Serum YKL-40 Predicts Relapse-Free and Overall Survival in Patients With American Joint Committee on Cancer Stage I and II Melanoma

PurposeTo evaluate the novel tumor biomarker YKL-40 in serial serum samples from patients with American Joint Committee on Cancer (AJCC) stage I and II melanoma from the time of diagnosis and during routine follow-up. Macrophages, neutrophils, and cancer cells secrete YKL-40, and a high serum level has been associated with poor prognosis in patients with several cancer types.Patients and MethodsSerum samples from 234 patients with stage I (n = 162) and II (n = 72) melanoma were analyzed for YKL-40 by enzyme-linked immunosorbent assay. Serial samples were obtained before definitive primary surgery and during follow-up.ResultsAfter a median follow-up period of 66 months (range, 1 to 97 months), 41 relapses (18%) and 39 deaths (17%) were observed. Serum YKL-40 treated as an updated continuous covariate were analyzed together with the covariates sex, age, primary tumor site, ulceration, thickness, Clark level and histologic subtype in a Cox proportional hazard model. Serum YKL-40 was an independent prognostic factor of relapse-free survival (hazard ratio [HR], 1.6; 95% CI, 1.1 to 2.5; P = .03) and overall survival (HR, 1.8; 95% CI, 1.2 to 2.6; P = .002) together with thickness and ulceration. The serum level of YKL-40 (dichotomized as normal or elevated) at the time of diagnosis was also an independent prognostic factor for overall survival (HR, 3.6, 95% CI, 1.7 to 7.7; P = .001).ConclusionSerum YKL-40 may be an early biomarker of relapse and survival in patients with AJCC stage I and II melanoma. Serum YKL-40 may also be useful for patient stratification and follow-up in clinical trials. Our results need confirmation in an independent study.

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Plasma Epstein-Barr Viral Deoxyribonucleic Acid Quantitation Complements Tumor-Node-Metastasis Staging Prognostication in Nasopharyngeal Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.7982 ◽

2006 ◽

Vol 24 (34) ◽

pp. 5414-5418 ◽

Cited By ~ 218

Author(s):

Sing-fai Leung ◽

Benny Zee ◽

Brigette B. Ma ◽

Edwin P. Hui ◽

Frankie Mo ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Nasopharyngeal Carcinoma ◽

Early Stage ◽

Independent Prognostic Factor ◽

Stage I ◽

Early Stage Disease ◽

Stage Disease ◽

Ebv Dna ◽

Epstein Barr

Purpose To evaluate the effect of combining circulating Epstein-Barr viral (EBV) DNA load data with TNM staging data in pretherapy prognostication of nasopharyngeal carcinoma (NPC). Patients and Methods Three hundred seventy-six patients with all stages of NPC were studied. Pretreatment plasma/serum EBV DNA concentrations were quantified by a polymerase chain reaction assay. Determinants of overall survival were assessed by multivariate analysis. Survival probabilities of patient groups, segregated by clinical stage (I, II, III, or IV) alone and also according to EBV DNA load (low or high), were compared. Results Pretherapy circulating EBV DNA load is an independent prognostic factor for overall survival in NPC. Patients with early-stage disease were segregated by EBV DNA levels into a poor-risk subgroup with survival similar to that of stage III disease and a good-risk subgroup with survival similar to stage I disease. Conclusion Pretherapy circulating EBV DNA load is an independent prognostic factor to International Union Against Cancer (UICC) staging in NPC. Combined interpretation of EBV DNA data with UICC staging data leads to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease. Validation studies are awaited.

