Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Prognostic Impact of Tumor Growth Velocity in Oropharyngeal Squamous Cell Carcinoma Treated by Radio(Chemo)Therapy

Summary: The purpose of this study is to determine the impact of tumor growth velocity on the survival of patients with oropharyngeal squamous cell carcinoma treated by (chemo-)radiotherapy.
  Patients with stages I to IV oropharyngeal primary squamous cell carcinoma (OPSCC) elected for radiotherapy or radiochemotherapy with curative intent will be selected. Tumor volume and number and size of pathological neck lymph nodes (small diameter > 1 cm) will be assessed on diagnostic CT-scan (DiCT) and treatment planning CT-scan (RtCT) using the summation of areas technique. Tumor progression and tumor doubling time will be calculated based on DiCT and RtCT. Tumor proliferation will be assessed on biopsy specimens by Ki67 immunohistochemistry and mitotic index. HPV status will be evaluated by PCR and p16 immunohistochemistry. Ulcerative or exophytic aspect will be noticed. Tumoral kinetics patterns will be correlated with disease free survival and overall survival of patients with OPSCC. These patterns will be compared to HPV status and proliferation markers in order to study their clinical signification [time frame: 5 years] and develop predictive markers of tumor progression for head and neck cancers.

Detailed description: Head and neck squamous cell carcinoma (HNSCC) represents more than 90 percent of head and neck tumors and is one of the most frequent human neoplasms (Jemal 2007). During the last decades, radiotherapy has emerged as a standard treatment of HNSCC and the number of patients treated with this modality has continuously increased. Moreover, treatment schedules for radiotherapy have improved and require more preparation and are therefore more time consuming. Thus, waiting time prior to radiotherapy becomes a major concern in many countries with reported delays of 70 days or even more.Clinicians involved in treating HNSCC face the problem of rapidly growing tumors but despite significant progress in the understanding of these tumors, their development and progression remain currently unpredictible at the time of diagnosis. In a retrospective trial, Laccourreye et al. studied the time of progression of symptoms and signs (TPSS) before diagnosis and treatment in 966 HNSCC cases and showed that for a given tumor stage, the longer was the TPSS, the better were the vital prognosis, the local and lymph node control. But there is no clear definition of fast growing tumor, with objective measurement.
  Oropharynx squamous cell carcinomas (OPSCC), the most frequent HNSCC localization, are mainly treated by radiotherapy and mostly present at advanced stage. A CT-scan is perfomed at the time of diagnosis. Several weeks later, a second CT-scan is necessary for treatment planning in order to define the tumoral target volume. This necessity provides the opportunity to compare tumoral volumes on both exams, and thus to assess tumoral progression. In a pilot study conducted with Institut Gustave Roussy, we studied retrospectively the tumor and loco-regional progression in the waiting time between diagnostic and treatment planning CT-scans in a cohort of patients with oropharyngeal squamous cell carcinoma, treated by radio(chemo)therapy between April 2005 and April 2007. We demonstrated that 53% of the patients presented a tumoral progression of > 50% within a mean waiting time of 42.1 +/- 15.7 days. We consider this situation as regrettable, and prospective trials are clearly needed to determine clinical consequences of these findings.
  The current project aims to study prospectively the loco-regional tumoral progression within the waiting time between diagnostic and treatment planning CT-scans in a cohort of patients with OPSCC. Patients with oropharyngeal primary squamous cell carcinoma elected for radiotherapy or radiochemotherapy with curative intent will be selected. Tumor volume, number and size of pathological cervical lymph nodes (small diameter > 1 cm) will be assessed on diagnostic CT-scan (DiCT) and treatment planning CT-scan (RtCT) using the summation of areas technique (computerized delineation). Tumoral progression and tumor doubling time will be calculated based on DiCT and RtCT in order to define different tumoral kinetics patterns. Human papillomavirus (HPV) status will be assessed by polymerase chain reaction (PCR) and p16 immunohistochemistry. As primary objective, we will study the tumoral kinetics patterns with disease free survival (DFS) and overall survival (OS) in patients with OPSCC in order to study their clinical signification [time frame: 5 years]. As secondary objectives, we will correlate the tumoral kinetics patterns with HPV status of patients with OPSCC, and compare tumoural kinetics to proliferation markers (Ki67, mitotic index) in order to develop predictive markers of tumour progression for head and neck cancers. An other complementary objective will compare tumor kinetics patterns with endoscopic aspect (ulcerative versus exophytic)

Eligibility: Inclusion Criteria:
  -  clinical and anatomopathological diagnosis of a oropharyngeal squamous cell carcinoma (T1 to T4)
  -  multidisciplinary decision for radiotherapy or concomitant radiochemotherapy eligibility
  Exclusion Criteria:
  -  metastatic disease
  -  primary surgical management
  -  contraindications to iodine contrast injection: anaphylaxis and renal insufficiency

Relevance to patient case: not relevant