Sandeep Samant

Head and Neck Cancers

Recent evidence suggests that dysregulated translation and its control significantly contribute to the etiology and pathogenesis of the head and neck cancers, specifically to that of squamous cell carcinoma (HNSCC). eIF4E is one of the most studied components of the translation machinery implicated in the development and progression of HNSCC. It appears that dysregulation of eIF4E levels and activity, namely by the PI3K/AKT/mTOR pathway, plays an important role in the etiology and pathogenesis of HNSCC and correlates with clinical outcomes. In this chapter, we will discuss the role of eIF4E and some other translation factors as they relate to the biology and treatment of HNSCC.

Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

PURPOSE Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. PATIENTS AND METHODS Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). RESULTS A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. CONCLUSION IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN.

Head and neck cancers, version 1.2015 featured updates to the NCCN guidelines

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).

Concomitant radiation therapy and targeted cisplatin chemotherapy for the treatment of advanced pyriform sinus carcinoma : disease control and preservation of organ function

Squamous cell carcinoma of the pyriform sinus is an unfavorable disease which frequently presents in advanced stages. Despite aggressive “standard treatment” involving debilitating surgery and postoperative radiation therapy treatments, the survival and functional outcome for pyriform sinus carcinoma remains poor. Hence, we reviewed our experience in the management of advanced pyriform sinus carcinoma using “organ preservation” chemoradiation therapy.

Factors predictive of poor functional outcome after chemoradiation for advanced laryngeal cancer.

OBJECTIVE: The study goal was to determine whether pretreatment parameters can be used to predict poor outcomes related to laryngeal function among survivors after organ preservation therapy for advanced laryngeal cancer. DESIGN: A retrospective analysis of patients treated in an ongoing chemoradiation trial. SETTING: Academic tertiary care referral medical center. PATIENTS AND METHODS: Among the 65 patients receiving concomitant intra-arterial cisplatin and radiation therapy for stage III and IV laryngeal cancer between 1993 and 1999, we identified 45 who were available for follow-up and were disease free 6 months after the completion of therapy. A nominal logistic regression analysis was performed to study the effect of age, gender, T and N classification, vocal cord fixation, massive cartilage destruction, and neck dissection on the likelihood of requiring a tracheostomy tube for breathing and/or a gastrostomy tube for feeding at 6 months after the completion of therapy. MAIN OUTCOME MEASURE: Persistent use of gastrostomy tube feedings and/or tracheostomy at 6 months after the completion of therapy. RESULTS: Sixteen patients (36%) required a feeding tube and/or a tracheostomy (tracheostomy 13, gastrostomy 13, both 10). Regression analysis of all pretreatment factors indicated vocal cord fixation as being the strongest predictor of a poor functional outcome (defined as the persistent need for a feeding tube and/or tracheostomy at 6 months after therapy). Among the 27 patients in this subset, 15 (56%) had a poor functional outcome. In contrast, only 1 (6%) of 18 patients without vocal cord fixation had poor laryngeal function. Although the history of pulmonary disease was not a significant parameter by itself, when combined with vocal cord fixation, 6 of 8 patients had a poor functional outcome. CONCLUSION: Pretreatment parameters may be used to predict a poor functional outcome after chemoradiation. Because of the high likelihood of poor function, laryngeal cancer patients seeking organ preservation therapy with chemoradiation should be cautioned if they present with a fixed vocal cord.

Pro-inflammatory genes as biomarkers and therapeutic targets in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a major health problem worldwide, and patients have a particularly poor 5-year survival rate. Thus, identification of the molecular targets in OSCC and subsequent innovative therapies are greatly needed. Prolonged exposure to alcohol, tobacco, and pathogenic agents are known risk factors and have suggested that chronic inflammation may represent a potential common denominator in the development of OSCC. Microarray analysis of gene expression in OSCC cell lines with high basal NF-κB activity and OSCC patient samples identified dysregulation of many genes involved in inflammation, wound healing, angiogenesis, and growth regulation. In particular IL-8, CCL5, STAT1, and VEGF gene expression was up-regulated in OSCC. Moreover, IL-8 protein levels were significantly higher in OSCC cell lines as compared with normal human oral keratinocytes. Targeting IL-8 expression by siRNA significantly reduced the survival of OSCC cells, indicating that it plays an important role in OSCC development and/or progression. Inhibiting the inflammatory pathway by aspirin and the proteasome/NF-κB pathway by bortezomib resulted in marked reduction in cell viability in OSCC lines. Taken together our studies indicate a strong link between inflammation and OSCC development and reveal IL-8 as a potential mediator. Treatment based on prevention of general inflammation and/or the NF-κB pathway shows promise in OSCCs.

The treatment of advanced sinonasal malignancies with pre-operative intra-arterial cisplatin and concurrent radiation

Introduction: Malignancies of the nasal and paranasal sinuses are uncommon tumors, accounting for only 3% of all aerodigestive tract neoplasms. Despite advances in surgical techniques and continued evolution of adjuvant therapies, the 5-year mortality remains unusually high at greater than 50%. In 1996, we begin utilizing a novel strategy in the treatment of advanced sinonasal carcinomas. This consisted of neoadjuvant selective intra-arterial cisplatin with concurrent radiation therapy (acronym RADPLAT) followed by a conservative craniofacial resection. We now report our results for 11 patients treated with this regimen.Methods: Between July 1996 and April 2003, 11 patients with advanced sinonasal malignancies underwent treatment utilizing the RADPLAT protocol followed by a planned surgical resection via a craniofacial approach. Patient charts, operative notes, follow-up clinic notes, and pre- and post-operative imaging studies were reviewed in detail for each subject.Results: Histopathological analysis of the tumors revealed seven squamous cell carcinomas (64%), two adenocarcinomas (18%), one adenoid cystic carcinoma (9%), and one sinonasal undifferentiated carcinoma (9%). T4N0M0 disease was present in nine patients (81%), and two patients had T3N0M0 disease (19%). Survival was calculated using the Kaplan–Meier method with an overall survival of 81% at 5 years and a progression-free survival at 5 years of 67%. Mean follow-up is 57.2 months ranging from 12 to 95 months.Conclusions: The treatment of advanced sinonasal malignancies with pre-operative intra-arterial cisplatin and concurrent radiation results in a significant improvement in survival. This can be done safely with high response rates and excellent loco-regional control in T3 and T4 disease. Although are results are encouraging, there is a need for a cooperative, multi-institutional, prospective study.

Gastrostomy Tubes in Patients with Advanced Head and Neck Cancer

Objectives: To measure the percentage of patients requiring gastrostomy tubes (G‐tubes) and the timing of their placement, in addition to studying whether pretreatment variables (T stage, tumor site, N stage) and intratreatment variables (weight loss during treatment) are valid predictors for the need for G‐tube placement.

Concurrent chemoradiation for adenoid cystic carcinoma of the head and neck

We performed a retrospective review of patients with nonresected head and neck adenoid cystic carcinoma (ACC) treated with concurrent chemoradiation.

Incidence and risk factors of bisphosphonate-associated osteonecrosis of the jaws.

Intravenous bisphosphonate therapy has been used for treatment of benign and malignant bone diseases and has been linked to osteonecrosis of the jaws.