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Muscle impairment during follow-up as an independent prognostic factor for poor overall survival in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16726 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16726-e16726

Author(s):

Aurélien Lambert ◽

Julia Salleron ◽

Céline Gavoille ◽

Auréline Viard ◽

Ahmet Ayav ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Prognostic Factor ◽

Univariate Analysis ◽

Independent Prognostic Factor ◽

Poor Overall Survival ◽

Risk Of Death ◽

Surgery Group ◽

Muscle Impairment

e16726 Background: We aimed to assess that muscle impairment during follow-up is as an independent prognostic factor for poor overall survival in pancreatic cancer (PC) and is more accurate than a single muscle mass evaluation. Methods: Data from all patients with pancreatic adenocarcinoma at our center from 2009 to 2015 were retrieved (N = 114). A retrospective review of the total psoas area (TPA) was performed using manual segmentation on a single cross-sectional image through the third lumbar vertebrae for each available scan (N = 713, median number of scans per patient was 6 [3; 8]). For each patient, when at least two CT scans were available, the decrease in the TPA from baseline (Muscle Impairment) was expressed by a percentage. Results: In the univariate analysis, a TPA level under 420 mm2/m2 during the follow-up, with a HR = 3.419 ([2.168; 5.394]; 95% CI; p < 0.0001) and a TPA decrease of more than 20% from the baseline with a HR = 7.169 ([4.526; 11.353]; 95% CI; p < 0.0001) were prognostic factors for death. The multivariate analysis confirmed the results with a HR = 5.799 ([3.418; 9.839]; 95% CI; p < 0.0001) in the non-surgery group and a HR = 8.089 ([2.157; 30.339]; 95% CI; p = 0.0019) in the surgery group for a decrease in the TPA of more than 20% from the baseline. Conclusions: Muscle impairment during follow-up is a strong and independent prognostic factor for poor overall survival in patients with PC. It is in favor of a higher risk of death.

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Macrophage Markers in Serum and Tumor Have Prognostic Impact in American Joint Committee on Cancer Stage I/II Melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.9919 ◽

2009 ◽

Vol 27 (20) ◽

pp. 3330-3337 ◽

Cited By ~ 177

Author(s):

Trine O. Jensen ◽

Henrik Schmidt ◽

Holger Jon Møller ◽

Morten Høyer ◽

Maciej Bogdan Maniecki ◽

...

Keyword(s):

Overall Survival ◽

Tumor Stroma ◽

Cox Proportional Hazards Model ◽

Stage I ◽

Macrophage Infiltration ◽

Enzyme Linked Immunosorbent Assay ◽

Prognostic Impact ◽

Invasive Front ◽

Ajcc Stage ◽

American Joint Committee

Purpose To evaluate the prognostic role of soluble CD163 (sCD163) in serum and macrophage infiltration in primary melanomas from patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma. The scavenger receptor CD163 is associated with anti-inflammatory macrophages, and it is shed from their surface. Patients and Methods Serum samples from 227 patients with stage I/II melanoma obtained before definitive surgery (baseline) and during 5 years of follow-up were analyzed for sCD163 by enzyme-linked immunosorbent assay. Excised formalin-fixed, paraffin-embedded primary melanomas from 190 patients were available for immunohistochemical analyzes of CD163+ and CD68+ macrophage infiltration. They were estimated semiquantitatively in three different tumor compartments: tumor nests, tumor stroma, and at the invasive front of the tumor. Results Serum sCD163 treated as an updated continuous covariate as well as the baseline value were analyzed together with the covariate's ulceration and thickness in a Cox proportional hazards model. sCD163 was an independent prognostic factor for overall survival (baseline, hazard ratio [HR] = 1.4; 95% CI, 1.1 to 1.7; P = .01; and updated, HR = 1.4; 95% CI, 1.1 to 1.8; P = .003). Melanomas with dense CD163+ macrophage infiltration in tumor stroma and CD68+ macrophage infiltration at the invasive front were associated with poor overall survival (CD163, HR = 2.7; 95% CI, 0.8 to 9.3; P = .11; and CD68, HR = 2.8; 95% CI, 1.2 to 6.8; P = .02) independent (borderline for CD163) of thickness and ulceration. Conclusion Both serum levels of sCD163 and the presence of CD68+ macrophage infiltration at the tumor invasive front are independent predictors of survival in AJCC stage I/II melanoma. CD163+ cell infiltration in tumor stroma may be predictive of survival.

