Favorable Prognostic Factor For Survival Research Articles

CNSC-45. EXTRINSIC ELECTRICAL MODULATION IMPACTS GLIOBLASTOMA TUMOR GROWTH BY DISRUPTING ITS INTERCELLULAR COMMUNICATION

Abstract Glioblastoma (GBM) is an incurable primary malignant neoplasm of the central nervous system. GBM as an electrically active neoplasm diffusely colonizes healthy brain tissues, disrupting the neurotransmission balance and causing glioma-related epilepsy (GRE) in up to 50% of patients. Interestingly, GRE is an independent favorable prognostic factor for survival in GBM. The therapeutic induction of seizure may have a previously unexplored oncologic value in GBM. We have previously reported in CT-2A-bearing mice subjected to daily extrinsic electrical modulation (EEM) diminished tumor progression and increased overall survival relative to sham-treated mice, but the mechanism by which EEM produces its anti-tumor effect remains uncertain. Therefore, GBM-bearing mice (CT-2A cells xenografted into 5-7 weeks old C57BL/6 female mice, n=5/group) received either a single EEM of 2.0 millicoulombs (mC) or sham treatment. The mice were terminated at 3 hours, 24 hours, 4, 7, and 10 days post-EEM, and tumors and contralateral brain cortex were analyzed using bulk RNA-sequencing and Sequential immunofluorescence (SeqIFTM). SeqIFTM revealed how EEM activates neuronal activity via cFOS expression and induces tumor-specific cell damage through cleaved caspase-3 expression, without affecting healthy brain tissue. Furthermore, RNA-seq performed post-EEM revealed gene expression changes of not only synapse organization markers but also of several tumor-tumor and tumor-neuron connectivity key markers, such as growth-associated protein 43 (GAP43), neuroligin-3 (NLGN3), and glutamate receptors such as GRIA4 and GRIN1 between others. However, the expression of these markers diminished significantly 96h after-EEM, indicating a reduction in intercellular electrical communication by the inhibition of the neoplasm cells electrical integration with neuronal circuits by downregulating glutamatergic receptor expression, blocking the synapse-forming protein NLGN3, and the network-connecting protein GAP43. Taken together, our findings reveal how by the disruption of these critical interactions within the tumor microenvironment though EEM impacts on GBM growth making it more susceptible to therapeutic interventions.

Association Between Quality of Life Questionnaire at Diagnosis and Survival in Patients With Lung Cancer

BackgroundPatients with lung cancer experience considerable symptom burden, which can decrease patients’ QOL. Our aim was to investigate the association between QOL questionnaire at diagnosis and survival of lung cancer. Patients and MethodsThis was a multicenter study of lung cancer patients at 7 medical centers of the Catholic University of Korea that responded to a quality of life questionnaire between December 1, 2017 and December 31, 2020. We analyzed 5 functional (physical, role, emotional, cognitive, and social functioning) and nine symptom (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) scales and examined their associations with survival. A Cox proportional hazards model was used to evaluate the prognostic value. ResultsIn total, 1297 lung cancer patients were enrolled. The results of multivariable analysis showed that female, younger age, never smoker, stage I or II cancer, higher physical functioning, and emotional functioning were statistically significant favorable predictors for survival. On subgroup analysis according to early (stage I and II) or advanced (stage III or IV) stage, higher physical functioning and emotional functioning were each found to be favorable prognostic factors for survival. Meanwhile, fatigue, pain, insomnia, and financial difficulties were found to be associated with low scores on the emotional functioning scale; fatigue, pain, dyspnea, and financial difficulties were associated with low scores on the physical functioning scale. ConclusionAssessing the physical functioning and emotional functioning scales of QOL questionnaire items at diagnosis can help clinicians predict the survival of patients with lung cancer.

Anaplastic lymphoma kinase fusion protein expression is associated with a favorable prognosis in resected invasive mucinous lung adenocarcinoma: A retrospective study from two Chinese tertiary hospitals.

