An Overview of Medullary Thyroid Cancer Cases Treated at Kuwait Cancer Control Center.

INTRODUCTION: Medullary thyroid cancers (MTC) constitute about 5% of all thyroid cancers. The 10-year overall survival (OS) rate of patients with localized disease in thyroid for this pathology is 80% to 90% which is comparable with differentiated thyroid cancers, figures drop to 75% for cases with nodal metastases. Only 20% of patients with distant metastases at diagnosis survive for 10 years. In metastatic disease there are variations with smoldering less active disease to progressive active disease. Surgery is cornerstone of the management with total thyroidectomy and nodal dissection as main treatment. Adjuvant treatment with radiotherapy is case selective, varies from case to case. The management of residual, recurrent disease is possible re-surgery with external beam radiation therapy. The development of targeted therapy has brought in a major advantage in management of metastatic disease. Two drugs -vandetanib and cabozantinib- have been approved for use in metastatic MTC. The optimum management in this group of patients is a challenge and long-term use of TKI needs to be balanced with monitoring side effects of TKI and dose adjustments of TKI. MATERIALS AND METHODS: A retrospective review of cases with diagnosis of medullary thyroid cancers treated or registered at Kuwait Cancer Control Center was conducted. The data of patients registered between 1987 till 2017 was analyzed. The data was collected and analyzed using SPSS (version 20) software program. For analysis we considered date of surgery as the date of diagnosis. Final state of disease along with emphasis on prognostic factors was correlated with Kaplan Meyer survival curves. RESULTS: There were total 31 cases out of which 15(48.4%) were male and 16(51.6%) females. The median age at presentation was 51.6 years (range-28years-77years). MEN syndrome was diagnosed in 6(19.4%) patients. Staging revealed Stage I - 7/31 (22.58%), Stage II-3/31(9.67%), Stage III-7/31(22.58%), Stage IVA (nonmetastatic) -12/31 (38.70%), Stage IVC (metastatic) - 2/31 (6.45%). Total thyroidectomy and central compartment neck dissection was optimum surgery (29%). Total thyroidectomy with central compartment neck dissection and unilateral neck dissection was done in 38.7% patients, comprehensive neck dissection and total thyroidectomy was done in 32.2% patients. External beam radiotherapy (EBRT) with conformal or IMRT technique was used in 13 out of 31 patients. One patient was treated for bony metastasis with palliative intent. Four patients were treated by TKI for metastatic disease or at progression. Median follow up was 79 months. Median overall survival was 93 months. Median progression free survival irrespective of stage was 62 months. At the end of 5 years 61% patients were alive irrespective of stage of disease. Due to the small sample size and natural history of advanced MTC the observed p-value for several pathological variables in relation with survival was not significant. CONCLUSION: Stage I and stage II cases of our study did well and were all alive and disease free till our last follow up. EBRT in our cohort of patient did not revealed any added benefits in survival. The use of TKI in metastatic disease was associated with many issues including availability of drug. Elevated serum calcitonin and CEA levels in absence of measurable disease should be dealt cautiously.

Phase II/III Randomized Controlled Trial of Concomitant Hyperfractionated Radiotherapy plus Cetuximab (Anti-EGFR Antibody) or Chemotherapy in Locally Advanced Head and Neck Cancer.

INTRODUCTION: Globally, there is marked variation in overall incidence and presentation of head and neck cancers, these cancers account for 11.5 per 100,000 population in G.C.C states. Concomitant chemotherapy and external beam radiotherapy (EBRT) is indicated in such cancers with aim of organ preservation, control and possible cure. Hyper fractionated radiotherapy with concomitant chemotherapy or cetuximab is a lesser explored option. In this study we wish to assess the tolerability and efficacy of cetuximab with altered fractionation and compare this with the chemotherapy (cisplatin). MATERIALS AND METHODS: This is a randomized controlled study from a single institute in Kuwait. Locally advanced head and neck cancer cases excluding cancer nasopharynx are enrolled for the study. Stage III or stage IV-A cases were enrolled with histopathology squamous cell carcinoma. Patients were randomized into 2 arms. Arm A: to receive platinum-based CT i.e. cisplatin in a dose of 100 mg/m2 3-weekly or 40 mg/m2 weekly during radiation; Arm B: received cetuximab with a loading dose 400 mg/m², one week before radiation followed by weekly dose of 250 mg/m² during radiation. Radiotherapy was delivered using intensity modulated radiotherapy (IMRT) or 3D-conformal radiotherapy (CRT). The primary objective was to evaluate whether the use of cetuximab with concurrent hyperfractionated radiation regimen will have loco regional control rates (LC) and Disease-free survival (DFS) that are comparable to concurrent cisplatin in patients with LAHNC. The secondary endpoints were to compare the impact of using concurrent cetuximab vs chemotherapy regimen on Overall Survival of patients (OS) and acute and late adverse events. RESULTS: From November 2012 to November 2017, 40 patients were randomized. The median age of was 51 years (range 27-72 years). Thirty-five patients are male and remaining was female. 14 patients have their primaries in larynx, 11 in oropharynx, 8 in oral cavity, and 5 has tumor in hypopharynx. Two patients had disease in nasal sinus or overlapping subsides. 50% has T4 lesions while 35% has T3 lesions, Nodal status was (N0-1) in 20 patients and (N2-3) in 20 patients. Overall staging showed a majority to have stage IV disease (63%). HPV was negative in 2 cases in Arm 1 and positive in 2 cases in Arm 2. 22 patients were randomly allocated in Arm A (platinum-based) while 18 were in Arm B (cetuximab). CR was achieved in 59% in arm A vs 50% in Arm B, while PR was 27.3% and 27.8% respectively. Disease progressed in 2 patients in Arm B only. Out of these 40 patients, 14 patients failed (6 and 8 in arm A and B respectively). Locoregional failure was documented in 6 (27.3%) vs 7 (38.9%) of arm A and B respectively, which was statistically not significant possibly related with lower number of cases. 2 years DFS was 56.5% vs 77.3% in cisplatin vs cetuximab arm (denoting nonsignificant increase of relapse rate in cisplatin arm). However, 2 years OS was 80.7% vs 57.3% in cisplatin and cetuximab arm respectively (p value=0.04). CONCLUSION: Though cetuximab has lesser side effects but it is not indicated in treatment of LAHNC. Concurrent cisplatin is a trusted option for concomitant setting regardless of the HPV status and tumor location. However, in the context of cisplatin ineligible patients, cetuximab should be used only with hyper fractionation. This preliminary study could represent a good core of large international multicenter RCT.