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Circulating Proteasome Level Is an Independent Prognostic Factor for Survival in Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.1486.1486 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1486-1486

Author(s):

Christian Jakob ◽

Karl Egerer ◽

Eugen Feist ◽

Ivana Zavrski ◽

Jan Eucker ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Prognostic Factor ◽

Proportional Hazards ◽

Therapy Response ◽

Independent Prognostic Factor ◽

Stage I ◽

Enzyme Linked Immunosorbent Assay ◽

20S Proteasome ◽

Kaplan Meier

Abstract The proteasome is a nonlysosomal proteolytic complex which is essentially involved in intracellular degradation of ubiquitinated proteins. This process includes the turnover of proteins which are involved in cell cycle regulation and apoptosis. A constitutively increased proteasome activity has been found in multiple myeloma. Treatment with the proteasome inhibitor bortezomib resulted in induction of remission in a substantial portion of patients with relapsed or refractory multiple myeloma. The objective of the present study was to investigate the clinical significance of circulating levels of the 20S proteasome in patients with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM). To detect proteasome concentrations in peripheral blood samples, we developed a sandwich enzyme-linked immunosorbent assay (ELISA) using anti-20S proteasome antibodies. Serum proteasome levels were measured in 200 individuals, 85 normal donors and 115 patients with MGUS or multiple myeloma. Patients with multiple myeloma had significantly (P<0.001) higher serum proteasome values (median 624 ng/mL, range 108–5181) than healthy controls (209.9 ng/mL, range 68–392). The proteasome levels increased significantly (P<0.001) from Durie and Salmon stage I to stage III. Furthermore the proteasome concentrations were significantly elevated in MM versus MGUS (P=0.026) and in MM stages II/III versus stage I (P<0.001). In 55 patients with multiple myeloma in stages II and III, who received chemotherapy, there was a significant (P<0.001) decrease from pre- to post-treatment proteasome concentrations in those patients, who achieved a remission after chemotherapy, while no difference could be found in refractory patients (P=0.981). In a univariate Kaplan-Meier analysis myeloma patients in stages II and III with elevated circulating proteasome levels had a significantly (log-rank: P<0.001) shorter overall survival than patients with proteasome levels lower or equal to the median value. Furthermore, circulating proteasome concentration, b2-microglobulin (b 2-MG) and C-reactive protein (CRP) were included in a Cox’s proportional-hazards regression analysis. In the multivariate analysis, circulating proteasome concentration and b 2-MG were found to be powerful independent prognostic factors (hazard ratio 6.79 and 2.95, respectively). Our study shows that advanced disease stages in multiple myeloma are associated with increased circulating proteasome concentrations and that remission after chemotherapy is accompanied by a significant decrease. Furthermore we demonstrate for the first time, that the circulating proteasome concentration is an independent prognostic factor for overall survival. We conclude that assessment of the circulating proteasome could be a novel tool to monitor disease activity and to predict therapy response and survival in multiple myeloma.

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Survival outcomes of left-sided versus right-sided colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.502 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 502-502 ◽

Cited By ~ 1

Author(s):

Jasmine Lizette Gowarty ◽

Charis Durham ◽

Lucas Wong ◽

Wencong Chen

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Prognostic Factor ◽

Tumor Location ◽

Independent Prognostic Factor ◽

Cox Proportional Hazards Model ◽

Stage I ◽

Colon Cancers ◽

Time To Recurrence ◽

Significant Difference

502 Background: Right-sided colon cancers (RCC) are defined up to the splenic flexure where as left-sided colon cancers (LCC) involve the descending, sigmoid, and rectosigmoid regions. The landmark CALGB/SWOG 80405 study concluded that sidedness was an independent prognostic factor for survival in stage IV adenocarcinoma of the colon or rectum, with a poorer prognosis in RCC. This raises the question as to whether or not stage of malignancy plays a role. We performed a retrospective analysis on survival for stage I to IV colon cancer treated at our institution in order to assess if tumor location is an independent prognostic factor as described in previous studies. Methods: Primary site of cancer, sex, age at diagnosis, vital status, and year of diagnosis for stage I, II, III, and IV colon cancer was collected from our institution’s tumor registry from 2007 to 2017. The inclusion criteria included those diagnosed with stage I to IV colon cancer at 18 years of age and above. Exclusion criteria included a diagnosis of both RCC and LCC and patients under age 18. The median of overall survival and time to recurrence between LCC and RCC were compared using Wilcoxon Rank Sum Test with two-sided significance level at 0.05. Results: Time to overall survival and time to recurrence was shown to have no significant difference between RCC and LCC (p = 0.3398 and 0.9467, respectively). Cox proportional hazards model adjusted for age and sex also support the claim (p = 0.1725 and 0.0633). There was a statistically significant difference in age between the two groups with the older mean age seen in RCC (68 versus 62). The distribution of recurrence was statistically significant with a higher recurrence in RCC (p = 0.0105). Conclusions: Unlike CALGB/SWOG 80405, our analysis included the transverse colon as part of RCC and examined stage I to IV colon cancer to ultimately conclude that there was no significant difference in overall survival or time to recurrence. Our study suggests that tumor location is not an independent prognostic factor on survival for all stages of colon cancer. However, a higher suspicion for recurrence may be needed for those diagnosed with RCC. Future investigations involving molecular subtypes and mutations are needed to further clarify prognosis and tumor sidedness.

