Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer.

PURPOSE: A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address (1) the validity of using pathologic risk features, established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); (2) the impact of accelerating PORT using a concomitant boost schedule; and (3) the importance of the overall combined treatment duration on the treatment outcome. METHODS AND MATERIALS: Of 288 consecutive patients with advanced disease registered preoperatively, 213 fulfilled the trial criteria and went on to receive therapy predicated on a set of pathologic risk features: no PORT for the low-risk group (n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group (n = 31); and, by random assignment, 63 Gy during 5 weeks (n = 76) or 7 weeks (n = 75) for the high-risk group. Patients were irradiated with standard techniques appropriate to the site of disease and likely areas of spread. The study end points were locoregional control (LRC), survival, and morbidity. RESULTS: Patients with low or intermediate risks had significantly higher LRC and survival rates than those with high-risk features (p = 0.003 and p = 0.0001, respectively), despite receiving no PORT or lower dose PORT, respectively. For high-risk patients, a trend toward higher LRC and survival rates was noted when PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery and PORT in the 7-week schedule was associated with significantly lower LRC (p = 0.03) and survival (p = 0.01) rates. Consequently, the cumulative duration of combined therapy had a significant impact on the LRC (p = 0.005) and survival (p = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant boost technique did not increase the late treatment toxicity. CONCLUSIONS: This Phase III trial established the power of risk assessment using pathologic features in determining the need for, and dose of, PORT in patients with advanced head-and-neck squamous cell cancer in a prospective, multi-institutional setting. It also revealed the impact of the overall treatment time in the combination of surgery and PORT on the outcome in high-risk patients and showed that PORT acceleration without a reduction in dose by a concomitant boost regimen did not increase the late complication rate. These findings emphasize the importance of coordinated interdisciplinary care in the delivery of combined surgery and RT.

Radiation effects on osteoblasts in vitro: a potential role in osteoradionecrosis.

OBJECTIVE: To evaluate the factors involved in bone remodeling and wound healing that may be altered by radiation therapy. DESIGN: A prospective, controlled study of biochemical activity in vitro. SUBJECTS: MC3T3-E1 mouse osteoblasts. INTERVENTIONS: Cells were irradiated at 0, 2, 4, or 6 Gy. Specimens were harvested at 1, 7, 14, 28, and 42 days following irradiation for immunohistochemical analysis of transforming growth factor beta(1) expression and transforming growth factor beta(1) type I and II receptor expression. Collagen production was measured at 1, 7, 28, 35, and 49 days after irradiation. The effects of dexamethasone on collagen production and cell proliferation were also examined. RESULTS: Irradiated cells demonstrated decreased cell proliferation and a dose-dependent, sustained reduction in collagen production when compared with control cells. An increase in transforming growth factor beta(1) type I and II receptor expression was noted in irradiated cells when compared with controls. CONCLUSION: Radiation-induced alterations of factors related to bone remodeling and wound healing have a potential role in the pathogenesis of osteoradionecrosis.

Risk factors associated with hypothyroidism after laryngectomy.

Hypothyroidism is a well-documented complication after treatment of head and neck cancer and is particularly significant among patients undergoing laryngectomy. The objective of this study was the identification of factors associated with the development of hypothyroidism in this population. Records of 136 patients treated with laryngectomy were retrospectively reviewed in an attempt to define a risk factor profile for patients in whom hypothyroidism is most likely to develop after laryngectomy. The Cox proportional hazards model was used to identify factors significantly related to an increased risk for development of hypothyroidism. The actuarial method was used to estimate the period of greatest risk for the development of hypothyroidism. Increased risks were found for patients who were female (P = 0.0049), received preoperative radiation therapy (P = 0.0022), had invasion of the thyroid gland by tumor (P = 0.0003), had presence of cervical metastases (P = 0.0022), and had postoperative fistula (P = 0.0095). From the actuarial method, we estimated that the period of time when patients were at greatest risk for development of hypothyroidism was between 0 and 14 months after surgical intervention. Wound complications were twice as frequent in hypothyroid patients. Perioperative awareness of risk factors associated with the development of hypothyroidism in patients undergoing laryngectomy allows for early recognition and management of hypothyroidism and may reduce the number of complications related to wound healing and fistula.

