation of prognosis in patients with SCLC.

Abstract 762: Clinical characteristics and prognostic value of the KRASmutation in Chinese colorectal cancer patients

Abstract Background: The KRAS mutation are high-frequency somatic mutations found in the colorectal cancer (CRC) patients both from Western and Asian countries, but except for exon 2 of KRAS, other prevalence and prognostic value have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutation of KRAS in Chinese CRC patients and to investigate their impact on prognosis. Methods: 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing (NGS) for detection the KRAS mutation. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at the third affliated Hospital of Soochow University (sCohort) and used ddPCR to detect KRAS mutations. Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutation. The most frequent mutations in KRAS were G12D (32.19%), G12V (17.96%) and G13D (17.59%). In the sCohort, 51 CRC patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%) and G14D (3.92%) were high-frequency mutations. The KRAS mutation was associated with shorter median overall survival (OS) than wild-type tumors (mOS, 69 vs 55 months; HR, 1.80; 95% Cl 1.22-2.64; P=0.0003). In Cox multivariate analysis, age (HR, 1.562; 95% Cl 1.10-2.22; P=0.013), tumor differentiation (HR, 0.417; 95% Cl 0.19-0.90; P=0.026) and KRAS mutation (HR, 1.897; 95% Cl 0.19-0.90; P=0.001) remained independent predictor of shorter OS. Among the common KRAS mutations, G12D was significantly associated with shorter OS (HR, 2.17; 95% Cl 1.31-3.58; P &amp;lt; 0.0001) compared with KRAS wild-type patients. Conclusions: Our findings indicate that KRAS genes are frequently mutated and over 30% harbored the KRAS G12D mutation subtype. Our finding that KRAS G12D mutation is associated with inferior survival and a biomarker of poor prognosis in Chinese patients. Our data emphasizes the importance of molecular features in CRC patients, which could potentially be improved by G12D-specific related inhibitors. Citation Format: Ye Yuan, Wei Wang, Jiemin Zhao, Junling Zhang, Shiqing Chen, Chunti Shen, Changping Wu, Wenwei Hu. Clinical characteristics and prognostic value of the KRASmutation in Chinese colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 762.

Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer.

Simple SummarySerum prostate-specific antigen (PSA) level is the most valuable biomarker in prostate cancer. This study investigates the predictive value of achieving >30% PSA decline at four weeks of first-line androgen signaling inhibitors (ASIs) using a multi-institutional cohort dataset of 254 mCRPC patients. The achievement of >30% PSA decline at four weeks is an independent predictor for overall survival (OS). Interestingly, in patients who did not achieve >30% PSA decline at four weeks—an achievement of the >30% PSA decline at 12 weeks is eventually observed in 30.9% of those patients. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks of the first-line treatment, a multivariate analysis is conducted. The duration of androgen deprivation therapy before CRPC < 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients.The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks—particularly in patients with a modest effect of ADT and poor performance status.

Effect of corticosteroids on the outcome of patients with advanced non–small cell lung cancer treated with immune-checkpoint inhibitors

IntroductionWe analysed patients with advanced non–small cell lung cancer (NSCLC) who were treated with immune-checkpoint inhibitors (ICIs) to address the effect of the timeline and reason for corticosteroid administration on survival outcomes. MethodsWe retrospectively collected clinical data of non-oncogenic driven, advanced NSCLC patients treated with ICIs at Karolinska University Hospital, including the timeline and reason for steroid administration. Steroid administration was defined as > 10 mg prednisolone equivalent for ≥10 days. We subcategorized patients based on the aetiology of steroid administration into three subgroups: a) steroids for supportive reasons but not for cancer palliation; b) steroids for the palliation of cancer-related symptoms; c) steroids for the management of immune-related adverse events (irAEs). Furthermore, to analyse the timeline, patients were categorised into two groups; those who received corticosteroids within 2 weeks before until 2 days after ICI initiation and those who received steroids later during their treatment course. ResultsAnalysed data from 196 patients showed 46.3% of patients received corticosteroids. Steroid administration due to irAEs did not affect overall survival (OS) (p = 0.38) compared with the steroid naïve group. Only steroid administration for the palliation of cancer-related symptoms was an independent predictor for shorter OS (HR = 2.7; 95% CI, 1.5–4.9). The timeline of steroid administration did not affect OS (p = 0.456) in our cohort. ConclusionsSteroids due to irAEs do not appear to hamper ICI efficacy. However, the administration of high-dose steroids to palliate malignancy-associated symptoms might reflect the dismal prognosis of this patient group.

