Adorján F. Kovács

Sentinel Node Biopsy in Head and Neck Cancer: Preliminary Results of a Multicenter Trial

Background: The aim was to determine the reliability and reproducibility of sentinel node biopsy (SNB) as a staging tool in head and neck squamous cell carcinoma (HNSCC) for T1/2 clinically N0 patients by means of a standardized technique.Methods: Between June 1998 and June 2002, 227 SNB procedures have been performed in HNSCC cases at six centers. One hundred thirty-four T1/2 tumors of the oral cavity/oropharynx in clinically N0 patients were investigated with preoperative lymphoscintigraphy (LSG), intraoperative use of blue dye/gamma probe, and pathological evaluation with step serial sectioning and immunohistochemistry, with a follow-up of at least 12 months. In 79 cases SNB alone was used to stage the neck carcinoma, and in 55 cases SNB was used in combination with an elective neck dissection (END).Results: In 125/134 cases (93%) a sentinel node was identified. Of 59 positive nodes, 57 were identified with the intraoperative gamma probe and 44 with blue dye. Upstaging of disease occurred in 42/125 cases (34%): with hematoxylin-eosin in 32/125 (26%) and with additional pathological staging in 10/93 (11%). The sensitivity of the technique with a mean follow-up of 24 months was 42/45 (93%). The identification of SNB for floor of mouth (FOM) tumors was 37/43 (86%), compared with 88/91 (97%) for other tumors. The sensitivity for FOM tumors was 12/15 (80%), compared with 30/30 (100%) for other tumor groups.Conclusion: SNB can be successfully applied to early T1/2 tumors of the oral cavity/oropharynx in a standardized fashion by centers worldwide. For the majority of these tumors the SNB technique can be used alone as a staging tool.

Joint Practice Guidelines for Radionuclide Lymphoscintigraphy for Sentinel Node Localization in Oral/Oropharyngeal Squamous Cell Carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

Positron Emission Tomography in Combination With Sentinel Node Biopsy Reduces the Rate of Elective Neck Dissections in the Treatment of Oral and Oropharyngeal Cancer

PURPOSE To assess the impact of a diagnostic ladder including [(18)F]fluorodeoxyglucose positron emission tomography (PET) and lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). PATIENTS AND METHODS Prospectively, 62 patients with resectable T1-3 OOSCC underwent computed tomography (CT) and PET. Patients without neck uptake in PET were defined as cN0 and were accrued for LS/SNB. Results were correlated with histopathology. The traditional guidelines according to CT findings were compared to the actual regimen and the outcome. RESULTS Sensitivity, specificity, validity, and positive and negative predictive value of PET versus CT were 72% v 89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant). Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were found in all 38 patients. Five patients had positive nodes (PET false-negatives) and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were CT-negative would have been treated with selective ND according to the guidelines, and at least 45 neck sides would have had to undergo extensive ND because of positive CT findings (96 of 124 neck sides). In contrast, PET in combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually underwent ND as a result of PET staging, LS/SNB, and intraoperative decision. After a median follow-up of 35 months, two patients (both cN+ve and pN+ve) suffered from neck relapses. CONCLUSION Diagnostics using PET in combination with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared to CT without locoregional hazard.

Cisplatin tumor concentrations after intra-arterial cisplatin infusion or embolization in patients with oral cancer

One neoadjuvant course of intra‐arterial high‐dose cisplatin (cis‐diamminedichloroplatinum [CDDP]) tumor perfusion combined with intravenous sodium thiosulfate (STS) (cisplatin neutralizer) infusion is part of a multimodality concept for treatment of oral cancer. Recently, crystalline cisplatin embolization has been described as a novel treatment variant with increased tumor response rates.