Factors affecting survival for floor-of-mouth carcinoma.

OBJECTIVES: The treatment of extensive floor-of-mouth carcinoma has remained a challenging problem for head and neck surgeons. We have reviewed our experience in the surgical management of floor-of-mouth cancer in an attempt to identify factors influencing survival. METHODS: A total of 144 patients with cancer involving the floor of the mouth were treated between March 1988 and November 1995. A retrospective chart review was conducted that captured information including clinical staging, therapeutic modalities, pathologic findings, and patient follow-up. Factors affecting survival were assessed by nonparametric analysis and analysis of variance. RESULTS: There was no statistical significance for the effects of vascular invasion (P = 0.4019), lymphatic invasion (P = 0.3430), bone invasion (P = 0.1548), or positive margins (P = 0.1113) on survival. Extranodal extension and recurrent disease were strongly suggestive of influencing survival but were not statistically significant (P = 0.0650 and P = 0.0504, respectively). Nodal disease significantly affected survival (P = 0.0138) but did not affect recurrence (P = 0.451). CONCLUSION: Mean survival for this cohort was 30.6 months. Positive node status significantly affected mean overall survival in this series, whereas extracapsular disease did not. These data suggest that aggressive surgical management of neck disease is mandated to maximize survival.

Frontal sinus fractures: anterior skull base.

The frontal sinus is fractured in 30% of patients sustaining maxillofacial injury. The CT scan has simplified the treatment plan allowing the surgeon to be more selective in the treatment choice, surgical approach, and follow-up. Fractures may involve the anterior, posterior, or both tables of the sinus. The frontal sinus repair or surgery takes place when there is minimal displacement and the frontal ducts are in tact. Obliteration of the sinus is suggested when the ducts are injured, but there is no significant bone loss or comminution of the posterior table. More extensive injuries of the posterior table require cranialization. The mucosa of the sinus must be reviewed completely, sealing off the nasal cavity to help decrease mucocele formation and other intracranial complications. Tedious repair of the dura (pericranial flap) decrease persistent CSF leak and intercranial infections. The anterior table must always be carefully repaired to optimize the cosmetic result. Careful follow-up is required to direct potential mucocele formation or delayed or persistent CSF leak. Judicious use of postoperative scars help to confirm these diagnosis.

Assessment of plate use for mandibular reconstruction: has changing technology made a difference?

Reconstruction of mandibular defects with a variety of alloplastic materials during a 22-year period was reviewed. Outcomes were examined to determine whether specific plating technology affected the incidence of plate-related complications including plate exposure, plate fracture, and plate removal. Repair with the miniplate, reconstruction plate, titanium hollow screw reconstruction plate, and locking reconstruction plate was evaluated. Although the incidence of plate fractures has decreased, there was no significant change in the rate of plate exposure. Recurrent disease was noted to be a significant contributing factor in the development of plate-related complications.

Auricular carcinoma with temporal bone invasion: outcome analysis.

Invasion of the temporal bone by cutaneous carcinoma of the auricle and periauricular skin is an ominous prognostic sign. Management includes aggressive resection of cutaneous disease as well as resection of temporal bone to obtain a medial margin. Analysis of data from 21 patients with temporal bone invasion caused by cutaneous malignancy is presented. Overall survival is approximately 63%. Cumulative survival is significantly decreased in patients with squamous cell carcinoma when compared with other invasive malignancies. Univariate and covariate analyses demonstrate that nodal status, positive microscopic soft tissue margins, and persistent perineural disease at the skull base did not significantly affect survival in this series. There is a trend toward increased survival in patients receiving postoperative radiation in this series.

