Faculty Bibliography

Dry mouth (xerostomia) is one of the most common complaints following radiation therapy (RT) for head and neck cancers. Notably, RT causes irreparable damage to salivary glands that increases the risk for severe and long-term oral and pharyngeal disorders. Several strategies in the treatment of head and neck cancers have been developed to prevent RT-induced salivary dysfunction while providing definitive oncologic therapy. These include salivary-sparing RT; cytoprotectants (such as amifostine); combination therapy of high-dose-rate intraoperative RT, external beam RT, plus a cytoprotectant; salivary gland surgical transfer; and gene therapy. Future research that incorporates biologic, pharmacologic, and technologic advancements that optimize therapeutic ratios and minimizes adverse oral sequelae is warranted.

PURPOSE: Present a case of bilateral foveal acute myelogenous leukemic tumors that responded to radiation therapy. DESIGN: Case report. METHODS: A patient was diagnosed with bilateral subfoveal infiltration of known systemic acute myelogenous leukemia. He received a standard induction chemotherapy, followed by consolidation therapy for his systemic leukemia. However, despite a complete marrow response, the intraocular tumors did not regress. Therefore, he was given low dose (1950-cGy) ocular external beam radiation therapy. RESULTS: One course of systemic cytarabine chemotherapy failed to control the subfoveal tumors, leaving the patient at risk for permanent vision loss. In contrast, external beam radiation therapy improved his vision from 20/60 in his right eye to 20/20 and from 20/70 in his left eye to 20/25. CONCLUSION: Although systemic chemotherapy can be used to treat intraocular metastasis, external beam radiation may provide more prompt resolution of vision-threatening tumors

BACKGROUND: Oral transmucosal fentanyl citrate (OTFC; ACTIQ) incorporates fentanyl into a lozenge allowing drug delivery through the oral mucosa resulting in rapid pain relief. OTFC is effective for breakthrough pain and could be particularly useful in patients with mucositis. METHODS: This randomized, double-blind, crossover study assessed two formulations of OTFC for tolerability in 14 patients with radiation-induced mucositis. On four separate days, patients with grade 3 or 4 mucositis received an OTFC unit 45 min before radiation treatment. Two units had a sweetened matrix formulation and two had a compressed powder formulation. One unit of each formulation contained 200 microg fentanyl and one was placebo. Tolerability, mucositis pain, and formulation preference were evaluated. Changes in oral mucosa were recorded. RESULTS: Both formulations of OTFC were well tolerated. There were no significant differences between formulations in tolerability, patient preference, or VAS pain scores. No changes in oral mucosa were noted. Common treatment-related adverse events included a burning sensation in the mouth, nausea, and vomiting. CONCLUSIONS: Both formulations of OTFC are well tolerated. The presence of fentanyl in either the sweetened matrix or the compressed powder did not alter tolerability or safety. The dose of fentanyl tested did not yield analgesia greater than placebo; future studies of OTFC efficacy in mucositis should evaluate higher doses than 200 microg.

Locoregional recurrence remains a major obstacle to achieving cure of locally advanced head and neck cancers despite maximal resection and postoperative external beam radiation therapy (EBRT). Locoregional failure occurs in 30% to 40% of high-risk resected head and neck cancer patients after standard postoperative EBRT. In an effort to overcome this problem, a number of strategies have been designed to enhance the effectiveness of radiation including concurrent postoperative chemoradiation, accelerated radiation schedules, incorporation of targeted biologic therapies, and improved radiation delivery techniques such as intensity modulated radiation and high-dose rate (HDR) intraoperative radiation therapy. Intraoperative radiation therapy (IORT) represents an important approach to improve outcome in head and neck cancer patients treated with definitive surgery. High-dose rate IORT is defined as the delivery of a single, large dose of radiation at the time of surgery when the tumor bed is exposed. In conjunction with EBRT, HDR-IORT offers several advantages including: (1) conformal delivery of a large dose of radiation while the tumor bed is precisely defined, minimizing the risk of a geographic miss; (2) potential for subsequent dose reduction of EBRT; (3) shortening overall treatment time; and (4) dose-escalation. Because mucositis represents the dose-limiting acute toxicity and xerostomia ranks as the most common long-term quality-of-life complaint, a reduction of the EBRT dose may provide an important benefit in reducing toxicity, especially when combined with the radioprotectant amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD). The purpose of this article is to review the rationale for integrating HDR-IORT with a reduced dose of postoperative EBRT combined with amifostine to improve locoregional control and quality of life outcomes in advanced-stage resected head and neck cancer patients.

Although several modalities have been discussed, a comprehensive intraoperative program should have IOERT, IOHDR, and perioperative brachytherapy facilities available to treat all sites. Interstitial brachytherapy is preferable for the treatment of gross residual tumor; IORT (IOERT for accessible sites and IOHDR for poorly accessible sites) is added to irradiate intraoperatively the surrounding margins after gross resection; and fractionated EBRT could be used in moderate doses post-operatively to irradiate the entire area of potential microscopic disease. Depending on the volume and location of the tumor, and the available expertise and equipment, IOERT, IOHDR, or perioperative brachytherapy could be used along with EBRT and surgery for the optimal management of malignancies. Finally, the best results of IOHDR are obtained when used as a conformal boost to the tumor bed after resection in conjunction with supplementary EBRT.

