Effect of endoscopic brow lift on contractures and synkinesis of the facial muscles in patients with a regenerated postparalytic facial nerve syndrome.

BACKGROUND: Delayed recovery after facial palsy results in aberrant nerve regeneration with symptomatic movement disorders, summarized as the postparalytic facial nerve syndrome. The authors present an alternative surgical approach for improvement of periocular movement disorders in patients with postparalytic facial nerve syndrome. The authors proposed that endoscopic brow lift leads to an improvement of periocular movement disorders by reducing pathologically raised levels of afferent input. METHODS: Eleven patients (seven women and four men) with a mean age of 54 years (range, 33 to 85 years) and with postparalytic facial nerve syndrome underwent endoscopic brow lift under general anesthesia. Patients' preoperative condition was compared with their postoperative condition using a retrospective questionnaire. Subjects were also asked to compare the therapeutic effectiveness of endoscopic brow lift and botulinum toxin type A. RESULTS: Mean follow-up was 52 months (range, 22 to 83 months). No intraoperative or postoperative complications occurred. During follow-up, patients and physicians observed an improvement of periorbital contractures and oculofacial synkinesis. Scores on quality of life improved significantly after endoscopic brow lift. Best results were obtained when botulinum toxin type A was adjoined after the endoscopic brow lift. Patients described a cumulative therapeutic effect. CONCLUSIONS: These findings suggest endoscopic brow lift as a promising additional treatment modality for the treatment of periocular postparalytic facial nerve syndrome-related symptoms, leading to an improved quality of life. Even though further prospective investigation is needed, a combination of endoscopic brow lift and postsurgical botulinum toxin type A administration could become a new therapeutic standard.

The lateral crural underlay spring graft.

The objective of this study is to evaluate the functional and aesthetic results obtained from the use of the lateral crural underlay spring (LCUS) graft for the treatment of internal and external nasal valve collapse. In this retrospective study, preoperative and postoperative functional and aesthetic results were compared in patients undergoing treatment for internal or external nasal valve collapse. Results were scored by means of a questionnaire and visual analog scale completed by the patients. Eight patients were recruited and included in this study: 6 (75%) had an improvement in their functional scores, 1 (12%) remained unchanged, and 1 (12%) scored worse. The mean difference in functional scores after the intervention was 9.4 points (p < 0.005). There was no significant difference in aesthetic scores. We found evidence that the LCUS graft is effective for relieving nasal obstruction in patients with internal, external, or combined nasal valve collapse. The amount of increased sidewall tension and rigidity as well as the increase in nasal valve angle and cross-sectional area are determined by the length of the graft, which can be varied according to need.

Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients.

UNLABELLED: Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter (89)Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans (89)Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the (89)Zr-labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. METHODS: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of (89)Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo radioactivity measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. RESULTS: (89)Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% +/- 16.9% [mean +/- SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, -8.4% +/- 34.5%). The mean absorbed red marrow dose was 0.07 +/- 0.02 mSv/MBq and 0.09 +/- 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 +/- 0.27 mSv/MBq in men and 1.35 +/- 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 +/- 0.03 mSv/MBq in men and 0.66 +/- 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. CONCLUSION: (89)Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients.

PURPOSE: Immuno-positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 ((89)Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with (89)Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases. EXPERIMENTAL DESIGN: Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq (89)Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with (18)F-fluoro-2-deoxy-d-glucose. Immuno-PET scans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis. RESULTS: Immuno-PET detected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumor-involved neck levels and sides, immuno-PET and (18)F-fluoro-2-deoxy-d-glucose PET gave comparable diagnostic results. CONCLUSION: In this study, immuno-PET with (89)Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.

Radioimmunodetection and radioimmunotherapy of head and neck cancer.

Radiolabeled monoclonal antibodies (MAbs) can add a dimension to diagnostic imaging and staging of metastatic head and neck cancer, as well as in eradication of this disease. The vast majority of malignancies arising in the oral cavity, pharynx and larynx are squamous cell carcinomas. This common cellular origin makes it attractive to search for appropriate tumor-associated antigens, which are preferentially expressed in these neoplasms. Radiolabeled MAbs directed against these antigens can be used for tumor detection and selective therapy, known as radioimmunoscintigraphy and radioimmunotherapy, respectively. The combination of MAbs with positron emission tomography (PET) is an attractive novel option to improve tumor detection and to facilitate MAb quantification in a therapeutic setting. Basic aspects of tumor targeting with MAbs, as well as a review of the clinical trials reported in the literature, including own results, are presented.

Dosimetric analysis of radioimmunotherapy with 186Re-labeled bivatuzumab in patients with head and neck cancer.