Reconstruction after temporal bone resection.

Reconstruction of soft tissue defects after temporal bone resection can vary from simple closure of the external auditory canal to complex flap coverage of extensive defects. Between 1987 and 1996, 34 patients underwent lateral skull base resections and reconstruction for invasive carcinoma of the temporal bone. Seven underwent sleeve resection and/or radical mastoidectomy. Sleeve resection was managed with tympanoplasty, canalplasty, or obliteration of the external auditory canal (10). There were 24 lateral temporal bone resections and four subtotal temporal bone resections. Larger defects created by lateral and subtotal temporal bone resections required closure with a combination of temporalis flaps and local rotational cutaneous flaps (13). Lower island trapezius flaps (five), free flaps (four), and pectoralis major flaps (two) were also used. Indications and efficacy of each method are discussed, and treatment outcomes are presented.

Evolution of the extracranial approach for repair of CSF leaks: review of the literature and clinical cases.

The management of cerebrospinal fluid rhinorrhea changed with the advent of endoscopes in the early 1990s. The majority of repairs are now approached endoscopically, i.e., extracranially. This article reviews the evolution of the extracranial approach, as reported in the literature, concluding with the experience of the authors. A total of 15 patients were treated by the primary author since 1987; an open external ethmoid approach was utilized in 3 patients, and an endoscopic approach was used to treat 12 patients. The success rate with the external ethmoid approach was 100%; with the endoscopic approach, the primary success rate was 75% (9/12). There were 3 failures: One was due to a graft shrinkage; another was secondary to inadequate visibility; and the reason for the third was unclear. Eventually, all three were successfully repaired. Based on this experience, cerebrospinal fluid rhinorrhea can be successfully managed via an extracranial approach 75% of the time.

Effects of radiation therapy on reconstruction of mandibular defects with a titanium reconstruction plate.

Titanium fixation plates are commonly used in reconstruction of mandibular defects resulting from tumor resections in head and neck surgery. The effects of radiation therapy on the interface of bone, plate, and soft tissue were examined in this in vivo study. Four conditioned beagles had 1-cm segmental mandibular defects that were reconstructed with titanium plates. Two of the four also had placement of vascularized bone grafts. Healing was evaluated with or without postoperative radiotherapy. After collection of tissues using histologic methods and analysis with energy-dispersive spectroscopy, we found that the effects of radiation on bone-plate and bone-screw interfaces is minimal. Although radiation decreased the bone density and the rate of bone repair at the bone-screw interface, this did not appear to affect stability of the plate repair or the viability of bone tissue.

Repair of mandibular fractures using the 2.0 mm system. A review.

The mandible is a commonly injured facial bone with mandibular fractures occurring 3 times more frequently than those in the zygoma. Requirements for repair vary with the type of fracture, the location of the fracture, and the condition of the teeth and bone. Repair of the mandible is complicated by the complex range of function of the mandible. This article presents a brief, historical overview of techniques and systems that have been used for fracture stabilization. The authors report on the results of a study in which the 2.0 mm plate was used to repair 89 fractures. The use of 2.0 mm mandibular plates appears to provide adequate stability for patients with healthy bone and minimal comminution.

Assessment of bone formation during osteoneogenesis: a canine model.