Paragangliomas most commonly occur in the carotid body, jugulotympanic area, and vagus nerve but have also been reported in other areas of the head and neck. These tumors are highly vascular and characteristically have early blood vessel and neural involvement, making their treatment particularly challenging. Surgery has traditionally been the preferred method of treatment, especially in light of recent advances in technique. However, compared to radiation therapy, it can result in a higher incidence of cranial nerve dysfunction. Radiation therapy has the advantage of avoiding the increased morbidity of surgery while offering an equal possibility of cure. Part 2 of this article discusses radiation therapy as primary treatment of patients who are ineligible for surgery and the elderly and infirm. Results with radiotherapy are comparable to those achieved with surgery. The efficacy of salvage therapy with either surgery or radiation is discussed, and a treatment algorithm for these tumors is proposed.

Paragangliomas most commonly occur in the carotid body, jugulotympanic area, and vagus nerve but have also been reported in other areas of the head and neck. These tumors are highly vascular and characteristically have early blood vessel and neural involvement, making their treatment particularly challenging. Surgery has traditionally been the preferred method of treatment, especially in light of recent advances in technique. However, compared to radiation therapy, it can result in a higher incidence of cranial nerve dysfunction. Radiation therapy has the advantage of avoiding the increased morbidity of surgery while offering an equal possibility of cure. Part 1 of this two-part article focuses on techniques for diagnosing paraganglioma and the indications for and use of surgery as primary treatment. The complications commonly associated with surgery are reviewed, and strategies for rehabilitation of affected patients are presented.

Intraoperative irradiation (IORT) refers to the delivery of a single high dose of radiation therapy at the time of surgery when the tumor bed can be precisely defined and adjacent normal tissue maximally protected. It can be effectively delivered using either electrons (IOERT) or photons produced from a high-dose-rate gamma emitting radioisotope (HDR-IORT) and has been explored primarily for locally advanced or recurrent tumors at high risk for local failure despite extensive resection and full dose external beam radiation. With coordinated multidisciplinary interaction, IORT can be integrated in a combined-modality setting without undue additional toxicity. The purpose of this review will be to summarize the growing HDR-IORT experience in the treatment of various cancers, to compare its efficacy and toxicity vis a vis the IOERT data, and to discuss future trials as well as new areas of potential application.

Local recurrence remains a major obstacle to achieving cure of many locally advanced solid tumors treated with definitive radiation therapy. The microenvironment of solid tumors is hypoxic compared with normal tissue, and this hypoxia is associated with decreased radiosensitivity. Recent preclinical data also suggest that intratumoral hypoxia, particularly in conjunction with an acid microenvironment, may be directly or indirectly mutagenic. Investigations of the prognostic significance of the pretreatment oxygenation status of tumors in patients with head and neck or cervical cancer have demonstrated that increased hypoxia, typically designated in these studies as pO(2) levels below 2.5-10 mm Hg, is associated with decreased local tumor control and lower rates of disease-free and overall survival. Hypoxia-directed therapies in the radiation oncology setting include treatment using hyperbaric oxygen, fluosol infusion, carbogen breathing, and electron-affinic and hypoxic-cell sensitizers. These interventions have shown the potential to increase the effectiveness of curative-intent radiation therapy, demonstrating that the strategy of overcoming hypoxia may be a viable and important approach. Anemia is common in the cancer population and is suspected to contribute to intratumoral hypoxia. A review of the literature reveals that a low hemoglobin level before or during radiation therapy is an important risk factor for poor locoregional disease control and survival, implying that a strong correlation could exist between anemia and hypoxia (ultimately predicting for a poor outcome). While having a low hemoglobin level has been shown to be detrimental, it is unclear as to exactly what the threshold for "low" should be (studies in this area have used thresholds ranging from 9-14.5 g/dl). Optimal hemoglobin and pO(2) thresholds for improving outcomes may vary across and within tumor types, and this is an area that clearly requires further evaluation. Nonetheless, the correction of anemia may be a worthwhile strategy for radiation oncologists to improve local control and survival.

The mainstay of treatment for rectal cancer over the past 100 years has been surgical resection. However, for the majority of rectal cancers treated conventionally by resection alone, locoregional recurrence is the major mode of failure. Over the past several decades, significant progress has been made in developing effective adjuvant regimens. In the United States, postoperative chemoradiation is standard treatment for T3 or node-positive patients. However, preoperative radiation with or without chemotherapy decreases local recurrence, increases sphincter preservation, and may improve survival. The purpose of this article is to review the role of adjuvant therapy in resectable rectal cancers and to update the status of ongoing randomized trials.