p16INKa immunocytochemistry in fine-needle aspiration cytology smears of metastatic head and neck squamous cell carcinoma.

OBJECTIVES: Patients with head and neck squamous cell carcinoma (HNSCC) may initially present with neck metastases diagnosed by fine-needle aspiration (FNA). In these patients, it is critical to locate the primary site so that targeted therapy can be administered. Nearly a quarter of HNSCC are associated with human papillomavirus (HPV) infection. The great majority of HPV-related primaries originate in the oropharynx. p16INKa (p16) functions as a surrogate marker of HPV infection. We sought to determine if expression of p16 by immunocytochemistry (ICC) in neck metastases could assist in localizing the primary site to the oropharynx. STUDY DESIGN: Diagnostic FNA cytology smears of neck metastases from 90 patients with biopsy-proven primary HNSCC were reviewed. Papanicolaou-stained slides were directly subjected to ICC, using p16 antibody. RESULTS: Twenty-seven (30%) tumors expressed p16 by ICC; 74% of these p16-positive tumors were metastases from oropharynx. There was a significantly higher proportion of p16 expression in patients with primary oropharyngeal carcinoma (47%) versus those whose primary tumor was non-oropharyngeal (15%; p = 0.0013). CONCLUSIONS: p16 expression in FNA cytology smears of metastatic HNSCC is a useful indicator of oropharyngeal origin and can be used to help localize the primary site in cases where this is not clinically evident.

A phase 1 trial of E7974 administered on day 1 of a 21-day cycle in patients with advanced solid tumors.

BACKGROUND: E7974, a synthetic analog of hemiasterlin, interacts with the tubulin molecule and overcomes resistance to other antitubulin drugs (taxanes and vinca alkaloids). METHODS: In a phase 1 study, E7974 was given intravenously over a 2- to 5-minute infusion on day 1 of every 21-day cycle. Adult patients with advanced refractory solid tumors who had adequate organ function and Eastern Cooperative Oncology Group performance status 0 to 2 were eligible for this study. A modified Fibonacci schema was used. The maximal tolerated dose (MTD) was the dose where <2 of 6 patients developed a dose-limiting toxicity (DLT). RESULTS: Twenty-eight patients (19 men and 9 women; median age, 64 years) treated at different cohort dose levels (0.18 mg/m(2) , 0.27 mg/m(2) , 0.36 mg/m(2) , 0.45 mg/m(2) , and 0.56 mg/m(2) ) received a total of 66 courses of E7974. The MTD was established at 0.45 mg/m(2) , where 1 of 6 patients experienced DLT (grade 4 febrile neutropenia). Of the 17 refractory colon cancer patients with a median of 3 prior treatments, stable disease was seen in 7 patients (41%). There were no tumor responses. Median progression-free survival was 1.2 months, and median overall survival was 6.7 months. In pharmacokinetic analysis, E7974 was characterized by a fast and moderately large distribution (37.95-147.93 L), slow clearance (2.23-7.15 L/h), and moderate to slow elimination (time to half-life, 10.4-30.5 hours). CONCLUSIONS: This study shows that E7974 once every 21-day cycle shows antitumor activity in patients with refractory solid tumors. The recommended phase 2 dose is 0.45 mg/m(2).

Accelerated partial breast irradiation is safe and effective using intensity-modulated radiation therapy in selected early-stage breast cancer.

PURPOSE: To report the feasibility, toxicity, cosmesis, and efficacy of using intensity-modulated radiation therapy (IMRT) with respiratory gating to deliver accelerated partial breast irradiation (APBI) in selected Stage I/II breast cancer after breast-conserving surgery. METHODS AND MATERIALS: Eligible patients with node-negative Stage I/II breast cancer were prospectively enrolled in an institutional review board approved protocol to receive APBI using IMRT after breast-conserving surgery. The target volume was treated at 3.8 Gy/fraction twice daily for 5 days, to a total dose of 38 Gy. RESULTS: Thirty-six patients were enrolled for a median follow-up time of 44.8 months. The median tumor size was 0.98 cm (range, 0.08-3 cm). The median clinical target volume (CTV) treated was 71.4 cc (range, 19-231 cc), with the mean dose to the CTV being 38.96 Gy. Acute toxicities included Grade 1 erythema in 44% of patients and Grade 2 in 6%, Grade 1 hyperpigmentation in 31% of patients and Grade 2 in 3%, and Grade 1 breast/chest wall tenderness in 14% of patients. No Grade 3/4 acute toxicities were observed. Grade 1 and 2 late toxicities as edema, fibrosis, and residual hyperpigmentation occurred in 14% and 11% of patients, respectively; Grade 3 telangiectasis was observed in 3% of patients. The overall cosmetic outcome was considered "excellent" or "good" by 94% of patients and 97% when rated by the physician, respectively. The local control rate was 97%; 1 patient died of a non-cancer-related cause. CONCLUSIONS: APBI can be safely and effectively administered using IMRT. In retrospective analysis, IMRT enabled the achievement of normal tissue dose constraints as outlined by Radiation Therapy Oncology Group 04-13/NSABP B-13 while providing excellent conformality for the CTV. Local control and cosmesis have remained excellent at current follow-up, with acceptable rates of acute/late toxicities. Our data suggest that cosmesis is dependent on target volume size. Further prospective multi-institutional trials should be performed to evaluate IMRT to deliver APBI.

Association between non-Hodgkin lymphoma and renal cell carcinoma.

The incidence of patients with multiple primary tumors has been increasing in recent years. The association between non-Hodgkin lymphomas (NHL) and renal cell carcinoma (RCC) is unclear. The presentation of 10 patients with co-existent NHL and RCC at our institution in the past 3 years led us to explore whether this was a chance association or a statistically significant phenomenon. We used the US Surveillance, Epidemiology and End Results (SEER) program (www.seer.cancer.gov) from 1973 to 2006 to identify a total of 892 445 537 subjects aged 18-84, with known values for race and gender at risk for NHL and RCC. Among these, 181 009 were diagnosed with NHL, 118 122 were diagnosed with RCC and 1039 had both NHL and RCC. This was significantly higher than the expected number of 24 with co-existent NHL and RCC (p < 0.0001). The observed number (O) of RCC after NHL was significantly higher than the expected number (E) (O/E: 1.51; 95% confidence interval [CI] 1.36-1.66), with the O/E ratio remaining elevated across the various follow-up time intervals. The observed number of NHL after RCC was not significantly different from the expected number (O/E: 1.09; 95% CI 0.98-1.22). In univariate analyses, race and gender were significantly associated with an increased cumulative incidence of RCC after NHL. Multivariate analysis with age, race and gender revealed that white males had a higher cumulative incidence of RCC after NHL. These findings suggest that patients with NHL are at increased risk for RCC.

Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer.

In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2-negative MBC received gemcitabine 1500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28-day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6-15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1-90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab-P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study.