Distraction osteoneogenesis, callotasis, has been demonstrated to be an effective means of lengthening long bones. A variation of Ilizarov's technique produces a transport disk from one cut surface of bone within a defect and advances the disk to the opposite surface to close the defect. This process, previously described by Costantino et al. (Arch Otolaryngol Head Neck Surg 1990; 116:535-45), demonstrated bone formation within the distraction site. The precise mechanism of bone formation has not yet been described for the mandible. Four conditioned beagles were studied, with one control dog maintained in neutral fixation and three dogs distracted at 0.25 mm every 8 hours. A two-cm defect was closed, and dogs were kept in fixation for 1 week after closure, after which they were killed. Three sites were evaluated: (1) the distraction seam, (2) the interface of the cortical and distracted bone, and (3) the cortexes at the closed defect. Each site was bisected, and one half was decalcified for immunohistochemical and hematoxylin and eosin pathologic evaluation. The vascular basement membrane was labeled for laminin and type IV collagen. Both of these substances demonstrate the differentiation of the vascular matrix component predisposing primary bone formation. Labels were intense at the distraction seam where intense angiogenesis occurred. No hyalin cartilage was observed at the distraction site, which indicates that the fixation was stable and that ossification occurred primarily without intermediate callous formation. This model demonstrated that osteoclasts within the canine model produce bone through primary bone formation within an angiogenic matrix rich in basement membrane laminin and type IV collagen. Likewise, bone is species specific in mineral composition for dog mandible. Understanding the formation and composition of distracted bone is essential for understanding application of this technique within the clinical setting.

Costal osteomyelitis after pectoralis major myocutaneous flap use in head and neck reconstruction.

Costal osteomyelitis and chondritis are rare complications of PMMF usage. They probably represent a secondary complication of a donor-site infection. This diagnosis must be considered in cases of PMMF donor-site infections, which fail to resolve with local wound care and antibiotics. Antibiotic coverage in these cases should be taylored to culture results, while having broad gram-positive activity. Workup of these patients should include CT and biopsy to rule out a neoplastic process.

Evaluation of distraction osteogenesis by scanning electron microscopy.

A model of bifocal distraction osteogenesis in the canine model was used to assess and quantitate the mineral content of the newly forming bone within the canine mandible. A 2-cm defect was created in the body of the mandible, and after a posterior osteotomy, the transport disk was advanced at 0.25 mm per 8 hours for 21 days and then held in rigid fixation for an additional week. As a control for this study, three additional dogs underwent the same procedure with the exception that the transport disk was not advanced. Electron dispersive spectroscopy analysis was performed on the newly formed regenerate bone and compared with areas of existing cortical bone of both the transport disk and the mandible. In the control model, special note was made of the pericortical callus at the osteotomy site as well as of the regenerative bone that filled the 2-cm defect in the body of the mandible. Calcium/phosphorous ratios were used to assess the composition of the mineralized regions of the mandible. The regenerate bone that filled the defect and the mineralized callus surrounding the site of osteoclasis in the control mandible were significantly different in composition when compared with the regenerate bone that formed during distraction osteogenesis. This suggests that distraction osteogenesis may effect an initial matrix production that is more similar in composition to the mature cortical bone from which it was derived than does periosteal regeneration and filling of an osseous defect.

Basement membrane of blood vessels during distraction osteogenesis.

A canine model of distraction osteogenesis has recently been developed that permitted the evaluation of bone formation and its vascularization during bifocal callotasis. In this model, the authors examined the composition of the blood vessels during distraction osteogenesis of the mandible for laminin and for Type IV collagen, both constituents of the vascular basement membrane. At the fibrous distraction site, at the juncture of the free cortical surface and the regenerated bone, and at the abutting cortical surfaces at the distal margin of the defect, laminin and Type IV collagen were present in all vessels.

Testing biomechanical strength of repairs for the mandibular angle fracture.

A biomechanical model using polystyrene mandibles with simple angle fractures was developed to evaluate the structural strength of a variety of commonly used plate repairs. The model standardized the fracture location, load site, plate location, and site of deformation measurement. The only variables in the study were the nine different reconstruction types tested. Precise measurements of the deformation under load demonstrated statistically significant intra-group reproducibility for each repair. Data support previous clinical and experimental studies demonstrating the superiority of a two-plate system applied to the tension and compression regions of the mandible when compared to single-plate repairs using either noncompression (bridging) or eccentric dynamic compression plates.