Significance of Co-expression of Epidermal Growth Factor Receptor and Ki67 on Clinical Outcome in Patients With Anal Cancer Treated With Chemoradiotherapy: An Analysis of NRG Oncology RTOG 9811

Doll, Corinne; Moughan, Jennifer; Klimowicz, Alexander C.; Ho, Clement; Kornaga, Elizabeth; Lees‐Miller, Susan P.; Ajani, Jaffer A.; Crane, Christopher H.; Kachnic, Lisa A.; Okawara, Gordon; Berk, Lawrence; Roof, Kevin; Becker, M.; Grisell, David L.; Ellis, Robert J.; Sperduto, Paul W.; Marsa, Gerald W.; Guha, Chandan; Magliocco, Anthony M.

doi:10.1016/j.ijrobp.2016.11.021

Cited by 14 publications

(5 citation statements)

References 44 publications

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“…In every case, all histopathological parameters were estimated per two high power fields a 0.16 mm 2 . Immunhistochemical expression was semiautomatically estimated using ImageJ and overall stained areas were measured according to previous descriptions [ 30 , 37 ]. Finally, PD1- expression was estimated in PD1- positive and PD1-negative manually by stained cancer cells [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study

Meyer

Höhn

2018

Oncotarget

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Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application.Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10−3mm2/s, p=0.04.Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction.

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Section: Methodsmentioning

confidence: 99%

Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study

Meyer

Höhn

2018

Oncotarget

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“…T staging according to AJCC classification has been evaluated as a prognostic factor with conflicting results. Tumor diameter > than 5 cm is reported as an independent variable predicting DFS and OS by The Radiation Therapy Oncology Group 9811 analysis[ 7 ], but not by the European Organization for Research and Treatment of Cancer 22861 study[ 8 , 9 ]. Moreover, no difference in survival has been reported for T1 or T2 tumors.…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of ultrasonography staging in patients with anal cancer

Nardi¹,

Arru²,

Guarneri³

et al. 2020

WJGO

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BACKGROUND Carcinomas of the anal canal are staged according to the size and extent of the disease; however, we propose including a novel ultrasound (US) staging system, based on depth of tumor invasion. In this study the clinical American Joint Committee on Cancer (AJCC) staging guidelines and the US classificationss in patients with anal cancer were compared. AIM To evaluate the prognostic role of the US staging system in patients with anal cancer. METHODS The data of 48 patients with anal canal squamous cells carcinoma, observed at our University Hospital between 2007 and 2017, who underwent pre-treatment assessment with pelvic magnetic resonance imaging (MRI), total body computed tomography (CT) scan and endoanal US were retrospectively reviewed. Anal canal tumors were clinically staged according to AJCC, determined by MRI by measurement of the longest tumor diameter, and CT scan. Endoanal US was performed with a high multi-frequency (9-16 MHz), 360° rotational mechanical probe; US classification was based on depth of tumor penetration through the anal wall, according to Giovannini’s study. All patients were treated with definitive radiation combined with 5-fluorouracile and Mitomycin-C. After treatment patients were followed-up regularly. RESULTS At baseline there were 30 and 32 T1-2, 18 and 16 T3-4, 31 and 19 N+ patients classified according to the clinical AJCC and US staging system respectively. After a mean follow-up of 98 months, 38 patients (79.1%) are alive and 28 (58.3%) are disease free. During follow up 20 patients (41.6%) experienced recurrences. After univariate analysis, American Society of Anesthesiologists (ASA) score ( P = 0.00000001) and US staging ( P = 0.009) were significantly related to disease-free survival (DFS). When overall survival and DFS functions were compared, a statistically significant difference was observed for DFS survival when the US staging was applied with respect to the clinical AJCC staging. By combining the 2 significant prognostic variables, namely the US staging with the ASA score, four risks groups with different prognoses were identified. CONCLUSION Our findings suggest that US staging may be superior to traditional clinical staging, since it is significantly associated with DFS in anal cancer patients.

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“…Ki-67 was reported as an independent predictor of DFS, demonstrating that a higher Ki-67 index correlated with improved DFS in patients treated with CRT [ 74 ]; moreover, the evaluation of EGFR and Ki-67 protein co-expression ratio in pretreatment tumor biopsies of patients treated with CRT indicated a positive correlation between EGFR expression and Ki-67 on immunohistochemistry. Furthermore, the study demonstrated that patients presenting a higher ratio (Ki-67 expression and EGFR staining) had a statistically significant lower OS, disease-free failure, and a higher risk of locoregional failure when compared to patients with a lower ratio, suggesting a possible role of this ratio as a possible biomarker and also raising questions of benefits regarding anti-EGFR therapy [ 75 ]. Of note, in the same study, considering tumor Ki67 and EGFR as single markers, no statistically significant differences were seen in any clinical endpoints.…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies

Mathias-Machado

Peixoto²,

Moniz

et al. 2022

Biomedicines

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Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. Fluoropyrimidine-based chemoradiotherapy remains the cornerstone of the treatment of non-metastatic disease, but the locally advanced disease still presents high rates of disease recurrence and systemic therapy of SCCA is an unmet clinical need. Despite sharing common molecular aspects with other HPV-related malignancies, such as cervical and head and neck cancers, SCCA presents specific epigenomic, genomic, and transcriptomic abnormalities, which suggest that genome-guided personalized therapies should be specifically designed for this disease. Actionable mutations are rare in SCCA and immune checkpoint inhibition has not yet been proven useful in an unselected population of patients. Therefore, advances in systemic therapy of SCCA will only be possible with the identification of predictive biomarkers and the subsequent development of targeted therapies or immunotherapeutic approaches that consider the unique tumor microenvironment and the intra- and inter-tumoral heterogeneity. In the present review, we address the molecular characterization of SCCA and discuss potential diagnostic, predictive and prognostic biomarkers of this complex and challenging disease.

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Significance of Co-expression of Epidermal Growth Factor Receptor and Ki67 on Clinical Outcome in Patients With Anal Cancer Treated With Chemoradiotherapy: An Analysis of NRG Oncology RTOG 9811

Cited by 14 publications

References 44 publications

Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study

Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study

Prognostic role of ultrasonography staging in patients with anal cancer

Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies

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