scholarly journals Case Report: EGFR-Positive Early-Stage Lung Adenocarcinoma Transforming to Squamous Cell Carcinoma After TKI Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiatao Liao ◽  
Yuan Li ◽  
Chang Liu ◽  
Qianqian Long ◽  
Jialei Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Squamous Differentiation ◽  
Egfr Inhibition ◽  
Histological Transformation ◽  
Tki Treatment

The histological transformation from epidermal growth factor receptor (EGFR)-mutated adenocarcinoma (ADC) to squamous cell carcinoma (SCC) after tyrosine kinase inhibitor (TKI) treatment is rare. We present a case of a patient who transitioned from early-stage primary lung ADC with partial squamous differentiation, EGFR mutation and amplification, to adrenal gland metastasis as SCC with EGFR amplification disappearance 115-months after surgery, during which gefitinib and local radiotherapy were utilized for the metastasis in the right femoral head and mediastinal lymph nodes. This case might indicate a possible mechanism of EGFR inhibition resistance with SCC transition and EGFR amplification loss from the initially well-responding ADC, especially those with SCC or partial squamous differentiation. The optimal post-progression therapy for ADC-SCC patients is challenging and further studies are needed.

scholarly journals Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Laveniya Satgunaseelan ◽  
Sean Porazinski ◽  
Dario Strbenac ◽  
Aji Istadi ◽  
Cali Willet ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Young Patients ◽  
Molecular Signature ◽  
Egfr Inhibition

There is an increasing worldwide incidence of patients under 50 years of age presenting with oral squamous cell carcinoma (OSCC). The molecular mechanisms driving disease in this emerging cohort remain unclear, limiting impactful treatment options for these patients. To identify common clinically actionable targets in this cohort, we used whole genome and transcriptomic sequencing of OSCC patient samples from 26 individuals under 50 years of age. These molecular profiles were compared with those of OSCC patients over 50 years of age (n=11) available from TCGA. We show for the first time that a molecular signature comprising of EGFR amplification and increased EGFR RNA abundance is specific to the young subset of OSCC patients. Furthermore, through functional assays using patient tumor-derived cell lines, we reveal that this EGFR amplification results in increased activity of the EGFR pathway. Using a panel of clinically relevant EGFR inhibitors we determine that an EGFR-amplified patient-derived cell line is responsive to EGFR inhibition, suggesting EGFR amplification represents a valid therapeutic target in this subset of OSCC patients. In particular, we demonstrate sensitivity to the second-generation EGFR tyrosine kinase inhibitor afatinib, which offers a new and promising therapeutic avenue versus current EGFR-targeting approaches. We propose that testing for EGFR amplification could easily be integrated into current diagnostic workflows and such measures could lead to more personalized treatment approaches and improved outcomes for this younger cohort of OSCC patients.

EGFR Inhibition in the Treatment of Squamous Cell Carcinoma of the Head and Neck

2014 ◽  
Vol 10 (02) ◽  
pp. 152
Author(s):  
Mersiha Hadziahmetovic ◽  
Mitchell Machtay ◽  
◽  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
External Beam Radiotherapy ◽  
Growth Factor Receptor ◽  
Definitive Treatment ◽  
Published Data ◽  
Egfr Inhibition ◽  
Definitive Therapy

Squamous cell carcinoma of the mucosal surfaces in the head and neck (SCCHN) remains a therapeutic challenge in much of the world. Most patients present with locally and/or regionally advanced disease, and are offered curative (definitive) therapy in the form of external beam radiotherapy with a concurrent radiosensitizing systemic agent, most commonly platinum-based or targeting an epidermal growth factor receptor (EGFR). In this review, we will cover the literature and published data evaluating the use of EGFR inhibitors as part of the concurrent or postoperative regimen in the context of definitive treatment for patients with SCCHN, as well as its use in patients with recurrent or distantly metastatic disease.

A phase I/Ib study of lenvatinib and cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6541-6541
Author(s):  
Lara Dunn ◽  
Alan Loh Ho ◽  
Juliana Eng ◽  
Loren S. Michel ◽  
James Vincent Fetten ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Oral Mucositis ◽  
Kinase Inhibitor ◽  
Primary Objective ◽  
Expansion Phase ◽  
20Mg Daily ◽  
Egfr Inhibition

6541 Background: Despite overexpression of EGFR in HNSCC, cetuximab monotherapy has limited benefit. Fibroblast growth factor receptor (FGFR) signaling is a known resistance mechanism to EGFR inhibition. Lenvatinib is a multi-targeted receptor tyrosine kinase inhibitor (RTKI) and has unique activity against FGFR 1,2,3, and 4. We are evaluating inhibition of EGFR and RTKs including FGFR through the combination of cetuximab and lenvatinib in patients (pts) with R/M HNSCC. Methods: In this phase I/Ib, single-institution study, pts with measurable disease per RECIST v1.1 that is incurable with surgery and radiation are eligible regardless of prior cetuximab therapy. The dose de-escalation phase included pts with HNSCC and cutaneous squamous cell carcinoma (cSCC) treated with standard cetuximab dosing and lenvatinib in 3 potential dose levels (DL): (0) 24mg, (-1) 20mg, (-2) 14mg oral daily in a standard 3+3 design. The primary objective was to determine the MTD of lenvatinib in combination with cetuximab. The expansion phase included an additional 5 pts with HNSCC treated at the MTD. Exploratory endpoints include ORR and PFS in HNSCC pts treated at the MTD. Results: 12 evaluable pts were treated on the dose de-escalation phase. There were no DLTs on DL 0; however, 3/6 pts were removed immediately following the 28-day DLT period due to toxicity that included extensive thrombotic events and athlerosclerotic disease. On DL -1, 0/6 pts (5 HNSCC/1 cSCC) had a DLT establishing lenvatinib 20mg daily as the MTD. 7 pts were enrolled onto the expansion phase; 4 are currently evaluable for response and 2 are unevaluable because of withdrawal due to a cetuximab reaction and required surgery. Of the 9 evaluable HNSCC pts treated with lenvatinib 20mg daily, 6 pts had a PR with a 67% ORR. For the 8 pts who have completed treatment, the median PFS is 3.6 months (range 1.6-10.4). Grade 3 AEs regardless of attribution included hypertension (3), oral mucositis (3) and oral cavity fistula (1). The most common AEs were acneiform rash (7), fatigue (6), and hypertension/hypothyroidism/oral mucositis (5 each). Conclusions: The MTD of lenvatinib 20mg daily with cetuximab appears to be active in R/M HSNCC with an impressive preliminary ORR, warranting further evaluation of the efficacy of this combination. Clinical trial information: NCT03524326 .