Combination of FLT3-ITD Allelic Ratio, NPM1 Mutation, and Immunophenotypic Markers to Modulate Outcome Prediction in Patients with Normal Karyotype Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

NPM1 mutation status and the allelic ratio (AR) of FLT3-internal tandem duplication (FLT3-ITD) are routinely tested for disease risk stratification in patients with normal karyotype (NK) acute myelogenous leukemia (AML); however, the predictive impact of immunophenotypic markers on different NPM1/FLT3 genotypes remains unclear. We performed a retrospective analysis of 423 patients with NK-AML subclassified into groups based onNPM1/FLT3 genotype. Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 124 of 423 patients (29%) and was significantly associated with longer event-free survival (EFS) and overall survival (OS), except for patients with the favorable genotype, defined as mutatedNPM1 (NPM1mut) combined with normal FLT3 status (FLT3-ITDneg) or FLT3-ITD AR <.5 (FLT3-ITDlow). A subset of AML patients bearing the favorable NPM1mut/FLT3-ITDneg/low genotype share similar outcomes with AML patients who have the intermediate FLT3/NPM1 genotype defined by normal NPM1 (NPM1wt) and FLT3-ITDneg/low. In these individuals, the lack of CD13 expression (CD13neg) was associated with shorter EFS (P=.041) and OS (P=.017). CD13neg was an independent predictor for shorter OS (hazard ratio, 1.985; P=.028).

Clinical characteristics and prognostic value of the KRAS G12C mutation in Chinese non-small cell lung cancer patients

BackgroundThe KRAS mutation is the second most common genetic variant in Chinese non-small cell lung cancer (NSCLC) patients. At the 2019th World Conference of Lung Cancer, the KRAS G12C-specific inhibitor AMG510 showed promising results in the phase I clinical trial. However, the frequency, clinical characteristics, and prognostic significance of the KRAS G12C mutation in Chinese NSCLC patients are rarely reported.MethodsNext-generation sequencing was used to confirm the KRAS mutation status in 40,804 NSCLC patients from multiple centers (mCohort). Survival data were collected retrospectively from 1456 patients at one of the centers, the Guangdong Lung Cancer Institute (iCohort).ResultsIn the mCohort, 3998 patients (9.8%) were confirmed to harbor a KRAS mutation, of whom 1179 (29.5%) had the G12C subtype. In the iCohort, 130 NSCLC patients (8.9%) had a KRAS mutation and 42 (32.3%) had the G12C subtype. The G12C subgroup included more male patients (85.2% vs 67.4%, P < 0.0001) and more smokers (76.2% vs 53.4%, P = 0.02) than did the non-G12C subgroup. Both the KRAS mutation group and KRAS G12C mutation subgroup were associated with a shorter median overall survival (OS) than wildtype tumors (15.1 vs 26.7 months, hazard ratio [HR]KRAS = 1.50, P = 0.002; 18.3 vs 26.7 months, HRG12C = 1.66, P = 0.007). In Cox regression analysis, smoking (HR = 1.39, P = 0.05) and stage IV disease (HR = 2.72, P < 0.001) remained as independent predictors of shorter OS. Both the KRAS mutation (HR = 1.30, P = 0.07) and KRAS G12C mutation (HR = 1.47, P = 0.07) reached borderline significance.ConclusionsIn the largest sample used thus for, our study found that approximately 10% of Chinese NSCLC patients had KRAS mutations. Of these, nearly 30% harbored the KRAS G12C mutation subtype, which was most common in male smokers. The KRAS G12C mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which could potentially be improved by G12C-specific inhibitors in the future.(296 words)

Radiological assessment of Peritoneal Cancer Index on preoperative CT in ovarian cancer is related to surgical outcome and survival.

To evaluate whether Peritoneal Cancer Index (PCI) assessed on preoperative CT (CT-PCI) can be used as non-invasive preoperative tool to predict surgical outcome, disease-free survival (DFS) and overall survival (OS). This is a retrospective, observational cohort study performed in a single institution. We considered all patients with diagnosis of ovarian cancer and preoperative CT, who had undergone upfront cytoreductive surgery between 2008 and 2010 and had post-operative clinical follow-up to December 2015. Two radiologists reviewed CT scans and assessed CT-PCI using Sugarbaker's diagram. We assessed the discriminatory capacity of the CT-PCI score on the surgical outcome by ROC curve analysis. DFS and OS were assessed by Kaplan-Meier nonparametric curves and by multivariable Cox-regression analysis. A total of 297 patients were included in the present analysis. CT-PCI was positively correlated with post-operative residual disease [odds ratio (OR) 1.04, 95% CI 1.01-1.07, p = 0.003]. ROC curve analysis returned AUC = 0.64 for the prediction of total macroscopic tumour clearance. In multivariable analysis, patients with no peritoneal disease seen on CT had a significantly longer DFS [Hazard ratio (HR) 2.28, p = 0.007]. Radiological serosal small bowel involvement was an independent predictor for shorter OS (HR 3.01, p = 0.002). Radiological PCI assessed on preoperative CT is associated with the probability of residual disease after cytoreductive surgery; however, it has low performance as a triage test to reliably identify patients who are likely to have complete cytoreductive surgery. CT-PCI is positively correlated with both DFS and OS and may be used as an independent prognostic factor, for example in patients with high FIGO stages.

