NBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx

Inclusion criteria:

* Patients aged ≥ 70 years old, or
* Patients aged ≥ 65 years old and \< 70 years old who are unable to receive cisplatin, or
* Patients who have contraindication to cisplatin or that are intolerant to cisplatin or cetuximab or that cannot receive the combination of chemoradiation, regardless the age
* Histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity or oropharynx
* T3 or T4 primary tumor or Stage III or IVA according to AJCC guidelines (8th Edition, 2018)
* No evidence of distant metastatic disease, as determined by a negative PET scan or CT scan
* Clinically eligible for intratumor implantation by injection
* Karnofsky Performance Status ≥ 70
* Adequate function of Bone marrow:

  * White Blood Cell (WBC) \> 3.0 x 10\^9/L
  * Absolute neutrophil count (ANC) \> or = 1.0 x 10\^9/L
  * Platelet count \> or = 100 x 10\^9/L
  * Hemoglobin \> or = 9.0 g/dL
* Adequate function of Kidney:

  o Creatinine \< or = 3.0 x ULN or creatinine clearance \> or = 30 mL/min/1.73m²
* Adequate function of the liver:

  * AST \< or = 5 x ULN
  * ALT \< or = 5 x ULN
  * Bilirubin \< or = 1.5 x ULN
* Negative pregnancy test ≤ 7 days of NBTXR3 injection in all females of child-bearing potential

Exclusion Criteria:

* Written Informed Consent not obtained, signed and dated
* Prior radiotherapy to any area within the planned radiotherapy field
* Tumor-related dyspnea
* Tumor ulceration which implies vascular risk
* Non measurable disease as defined by RECIST criteria
* History of stroke, CABG, or significant blockage of carotid arteries or coronary arteries or current blockage of coronary or carotid arteries equal to or in excess of 50% blockage
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active severe infection, symptomatic congestive heart failure, acute coronary syndrome, etc.
* Medical history of life-threatening ventricular arrhythmia
* Prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, and in situ cervical cancer, and any other cancer from which the subject has been cancer free for 5 years
* Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study
* Patients unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures or those with severe psychiatric illness/social situations that would limit compliance with study requirements
* Patients participating in another clinical investigation at the time of signature of the informed consent.