Comparative evaluation of two hypofractionated radiotherapy regimens for painful bone metastases.

AIMS AND BACKGROUND: In 75% of the patients with bone metastases (BM) pain is the dominant symptom. Radiotherapy (XRT) plays a major role in the palliation of pain in patients with BM. Several schedules of short and long fractionation XRT are used in clinical practice, with hypofractionated treatments being even more attractive for practical reasons. A considerable body of evidence supports the clinical use of short schedules and single-dose XRT. We retrospectively evaluated the efficacy of two short fractionated schedules of 8 Gy as a single dose and 20 Gy in 5 fractions in relieving pain in patients with multiple uncomplicated BM. METHOD: From January to December 2001, 130 patients with 146 painful BM were treated with palliative localized XRT. There were 42 males and 88 females with a median age of 58 years (range 28-84). The commonest sites of treatment were the spine (59.6%) and pelvis (14.4%). The primary endpoint was clinically significant pain relief in the first six months of follow-up evaluated with the IAEA (International Atomic Energy Agency) pain measurement score measuring pain severity and pain frequency. Analgesic use was also recorded before and after treatment as drug frequency and drug severity. Patients with painful BM from any primary tumor site were irradiated. Treatment schedules consisted of a course of XRT with 4 Gy/fraction/day (total dose: 20 Gy/5 fractions) (group A, 59 lesions) or with a single dose of 8 Gy (group B, 87 lesions). RESULTS: There was no significant difference in complete response (CR) rates between treatment schedules: complete pain relief was achieved in 17/59 lesions (29%) in the fractionated group and in 29/87 lesions (33%) in the single-dose group. Also the overall response (complete + partial) was similar: 35/59 lesions (60%) in group A and 60/87 (69%) in group B. The minimum, maximum and median follow-up was 3, 23, and 9 months, respectively, for group A and 3, 20, and 11 months for group B. The actuarial median duration of pain relief was similar: 4.5 months in group A and 4 months in group B. No particular side effects were recorded in either group. CONCLUSIONS: There were no differences between the two fractionation schedules used in our study with regard to pain relief and use of analgesics. Palliation of pain was obtained in approximately two thirds of patients with both schedules, providing further evidence of the similar efficacy between single and multiple fractions. With regard to pain response these data justify a recommendation for the use of a more simple and convenient 8 Gy single fraction for the palliation of uncomplicated BM.

Comparisons of pain relief mechanisms between needling to the muscle, static magnetic field, external qigong and needling to the acupuncture point.

pain relief mechanisms of needling to the pain-producing muscle, application of a static magnetic field or external qigong, and needling to the acupuncture point were investigated in an experimentally designed pain producing muscle of animals. Single isometric twitch height in situ was reduced gradually by 10 Hz tetanic stimulation for one hour of the gastrocnemius muscle of guinea pigs. This reduction of twitch height was recovered by injection of 0.3-1 ml saline to the artery of this muscle, or of injection of a vasodilator, isoproterenol dissolved in 0.1 ml saline. Hence, reduction of twitch height could be induced by reduction of circulation in the muscle and recovery of it could be induced be recovery of circulation. Since it is easily considered that a pain substance might be accumulated in a muscle under reduced circulation, and such an accumulated substance might be eliminated by recovery of circulation, the reduction of twitch height after tetanic stimulation could be estimated as the pain-producing muscle and recovery of twitch, as the pain relieving muscle. 1) Needling to the pain muscle, 2) application of a static magnetic field or external qigong to the muscle, and 3) needling to the acupuncture point recovered the reduced twitch height due to tetanic stimulation. Atropine abolished this effect induced by the above 1, 2 and 3 procedures. Hence, the cholinergic vasodilator nerve might be involved in the induction of this effect. A sciatic nerve cut did not influence the effect of 1), but abolished the effect of 3). Denervation and capsaicin abolished the effect of 1). Substance P and a calcitonin gene- related peptide (CGRP) recovered the reduced twitch height, and atropine blocked the effect of CGRP, but did not block that of substance P. The effect of 2) was equivalent to that of anticholinesterase. A rostral lesion of the contralateral anterior hypothalamus did not abolish the effect of 3, but a caudal lesion of this region did. Electrical stimulation of this region produced an effect similar to that of 3). From these results, it was concluded that muscle pain relief by these procedures might be induced by recovery of circulation due to the enhanced release of acetylcholine as a result of activation of the cholinergic vasodilator nerve endings innervated to the muscle artery. However, manners of activation of the cholinergic nerve was different in effects of 1), 2) and 3). 1) might be induced by axon reflex of the CGRP nerve, 2) might be induced by inhibition of cholinesterase and 3) might be induced by a somato-autonomic reflex. The reflex center of this might be in the anterior hypothalamus.

Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review.

BACKGROUND: Rofecoxib is a cyclo-oxygenase 2 selective inhibitor. This systematic review of rofecoxib in acute pain examined studies in adults of analgesic efficacy over six hours, the amount and quality of the evidence on extended duration of analgesia, and the quality and quantity of evidence on adverse events. METHODS: Cochrane Library (issue 4, 2001), Biological Abstracts (March 2002), MEDLINE (March 2002) and PubMed (March 2002) were searched using rofecoxib as a free text term. The area under the pain relief versus time curve was dichotomized using validated equations to derive the proportion of patients on rofecoxib 50 mg or placebo with at least 50% pain relief over six hours. This was used to calculate the number needed to treat for at least 50% pain relief over six hours for rofecoxib compared with placebo. Information on duration of analgesia and adverse events was also collected. RESULTS: Five included trials investigated 1,118 patients, of whom 211 received placebo and 464 received rofecoxib 50 mg. The NNT for rofecoxib 50 mg was 2.3 (95% confidence interval 2.0 to 2.6). The weighted mean remedication time was 1.9 hours for placebo (126 patients), 7.4 hours for Ibuprofen ( Motrin ) 400 mg (97 patients) and 13.6 hours for rofecoxib 50 mg (322 patients). CONCLUSION: Rofecoxib at 2-4 times the standard daily dose for chronic pain is an effective single dose oral analgesic in acute pain. Limitations in trial reporting constrain conclusions about longer duration of analgesia and adverse event profile.

Treatment of pain of diffuse metastatic cancer by stereotactic chemical hypophysectomy: long term results and observations on mechanism of action.

Stereotactic instillation of absolute alcohol into the sella turcica for pituitary destruction was carried out in 29 patients divided into two groups. Seventeen with prostatic carcinoma underwent a total of 19 injections with 94% good to excellent results that persisted throughout the remainder of the patient's life-span. The longest survival was 9 months. Brief relapses did occur, but spontaneous remissions were the rule. A second group of mixed cancers contained 12 patients who received a total of 13 injections. Eleven patients had good to excellent results that persisted in all but 1 patient. The longest survival was 7 months. Hormonal levels and prolactin stimulation tests failed to show any correlation between hormonal changes and pain relief. Naloxone reversal of analgesia did not occur. There was no loss of cognitive function shown on psychological testing. Pathological studies showed destruction of the pituitary gland, which was subtotal in some patients despite good pain relief. All examinations showed that the pituitary stalk was destroyed. Patients who survived longer also showed degeneration of the supraoptic and paraventricular nuclei of the hypothalamus and the median eminence. All but 1 patient with pain relief exhibited a lack of antidiuretic hormone (ADH) production. Interpretation of the data indicates that ADH or its associated neurophysins act as central pain transmitters. The production of these transmitters is decreased or abolished by chemical hypophysectomy through the destruction of hypothalamic nuclei.