Invasive mucinous adenocarcinoma (IMA) is a distinct variant of lung adenocarcinoma, which typically has a worse survival. However, its pathogenesis is potentially associated with a high degree of molecular heterogeneity, which might determine its different prognosis. We retrospectively analyzed 2207 consecutive lung adenocarcinoma patients who underwent radical resection at Qilu Hospital of Shandong University and Shandong Provincial Hospital from 2013 to 2019. Anaplastic lymphoma kinase (ALK) fusion protein expression was routinely detected by immunohistochemistry. The clinicopathological characteristics and treatment outcomes of IMA patients were retrieved, and compared between ALK-positive and ALK-negative IMA patients as well as between pure IMA and mixed IMA patients. The last follow-up was on December 31, 2020, and the median follow-up was 42 months. A total of 98 patients (4.4%) were diagnosed with IMA. ALK protein expression was positive in 24.5% of IMAs, which was significantly higher than that of non-IMA lung adenocarcinomas (4.7%, P < 0.001). ALK-positive and ALK-negative IMA, as well as pure IMA and mixed IMA, showed similar distribution in terms of patients' age, gender and smoking history, stage, and primary tumor location, except for a higher rate of lymph node metastasis in mixed IMA (22.0% vs. 46.2%, P = 0.012). Five cases (20.8%) of ALK-positive IMAs and 28 cases (40.6%) of ALK-negative IMAs experienced recurrence. Multivariable-adjusted Cox regression analysis demonstrated that ALK expression was a favorable prognostic factor for both disease-free survival (hazard ratio [HR]: 0.354; 95% confidence interval [CI]: 0.131-0.960; P = 0.041) and overall survival (HR: 0.138; 95% CI: 0.029-0.658; P = 0.013) in resected IMA. No difference in disease-free survival (HR: 0.524; 95% CI: 0.237-1.157; P = 0.110) and OS (HR: 0.553; 95% CI: 0.199-1.537; P = 0.256) was observed between pure IMA and mixed IMA. Invasive mucinous lung adenocarcinoma showed higher ALK protein expression, which was a favorable prognostic factor for survival in early resected patients.

Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early-stage large-cell neuroendocrine carcinoma.

BackgroundWe investigated whether adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers affected survival of patients with the early stage of large‐cell neuroendocrine cancer.MethodsThis was a retrospective multicenter study including consecutive patients undergoing resection of node negative large‐cell neuroendocrine carcinoma. Five‐year survival and disease‐free survival rate were evaluated by the Kaplan–Meier method and the log‐rank test in relation to adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers (synaptophysin, chromogranin A, and neuron‐specific enolase).ResultsOur study population included 117 patients; 47 (40%) of these received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy had better survival (74% vs. 45%, p = 0.002) and disease‐free survival (79% vs. 40%, p = 0.001) in all cases except patients with tumor <20 mm (79.5% vs. 57.4%, p = 0.43). Lobectomy compared to sublobar resection was associated with better survival (67% vs. 0.1%, p < 0.0001) and disease‐free survival (65% vs. 0.1%, p < 0.0001) also in patients with tumor <20 mm (79% vs. 28%, p = 0.001). Patients with triple‐positive neuroendocrine markers had better survival (79% vs. 35%, p = 0.0001) and disease‐free survival (69% vs. 42%, p = 0.0008). Regression analysis showed that tumor size <20 mm, lobectomy, adjuvant chemotherapy, and triple‐positive immunistochemical neuroendocrine markers were significant favorable prognostic factors for survival outcomes.ConclusionsLobectomy seems to be the management of choice in patients with large‐cell neuroendocrine cancer <20 mm while adjuvant chemotherapy should be administered only in patients with tumor >20 mm.

Outcomes with Early Response to First Line Treatment in Patients with Newly Diagnosed Multiple Myeloma

