Definitive Concurrent Hypofractionated Rth With Weekly Cisplatin in Locally Advanced SCCHN
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Study type: Observational

Summary: 
      The primary endpoint will be acute toxicity. Secondary endpoints included: late toxicity and
      quality of life; loco-regional control, disease free survival and overall survival.
    

Detailed description: 
      Head and neck cancer is considered the 6th most common cancer all over the world, with
      890,000 new cases and 450,000 deaths in 2018 (1). The histologic type in more than 90% of
      head and neck cancer is squamous cell carcinoma (SCC) (2). The incidence of SCC in head and
      neck (SCCHN) continues to rise and is expected to increase by 30% in 2030, which means about
      1.08 million new cases annually (3). Hospital-based studies in Egypt showed that SCCHN
      represents about 20% of all malignancies. The overall incidence of SCCHN in Egypt from 1999
      to 2006 was approximately twice among males (476,000) than in females (273,000) (4). Males
      are affected significantly more than females, with a ratio ranging from 2:1 to 4:1 (5).

      Tobacco and alcohol consumption are the high-risk factors of SCCHN (6). Human papilloma virus
      (HPV), especially subtypes 16 and 18 are implicated risk factors in oropharyngeal cancer (7).
      Some studies found an association between HPV and P53 gene mutation, as HPV expresses two
      viral proteins (E6 and E7 proteins) that inactivates P53 and pRB genes, causing genomic
      instability and malignant transformation ((8)). SCCHN arises from the mucosal epithelium of
      the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. HPV associated SCCHN
      arises primarily from the palatine and lingual tonsils of the oropharynx, whereas tobacco
      associated SCCHN arises primarily in the oral cavity, hypopharynx, and larynx.

      SCCHN is being increasingly treated by multimodality approaches combining surgery,
      radiotherapy (RT), and chemotherapy (CTH). Randomized controlled trials have demonstrated
      major improvements in loco-regional tumor control (LRC) from altered fractionation RT with
      CTH as compared with conventional fractionated RT (CFRT) (9). Altered fractionation schedules
      reduces tumor repopulation effect and seek to improve the therapeutic ratio between tumor
      cell killing and normal tissue damage. Additionally, some data showed that cancer patients
      are at higher risk of COVID-19 infection comparing with the general population due to many
      treatment visits, so hypo-RT schedules are better for these patients. hypo-RT utilizes a
      small number of fractions with a larger dose per fraction (> 2Gy per fraction), shortening
      overall treatment time compared to a CFRT (9). Although a shorter treatment time can be
      obtained by applying a higher dose per fraction, it might also result in an increase in the
      incidence of late complications.

      The aim of this study was to investigate hypo fractionated intensity modulated RT (hypo-IMRT)
      with 62.5 Gy in 25 daily fractions over five weeks (2.5 Gy per fraction with weekly cisplatin
      40mg/m2 in patients with high-risk stage II (T2N0, excluding glottic laryngeal) disease,
      stage III (T1-3 N1 or T3N0) and stage IV (T1-4N2 orN3). The primary endpoint will be
      assessment of acute toxicity. Secondary endpoints included: late toxicity and quality of
      life; LRC, disease free survival (DFS) and overall survival (OS).
    

Intervention name(s): hypofractionated Rth with platinol
Intervention type(s): Radiation
Intervention description(s): hypofractionated Rth with weekly cisplatin 40mg/m2
Intervention MeSH terms: Cisplatin
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        A planned 62 patients were recruited in the period from 2018 to 2021, 52(83.9%) were males
        and the remaining 10 (16.1%) were females. 22 of patients were current smoker. Patients had
        histologically or cytologically proven oropharyngeal (32.3%), laryngeal (32.3%) or
        hypopharyngeal squamous cell carcinoma (18.2%); with AJCC high risk stage II (T2N0,
        excluding glottic laryngeal) disease (22.6%), stage III (T1-3N1 or T3N0) (30.6%) and stage
        IV (T1-4N2 or N3) (46.8%). Human papilloma virus status was not tested at the time of paper
        design.
      
Keywords: chemoradiation, IMRT, Head and neck cancer