Modified bi-weekly cetuximab-cisplatin and 5-FU/leucovorin based regimen for effective treatment of recurrent/metastatic head and neck squamous cell carcinoma to reduce chemotherapy exposure of patients.

BACKGROUND: The standard chemotherapy treatment protocol for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) requires as long as 56 days of hospitalization over six months. Where the 5-Fluorouracil (5-FU) pump is available, most treatment will be on outpatient bases, however patients will still be under chemotherapy treatment for a comparable period of time (around 50 days). AIM: A modified protocol was assessed to decrease hospitalization and/or chemotherapy treatment time without sacrificing outcomes, to potentially increase patient quality of life. METHODS AND RESULTS: A retrospective analysis (2005-2018) of recurrent/metastatic HNSCC patients with a modified treatment protocol was performed. Treatment consisted of cisplatin, cetuximab, 5-fluorouracil bolus and leucovorin administered on day 1 of a 2-week cycle, and a continuous infusion of 5-fluorouracil on days 1-2 of the cycle. Outcomes were measured by progression-free survival, overall survival, and patient hospitalization time. Analysis was done using the Kaplan-Meier survival function curve. The study cohort consisted of 27 patients. The modified treatment protocol resulted in a median progression-free survival of nine months and median overall survival of 14 months, while hospitalization time was reduced by almost 80% in the first six months of treatment. CONCLUSIONS: Modification of the cisplatin, cetuximab, 5-FU and leucovorin protocol to a bi-weekly regimen utilizing alternative drug delivery methods, significantly reduced patient hospitalization from 56 days to 12 days in the first 6 months of treatment. This was achieved without compromising treatment outcome, while significantly reducing the days patients were exposed to chemotherapy, and thus potentially improving quality of life.

The potential of somatostatin receptor 2 as a novel therapeutic target in salivary gland malignant tumors.

BACKGROUND: Treatment regimens for patients with metastatic or recurrent post-radiation, locoregional, unresectable salivary cancer are limited. An inverse correlation between somatostatin receptor 2 (SSTR2) and the proliferating marker Ki-67 in neuroendocrine tumors has enabled a treatment plan for metastatic disease, utilizing peptide receptor radionuclide therapy. Interestingly, healthy salivary glands express high levels of SSTR2. In this study, the presence of SSTR2, its correlation with Ki-67 in glandular salivary carcinomas and the clinical applicability thereof was determined. METHODS: In the retrospective part of this study, 76 adequate tumor tissue specimens obtained from patients diagnosed with primary or metastatic salivary carcinomas between 1988 and 2016, were collected for tissue array and histologically classified. Immunohistochemistry was performed to determine the presence, relative expression and potential correlation of SSTR2 and Ki-67. The clinical significance of SSTR2 expression was determined by prospectively assessing 68Ga-DOTATATE uptake using PET-CT imaging, in patients diagnosed with metastatic salivary gland malignant tumors between 2015 and 2016. RESULTS: Sixty-three primary cancer tumors and 14 metastatic tumors were tested. All tumor subtypes were found to express SSTR2 to some extent. The highest expression was seen in Mucoepidermoid carcinoma (MEC) tissues where the majority of specimens (86.4%) expressed SSTR2. A relatively strong immunohistochemical staining score for SSTR2 was observed in MEC, adenoid cystic carcinoma and polymorphous adenocarcinoma. Interestingly, an inverse correlation between SSTR2 and Ki-67 expressions was observed (44%) in MEC tissue. Uptake of 68Ga-DOTATATE was visualized using PET-CT imaging in 40% of patients, across metastatic MEC and ACC. All observations were found to be statistically significant. CONCLUSION: This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.

Assessment of jaw osteonecrosis diagnostic criteria in cancer patients with a history of radiation therapy and exposure to bone-modifying agents.

BACKGROUND: Osteoradionecrosis (ORN) of the jaw is currently defined by the development of osteonecrosis in head/neck irradiated patients, regardless of lesion exposure. To diagnose medication-related osteonecrosis of the jaw (MRONJ), a history of any radiation therapy to the jaw region must be ruled out. The aim of this study was to assess the accuracy of current osteonecrosis criteria, while introducing new modifications for improved diagnosis and treatment. METHODS: One hundred and forty-one necrotic lesions were analyzed from patients exposed to bone-modifying agents (BMAs) and/or received head and neck regional radiation therapy, where the maximal dose of radiation exposure to the jaw osteonecrosis site was calculated. Modified diagnostic criteria were used to reassess all cases and a comparison of outcomes was performed using Pearson's Chi-Square/Fisher's exact test. RESULTS: Only in patients with primary head and neck carcinomas did the maximal mean radiation dose in the necrotic jaw site reach ranges associated with ORN formation (>40 Gy), with individual cases showing exposures as low as 0-2 Gy. Based on the modified diagnostic criteria almost 2/3 of the necrotic cases diagnosed as ORN should be diagnosed as MRONJ. CONCLUSIONS: ORN diagnosis should only be considered in cases of radiation exposure >40 Gy to prevent misdiagnosis and suboptimal treatment. A modified criterion for MRONJ diagnosis is recommended where radiation exposure <40 Gy in the necrotic site is included. In cases with exposure >40 Gy and BMA administration, an additional modification to diagnostic criteria of 'medication- and radiation-related osteonecrosis of the jaw', should be used.