Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.

BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer.

Impact of 3T multiparametric MRI and FDG-PET-CT in the evaluation of occult primary cancer with cervical node metastasis.

BACKGROUND: This study aimed to determine the ability of multimodal evaluation with multiparametric 3T-MRI (MPMRI) and positron emission tomography - computed tomography (PET/CT) to detect cancer of unknown primary origin (CUP) with neck lymph node (LN) metastasis. METHODS: The study group comprised 38 retrospectively analysed consecutive patients with LN metastasis in the head and neck (HN) region without known primary tumours (PTs). Statistical values of 3T-MRI and of FDG-PET/CT scans were evaluated. RESULTS: Of the 38 CUPs, conventional native T1-, T2-weighted and STIR sequences detected 6 PTs. Native sequences plus diffusion-weighted imaging (DWI) found 14-, and with fat suppression contrast-enhanced T1-weighted measurement as well as with the complex MPMRI found 15 primaries and with PET/CT 17 CUPs could be evaluated, respectively. The detection rates were 15.8, 36.8, 39.5, 39.5 and 44.7 % for conventional native MRI, native plus DWI, native with contrast-enhanced MRI (CE-MRI), for MPMRI, and for PET/CT, respectively. The overall detection rate proved by histology was 47.4 %. PET/CT provided the highest sensitivity (Sv: 94.4 %) but a lower specificity (Sp: 65.0 %), using MPMRI (Sv: 88.2 %) the specificity increased to 71.4 %. DWIincreased specificity of the native sequences (Sp: 76.2 %). Conventional native sequences plus DWI as well as 3T-MPMRI and PET/CT were same accurate (Acc: 79.0 %) and had similar likelihood ratio (LR: 3.42, 3.03 and 2.62) in detecting unknown PT sites. CONCLUSIONS: The accuracy of FDG-PET/CT and MPMRI in case of CUP in finding the primary cancer in the neck regions is identical. While using PET/CT whole body information can be obtained in one examination. MPMRI shows the local soft tissue status more accurately. In cases of CUP PET/CT should be the first method of choice if it is available. MPMRI can clarify the exact primary tumor stage, and it can be advantageous in clarifying the prognostic factors, which is necessary in case of advanced tumor stage and when surgery is under consideration. In case low N stage is likely after the clinical examination and wait and see policy can be considered, MPMRI is recommended, and in this case the significance the of radiation free MPMRI is increasing.