IntroductionOne of the most important prognostic factor associated with improved survival in patients with newly diagnosed multiple myeloma (NDMM) is quality of response to first line treatment, especially attainment of complete response (CR) or very good partial response (VGPR). Studies prior to routine use of novel agents had suggested an inferior outcome associated with very rapid response. We designed the current study to evaluate the prognostic impact to the kinetics of response in newly diagnosed myeloma.MethodsData from 2,707 consecutive patients with NDMM seen at Mayo Clinic, within 90 days of diagnosis, between 2004 and 2015, was analyzed retrospectively. Of these, 381 (14.1%) patients were lost to follow-up. The data for response assessment was available for 1,086 patients after 2 cycles, 1,207 patients after 4 cycles and 1,636 patients overall. The progression free survival (PFS) was calculated from the date of start of first line therapy till progression or death from any cause or the date of last follow up. The overall survival (OS) was calculated from the date of start of first line therapy till death from any cause or the date of last follow up. The survival curves were generated using Kaplan-Meier method and their differences were estimated using log rank test.ResultsPatients with ≥ VGPR [292 (26.9%) after 2 cycles, 497 (41.2%) after 4 cycles and 983 (60%) overall best response] were compared with those who achieved < VGPR [794 (73.1%) after 2 cycles, 710 (58.8%) after 4 cycles and 653 (40%) overall best response].The comparison of the patients with ≥ VGPR and < VGPR after 2 cycles is provided in Table 1, along with baseline characteristics and details of first line treatment. Overall, early responders (≥ VGPR by 2 cycles) appear to have higher rate of light chain only disease and high risk cytogenetics, especially t(4;14).The median follow-up for the entire cohort was 68.2 months (95% CI; 65.3, 70.7) from the start of first line treatment. The PFS as well as OS were not significantly different among patients who achieved ≥ VGPR and < VGPR after 2 cycles (Figure 1A and 2A, respectively) and after 4 cycles (Figure 1B and 2B, respectively), though both are significantly improved among those who achieved VGPR or better as the overall best response to first line treatment (Figure 1C and 2C, respectively).ConclusionThe quality of response with attainment of CR / VGPR and the kinetics of response with increasing depth of response over time is an important favorable prognostic factor for survival in patients with NDMM. Patients with high risk disease appear to achieve early response (≥ VGPR by 2 cycles). A rapid achievement of a deep response does not affect long term outcomes. [Display omitted] DisclosuresSidana:Janssen: Honoraria. Kapoor:Takeda, Celgene and Amgen: Research Funding. Dispenzieri:Celgene, Millenium, Pfizer, Janssen: Research Funding. Gertz:Millennium: Consultancy, Honoraria; Celgene, Novartis, Smith-Kline, Prothena, Ionis, Amgen: Honoraria. Dingli:Karyopharm Therapeutics: Research Funding; Millenium: Consultancy; Alexion Pharmaceuticals: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Russell:Imanis Life Sciences: Equity Ownership; Vyriad: Equity Ownership. Kumar:Celgene, Millennium, BMS, Onyx, Janssen, Noxxon, AbbVie, Amgen, Merck, Oncopeptides, Skyline Diagnostics, Takeda: Consultancy; Skyline: Honoraria; Celgene, Millennium/Takeda, Onyx, AbbVie, Janssen, Sanofi, Novartis, Amgen, Genentech, Merck, Oncopeptides, Roche, Skyline Diagnostics: Research Funding.

Analysis of prognostic factors and survival of Thoracic solitary fibrous tumors: a SEER population-based study

Background: Thoracic solitary fibrous tumors (TSFT) are a rare disease. We aim to determine the prognostic factors related to survival of TSFT patients through the use of The Surveillance, Epidemiology, and End Results database to analyze demographic and clinical characteristics. This study is intended to determine the prognostic factors associated with TSFT and has clinical value. Patients and Methods: This is a retrospective study of patients who were diagnosed with TSFT in the SEER database from 2001 to 2015. The kaplan-Meier method and Cox regression analysis were used to identify prognostic factors for patient survival. Results: From the SEER database (2001-2015), 227 patients with TSFT were detected. The 5-year survival rate was 82.7%, and the 10-year survival rate was 62.4%. Surgical resection [HR 0.314, 95% CI 0.201-0.491, P <0.001] was just an independent factor in the improvement of patient prognosis. Conclusion: The results of this study indicate that the prognostic factors for TSFT patients are age, grade, surgery, and chemotherapy. Age <65 years old, well-differentiated, surgery instead of chemotherapy is a favorable prognostic factor for survival of TSFT patients.

