scholarly journals 3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5313
Author(s):  
Hugh Andrew Jinwook Kim ◽  
Mushfiq Hassan Shaikh ◽  
Mark Lee ◽  
Peter Y. F. Zeng ◽  
Alana Sorgini ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Survival Data ◽  
Statistical Power ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cytokine Signaling ◽  
Molecular Characteristics ◽  
Chromosome 3P

Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had <1% or >97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid–non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.

Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.

1991 ◽  
Vol 9 (8) ◽  
pp. 1376-1384 ◽  
Author(s):  
E E Vokes ◽  
R Mick ◽  
E P Lester ◽  
W R Panje ◽  
R R Weichselbaum
Keyword(s):  
Head And Neck Cancer ◽  
Adjuvant Chemotherapy ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Neck Cancer ◽  
Survival Data ◽  
Locally Advanced ◽  
Local Therapy ◽  
Complete Response ◽  
Advanced Head

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.

Frequent allelic loss at chromosome 3p distinct from genetic alterations of the 8-oxoguanine DNA glycosylase 1 gene in head and neck cancer

1999 ◽  
Vol 26 (4) ◽  
pp. 254-260 ◽  
Author(s):  
H�l�ne Blons ◽  
J. Pablo Radicella ◽  
Ollivier Laccourreye ◽  
Daniel Brasnu ◽  
Philippe Beaune ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Genetic Alterations ◽  
Dna Glycosylase ◽  
Allelic Loss ◽  
Chromosome 3P

scholarly journals Intra-tumor Genetic Heterogeneity and Mortality in Head and Neck Cancer: Analysis of Data from The Cancer Genome Atlas

PLoS Medicine ◽  
2015 ◽  
Vol 12 (2) ◽  
pp. e1001786 ◽  
Author(s):  
Edmund A. Mroz ◽  
Aaron M. Tward ◽  
Rebecca J. Hammon ◽  
Yin Ren ◽  
James W. Rocco
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Genetic Heterogeneity ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Radiosensitization with a COX2 inhibitor with chemoradiation for head and neck cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5582-5582 ◽  
Author(s):  
P. Prellop ◽  
G. Peters ◽  
W. Carroll ◽  
L. Nabell ◽  
S. Spencer ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Febrile Neutropenia ◽  
Head And Neck ◽  
Local Control ◽  
Neck Cancer ◽  
Survival Data ◽  
Locally Advanced ◽  
Radiation Dermatitis ◽  
Published Data ◽  
Cox2 Inhibitor

5582 Background: Cyclo-oxygenase 2 (COX2) inhibitors have shown promise as radio- and chemosensitizers. We conducted a phase IB/II study to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with carboplatin, paclitaxel, and radiation for locally advanced or recurrent head and neck cancer. Methods: Patients with stage III/IV or recurrent squamous cell carcinoma of the oropharynx, oral cavity, hypopharynx, or larynx were eligible. Primary endpoints were toxicity, local control and survival. Patients were treated with weekly carboplatin (AUC = 2.0), paclitaxel (30 mg/m2) and concurrent radiation (70 Gy). Celecoxib (400 mg bid) was started 1 week prior to the initiation of radiotherapy and was given for a total of 2 years. In 12/04, the study closed due to concerns of cardiotoxicity with COX-2 inhibitors. Celecoxib was discontinued in all patients. The study restarted in 5/06 with the modification that celecoxib would be given only during radiation. Results: Between 12/02 and 1/06, a total of 28 patients were enrolled: 89% were male, median age was 56.5, 3 with recurrent cancer and 25 treated definitively. Five patients have been treated on the modified study. Grade 3/4 toxicities include: mucositis (35% G3), dermatitis (18% G3; 7% G4), febrile neutropenia (21% G3; 3% G4), dysphagia (57% G3), nausea/vomiting (29% G3). Thirty percent did not complete prescribed chemotherapy due to myelosuppression. Acturarial 2 year outcomes in the 20 evaluable, definitively treated patients: 65% survival, 76% local control. Conclusions: Compared to published data using carbo/taxol and RT, an unexpectantly high incident of febrile neutropenia was observed but no increase in radiation dermatitis or mucositis. Two year survival data is comparable to published data. No significant financial relationships to disclose.

An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer

2003 ◽  
Vol 21 (1) ◽  
pp. 92-98 ◽  
Author(s):  
David J. Adelstein ◽  
Yi Li ◽  
George L. Adams ◽  
Henry Wagner ◽  
Julie A. Kish ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Survival Data ◽  
Single Agent ◽  
Phase Iii ◽  
High Dose ◽  
Fractionated Radiation

Purpose: The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer. Patients and Methods: Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test. Results: Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P < .0001) and 77% enrolled in arm C (P < .001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P = .014) and 27% for arm C (P = not significant). Conclusion: The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery.

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