Treatment of oropharyngeal squamous cell carcinoma with IMRT: patterns of failure after concurrent chemoradiotherapy and sequential therapy.

BACKGROUND: The optimal management of oropharyngeal squamous cell carcinoma (OPSCC) is controversial. Modern radiotherapy typically employs intensity-modulated radiation therapy (IMRT), and herein, we report the Dana-Farber Cancer Institute (DFCI) experience with IMRT-based treatment of OPSCC. DESIGN: Retrospective study of all patients treated at DFCI for OPSCC with definitive or adjuvant IMRT between 8/04 and 8/09. The primary end point was overall survival (OS); secondary end points were locoregional control (LRC) and freedom from distant metastases (FFDM). Propensity score matching was used to create concurrent chemoradiotherapy (CCRT) and sequential therapy (ST) cohorts equally balanced for patient and disease characteristics. RESULTS: One hundred and sixty-three patients were included with 75% presenting with stage IV disease. Fifty-six patients (34%) were treated with ST. The three-year actuarial OS, LRC, and FFDM rates for the entire cohort/ST subset were 86%/89%, 86%/87%, and 88%/93%, respectively. There were no differences in OS, LRC, or FFDM between CCRT and ST in the propensity-matched cohort. CONCLUSIONS: IMRT was associated with excellent OS, LRC, and FFDM. Although the results following ST were superb, there was no obvious benefit to ST after adjustment for selection bias. We recommend that ST be reserved for medically fit patients with a high risk of distant metastases.

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck.

BACKGROUND: Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III-IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT. RESULTS: Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m(2) (n = 3) and 30 mg/m(2) (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free. CONCLUSIONS: Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.

Phase I/II trial of outpatient docetaxel, cisplatin, 5-fluorouracil, leucovorin (opTPFL) as induction for squamous cell carcinoma of the head and neck (SCCHN).

The purpose of this study was to establish the maximum tolerated dose (MTD) of docetaxel in an outpatient docetaxel (T), cisplatin (P), 5-fluorouracil (5-FU) (F), and leucovorin (L) (opTPFL) regimen and to obtain preliminary assessment of opTPFL efficacy. Thirty-four patients with stage III or IV squamous cell carcinoma of the head and neck were treated with opTPFL. Docetaxel was escalated from 60 to 95 mg/m(2) in combination with 100 mg/m(2) cisplatin intravenous bolus, and 2,800 mg/m(2) 5-FU continuous infusion and 2,000 mg/m(2) leucovorin continuous infusion with prophylactic growth factors and antibiotics. Patients who achieved a complete (CR) or partial (PR) response to three cycles received definitive twice-daily radiation therapy. A total of 97 cycles were administered to 34 patients. The major acute toxicities were neutropenia and mucositis. The MTD of docetaxel was 90 mg/m(2) . Seventy-seven of 97 cycles of were administered on an outpatient basis. The overall clinical response rate to opTPFL was 94%, with 44% CRs and 50% PRs. The MTD of opTPFL is 90 mg/m(2) docetaxel. Outpatient administration of opTPFL is tolerable, feasible, and does not alter the ability to administer definitive radiation therapy on schedule.

Self-induced pneumoparotitis.

Pneumoparotitis is a rare cause of enlargement of the parotid gland; it is often misdiagnosed and therefore incorrectly treated. We report three pediatric cases of self-induced pneumoparotitis and detail the clinical presentation, pathogenesis, radiographic findings, and treatment options. We also review the literature on the subject. In children, inflammatory swelling of the parotid gland is usually due to acute viral or bacterial infection, juvenile recurrent parotitis, or allergic, autoimmune, or systemic disease. Infrequently, swelling may result from air being forced through Stensen's duct, resulting in pneumoparotitis. This may occur as a transient or recurrent phenomenon. Recurrent parotid insufflation is not entirely benign and may predispose to sialectasias, recurrent parotitis, and even subcutaneous emphysema.

Representations of self across the life span.

This research extends a cognitive-developmental approach to examining age differences in self-representation from adolescence to mature adulthood and later life. The authors suggest that mature adults move from representations of self that are relatively poorly differentiated from others or social conventions to ones that involve emphasis on process, context, and individuality. Participants (n men = 73, n women = 76), ranging in age from 11 to 85 years, provided spontaneous accounts of their self-representations and responded to measures assessing cognitive and emotional functioning and broad dimensions of personality. On average, self-representation scores peaked in middle-aged adults and were lowest in the preadolescent and older adult age groups. Level of self-representation was related to cognitive and personality variables, but there was some evidence that the pattern of correlates shifted from younger (ages 15-45) to older (ages 46-85) age segments.

Distraction osteogenesis for reconstruction of mandibular symphyseal defects.

OBJECTIVE: We investigated the feasibility of arched trifocal distraction osteogenesis for reconstruction of mandibular symphyseal defects. DESIGN: Four adult canine subjects were used. An external apparatus was designed to allow trifocal distraction around an arc. An anterior mandibulectomy was performed between the third premolars bilaterally. The bony defect was regenerated using trifocal distraction osteogenesis at a rate of 1 mm a day bilaterally. New arced bone was produced over a period of 20 to 35 days. The apparatus functioned as an external fixator for the ensuing 6 weeks. The apparatus was then removed, the dogs were returned to their preoperative diet, and were killed after 2 weeks of observation. MAIN OUTCOME MEASURES: Grossly a smooth arc of bone was formed measuring 4.5 to 5.5 cm in length, 2.2 to 3.0 cm in height, and 1.3 to 1.5 cm in width. Histologically all specimens demonstrated direct membranous bone growth. Radiographically opaque columns were seen streaming in the direction of distraction. CONCLUSIONS: Symphyseal bony defects resulting from oncologic resection, trauma, and congenital deformities create tremendous cosmetic and functional handicaps and have remained extremely challenging to surgically reconstruct. This study demonstrates the ability to use arced trifocal distraction osteogenesis to reconstruct anterior mandibulectomy defects in a canine model. This method may provide a satisfactory solution to a difficult problem in human mandibular reconstruction.