Risk factors and survival outcomes of laryngeal squamous cell carcinoma patients with lung metastasis: A population-based study

ObjectiveIt remains elusive which factors may influence the morbidity and mortality of lung metastasis (LM) in Laryngeal Squamous Cell Carcinoma (LSCC) patients. The aim of the present study was to investigate factors influencing LM and the survival outcomes of LSCC patients with LM. MethodsWe identified 10,935 patients with LSCC from 2010 to 2014 using the Surveillance, Epidemiology and End Results database. Multivariate logistic regression analysis was used to determine the factors associated with the presence of LM. Multivariate cox regression analysis was used to identify covariates associated with increased all-cause mortality in patients with LM. ResultsAmong 10,935 patients with LSCC, 232 (2.12%) patients had LM. The median survival time of patients with LM was 8 months, and 8.37% of patients survived after 3 years. Patients with age ≥ 60 years old, unmarried status, supraglottis, overlapping lesion of larynx, subglottis, pathological grade III, T4 stage, N1 stage, N2 stage, N3 stage and bone, brain or liver metastases were more likely to have LM. Survival analysis showed that chemotherapy and radiotherapy suggested better survival of LSCC patients with LM while pathological grade IV was associated with an increased all-cause mortality. ConclusionThe incidence of LSCC patients with LM varied by age, married status, and tumor subtypes. LSCC patients with LM had poor survival, and only 8.37% of patients survived after 3 years. However, chemotherapy and radiotherapy were found as independent favorable prognostic factors for survival.

Effect of Handgrip Strength on Clinical Outcomes of Patients with Hepatocellular Carcinoma Treated with Lenvatinib

Previous studies have reported prognostic factors for hepatocellular carcinoma (HCC) patients receiving lenvatinib; however, no studies have evaluated the effects of both handgrip strength and skeletal muscle mass on the clinical outcomes. Therefore, this retrospective study investigated the individual effect of handgrip strength, skeletal muscle mass, and sarcopenia on clinical outcomes of 53 HCC patients treated with lenvatinib. Before receiving lenvatinib, handgrip strength and skeletal muscle index (SMI) were measured. Low handgrip strength and muscle depletion were defined as &lt;26 and &lt;18 kg and SMI &lt;42 and SMI &lt;38 cm2/m2 in men and women, respectively. Sarcopenia was defined as having low handgrip strength and muscle depletion. Multivariate analysis identified modified albumin–bilirubin grade 1–2a (p = 0.010), Barcelona Clinic Liver Cancer stage A–B (p = 0.011), and absence of low handgrip strength (p = 0.015) as favorable prognostic factors for survival. Furthermore, sarcopenia was an independent significant prognostic factor for survival. Time to treatment failure was associated with handgrip strength and sarcopenia. Our findings suggest that handgrip strength may be a useful marker of clinical outcomes in HCC patients treated with lenvatinib.

Hypo- and hyperthyroidism and survival of ovarian cancer patients

Background. The non-genomic effects of thyroid hormones, mediated through exposure to the membrane receptor CD51/CD61, are expressed in the activation of atypical cell proliferation, stimulation of tumor angiogenesis and cell migration. In connection with these cellular effects, the thyroid status of cancer patients can have prognostic value. The aim of study: to assess the effect of thyroid status on disease-free survival of patients with stage III ovarian cancer (OC). Materials and methods . Prospective trial with eligibility criteria for the inclusion and exclusion of participants was conducted. The study included 128 patients with stage III OC aged 45 to 70 years. All patients before treatment was determined thyroid status by examining the serum levels of thyroid hormones and performing an ultrasound examination of the thyroid gland. All patients received a comprehensive treatment of OC, including surgery and chemotherapy, and have complete remission following after treatment. After confirming the recurrence of the disease and/or death of the patient, the duration of the disease-free survival was determined. Results. Medians disease-free survival were 13.5 months, 17.8 months and 11.1 months for the euthyroid, hypothyroid and hyperthyroid groups, respectively, while significant differences in the medians disease-free survival occurred between the euthyroid and hypothyroid groups (p = 0.0206) and between the hypo- and hyperthyroid groups (p = 0.0156). Conclusions. Patients with hypothyroidism before the treatment of advanced OC have better disease-free survival. Thyroid status is independent favorable prognostic factor for survival in OC.

Programmed cell death-ligand 1 expression in stromal immune cells is a marker of breast cancer outcome.