Multimodality Treatment Including Postoperative Radiation and Concurrent Chemotherapy with Weekly Docetaxel is Feasible and Effective in Patients with Oral and Oropharyngeal Cancer

Background:To examine the feasibility and efficacy of weekly docetaxel with concurrent radiation as postoperative treatment in a multimodality approach to oral and oropharyngeal cancer.Patients and Methods:94 patients (Table 1) with primary resectable squamous cell carcinoma of the oral cavity and oropharynx (UICC stage I 14%, II 15%, III 18%, IV 53%; Table 2) were treated with a multimodality therapy program consisting of neoadjuvant intra-arterial high-dose chemotherapy (cisplatin 150 mg/m2 with parallel systemic sodium thiosulfate 9 g/m2 for neutralization), followed by surgery of the primary and neck, and postoperative concurrent radiation and chemotherapy with weekly docetaxel (20–30 mg/m2; Table 3). Chronic toxicities were followed over a period of 5 years.Results:At a median follow-up of 4 years, the 5-year survival rate for all 94 patients was 80%, and disease-free survival was 73% (Figures 1 and 2). Among patients with advanced disease (stage III and IV), survival was 83 and 59%, respectively (Figure 4). Grade 3 and 4 mucositis was the main acute toxicity necessitating supportive care. Long-term toxicity appears to be moderate (Table 4). The maximum tolerated dose of weekly docetaxel was 25 mg/m2.Conclusions:Concurrent radiation and chemotherapy with weekly docetaxel is a feasible postoperative treatment in a multimodality approach to oral and oropharyngeal cancer, resulting in high overall and disease-free survival. This approach warrants further evaluation in prospective randomized trials.Hintergrund:Untersuchung der Durchführbarkeit und Effektivität einer wöchentlichen Docetaxelapplikation bei konkomitanter Bestrahlung in einem multimodalen Behandlungskonzept von Mundhöhlen- und Oropharynxkarzinomen.Patienten und Methoden:94 Patienten (Tabelle 1) mit primären resektablen Plattenepithelkarzinomen der Mundhöhle und des Oropharynx (UICC-Stadium I 14%, II 15%, III 18%, IV 53%; Tabelle 2) wurden mit einem multimodalen Therapiekonzept behandelt, das aus einer neoadjuvanten intraarteriellen Hochdosischemotherapie (150 mg/m2 Cisplatin mit paralleler systemischer Neutralisierung durch 9 g/m2 Natriumthiosulfat), einer Radikaloperation des Primarius und des Halses sowie einer postoperativen konkomitanten Bestrahlung und Chemotherapie mit wöchentlicher Docetaxelgabe (20–30 mg/m2) bestand (Tabelle 3). Chronische Nebenwirkungen wurden über 5 Jahre hinweg beobachtet.Ergebnisse:Nach einem medianen Follow-up von 4 Jahren lag die 5-Jahres-Überlebensrate aller 94 Patienten bei 80% und das krankheitsfreie Überleben bei 73% (Abbildungen 1 und 2). Bei Patienten mit fortgeschrittener Erkrankung (Stadium III und IV) lag das Überleben bei jeweils 83% und 59% (Abbildung 4). Eine Mukositis der Grade III und IV war die hauptsächliche Akuttoxizität, die eine supportive Therapie nötig machte. Die Langzeittoxizität schien moderat zu sein (Tabelle 4). Die maximal tolerierte wöchentliche Docetaxeldosis war 25 mg/m2.Schlussfolgerungen:Die konkomitante Bestrahlung und Chemotherapie mit wöchentlicher Docetaxelgabe ist eine durchführbare postoperative Behandlung in einem multimodalen Therapiekonzept für Mundhöhlen- und Oropharynxkarzinome, die in einem hohen Gesamt- und krankheitsfreien Überleben resultiert. Dieser Therapieansatz erfordert eine weitere Bewertung in prospektiven randomisierten Studien.

Resorbable plate osteosynthesis of dislocated or pathological mandibular fractures: a prospective clinical trial of two amorphous L-/DL-lactide copolymer 2-mm miniplate systems.

