Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. A pilot randomised comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study. Lumbar spinal stenosis: conservative or surgical management?: A prospective 10-year study. Final results of the Royal College of Radiologists' trial comparing two different radiotherapy schedules in the treatment of cerebral metastases. Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. High-dose radiation therapy for inoperable non-small cell lung cancer without mediastinal involvement (clinical stage N0, N1). Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.
The standard treatment for spinal cord compression caused by metastatic cancer is corticosteroids and radiotherapy. The role of surgery has not been established. We assessed the efficacy of direct decompressive surgery.
                In this randomised, multi-institutional, non-blinded trial, we randomly assigned patients with spinal cord compression caused by metastatic cancer to either surgery followed by radiotherapy (n=50) or radiotherapy alone (n=51). Radiotherapy for both treatment groups was given in ten 3 Gy fractions. The primary endpoint was the ability to walk. Secondary endpoints were urinary continence, muscle strength and functional status, the need for corticosteroids and opioid analgesics, and survival time. All analyses were by intention to treat.
                After an interim analysis the study was stopped because the criterion of a predetermined early stopping rule was met. Thus, 123 patients were assessed for eligibility before the study closed and 101 were randomised. Significantly more patients in the surgery group (42/50, 84%) than in the radiotherapy group (29/51, 57%) were able to walk after treatment (odds ratio 6.2 [95% CI 2.0-19.8] p=0.001). Patients treated with surgery also retained the ability to walk significantly longer than did those with radiotherapy alone (median 122 days vs 13 days, p=0.003). 32 patients entered the study unable to walk; significantly more patients in the surgery group regained the ability to walk than patients in the radiation group (10/16 [62%] vs 3/16 [19%], p=0.01). The need for corticosteroids and opioid analgesics was significantly reduced in the surgical group.
                Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer. Hypofractionated radiotherapy (RT) is often used in the treatment of metastatic spinal cord compression (MSCC). This randomized trial was planned to assess the clinical outcome and toxicity of two different hypofractionated RT regimens in MSCC.
                Three hundred patients with MSCC were randomly assigned to a short-course RT (8 Gy x 2 days) or to a split-course RT (5 Gy x 3; 3 Gy x 5). Only patients with a short life expectancy entered the protocol. Median follow-up was 33 months (range, 4 to 61 months).
                A total of 276 (92%) patients were assessable; 142 (51%) treated with the short-course and 134 (49%) treated with the split-course RT regimen. There was no significant difference in response, duration of response, survival, or toxicity found between the two arms. When short- versus split-course regimens were compared, after RT 56% and 59% patients had back pain relief, 68% and 71% were able to walk, and 90% and 89% had good bladder function, respectively. Median survival was 4 months and median duration of improvement was 3.5 months for both arms. Toxicity was equally distributed between the two arms: grade 3 esophagitis or pharyngitis was registered in four patients (1.5%), grade 3 diarrhea occurred in four patients (1.5%), and grade 3 vomiting or nausea occurred in 10 patients (6%). Late toxicity was never recorded.
                Both hypofractionated RT schedules adopted were effective and had acceptable toxicity. However, considering the advantages of the short-course regimen in terms of patient convenience and machine time, it could become the RT regimen of choice in the clinical practice for MSCC patients. To test the viability of a full-scale randomised comparison of two steroid doses given with radiotherapy for malignant spinal-cord compression (MSCC), to test Internet randomisation and to compare different functional outcome measures.
                A log of screened patients at eight recruiting centres was maintained. Patients were randomised via the Superdex website to either 96 mg or 16 mg daily of dexamethasone. Radiotherapy treatment was 30 Gy in 10 fractions. Outcomes assessed used ambulation, Barthel Index ambulation, Functional Independence Measure (FIM) ambulation and Functional Improvement Score (FIS) at 1 month.