Purpose: The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in antitumor immune responses. However, there is considerable inconsistency regarding the prognostic value of PD-L1 expression status in breast cancer. We sought to evaluate the differential prognostic impacts of tumoral versus stromal immune cell PD-L1 expression in primary breast cancer.Materials & Methods: Both tumoral and stromal immune PD-L1 expression in formalin-fixed, paraffin-embedded tumor samples from 233 breast cancer patients without initial stage IV metastases were evaluated by immunohistochemistry using a mouse monoclonal anti-PDL1 antibody. Clinicopathological variables were also documented. A Cox regression model was used to assess the association of tumoral/stromal immune PD-L1 expression with clinical outcome using disease-free survival (DFS) as the primary end point.Results: Both tumoral and stromal immune PD-L1 expression were associated with aggressive tumor characteristics, including higher histologic grade, as well as negative estrogen receptor, negative progesterone receptor, and positive human epithelial growth factor receptor 2 (HER2) status Multivariate analyses further demonstrated that stromal immune cell, but not tumoral, PD-L1 expression was a favorable prognostic factor for survival.Conclusions: Despite its association with aggressive tumor features, PD-L1 expression on stromal immune cells emerged as a positive prognostic biomarker in breast cancer. This pro-survival effect might reflect the presence of a strong antitumor immune response that leads to PD-L1 expression.

The incidence, risk factors, and survival of acute myeloid leukemia secondary to myelodysplastic syndrome: A population-based study.

To determine the incidence, risk factors, and relative survival of acute myeloid leukemia (AML) secondary to myelodysplastic syndrome (MDS) in the Surveillance, Epidemiology, and End Results (SEER) database. Retrospective analysis of all patients with new MDS onset in the SEER‐18 database from 2001 to 2013. We identified 36 558 patients with primary MDS. The rate of secondary AML (sAML) was 3.7% among patients 40 years or younger and 2.5% among those older than 40 (P = .039). The median transformation interval was significantly shorter for the younger group (4.04 vs 13.1 mo; P < .001). For both age groups, median overall and cancer‐specific survival were significantly longer for patients who did not develop sAML. Although the younger patients survived longer than the older patients, sAML development had a more negative effect on the survival of younger patients. Female sex, age, and World Health Organization (WHO) type MDS with single lineage dysplasia (MDS‐SLD) were associated with a decreased risk of sAML for older but not younger patients. Among older patients with MDS, a married status, Black race, female sex, shorter time to sAML, and WHO type MDS‐SLD or MDS with ringed sideroblasts were favorable prognostic factors for survival. In the SEER database, the rate of sAML among patients with MDS is lower than that in previous reports, but these patients still have worse survival. Risk assessment should include clinical and demographic factors.

Prognostic factors in patients with glioblastoma multiforme: focus on the pathologic variants.

The aim of this study was to offer predicting factors for survival in adult patients with glioblastoma multiforme. 153 consecutive patients with high-grade glioma (WHO grade IV) were studied in Imam Reza hospital, Kermanshah University of Medical Science, Kermanshah, Iran, between April 2003 and April 2017. All patients treated with surgical resection and standard postoperative radiotherapy (54Gy). Using the patients' charts and electronic medical records system, the following data were obtained: gender, age, Karnofsky performance status (KPS) score on admission, primary vs. secondary type, extent of surgery, tumor location, tumor size, necrosis size, use of Temozolomide (TMZ), pathology subtype, and immunohistochemistry results. Patients were followed from the time of the surgery until the death occurred. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Survival time curves for various subgroups were compared by the log-rank test. The impact of the suggested prognostic factors on survival was evaluated by univariate and multivariate analyses. Age, gender, KPS, extent of surgery, tumor location, necrosis size, and reoperation in recurrence had not any statistically significant effect on survival. Univariate analysis revealed a significant impact on outcome for pathology subtype (PFS: P < 0.001, OS: P < 0.001), tumor type (primary vs. secondary) (PFS: P = P < 0.001, OS: P < 0.001), tumor size (PFS: P = 0.044, OS: P = 0.04), TMZ therapy (PFS: P < 0.001, OS: P < 0.001), P53 (PFS: P < 0.001, OS: P < 0.001), and Ki67 (PFS: P < 0.001, OS: P < 0.001). In multivariate analysis, independent favorable prognostic factors for survival were pathology subtype (PFS: P < 0.001, OS: P < 0.001), type (PFS: P < 0.001, OS: 0.012), TMZ (PFS: P < 0.001, OS: P < 0.001), P53 (PFS: P < 0.001, OS: P < 0.001), and Ki67 (PFS: P < 0.001, OS: P < 0.001). The results suggest that pathology subtype, primary vs. secondary type, TMZ therapy, P53, and Ki 63 may play an important role in the survival of patients with glioblastoma multiforme. There is no relationship detected between age, gender, KPS, tumor size and location, necrosis size, extent of surgery, reoperation in recurrence, and patient survival.