&NA; The purpose of this study was to evaluate the indication for resorbable miniplates in traumatic and pathological mandibular fractures. Two resorbable miniplate systems, the 2.0‐mm MacroSorb (Macropore, San Diego, Calif.) and the PolyMax (Synthes, Oberdorf, Switzerland), were prospectively used in 24 mandibular osteosyntheses. Made from amorphous 70:30 poly‐L/DL‐lactide, amorphous copolymer plates have not yet been evaluated for mandibular osteosyntheses. The main advantage of the amorphous copolymer‐structure is continuous hydrolysis through water penetration into the implant body during the first 6 months. Hydrolysis breaks the copolymer chains into smaller particles that later become degraded through phagocytotic cells. Twelve patients, aged 13 to 83 years, were treated after providing informed consent. Fourteen dentate patients with moderately dislocated traumatic fractures and two edentulous atrophic and dislocated traumatic mandibular fractures were treated. Two patients with pathological fractures due to osteomyelitis received osteosynthesis after sequestrectomy. Histological specimens of the plates, screws, and surrounding soft tissues were taken after 3, 6,9, and 12 months in secondary dental implant operations. A total of 22 osteosyntheses healed well without clinical or radiological signs of dislocation, insufficient or excess formation of callus, pseudarthrosis, or plate fracture. The follow‐up time ranged from 4 to 22 months. One patient with osteomyelitis worsened because of widespread osseous infection, and one with atrophic fracture developed a bland fibrous pseudarthrosis. The histological specimens showed a moderate inflammatory foreign body reaction. No sinuous drainage or clinically apparent inflammation occurred. The presented osteosynthesis systems showed reliable stability for mandibular osteosynthesis in cooperative patients; however, two treatment failures occurred (8 percent). Disadvantages of the resorbable osteosyntheses were costs, greater diameter, screw breakage, and the need to place the screws vertically to the plate. The use of resorbable osteosyntheses in dislocated fractures should be further evaluated in controlled studies. (Plast. Reconstr. Surg. 111: 601, 2003.)

The fate of osseointegrated implants in patients following oral cancer surgery and mandibular reconstruction.

The feasibility of implant treatment in patients after oral ablative tumor surgery and defect reconstruction has not yet been investigated in terms of the requisite high standards of success assessment. A report on this topic must address not only implant survival but implant health, bone response, soft tissue health, failure pattern, and time of failure, as well.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.

Does Tumor Depth Affect Nodal Upstaging in Squamous Cell Carcinoma of the Head and Neck

Purpose: The aim of this study was to determine whether tumor depth affects upstaging of the clinically node‐negative neck, as determined by sentinel lymph node biopsy with full pathologic evaluation of harvested nodes including step‐serial sectioning (SSS) and immunohistochemistry (IHC).

Sentinel Node Biopsy as Staging Tool in a Multimodality Treatment Approach to Cancer of the Oral Cavity and the Oropharynx

OBJECTIVES: Feasibility of sentinel lymph node (SLN) biopsy in head and neck cancer as a staging tool embedded in a multimodality regimen including neoadjuvant intraarterial chemotherapy. STUDY DESIGN AND SETTING: 39 patients with oral and anterior oropharyngeal cancer classified N0 by [18F]FDG-PET underwent SLN scintigraphy. Selective SLN biopsy without elective neck dissection (ND) was performed, immediately followed by radical resection of the primary tumor. Histopathology included step-serial sections and immunocyto-chemistry. RESULTS: Lymphoscintigraphy detected 104 spots. In 15 patients there was bilateral drainage. 114 SLN were excised due to additional intraoperative discrimination. 95% of visualised SLN could be removed. Histology was positive in 3 patients (8%), all underwent ND which yielded another positive node in 2 cases. Median observation time was 30 months. Two patients (5%) had a neck relapse in combination with a second primary. CONCLUSIONS: SLN biopsy as only surgical staging tool seems to be feasible. SIGNIFICANCE: Method promises reduction of elective ND and morbidity in N0 patients.