Faculty Bibliography

Osteoradionecrosis (ORN) of the mandible is a significant complication of radiation therapy for head and neck cancer. In this condition, bone within the radiation field becomes devitalized and exposed through the overlying skin or mucosa, persisting as a non-healing wound for three months or more. In 1926, Ewing first recognized the bone changes associated with radiation therapy and described them as "radiation osteitis". In 1983, Marx proposed the first staging system for ORN that also served as a treatment protocol. This protocol advocated that patients whose disease progressed following conservative therapy (hyperbaric oxygen (HBO), local wound care, debridement) were advanced to a radical resection with a staged reconstruction utilizing a non-vascularized bone graft. Since the introduction of Marx's protocol, there have been advances in surgical techniques (i.e. microvascular surgery), as well as in imaging techniques, which have significantly impacted on the diagnosis and management of ORN. High resolution CT scans and orthopantamograms have become a key component in evaluating and staging ORN, prior to formulating a treatment plan. Patients can now be stratified based on imaging and clinical findings, and treatment can be determined based on the stage of disease, rather than determining the stage of disease based on a patient's response to a standardized treatment protocol. Reconstructions are now routinely performed immediately after resection of the diseased tissue rather than in a staged fashion. Furthermore, the transfer of well-vascularized hard and soft tissue using microvascular surgery have brought the utility of HBO treatment in advanced ORN into question.

BACKGROUND: Radiation is a known risk factor for poor wound healing. Patients undergoing intraoperative radiation therapy (IORT) typically receive higher cumulative doses to their wound beds than patients treated with conventional radiation therapy. We review our experience with IORT in patients undergoing resection of head and neck cancer and flap reconstruction. Logistics of delivery and outcomes are discussed. METHODS: A retrospective chart review was performed on all patients at Beth Israel Medical Center who underwent IORT for head and neck cancer between 2000 and 2007. Twenty-one patients receiving 22 treatments involving flap reconstruction were identified. The results of these reconstructions were evaluated for complications and functional outcome. RESULTS: All patients had complex surgical wounds of the face, upper aerodigestive tract, or neck who received IORT in conjunction with pedicled or free flap closure. Twenty-five flaps in 21 patients were performed in the setting of IORT. All patients received between 10 and 15 Gy of IORT administered directly to the wound bed. There were no perioperative mortalities. Wound breakdown occurred in three cases, all of which were treated successfully by operative revision. Functionally, most patients did well and performed similarly to historic controls for their type of reconstruction. CONCLUSIONS: Reconstruction using flaps in the context of IORT can be achieved with expectation of good wound healing in the majority of cases despite heavy cumulative doses of radiation to recipient wound beds.

PURPOSE: To establish the safety and toxicity profile of daily gefitinib with radiation alone or with concurrent chemoradiotherapy in previously untreated patients with locally advanced squamous cell head and neck cancer (LAHNC). PATIENTS AND METHODS: Patients with intermediate-stage LAHNC were treated with concomitant boost radiation (RT) alone with escalating doses of daily gefitinib (250 or 500 mg; cohort I). Once a safety profile was determined with RT alone, patients with high-risk disease were then treated with daily gefitinib (250 or 500 mg), weekly cisplatin (CDDP; 30 mg/m2), and once-daily RT (cohort II). Patients also received post-RT gefitinib at 250 mg daily for a period of up to 2 years. RESULTS: Twenty-three patients were enrolled and assessable for toxicity. No dose-limiting toxicities (DLTs) were observed in patients treated in cohort I at either 250 or 500 mg of gefitinib daily with concomitant boost RT to 72 Gy. In patients receiving chemoradiotherapy and gefitinib (cohort II), DLTs included one grade 4 diarrhea and one grade 4 neutropenic fever. Fifteen patients started maintenance gefitinib, and eight (53%) experienced grade 1 to 2 acne-like skin rash and diarrhea, but no grade 3 or 4 toxicity occurred. CONCLUSION: Gefitinib (250 or 500 mg daily) was well tolerated with concomitant boost RT or concurrent chemoradiotherapy with weekly CDDP. Protracted administration of gefitinib for up to 2 years at 250 mg daily was also tolerated well.

OBJECTIVE: To examine the Epstein-Barr virus (EBV) IgA and DNA assays as a screening tool for nasopharyngeal carcinoma (NPC) in a nonendemic US population. STUDY DESIGN AND SETTING: Prospective study performed at a teaching hospital in New York City. There were two groups of 155 patients: new NPC patients and controls. An otolaryngologic examination and serial blood testing for serologic markers were performed. RESULTS: Sensitivity and specificity of EBV IgA and DNA assays were determined. Screening scenarios involving series and parallel testing were evaluated to determine economic feasibility. Series testing provided a sensitivity, specificity, and positive and negative predictive values of 90.6, 93.5, 78.4, and 97.5 percent, respectively. Parallel testing increased the sensitivity to 100 percent. CONCLUSION: NPC screening in a high-risk, nonendemic population using EBV-specific serologic markers is effective. Series testing is a statistically sound and economically feasible strategy. SIGNIFICANCE: The development of a cost-effective NPC screening strategy in a high-risk, nonendemic population in the United States.

