567: The impact of chronic cisplatin treatment on DNA repair in head and neck squamous cell carcinoma

TPS6096 Background: Novel agents are often investigated in unselected end-stage cancer patients and their efficacy is evaluated by the classical RECIST criteria making unlikely to fully exploit the antitumor potential of these targeted agents. Olaparib (O) is a potent inhibitor of PARP especially active in tumors that have homologous recombination DNA repair pathway deficiencies. Durvalumab (D) is a selective, high-affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, overcoming PD-L1-mediated inhibition of T-cell activation. There is substantial evidence that tumor cells use PARP to repair platinum-induced DNA damage and thus escape apoptosis. In addition, O may complement the antitumor activity of D by increasing DNA damage through repair inhibition. Methods: OPHELIA is an open-label randomized multicenter phase II (window) trial in patients (pts) with head and neck squamous cell carcinoma (HNSCC). Treatment-naive HNSCC pts selected for primary curative study are randomized 3:3:3:1 in 4 neoadjuvant treatment groups: D 1500 mg on day 1 followed by O 600mg daily for 21-28 days (12 pts), cisplatin 60 mg/m2 on day 1 followed by O 75mg daily for 5 days (12 pts), monotherapy with O 600mg daily for 21-28 days (12 pts) and no treatment (5 pts). Preoperative therapy is discontinued 24 to 36 hours before surgery. Tumor biopsies, CT scans, PET and blood specimens are obtained at diagnosis and at surgery. Primary endpoint is the change in the tumor Ki-67 before and after treatment. Secondary endpoints are objective response rate according to RECIST 1.1 criteria, pathologic complete response rate and metabolic response rate assessed by FDG-PET/CT scan. Exploratory endpoints will include tumor and blood biomarkers. Translational correlates will be tested in tumor tissue, plasma and germline DNA and will include mutations in genes associated with DNA repair assessed by next generation sequencing and circulating tumor cells (CTCs) evaluated for DNA repair biomarkers and PD-L1. Trial is open to enrollment. Clinical trial information: NCT02882308.

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Erratum to “The effect of human papillomavirus on DNA repair in head and neck squamous cell carcinoma” [Oral Oncol. 61 (2016) 27–30]

Oral Oncology ◽

10.1016/j.oraloncology.2016.10.017 ◽

2016 ◽

Vol 62 ◽

pp. e5 ◽

Cited By ~ 1

Author(s):

Garren M. Low ◽

David S. Thylur ◽

Vicky Yamamoto ◽

Uttam K. Sinha

Keyword(s):

Squamous Cell Carcinoma ◽

Dna Repair ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma

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Head and neck squamous cell carcinoma: Better to be young

Otolaryngology ◽

10.1016/s0194-5998(00)70249-x ◽

2000 ◽

Vol 122 (2) ◽

pp. 253-258 ◽

Cited By ~ 49

Author(s):

Peter D. Lacy ◽

Jay F. Piccirillo ◽

Michael G. Merritt ◽

Maria R. Zequeira

Keyword(s):

Squamous Cell Carcinoma ◽

Survival Rate ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Young Patients ◽

Neck Squamous Cell Carcinoma ◽

Middle Aged ◽

Old Patients ◽

The Impact

Most head and neck squamous cell carcinoma patients are elderly, with few younger than 40 years. Controversy exists in the literature regarding outcomes for younger patients. The goal of this research project was to compare baseline features and outcomes for young patients (≤40 years), middle-aged patients (41–64 years), and old patients (≥65 years). To investigate the relationship between age and important presenting features and outcomes, 1160 recently diagnosed patients first treated at Washington University between 1980 and 1991 were identified from an existing database. Full 5-year survival information was available for 1030 patients (89%). Overall, the 5-year survival rate was 46% (478/1030); young patients (65%, 26/40) had a significantly better survival rate than middle-aged (52%, 292/566) or old patients (38%, 160/424) (χ2 = 24.5; P = 0.001). Survival was also related to smoking, comorbidity, primary site, TNM stage, and nodal disease. Age remained a significant factor even after we controlled for these other factors. Young patients developed fewer recurrent and new primary tumors. We conclude that young patients have a much better overall prognosis than older patients. The reasons for this difference are unclear, but it appears that the impact of age goes beyond an actuarial effect.

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The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma

ORL ◽

10.1159/000485515 ◽

2018 ◽

Vol 80 (1) ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Daisuke Nishikawa ◽

Nobuhiro Hanai ◽

Hidenori Suzuki ◽

Yusuke Koide ◽

Shintaro Beppu ◽

...

Keyword(s):

Skeletal Muscle ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

The Impact

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Preliminary insights into the impact of primary radiochemotherapy on the salivary microbiome in head and neck squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-020-73515-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Christina Kumpitsch ◽

Christine Moissl-Eichinger ◽

Jakob Pock ◽

Dietmar Thurnher ◽

Axel Wolf

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Treatment Options ◽

Well Being ◽

Amplicon Sequencing ◽

Neck Squamous Cell Carcinoma ◽

Rrna Gene ◽

The Impact

Abstract Squamous cell carcinoma is the most common type of throat cancer. Treatment options comprise surgery, radiotherapy, and/or chemo(immuno)therapy. The salivary microbiome is shaped by the disease, and likely by the treatment, resulting in side effects caused by chemoradiation that severely impair patients’ well-being. High-throughput amplicon sequencing of the 16S rRNA gene provides an opportunity to investigate changes in the salivary microbiome in health and disease. In this preliminary study, we investigated alterations in the bacterial, fungal, and archaeal components of the salivary microbiome between healthy subjects and patients with head and neck squamous cell carcinoma before and close to the end point of chemoradiation (“after”). We enrolled 31 patients and 11 healthy controls, with 11 patients providing samples both before and after chemoradiation. Analysis revealed an effect on the bacterial and fungal microbiome, with a partial antagonistic reaction but no effects on the archaeal microbial community. Specifically, we observed an individual increase in Candida signatures following chemoradiation, whereas the overall diversity of the microbial and fungal signatures decreased significantly after therapy. Thus, our study indicates that the patient microbiome reacts individually to chemoradiation but has potential for future optimization of disease diagnostics and personalized treatments.

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