Prognostic value of [18F]FDG PET/CT parameters in surgically resected primary lung adenocarcinoma: a single-center experience.

To evaluate the prognostic role of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) measured by FDG-positron emission tomography (PET)/computed tomography (CT) in patients with primary lung adenocarcinoma undergoing surgical resection. All consecutive patients undergoing curative surgery for primary lung adenocarcinoma at the Thoracic Surgery Unit of the University Hospital of Parma between January 2009 and December 2014 were retrospectively analyzed. The cutoff point of each continuous PET parameter was determined through receiver operating characteristic curve and Youden index, using overall survival (OS) as the classification status. Univariate and multivariate Cox proportional hazards models were applied to evaluate the association between OS and potential prognostic variables, including SUVmax, MTV, and TLG. A total of 193 patients were considered eligible for this study. The mean 5-year OS rate was 70.5 ± 3.5%. Acinar and lepidic patterns were more frequently associated with absent or low (<2.5) SUVmax values [18F]FDG uptake. At univariate analysis, male sex, advanced stage, micropapillary and solid pattern, lymphatic, blood vessels and pleural invasion, high SUVmax, MTV, and TLG were significantly associated with poorer OS. Multivariate analyses revealed that only sex, stage, and TLG were independent factors for OS, with male sex, stage 3+4, and high TLG value (p = 0.041) significantly associated with poorer OS. In this study, [18F]FDG PET/CT parameters SUVmax, MTV, and TLG were prognostic factors in patients with surgically resected lung adenocarcinoma, able to predict OS and helping to further stratify these patients into prognostic subsets. Elevated TLG was also an independent predictor for shorter OS.

The platelet-to-lymphocyte ratio as a significant prognostic factor to predict survival outcomes in patients with synchronous metastatic renal cell carcinoma.

PurposeThe clinical impact of the platelet-to-lymphocyte ratio (PLR) on the prognosis of patients with metastatic renal cell carcinoma (mRCC) remains controversial. We investigated the associations between elevation of the PLR and disease prognosis in patients with synchronous mRCC.Materials and MethodsThe data of 1,505 patients with synchronous mRCC were retrospectively analyzed. The entire cohort was stratified into two subgroups according to PLR. Kaplan–Meier and Cox proportional analyses were performed to investigate the possible associations between the PLR and disease prognosis.ResultsThere were 921 patients with a high PLR and 584 patients with a low PLR by use of the cutoff of 146. The patients with a high PLR had worse clinical characteristics in terms of advanced clinical stage (p<0.001) and rate of lymph node invasion (p=0.036). The Kaplan–Meier analysis showed that patients with a high PLR had significantly shorter overall survival (OS) (p<0.001) and cancer-specific survival (CSS) (p<0.001). The multivariate Cox analysis revealed that the PLR was an independent predictor for shorter OS (hazard ratio [HR], 1.345; 95% confidence interval [CI], 1.183–1.530; p<0.001) and CSS (HR, 1.318; 95% CI, 1.156–1.502; p<0.001). In the subgroup analyses, the PLR showed a significant association with survival outcomes in the subgroup with clear cell type (all p<0.05) but not in the subgroup with the non–clear cell type.ConclusionsThe PLR was an independent prognostic factor for survival outcomes in patients with mRCC. However, the association was statistically significant only in patients with clear cell type mRCC.

Correlation Analysis Between Preoperative Serum Iron Level and Prognosis as Well as Recurrence of HCC After Radical Resection.

BackgroundThe purpose of this retrospective study was to investigate the relationship between serum iron levels and the prognosis and risk of recurrence in patients with hepatocellular carcinoma (HCC).MethodsA total of 253 HCC patients who underwent radical resection were involved in this study.ResultsAccording to the receiver operating characteristic (ROC) curve, the optimal cut-off value for preoperative serum iron in the assessment of HCC postoperative prognosis was 94 ug/dL. The overall survival (OS) of patients in the high iron group was significantly better than that in the low iron group (p < 0.001). The recurrence rate of patients in the low iron group was higher than that in the high iron group (p = 0.011). Correlation analysis showed that preoperative serum iron level was correlated with tumor size >5 cm (χ2 = 11.590, p < 0.001), recurrence (χ2 = 5.714, p = 0.017) and microvascular invasion (χ2 = 5.087, p = 0.024). In addition, univariate analysis showed that OS and disease-free survival (DFS) of HCC patients with high iron level were better than those with low iron level. Furthermore, multivariate COX proportional hazards regression analysis showed that serum iron ≤94 μg/dL, tumor size >5 cm, and microvascular invasion were independent predictors for shorter OS and DFS in HCC patients after operation, while recurrence was for shorter OS.ConclusionPatients with low preoperative serum iron level had worse postoperative survival and higher recurrence rate in HCC. Preoperative serum iron is an independent predictor of HCC patients. For HCC patients with low iron levels, prognosis of patients may be improved if appropriate iron is supplemented.