151751-Najiba-Chargi

14 CHAPTER 1 considered for persistent or recurrent disease at the primary tumor site or the regional lymph nodes after definitive chemoradiotherapy. The MACH-NC meta-analysis showed that cispla - tin-based chemoradiotherapy is a curative treatment option when surgical resection is less feasible or would result in poor long-term functional outcomes. 12 An absolute survival benefit of 4.5% at 5 years has been found when chemotherapy was added to locoregional treatment (radiotherapy).The most effective treatment modality was concomitant chemoradiotherapy with a hazard ratio of death of 0.81 (95%CI 0.78-0.86) and an absolute survival benefit of 6.5% at 5 years. 12 Chemoradiotherapy in the primary setting can be given for locally advanced HNSCC patients for two reasons (1) organ and function preservation or (2) unresectable dis - ease. The Radiation Therapy Oncology Group (RTOG) found that chemoradiotherapy given in a concomitant setting was most effective for organ preservation in laryngeal cancer and locoregional control. In head and neck cancer, platinum-based drugs are the most effective andmost studied chemotherapy drugs used to treat head and neck cancer. The RTOG schedule is the most commonly used schedule in head and neck cancer, consisting of cisplatin 100mg/ m 2 on days 1, 22 and 43 combined with conventional radiotherapy (70 Gy in 35 fractions in 7 weeks). 13 In the adjuvant setting, after surgery, the addition of cisplatin to radiotherapy is more effective than radiotherapy alone in HNSCC patients with high-risk pathological features i.e. irradical resection (positive surgical margins) or extracapsular extension of lymph node metastasis. 14,15 Concurrent chemoradiotherapy is associated with various in-field and systemic acute and chronic toxicities. Common side effects encountered in patients treated with cisplatin-based chemoradiotherapy are ototoxicity, nephrotoxicity and bone marrow depression, these side effects can be dose-limiting which causes patients not to complete all prescribed cisplatin cycles. Therefore, its use is predominantly for non-elderly patients who have a good perfor - mance status without major comorbidities. In patients who are not cisplatin-fit, e.g., patients with hearing problems or decreased renal function, other systemic therapeutics are carbo- platin and cetuximab. Carboplatin is sometimes used when head and neck cancer patients have co-existent renal impairment, but treatment with carboplatin is less effective than high-dose cisplatin for curative therapy. 16 The combination of the epidermal growth factor receptor (EGFR) antibody cetuximab and radiotherapy, also called bioradiotherapy, improves locoregional control, progression-free survival and overall survival compared to radiother- apy alone. 17 Common side effects of bioradiotherapy include acneiform rash and infusion reactions. Recent trials have shown that locoregional control and overall survival rates are in favor for cisplatin-based chemoradiotherapy compared to cetuximab-based bioradiotherapy in patients with (mainly HPV-positive) locally advanced HNSCC. 18–20 PROGNOSIS OF PATIENTS DIAGNOSED WITH HEAD AND NECK CANCER Prognosis of patients with head and neck cancer varies depending on epidemiological fac- tors (e.g. HPV-status), anatomical location and stage. 4 Recent advances such as the introduc- tion of immunecheckpoint inhibitors for treatment of recurrent or metastatic head and neck cancer have led to increased benefit for some patients. 21 Other treatment advances such as