Prognostic Impact of Tumor Growth Velocity in Head and Neck Squamous Cell Carcinoma Treated by Radio(Chemo)Therapy
Prognostic Impact of Tumor Growth Velocity in Head and Neck Squamous Cell Carcinoma Treated by Radio(Chemo)Therapy
The purpose of this study is to determine the impact of tumor growth velocity on the survival
 of patients with hea and neck 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 HNSCC. 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.
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. 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.

 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, the investigators
 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.
 The study demonstrated that 53% of the patients presented a tumoral progression of > 50%
 within a mean waiting time of 42.1 +/- 15.7 days. The investigators 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, the investigators 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,
 the investigators 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)
Inclusion Criteria:

 -  clinical and anatomopathological diagnosis of a head and neck squamous cell carcinoma
 (T1 to T4) (oral cavity, oropharynx, larynx, hypopharynx)

 -  multidisciplinary decision for radiotherapy or concomitant radiochemotherapy
 eligibility

 Exclusion Criteria:

 -  metastatic disease

 -  primary surgical management

 -  contraindications to iodine contrast injection: anaphylaxis and renal insufficiency

 -  tumor not visible on CT