Effect of body composition on survival benefit of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: A comparison with sorafenib therapy.

AimSorafenib is used as a first-line treatment for advanced hepatocellular carcinoma (HCC). However, hepatic arterial infusion chemotherapy (HAIC) has also gained acceptance, but only in Japan. We explored the role of body composition as a factor affecting the survival benefit of HAIC compared to sorafenib for the treatment of advanced HCC.MethodsWe conducted a retrospective study using the clinical records of 133 patients with advanced HCC treated either with HAIC or sorafenib. Prior to treatment induction, skeletal muscle index and visceral fat area (VFA) were measured at the third lumbar vertebral and umbilical levels, respectively, using computed tomography. Muscle depletion and high-VFA (H-VFA) were defined using published cut-offs. We analyzed clinical parameters, including body composition as prognostic factors.ResultsIn the HAIC group, multivariate analysis identified a positive response to HAIC (hazard ratio [HR], 0.438; p = 0.022), and conversion from HAIC to sorafenib (HR, 0.374; p = 0.008) as favorable prognostic factors for survival. In contrast, tumor number < 7 (HR, 0.475; p = 0.008), absence of extra-hepatic spread (HR, 0.511; p = 0.015), absence of muscle depletion (HR, 0.555; p = 0.044), and H-VFA (HR, 0.483; p = 0.015) were studied in the sorafenib group.ConclusionsBody composition was identified as a prognostic factor for patient survival after treatment with sorafenib, but not for HAIC, and may be used as a biomarker when selecting between HAIC or sorafenib treatment of patients with advanced HCC. Additionally, conversion to sorafenib in patients receiving HAIC could improve survival regardless of response status.

Hepatitis B Virus Infection is a Prognostic Biomarker for Better Survival in Operable Esophageal Cancer: Analysis of 2,004 Patients from an Endemic Area in China.

Hepatitis B Virus (HBV) infection has been proven to be associated with the survival of many cancers. However, the prevalence and prognostic value of HBV infection in esophageal cancer has not been investigated yet. A total of 2,004 consecutive esophageal cancer patients who underwent esophagectomy between 2000 and 2008 were recruited in our study. ELISA was used to test serum HBV markers. Patients were divided into HBsAg-positive group (HBV infection) and HBsAg-negative group. The impact of HBV infection on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. HBV infection was found in 12.6% (253/2,004) of patients. HBsAg-positive patients had significantly higher percentage of early pathologic T stage, lower frequency of liver metastasis, and extrahepatic metastasis than HBsAg-negative. HBsAg-positive patients had a favorable DFS [HR = 0.79; 95% confidence interval (CI): 0.66-0.94, P = 0.007) and OS (HR = 0.80; 95% CI: 0.65-0.95, P = 0.020] respectively, when compared with HBsAg-negative patients. Subgroup analysis showed that the association with HBV infection and better DFS and OS was observed in patients with esophageal squamous cell carcinoma and advanced pathologic stage (III-IV).Conclusion: HBV infection was an independent favorable prognostic factor for survival in operable esophageal cancer. Our large cohort study provided more definite and quantitative evidence that HBV infection is an independent favorable prognostic biomarker in patients with esophageal cancer, especially in patients with esophageal squamous cell carcinoma and advanced pathologic stage (III-IV).

P3.13-10 Factors Associated with Long-Term Survival of Stage IV NSCLC Patients on First-Line EGFR-Targeting Therapy