UNLABELLED: From December 1999 until July 2001, a phase I dose escalation study was performed with (186)Re-labeled bivatuzumab, a humanized monoclonal antibody against CD44v6, on patients with inoperable recurrent or metastatic head and neck cancer. The aim of the trial was to assess the safety and tolerability of intravenously administered (186)Re-bivatuzumab and to determine the maximum tolerated dose (MTD) of (186)Re-bivatuzumab. The data were also used for dosimetric analysis of the treated patients. Dosimetry is used to estimate the absorbed doses by nontarget organs, as well as by tumors. It can also help to explain toxicity that is observed and to predict organs at risk because of the therapy given. METHODS: Whole-body scintigraphy was used to draw regions around sites or organs of interest. Residence times in these organs and sites were calculated and entered into the MIRDOSE3 program, to obtain absorbed doses in all target organs except for red marrow. The red marrow dose was calculated using a blood-derived method. Twenty-one studies on 18 patients, 5 female and 16 male, were used for dosimetry. RESULTS: The mean red marrow doses were 0.49 +/- 0.03 mGy/MBq for men and 0.64 +/- 0.03 mGy/MBq for women. The normal organ with the highest absorbed dose appeared to be the kidney (mean dose, 1.61 +/- 0.75 mGy/MBq in men and 2.15 +/- 0.95 mGy/MBq in women; maximum kidney dose in all patients, 11 Gy), but the doses absorbed are not expected to lead to renal toxicity. Other organs with doses exceeding 0.5 mGy/MBq were the lungs, the spleen, the heart, the liver, the bones, and the testes. The doses delivered to the tumor, recalculated to the MTD level of 1.85 GBq/m(2), ranged from 3.8 to 76.4 Gy, with a median of 12.4 Gy. A good correlation was found between platelet and white blood cell counts and the administered amount of activity per kilogram of body weight (r = -0.79). CONCLUSION: Dosimetric analysis of the data revealed that the range of doses to normal organs seems to be well within acceptable and safe limits. Tumor doses ranged from 4 to 76 Gy. Given the acceptable tumor doses, (186)Re-labeled bivatuzumab could be a good candidate for future adjuvant radioimmunotherapy in patients with minimal residual disease.

Phase I therapy study with (186)Re-labeled humanized monoclonal antibody BIWA 4 (bivatuzumab) in patients with head and neck squamous cell carcinoma.

PURPOSE: In previous studies, we have shown the potential of radioimmunotherapy (RIT) with (186)Re-labeled chimeric monoclonal antibody (MAb) U36 for treatment of head and neck cancer. A limitation of this anti-CD44v6 MAb, however, appeared to be its immunogenicity, resulting in human antichimeric antibodies in 40% of the patients. Aiming for a less immunogenic anti-CD44v6 MAb, the humanized MAb BIWA 4 (bivatuzumab) was introduced. In the present Phase I RIT study, we determined the safety, maximum tolerated dose (MTD), pharmacokinetics, immunogenicity, and therapeutic potential of (186)Re-labeled BIWA 4 in patients with squamous cell carcinoma of the head and neck. EXPERIMENTAL DESIGN: Twenty patients with inoperable recurrent and/or metastatic head and neck squamous cell carcinoma received a single dose of (186)Re-labeled BIWA 4 in radiation dose-escalation steps of 20, 30, 40, 50, and 60 mCi/m(2). Three patients received a second dose at least 3 months after the initial dose. After each administration, whole-body images as well as planar and tomographic images of the head and neck region were obtained, and the pharmacokinetics and the development of human antihuman antibody responses were determined. Radiation absorbed doses were calculated for whole body, red marrow, organs, and tumor. RESULTS: First and second administrations were all well tolerated, and targeting of tumor lesions proved to be excellent. The only significant manifestations of toxicity were dose-limiting myelotoxicity consisting of thrombo- and leukocytopenia and, to a lesser extent, oral mucositis (grade 2). Grade 4 myelotoxicity was seen in two patients treated with 60 mCi/m(2). The MTD was established at 50 mCi/m(2), at which level dose-limiting myelotoxicity was seen in one of six patients. Stable disease, varying between 6 and 21 weeks, was observed in three of six patients treated at the MTD level. The median tumor dose, recalculated to MTD level, was 12.4 Gy. The absorbed dose in red marrow was 1.82 +/- 0.11 cGy/mCi for males and 2.35 +/- 0.10 for females. Two patients experienced a human antihuman antibody response. Pharmacokinetics showed consistency across patients and within the three patients receiving (186)Re-BIWA 4 on two occasions. CONCLUSIONS: This study shows that (186)Re-labeled BIWA 4 can safely be administered, also in a repeated way. The MTD was established at 50 mCi/m(2). In comparison with the previously described anti-CD44v6 MAb U36, the humanized MAb BIWA 4 seems to be less immunogenic. The fact that antitumor effects were seen in incurable patients with bulky disease justifies the evaluation of RIT with (186)Re-labeled BIWA 4 in an adjuvant setting.