Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer.

PURPOSE: The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO(2)) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy. EXPERIMENTAL DESIGN: Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment. RESULTS: Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2 mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses. CONCLUSIONS: This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation.     

Does amifostine have a role in chemoradiation treatment?

For many years, scientists have been investigating use of drugs to protect normal tissue from injury during radiation therapy, thereby increasing the amount of radiation that can be safely administered to patients. Despite the introduction of modern shielding techniques, dose modulation, and tissue-volume mapping, a small amount of normal tissue surrounding the target volume is inevitably irradiated during treatment, which can lead to severe side-effects. The most recent chemical radioprotector to become available clinically is amifostine. On the basis of efficacy data from a phase III randomised trial in patients with head and neck cancer, which showed reduced acute and chronic xerostomia with preserved antitumour response, some institutions are now adding amifostine to their chemoradiation regimens. However, much controversy surrounds the use of this drug. Some investigators are worried that radioprotectors may stop tumour tissue responding to radiation and therefore reduce treatment effectiveness. Moreover, amifostine opponents argue that the evidence is insufficient to justify routine use of this drug. In this Debate, David Brizel, who worked on the phase III amifostine efficacy study, and Jens Overgaard, a vehement opponent of amifostine therapy, provide thought-provoking arguments for two opposing perspectives on this contentious issue.     

Conformal radiation therapy treatment planning reduces the dose to the optic structures for patients with tumors of the paranasal sinuses.

PURPOSE: Compare dose distributions of traditional versus conformal beam orientations in paranasal sinus malignancies. MATERIALS AND METHODS: Maximum normal tissue doses, dose volume histograms (DVH), normal tissue complication probabilities (NTCP), and the percentage of each normal tissue receiving >80% of the average target dose (V80) were calculated. RESULTS/CONCLUSIONS: Conformal planning reduced the V80 to the optic nerves and chiasm as well as the normal tissue maximum doses to the ipsilateral and contralateral optic nerves and chiasm, and mean NTCPs.     

Review of methods used to study oxygen transport at the microcirculatory level

The existence of hypoxic regions in tumors has long been recognized as a key factor leading to radiation resistance. More recently, it has been found that low oxygen levels also affect drug resistance, angiogenesis, cytokine production, cell cycle control, apoptosis, and metastatic propensity of tumors. Until now, most approaches to eliminating hypoxia have been empirical. However, improved understanding of the underlying mechanisms may permit the development of more soundly based, effective approaches. As discussed in this review, critical evaluation of the factors governing oxygen transport in tumors requires a thorough understanding of the methods used to study this process. Many experimental methodologies can be used to address these issues. In this review, the emphasis is placed on techniques that measure parameters on the scale of the diffusion distance of oxygen. Studies at the microregional level provide the most detailed physiological information on such processes. Over the past few years, significant progress in technology has allowed us to measure tumor oxygenation, yet spatial and temporal heterogeneities continue to provide significant challenges to obtaining clear knowledge of oxygen transport.     

Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies

BACKGROUND: Angiosarcoma of the face is a vascular tumor with poor local control and short median survival despite standard treatment. Bevacizumab is a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), which can inhibit tumor growth. It is synergistic with radiotherapy in gastrointestinal malignancies. Given the vascular nature of angiosarcoma and the need for better treatment of this disease, we investigated the concurrent use of bevacizumab with preoperative radiotherapy for head and neck angiosarcoma. METHODS: Two patients diagnosed with angiosarcoma of the nose were treated preoperatively with bevacizumab (5-10 mg/kg) and concurrent radiotherapy (50 Gy), followed by resection of the tumor bed. RESULTS: Both patients had a complete pathologic response with no residual disease. Neither has developed recurrence, with follow-up of 8.5 months and 2.1 years. CONCLUSIONS: The neoadjuvant combination of bevacizumab and radiation therapy is promising and should be further studied in the setting of vascular malignancies.     

A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

PURPOSE: Intravenous amifostine 200 mg/m2 reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. PATIENTS AND METHODS: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of > or =Grade 2 acute xerostomia. RESULTS: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of > or =Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of > or =Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. CONCLUSIONS: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.