To determine factors associated with long term survival in Stage IV, non-small cell lung cancer (NSCLC) patients receiving EGFR-targeting agents (EGFR-TA) as systemic anti-cancer treatment in the first-line setting at a Canadian tertiary cancer centre. Retrospective analysis was conducted on patients diagnosed with Stage IV (AJCC 7th edition) NSCLC between 1999 and 2014, and receiving EGFR-TA as first-line treatment. Demographic, clinical, histopathological, treatment and outcome data was extracted from the large, population-based institutional Glans-Look Lung Cancer Database. Long-term survivors (LTS) were defined as those surviving ≥ 18 months post EGFR-TA initiation. Correlates of survival were investigated via univariate analysis, Kaplan-Meier analysis using the log-rank test, and multivariate Cox regression. We identified 117 eligible patients. Median age was 65 (IQR 54.5-74) years, 61% female, 91% adenocarcinoma, 60% never smoking history, and 80% were identified as EGFR-mutant (remainder were untested and accessed EGFR-TA before routine testing was performed). Most common ethnicity (by place of birth) was North American (47%), followed by Asian (37%). 21% survived ≥ 18 months post-EGFR-TA initiation, with a median overall survival (mOS) of 46 vs. 13 months in those surviving < 18 months post-EGFR-TA initiation (p <0.001). LTS were more likely to be over the age of 65 years at diagnosis (76% vs. 46%, p=0.012), receive palliative radiation therapy (72% vs. 27%, p<0.001), and possess Asian ethnicity (60% vs. 30%, p=0.044), although impact of age and radiation therapy did not retain prognostic significance in multivariate analysis after controlling for other measured confounders; Asian ethnicity was retained as a favorable prognostic factor for survival [HR: 0.5, 95%CI 0.3-0.8, p=0.005)]. Patients with Asian ethnicity revealed no significant demographic or clinical characteristics (notably gender, smoking status and EGFR mutation type) between LTS and non-LTS, with the exception of age. Asian LTS were significantly more likely to be ≥ 65 years of age at diagnosis (87% vs. 32%, p<0.001), a factor which retained significance as a favorable prognostic factor in multivariate analysis [HR: 0.3, 95% CI 0.2-0.7), p=0.004)]. Analysis of this population-based cohort identifies Asian ethnicity, and within this ethnic group, older age at diagnosis, as favorable prognostic factors for patients with Stage IV, NSCLC accessing EGFR-TA in the first-line setting. These findings help identify patients who derive the most benefit from EGFR-TA, and suggest that older, Asian patients represent a unique sub-population within metastatic NSCLC, who may possess different biological underpinnings of NSCLC, outside of a propensity to harbor EGFR mutations.

Hyperdiploidy is a Positive Prognostic Factor for Progression-Free Survival in Multiple Myeloma with High and Intermediate Risk Cytogenetics

Background: Risk stratification in Multiple Myeloma is typically done based on a set of chromosomal abnormalities including translocations and deletions and karyotype abnormalities such as hypodiploidy and hyperdiploidy. Hyperdiploidy has been considered a favorable prognostic factor for survival of Multiple Myeloma patients. Methods: We analyzed data from 48 Multiple Myeloma cases at the King Fahad specialist hospital in Saudi Arabia and detected an array of endpoints including riskassociated cytogenetic endpoints. We analyzed data from 48 Multiple Myeloma cases at the King Fahad specialist hospital in Saudi Arabia and detected an array of endpoints including risk-associated cytogenetic endpoints. We sought to test if and how hyperdiploidy affects the survival outcomes of 14 multiple myeloma patients classified as high or intermediate risk based on cytogenetic abnormalities. Results: Kaplan-Meier survival analysis with a Cox proportional hazards regression model showed that progression-free survival (PFS) of Multiple Myeloma patients was higher (hazard ratio 1.9) in those with hyperdiploidy compared to non- hyperdiploidy group. Overall survival in our study appeared to be unaffected (hazard ratio 1.0) by hyperdiploidy. Survival percentage for hyperdiploidy cases was >50% at the median time point. Conclusion: Our data indicates that hyperdiploidy is a favorable prognostic factor for progression-free survival in Multiple Myeloma. Further studies are warranted to investigate hyperdiploidy subtypes and cytogenetic parameters which may be of value in risk stratification and prognosis of Multiple Myeloma cases.

