Induction chemotherapy followed by concurrent chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma with HPV and P16 testing.

OBJECTIVE: The objective was to report our experience with advanced stage oropharyngeal squamous cell carcinoma treated sequentially with induction chemotherapy followed by concurrent chemoradiotherapy. METHODS: Retrospective chart review identified 49 eligible patients with advanced stage oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiotherapy. HPV and p16(INK4A) testing was performed on pathology specimens. Follow-up of over 11 months was required unless a death or treatment failure occurred before that time. RESULTS: Treatment with induction chemotherapy followed by concurrent chemoradiotherapy resulted in 44/48 (90%) complete durable response. One death occurred from pulmonary embolism. Toxicity profiles were comparable to other published data. Average follow-up was 3.9 years. Oncologic failure rates among subgroups showed 5.7% failure for HPV+/p16+ cancer, 9.1% failure for HPV-/p16+ cancer, 100% failure for HPV-/p16- cancer, 0% failure for nonsmokers, and 17.9% failure for smokers. CONCLUSIONS: This study showed favorable outcomes in terms of durable oncologic response and acceptable toxicity profiles. It is notable that 36/49 patients were HPV+/p16+ and 11/49 were HPV-/p16+. Only 2 patients were HPV-/p16-, and both died as a result of oncologic failures. This highlights the importance of obtaining HPV and p16 testing in studies evaluating the efficacy of treatments for oropharyngeal squamous cell carcinoma.

Impact of treatment sequence of multimodal therapy for advanced oral cavity cancer with mandible invasion.

OBJECTIVE: To determine the effect of treatment sequence of multimodal therapy for clinically advanced squamous cell carcinoma (SCC) of the oral cavity (OC) with mandible invasion. STUDY DESIGN: Case series with chart review. SETTING: University-based, tertiary care hospitals. SUBJECTS AND METHODS: The authors retrospectively analyzed 70 patients presenting between January 2000 and January 2010 with newly diagnosed, previously untreated SCC of the OC with mandible invasion that we deemed resectable (stages IVa, b). Patients with evidence of distant metastases or a second primary malignancy were excluded. All patients were presented at a multidisciplinary tumor board for prospective planning of trimodality therapy (surgery, radiation therapy, chemotherapy). When performed, surgery included segmental mandibulectomy. Radiotherapy was delivered using standard intensity-modulated radiation therapy technique. Study patients were divided into 2 groups: group 1 received induction chemotherapy and/or concurrent chemoradiation followed by surgery, and group 2 was treated with primary resection followed by chemoradiation. MAIN OUTCOME MEASURE: Progression-free survival (PFS). RESULTS: Eighteen patients (26%) comprised group 1, and 52 patients (74%) comprised group 2. The groups were matched in oral cavity subsite, tumor differentiation, tumor characteristics of aggressiveness (perineural and lymphovascular invasion), extent of mandible invasion, and cervical node status. The 5-year PFS for group 1 (33.3%) was not significantly different from that for group 2 (32.3%; P = .643). CONCLUSION: Advanced OC cancer with mandible invasion is an ominous disease. Although treatment must be individualized, our data suggest no clear advantage to any specific sequence of multimodality therapy affecting PFS.

uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues.

Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively.

Routine computed tomography screening of the chest in high-risk cardiac transplant recipients may improve survival.

BACKGROUND: Multiple studies have demonstrated an increased incidence of lung cancer in the heart transplant population. We reviewed our cardiac transplantation experience with respect to the development of bronchogenic carcinoma and explored the role of routine chest computed tomography (CT) in its surveillance. METHODS: We performed a review of our cardiac transplantation experience, highlighting the incidence of lung cancer, and we analyzed our recent experience with screening chest CT in lung cancer surveillance in this patient group. RESULTS: Eighteen patients developed 20 cases of bronchogenic carcinoma for an incidence of 6.83%. In 10 cases, the patients underwent surgical resection; however, in the remaining cases, the patients were either treated with chemotherapy and/or radiation or they died before initiation of therapy. The actuarial 1-, 2- and 5-year overall survival rates were 49%, 29% and 13%, respectively. The median survival of patients who underwent surgical resection was 28 months (3 to 85 months), whereas the median survival of patients who were either ineligible for surgery or died before initiation of treatment was only 1 month (1 to 13 months). All patients diagnosed with lung cancer by chest CT underwent surgical resection; however, only 37.5% of patients diagnosed with lung cancer by chest X-ray were found at an appropriate stage for resection (p = 0.025). CONCLUSIONS: Cardiac transplant recipients have a significant risk of developing bronchogenic carcinoma. Routine chest CT screening in high-risk patients may enable clinicians to identify disease earlier, which is essential for the option of surgical resection and, therefore, prolonged survival.

HER-2 gene amplification can be acquired as breast cancer progresses.

Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 +/- 2.72 vs. 2.8 +/- 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.