scholarly journals A nomogram to predict lymph node metastasis risk for early esophageal squamous cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaofeng Duan ◽  
Xiaobin Shang ◽  
Jie Yue ◽  
Zhao Ma ◽  
Chuangui Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Derivation Cohort ◽  
Node Metastasis

Abstract Background A nomogram was developed to predict lymph node metastasis (LNM) for patients with early-stage esophageal squamous cell carcinoma (ESCC). Methods We used the clinical data of ESCC patients with pathological T1 stage disease who underwent surgery from January 2011 to June 2018 to develop a nomogram model. Multivariable logistic regression was used to confirm the risk factors for variable selection. The risk of LNM was stratified based on the nomogram model. The nomogram was validated by an independent cohort which included early ESCC patients underwent esophagectomy between July 2018 and December 2019. Results Of the 223 patients, 36 (16.1%) patients had LNM. The following three variables were confirmed as LNM risk factors and were included in the nomogram model: tumor differentiation (odds ratio [OR] = 3.776, 95% confidence interval [CI] 1.515–9.360, p = 0.004), depth of tumor invasion (OR = 3.124, 95% CI 1.146–8.511, p = 0.026), and tumor size (OR = 2.420, 95% CI 1.070–5.473, p = 0.034). The C-index was 0.810 (95% CI 0.742–0.895) in the derivation cohort (223 patients) and 0.830 (95% CI 0.763–0.902) in the validation cohort (80 patients). Conclusions A validated nomogram can predict the risk of LNM via risk stratification. It could be used to assist in the decision-making process to determine which patients should undergo esophagectomy and for which patients with a low risk of LNM, curative endoscopic resection would be sufficient.

scholarly journals The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chi T. Viet ◽  
Gary Yu ◽  
Kesava Asam ◽  
Carissa M. Thomas ◽  
Angela J. Yoon ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Early Stage ◽  
Genome Wide Association Studies ◽  
Gene Methylation ◽  
Poor Survival ◽  
Risk Of Death

Abstract Background Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. Methods We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. Results 5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. Conclusions The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.

scholarly journals De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2099
Author(s):  
Eric Miller ◽  
Jose Bazan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Intensity Modulated Radiation Therapy ◽  
Late Toxicity ◽  
Standard Of Care ◽  
The Elderly ◽  
Current Standard

The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.

5-Aminolevulinic acid photodynamic therapy for early-stage lip squamous cell carcinoma

2021 ◽  
pp. 102321
Author(s):  
Peiru Wang ◽  
Guolong Zhang ◽  
Linglin Zhang ◽  
Zhongxia Zhou ◽  
Lei Shi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Photodynamic Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Aminolevulinic Acid ◽  
Early Stage

scholarly journals Retrospective analysis of Ca cervix postoperative: An institutional study

2016 ◽  
Author(s):  
Chandra Prakash
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Time ◽  
Residual Disease ◽  
Early Stage ◽  
Treatment Length ◽  
Recommended Treatment ◽  
Carcinoma Of Cervix ◽  
Well Differentiated

Introduction: Carcinoma of cervix is one of the leading causes of death worldwide and in developing countries like India. Cervical cancer is third most common cancer among women however there is a good chance of curability if diagnosed in early stage. Materials and Methods: We had analysed 78 patient of carcinoma of cervix post op who were registered from 2012 to 2015 at Dr. Ram Manohar Lohia Institute of Medical Sciences. Results: We analysed 78 patients between age of 32-70 years and median age is 50 year. Among all patients squamous cell carcinoma is most common (65 patient), adenocarcinoma were 12 and lieomyosarcoma was 1 patient. Among all patient 12 were of adenocarcinoma, 1 of lieomyosarcoma and 65 patient of squamous cell carcinoma. On examination 55 patients were NAD and 23 were residual. Among squamous cell carcinoma 35 were moderate differentiated, 18 were well differentiated and 12 were of poorly differentiated. On examination 55 patients were NAD rest were having disease. Gap between EBRT and SORBO ranging from 3 to 99 days and median is 27 days and median is 29 days. Treatment length varies from 4 cm to 8 cm and median is 6 cm. Ovoide size ranges from 2.5 cm to 3.5 cm and median is 2.5 cm. Dose per fraction ranges from 5 Gy to 9 Gy and median was 9 Gy. Median fraction of session were 2. Out of 78 patients 2 were developed metastasis and 6 having residual disease. 28 patients were NAD and rest were referral and send back to parent hospital. Conclusion: Due to lack of resources and awareness of disease maximum number of patient presented with advanced stage. The recommended treatment time could not be achieved due to scarcity of cancer centres, treatment time is prolonged. We have not found any relation between treatment length and outcome. We are still investigating to conclude to found out relation among these variables.

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