Lymphocytic infiltration as a prognostic factor in papillary thyroid carcinoma

Introduction/Objective. We examine the prognostic significance and association between lymphocytic infiltration and papillary thyroid carcinoma. This manuscript aims to establish whether the presence of lymphocytic infiltration in the classical type of papillary thyroid carcinoma is a favorable prognostic factor for survival. Methods. This is a retrospective study of patients treated for papillary thyroid carcinoma at the Clinical Centre of Montenegro over a period of seven years (2010?2017). A total of 105 patients aged 12 to 84 years were included in the study, of which 74% showed concomitant histological evidence of lymphocytic infiltration. The patients were divided into two groups ? one with lymphocytic infiltration and the other without it. Anti-CD3 and anti-CD20 antibodies were used to identify T and B lymphocytes. The prognostic outcome was assessed using the Kaplan?Meier survival plots. Results. The cohort with lymphocytic infiltration revealed a lower frequency of extrathyroidal invasion (p &lt; 0.0001), nodal metastases (p &lt; 0.0001), and the absence of distant metastases, compared with those without lymphocytic infiltration. Chronic lymphocytic thyroiditis is a favorable prognostic factor for survival in our examined group (p &lt; 0.0001). Conclusion. The present study shows that immune reaction involving lymphocytic infiltration plays a role in extrathyroidal tumor growth and development of nodal and distant metastases in patients with papillary thyroid cancer. The presence of lymphocytic infiltration is a favorable factor for survival in the classical form of papillary thyroid carcinoma.

Molecular detection of minimal residual disease in multiple myeloma.

Despite the significantly higher complete remission rates and improved survival achieved in the last decade, multiple myeloma (MM) patients continue to relapse due to persistence of minimal residual disease (MRD). Generally, MRD refers to persistence of low levels of disease in the order of one tumour cell in ≥105 normal cells. Currently, molecular and immunophenotypic techniques are employed for MRD detection. This review focuses on MRD detection by molecular techniques, including allele-specific oligonucleotide polymerase chain reaction (ASO-PCR), next-generation sequencing (NGS) and digital PCR (dPCR), in addition to a brief description of, and comparison with, multiparameter flow cytometry. The basic principles, technical advantages and limitations, and the clinical impact of all three molecular techniques are reviewed and compared. They all have a sensitivity of at least 10-5 , among which ASO real-time quantitative PCR is the most well-standardized, and NGS carries the highest sensitivity and applicability, while dPCR is still under investigation. Furthermore, molecular MRD negativity is a favourable prognostic factor for survival of patients with MM. However, several challenges inherent to molecular detection of MRD still remain to be overcome, particularly false negativity and failure to detect extramedullary disease. Finally, detection of MRD from peripheral blood remains challenging.

Chitinase 3-like 1 secreted by peritumoral macrophages in esophageal squamous cell carcinoma is a favorable prognostic factor for survival.

AIMTo identify whether chitinase 3-like 1 (CHI3L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma (ESCC) and to analyze this protein’s cellular source.METHODSAn ELISA was conducted to detect the concentration of CHI3L1 in the serum of 150 ESCC patients diagnosed between January 2001 and February 2005. The prognostic relevance of CHI3L1 was evaluated by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was reanalyzed, and fluorescent staining was utilized to explore the cellular origins of CHI3L1. We stimulated monocyte-derived macrophages (MDMs) with either IL-6 or the supernatant of the ESCC cell line Eca-109 and later investigated the level of CHI3L1 by qPCR and ELISA.RESULTSThe level of serum CHI3L1 was higher in older patients (≥ 60) than in patients under the age of 60 (P = 0.001). The patients with higher levels of CHI3L1 had a significantly shorter overall survival, whereas the traditional markers, carcinoembryonic antigen and squamous cell carcinoma antigen, were less effective (P > 0.05). A multivariate Cox analysis (P = 0.001) indicated that CHI3L1 was an independent prognostic factor for ESCC patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3L1. Interleukin-6 (IL-6) and the supernatant of Eca-109 containing IL-6 stimulated MDMs to secrete CHI3L1. The serum concentration of CHI3L1 in the ESCC patients showed a weak correlation with the laboratory inflammatory parameters neutrophil (NEU, P = 0.045), neutrophil/lymphocyte rate (NLR, P = 0.016), and C-reactive protein (CRP, P < 0.001).CONCLUSIONOur study first established a connection between the pretreated CHI3L1 and patients with ESCC, and the serum CHI3L1 was primarily secreted by ESCC-surrounded macrophages.

Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia.

Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y ) was 39±4% for the whole group and 43±4% for the 190 patients given re-induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) ± anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens. Late relapse ≥1year from diagnosis, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS5y was 61±5%. Four of 19 children (21%) survived without receiving SCT as part of relapse therapy. Our data show that intensive re-induction followed by SCT can give cure rates of 40% in children with relapsed AML.