Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.     

Stereotactic radiosurgery: dose-volume analysis of linear accelerator techniques.

Stereotactic radiosurgery of the brain may be accomplished with a linear accelerator by performing several noncoplanar arcs of a highly collimated beam focused at a point. The shape of the radiation distribution produced by this technique is affected by the beam energy, field size, and the number and size of the arcs. The influence of these parameters on the resulting radiation distributions was analyzed by computing dose volume histograms for a typical brain. Dose volume functions were computed for: (a) the energy range of 4-24 MV x rays; (b) target sizes of 1-4 cm; and (c) 1-11 arcs and dynamic rotation. The dose volume histograms were found to be dependent on the number of arcs for target sizes of 1-4 cm. However, these differences were minimal for techniques with 4 arcs or more. The influence of beam energy on the dose volume histogram was also found to be minimal.     

A rapid method for electron beam energy check.

Assessment of electron beam energy and its long term stability is part of standard quality assurance practice in radiation oncology. Conventional depth-ionization or depth-film density measurements are time consuming both in terms of data acquisition and analysis. A procedure is described utilizing ionization measurements at two energy specific depths. It is based on a linear relationship between electron beam energy and its practical range. Energy shifts within the range covered by the two measurement depths are easily resolved. Within a range of +/- 0.50 MeV (+/- 1.30 MeV) around the established mean incident energy of 5.48 MeV (20.39 MeV), the method accuracy is better than 0.10 MeV.     

Diazepam tolerance effects on vestibular function testing, Part I: Saccadic parameters during electronystagmography

OBJECTIVES: Benzodiazepines, particularly diazepam (DZ), are used in clinical practice to suppress acute vestibular symptoms. There have been limited studies looking at the effects of tolerance to DZ on parameters designed to measure the integrity of the vestibular system and its interaction with the oculomotor and balance systems. METHODS: In a double-blinded, repeated-measures design, we randomized 30 young healthy men into one of two treatment groups (diazepam and placebo) and assessed with electro-oculography the effects of clinical divided doses of DZ on saccadic eye movements and sedation over 16 days. RESULTS: Only sedation and saccadic latency were significant (p < .05) for treatment group, indicating selective effects on different central nervous system mechanisms. No significant effect for time was seen in any of the variables measured. Bonferroni t-test comparisons of the DZ group among 3 days were significant (p < .017) between baseline and day 3 for saccadic latency and accuracy and between day 3 and day 16 for self-ratings of sedation. CONCLUSIONS: Saccadic latency and accuracy and sedation ratings appear to be more sensitive to changes over time and less affected by subject variability than saccadic eye velocity. It remains questionable whether patients who have been on DZ for acute or extended periods of time need to discontinue the drug 48 hours before testing.     

Follow-up neurological evaluation in patients with small cell lung carcinoma treated with prophylactic cranial irradiation and chemotherapy

The safety of prophylactic cranial irradiation (PCI) has recently been questioned, based on reports of computerized tomographic abnormalities mainly seen in children, who received PCI and chemotherapy, primarily for acute lympbocytic leukemia. In order to clarify the significance of these findings, we examined a series of adult patients who were long term survivors (18–48 months, median 26 months, after all treatment). These patients were treated with combination radiotherapy and chemotherapy for small cell lung carcinoma and received cranial irradiation in the absence of known brain involvement by tumor. Patients were divided into three groups: three patients who received PCI + intrathecal metbotrexate (MTX) (Group 1), and ten who received only PCI (Group 2). An additional three patients (Group 3) were identified as long term survivors (41–70 months after all treatments) of a similar treatment program without any central nervous system (CNS) prophylaxis. All patients received an extensive evaluation of a variety of clinical parameters, EEG, and computer tomography (CT). Although CT abnormalities were detectable (mild cerebral atrophy in eight patients, encephaiomalacia in one of the 13 patients with CNS prophylaxis, and wild atrophy in two of the three patients without CNS prophylaxis~ so significant clinical abnormalities or EEG changes were detectable. While this group of patients is small, it is a unique cohort: adults who have received cranial irradiation in the absence of known brain tumor with long term follow-up. The precise role of CNS prophylaxis in the etiology of CT abnormalities is unclear, and the lack of clinically significant changes would suggest no contraindication to PCI when indicated.