OBJECTIVES/HYPOTHESIS: Since 1998, at our academic, multidisciplinary head and neck cancer treatment center, it has been our policy to treat appropriate patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) with concomitant radiochemotherapy followed within 6 weeks by planned neck dissection(s). Our objective was to investigate the oncologic efficacy of planned neck dissection, to date, in this patient population with a focus on outcomes in the neck. STUDY DESIGN: Retrospective analysis of a cumulative patient database. METHODS: The medical records of all patients who underwent planned neck dissection(s) after concomitant radiochemotherapy for locoregionally advanced SCCHN at Beth Israel Medical Center and The Institute for Head and Neck Cancer in New York City were reviewed. For each patient, preradiochemotherapy primary and neck stage, postradiochemotherapy/preneck dissection clinical and radiographic neck status, type of neck dissection(s) performed, pathologic status of the neck dissection specimen(s), length of follow-up (after planned neck dissection), disease status at last follow-up, and site(s) of recurrence were recorded. Local, regional, and distant disease control rates were calculated by the Kaplan-Meier method. RESULTS: Fifty-one planned neck dissections were performed on 39 radiochemotherapy patients (12 patients had bilateral operations) between early 1998 and October, 2003. Thirty-two (82%) patients had N2 or greater neck disease, with 29 (74%) having T3/T4 disease at various upper aerodigestive tract primary sites. Patients received an average of 6,700 cGy and 6,000 cGy external beam radiation therapy to primary disease sites and involved cervical lymphatics respectively, concomitant with one of three platinum-based chemotherapy schedules. At a mean follow-up time of 24 (range 8-57) months for the entire study population, there has been only one neck recurrence (N2A neck). No patient with N2B (n = 11), N2C (n = 13, with majority of heminecks staged N2B), or N3 (n = 5) disease has recurred in the neck. No recurrences have occurred in the 41 heminecks (in 33 patients) where modified neck dissection (including 24 selective procedures) was performed despite the presence of residual carcinoma in 13 (32%) of these heminecks on pathologic review. Among all heminecks with residual carcinoma present (n = 18) in the neck dissection specimen, there has been only one neck recurrence. There have been no recurrences in the 26 heminecks (in 19 patients) with incomplete clinical response after radiochemotherapy despite the presence of residual carcinoma in 14 (54%) of these necks on pathologic review. The clinical and radiographic absence of residual disease after radiochemotherapy did not always predict a complete pathologic response. Surgical complications have been limited (1 chyle leak, 1 wound breakdown). CONCLUSIONS: The integration of planned neck dissection into the multidisciplinary management of patients with locoregionally advanced SCCHN is highly effective in controlling cervical metastatic disease. Modified and selective neck dissection procedures can be performed in the majority of patients, regardless of the response in the neck subsequent to concomitant radiochemotherapy. We recommend a planned neck dissection(s) in all patients staged (pretreatment) with N2 or greater neck disease and in select N1 cases.

The management of base of tongue cancer has evolved steadily over time. Organ preservation with primary radiation therapy has produced excellent oncologic and functional outcomes. Concomitant chemotherapy has become important in patients with locoregionally advanced disease. Planned neck dissection after organ preservation therapy continues to be an integral step for regional control. This article reports the results of a literature review of base of tongue cancer emphasizing a multidisciplinary approach to obtain optimal results in terms of cure and quality of life.

Locoregional recurrence remains a major obstacle to achieving a cure of locally advanced head and neck cancers, despite multimodality therapy. Multiple studies report that a low hemoglobin (Hgb) before or during radiation therapy is an important risk factor for poor locoregional disease control and survival. Anemia is common in the head and neck cancer population and is suspected to contribute to intratumoral hypoxia with resultant radioresistance. Although having a low Hgb level has been shown to be detrimental, it is unclear as to exactly what the threshold should be for low Hgb (studies in this area have used thresholds ranging from 9-14.5 g/dL). Quality-of-life studies suggest that correction of moderately severe anemia may result in significant gains. Optimal Hgb levels for improving outcomes may vary across and within tumor types, and this is an area that requires further evaluation. However, the correction of anemia may be a worthwhile strategy for radiation oncologists to improve local control and survival. This article reviews the impact of anemia on outcomes after radiotherapy of head and neck cancers.