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Low value of whole-body dual-modality [18f]fluorodeoxyglucose positron emission tomography/computed tomography in primary staging of stage I–II nasopharyngeal carcinoma: a nest case-control study

European Radiology ◽

10.1007/s00330-020-07478-1 ◽

2021 ◽

Author(s):

Bei-Bei Xiao ◽

Qiu-Yan Chen ◽

Xue-Song Sun ◽

Ji-Bin Li ◽

Dong-hua Luo ◽

...

Keyword(s):

Overall Survival ◽

Lymph Node ◽

Lymph Nodes ◽

Stage I ◽

Relapse Free Survival ◽

Retropharyngeal Lymph Node ◽

Free Survival ◽

Pet Ct ◽

Pre Treatment

Abstract Objectives The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients.

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S-phase Fraction as an Independent Prognostic Factor in Invasive Breast Carcinoma -A Study of Long-term Follow-up

Journal of Breast Cancer ◽

10.4048/jbc.2007.10.1.36 ◽

2007 ◽

Vol 10 (1) ◽

pp. 36

Author(s):

Jin Hae Bae ◽

Jeong Won Bae ◽

Sang Uk Woo ◽

Chul Whan Kim ◽

Jae Bok Lee ◽

...

Keyword(s):

Prognostic Factor ◽

Breast Carcinoma ◽

S Phase ◽

Independent Prognostic Factor ◽

Invasive Breast Carcinoma ◽

Phase Fraction ◽

Long Term Follow Up

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Prognostic Significance of Molecular Upstaging of Paraffin-Embedded Sentinel Lymph Nodes in Melanoma Patients

Journal of Clinical Oncology ◽

10.1200/jco.2004.12.009 ◽

2004 ◽

Vol 22 (13) ◽

pp. 2671-2680 ◽

Cited By ~ 109

Author(s):

Hiroya Takeuchi ◽

Donald L. Morton ◽

Christine Kuo ◽

Roderick R. Turner ◽

David Elashoff ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Lymph Nodes ◽

Risk Ratio ◽

Disease Recurrence ◽

Sentinel Lymph Nodes ◽

Independent Prognostic Factor ◽

Number Of Patients ◽

Significant Independent Prognostic Factor ◽

Melanoma Patients

PurposeDetection of micrometastases in sentinel lymph nodes (SLNs) is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative SLNs subsequently develop recurrent disease. We hypothesized that a quantitative realtime reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded (PE) SLNs to upstage and predict disease outcome.Patients and MethodsqRT was performed on retrospectively collected PE SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least 8 years. PE SLNs (n = 308) from these patients were sectioned and assessed by qRT for mRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family), GalNAc-T (β1→4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3).ResultsFifty-three (25%) patients had histopathology-positive SLNs by hemotoxylin and eosin and/or immunohistochemistry. Of the 162 patients with histopathology-negative SLNs, 48 (30%) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by a Cox proportional hazards model analysis (P < .0001; risk ratio, 7.48; 95% CI, 3.70 to 15.15). The presence of ≥ one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P = .0002; risk ratio, 11.42; 95% CI, 3.17 to 41.1).ConclusionMolecular upstaging of PE histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early-stage melanoma.

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