                One hundred and thirty-one patients were screened. Ninety-three (71%) were ineligible, 65% of these were because duration of prior steroid use was greater than 12 h, failure to meet strict definition of magnetic resonance imaging, defined MSCC, multi-level disease or previous spinal-cord compression treatment. Twenty of the 38 eligible patients were randomised, including seven outside standard office hours. There was a high rate of serious adverse events (n = 9), but only one was considered likely to be related to study medication. At baseline, 75% were ambulant, 70% had FIM ambulation scores greater than 5 and 50% had Barthel Index ambulation scores greater than 2. At day 28, including all randomised patients (by scoring four dead patients as non-ambulant), ambulation scores by the various definitions were 60%, 45% and 40%, respectively. For the 16 patients evaluable at day 28, the mean FIS was -1.4. Median survival was 69 days and 1-year survival 13%.
                Web randomisation was successful; however, the high ineligibility rate precludes a full-scale dexamethasone dose trial in Australia. Choice of measure of ambulation has potentially significant effects on outcomes and implications for the design of any future MSCC trials. Referral delays are of concern. A cohort of 100 patients with symptomatic lumbar spinal stenosis, characterized in a previous article, were given surgical or conservative treatment and followed for 10 years.
                To identify the short- and long-term results after surgical and conservative treatment, and to determine whether clinical or radiologic predictors for the treatment result can be defined.
                Surgical decompression has been considered the rational treatment. However, clinical experience indicates that many patients do well with conservative treatment.
                In this study, 19 patients with severe symptoms were selected for surgical treatment and 50 patients with moderate symptoms for conservative treatment, whereas 31 patients were randomized between the conservative (n = 18) and surgical (n = 13) treatment groups. Pain was decisive for the choice of treatment group. All patients were observed for 10 years by clinical evaluation and questionnaires. The results, evaluated by patient and physician, were rated as excellent, fair, unchanged, or worse.
                After a period of 3 months, relief of pain had occurred in most patients. Some had relief earlier, whereas for others it took 1 year. After a period of 4 years, excellent or fair results were found in half of the patients selected for conservative treatment, and in four fifths of the patients selected for surgery. Patients with an unsatisfactory result from conservative treatment were offered delayed surgery after 3 to 27 months (median, 3.5 months). The treatment result of delayed surgery was essentially similar to that of the initial group. The treatment result for the patients randomized for surgical treatment was considerably better than for the patients randomized for conservative treatment. Clinically significant deterioration of symptoms during the final 6 years of the follow-up period was not observed. Patients with multilevel afflictions, surgically treated or not, did not have a poorer outcome than those with single-level afflictions. Clinical or radiologic predictors for the final outcome were not found. There were no dropouts, except for 14 deaths.
                The outcome was most favorable for surgical treatment. However, an initial conservative approach seems advisable for many patients because those with an unsatisfactory result can be treated surgically later with a good outcome. Between February 1990 and February 1993, 25 centres in the UK recruited 544 patients into a prospective randomized trial comparing two whole-brain radiotherapy regimens (30 Gy in ten fractions over 2 weeks versus 12 Gy in two fractions on consecutive days) for the treatment of patients with symptomatic cerebral metastases. Of these patients 533 were eligible for analysis: 270 assigned to the two-fraction arm and 263 to the ten-fraction arm. The two groups were well balanced with respect to patient characteristics. Median survival was 77 days with two fractions (95% CI 68-89) and 84 days for the longer schedule (95% CI 67-102). Analysis of the survival curves showed a marginal advantage for ten fractions (P = 0.04). Performance status (P = 0.0001), site of primary tumour (P = 0.006), dose of dexamethasone (P = 0.004), age (P = 0.04) and randomization treatment (P = 0.03) were independant factors associated with survival. The classification of patients into good or poor risk groups based on these factors, excluding treatment, showed highly significant differences in survival (P < 0.0001). Predictive models suggested that any benefit attributable to the longer radiotherapy schedule was confined to those in a good prognostic group (these patients formed 22% of the study population). Radiation related side effects, other than alopecia, were seen in 12% of patients receiving two fractions and 8% of those given ten fractions. The short survival of many patients hampered the assessment of response, but overall responses were seen in 39% of those given two fractions and 44% of patients receiving ten fractions. These results suggest that any increase in survival due to longer radiotherapy treatment is confined to good prognosis patients, but, for the majority, there is no advantage and the value of radiotherapy for these patients relates purely to the possibility of control or relief of distressing symptoms. Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year. The control group was evaluated at six-week intervals without adjuvant chemotherapy, but these patients were offered this chemotherapy later if they had progressive disease excised. Although 30% of the 61 patients experienced local recurrence of disease within the first five years after randomization, and only 54% were continuously disease free for five or more years, 82% were surviving at five years (Kaplan-Meier calculations) with a median follow-up of 64.3 months. Partial suppression of distant metastasis by adjuvant chemotherapy was apparent in the overall study, in the extremity tumor category, and in the subgroup of patients who had received limb-sparing surgery; however, no survival advantage for chemotherapy-treated patients was demonstrated. The 30 adjuvant chemotherapy-treated patients received a total of three thoracotomies as compared with 17 salvage thoracotomies for the 31 control patients; however, salvage surgery for local recurrences has been similar in the two groups. Recent improvement in the survival of patients with soft-tissue sarcomas is not necessarily a result of adjuvant chemotherapy or radiation therapy. We performed a randomised single blind trial of high-dose dexamethasone as an adjunct to radiotherapy in patients with metastatic spinal cord compression from solid tumours. After stratification for primary tumour and gait function, 57 patients were allocated randomly to treatment with either high-dose dexamethasone or no steroidal treatment. Dexamethasone was administered as a bolus of 96 mg intravenously, followed by 96 mg orally for 3 days and then tapered in 10 days. A successful treatment result defined as gait function after treatment was obtained in 81% of the patients treated with dexamethasone compared to 63% of the patients receiving no dexamethasone therapy. Six months after treatment, 59% of the patients in the dexamethasone group were still ambulatory compared to 33% in the no dexamethasone group. Life table analysis of patients surviving with gait function showed a significantly better course in patients treated with dexamethasone (P < 0.05). Median survival was identical in the two treatment groups. Similar results were found in subgroup analysis of 34 patients with breast cancer as the primary malignancy. Significant side-effects were reported in 3 (11%) of the patients receiving glucocorticoids, 2 of whom discontinued the treatment. We conclude that high-dose glucocorticoid therapy should be given as adjunct treatment in patients with metastatic epidural spinal cord compression. To evaluate the usefulness of radiation therapy alternative to surgery for clinical N0-N1 non-small cell lung cancer (NSCLC).
                From 1976 through 1989, 116 patients with NSCLC without mediastinal involvement were treated with definitive radiation therapy alone at Gunma University Hospital. All patients were treated with once-daily standard fractionation using 10 MV X-rays. The total dose ranged from 60 Gy to 80 Gy.
                The actuarial 2- and 5-year survival rates of the entire group were 43% and 20%, respectively with a median survival time of 19 months. The survival of 76 patients with stage T2 tumors was significantly better than that of 28 patients with T3 tumors (mean survival time 21 versus 15.5 months; p < 0.05). Sixty-two patients with tumors less than 5 cm in diameter had a 2-year progression rate of 20%, in comparison with 39% of 54 patients with tumors greater than 5 cm. The difference of survivals for these 2 groups was statistically significant. Twelve patients given a total dose of 80 Gy or more had only 17% local progression at the time of last follow-up, however, 5 of them developed severe stenosis of proximal bronchus after 6 to 15 months.
                These results should provide support for definitive radiation therapy using 60 to 70 Gy to manage the patients with medically inoperable NSCLC without mediastinal involvement. Neoadjuvant chemoradiotherapy does not alter anal sphincter preservation or postoperative complications compared with short-course radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal cancer. The aim of this study was to compare survival, local control and late toxicity in the two treatment groups.
                The study randomized 312 patients to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus 5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up of living patients was 48 (range 31-69) months.
                Early radiation toxicity was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The actuarial 4-year overall survival was 67.2 per cent in the short-course group and 66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was 58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was 9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1 per cent (P = 0.360) respectively.
                Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone.
Patients with stable spines retaining the ability to walk may be treated with radiotherapy. One trial indicates that short course radiotherapy suffices in patients with unfavourable histologies or predicted survival of less than six months. There is some evidence of benefit from decompressive surgery in ambulant patients with poor prognostic factors for radiotherapy; and in non-ambulant patients with a single area of compression, paraplegia < 48 hours, non-radiosensitive tumours and a predicted survival of more than three months. High dose corticosteroids carry a significant risk of serious adverse effects.