Biomedical subjects
Publications and source records attributed to B Jeremic.
External beam radiotherapy is effective in the management of bone metastases for both local and more widespread pain. It is effective in spinal canal compression and pathological fracture where it also may have a prophylactic role. Single dose radiotherapy for bone metastases is a highly cost effective palliative treatment.
BACKGROUND: Despite several randomised trials comparing radiotherapy alone with concomitant radio-chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC), it is not clear whether the addition of chemotherapy improves survival. PATIENTS AND METHODS: This meta-analysis was based on individual patient data from published and unpublished randomised trials which compared radiotherapy alone with the same radiotherapy combined with concomitant cisplatin- or carboplatin-based chemotherapy. Trials with accrual completed after 2000 were excluded. Trials were sought in electronic databases, clinical trial registries and by additional manual searches. The primary endpoint was overall survival analysed using the log-rank test stratified by trials. RESULTS: There were twelve eligible trials that included a total of 1921 patients. The data from 3 trials were not available. Therefore, the analysis was based on 9 trials including 1764 patients. Median follow-up was 7.2 years. The hazard ratio of death among patients treated with radio-chemotherapy compared to radiotherapy alone was 0.89 (95% confidence interval, 0.81-0.98; P = 0.02) corresponding to an absolute benefit of chemotherapy of 4% at 2 years. There was some evidence of heterogeneity among trials and sensitivity analyses did not lead to consistent results. The combination of platin with etoposide seemed more effective than platin alone. CONCLUSIONS: Concomitant platin-based radio-chemotherapy may improve survival of patients with locally advanced NSCLC. However, the available data are insufficient to accurately define the size of such a potential treatment benefit and the optimal schedule of chemotherapy.
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BACKGROUND: Primary optic nerve sheath meningioma (ONSM) is a rare but almost invariably blinding tumour when its natural history is observed in a "wait and see" strategy. Surgery has hitherto only been advocated in case of progressive disease involving intracranial structures, as it leads to iatrogenic blindness in the overwhelming majority of cases. Therefore, treatment options bearing lesser risk of functional deterioration are highly desirable, both in cases of intracranial involvement as well as during earlier phases of the disease which are currently generally left untreated. The authors report the outcome of the largest series of patients to date treated by stereotactic fractionated irradiation as a new treatment approach in ONSM at all stages. METHODS: 15 patients (16 nerves) underwent stereotactic fractionated conformal irradiation with a total dose of 54 Gy, using standard fractionation. Main outcome parameters included visual acuity and visual field, as well as three dimensional remission as documented by imaging. RESULTS: Tumour control was confirmed in all 15 patients undergoing stereotactic fractionated conformal irradiation (mean follow up 37 (range 12-71) months). No patient developed functional deterioration during or after treatment. Moreover, visual acuity improved by more than two lines in one patient and the visual field improved in six cases. Visual outcome in the other patients remained unchanged. There were no significant side effects of radiation therapy. CONCLUSION: These data provide convincing evidence that stereotactic fractionated conformal irradiation is an effective treatment option for primary ONSM with minimal treatment related morbidity. It should therefore be considered as therapeutic option both in early stage ONSM where surgery cannot be justified as well as in later stages, where surgery is so far considered the first line approach.
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PURPOSE: To investigate the influence of the interfraction interval (IFI) on treatment outcome and toxicity in hyperfractionated (HF) radiotherapy (RT) for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: Data for 301 patients treated with 1.2 Gy b.i.d. to a total of 69.6 Gy and concurrent chemotherapy in our 3 prospective studies were analyzed. The chemotherapy regimen was either (1) 50 mg each of carboplatin and etoposide (CE) given on RT days (163 patients) or (2) 30 mg of CE on RT days and 100 mg of CE on Saturdays and Sundays during the RT course (138 patients). An IFI of 4.5-5 h or 5.5-6 h had been nonrandomly assigned for each patient, and this interval was kept throughout the treatment. RESULTS: No difference was observed in treatment outcome due to the chemotherapy protocol, and the 2 groups were combined. Patients treated with the shorter IFI had a better local control rate (38% at 5 years) and survival rate (30% at 5 years) than those treated with the longer interval (23% and 14%, respectively; p < 0.001). However, female patients and those with a high Karnofsky performance status score (KPS), weight loss of < or =5% in the previous 6 months, or Stage IIIA disease had been more often treated with the shorter IFI, and these characteristics were associated with better treatment outcome. In multivariate analysis, only gender, KPS, and weight change proved to be significant prognostic factors influencing both local control and survival, and the effect of IFI was not significant. The incidence of Grade 4 acute esophagitis tended to be higher in the shorter interval group (p = 0.072), but there were no differences in the incidence of late or other acute RT-related toxicities between the 2 groups. CONCLUSIONS: The possible influence of the IFI on local control and survival could not be verified using multivariate analysis. To better understand the influence of the IFI, randomized studies with more patients and wider ranges of intervals (e.g., 5 h vs. 8 h) seem to be necessary.
PURPOSE: To investigate whether the addition of weekend chemotherapy consisting of carboplatin/etoposide to hyperfractionated radiation therapy (Hfx RT) and concurrent daily carboplatin/etoposide offers an advantage over the same Hfx RT/daily carboplatin/etoposide. METHODS AND MATERIALS: A total of 195 patients (Group I, 98; Group II, 97) were treated with either Hfx RT to a total tumor dose of 69.6 Gy via 1.2 Gy b.i.d. fractionation and daily 50 mg each of carboplatin and etoposide during the RT course (Group I) or the same Hfx RT with daily carboplatin/etoposide consisting of 30 mg each of carboplatin and etoposide and with weekend (Saturdays and Sundays) 100 mg each of carboplatin and etoposide during the RT course (Group II). RESULTS: No difference was found regarding median survival time and 5-year survival rates (20 vs. 22 months and 20% vs. 23%; p = 0.57). Median time to local progression was 20 and 19 months, respectively, while 5-year local progression-free survival rates were 28% and 27%, respectively (p = 0.66). Also, there was no difference regarding either median time to distant metastasis and 5-year distant metastasis-free survival (21 vs. 25 months and 29% vs. 34%, p = 0.29). There was no difference in the incidence of various nonhematologic toxicities between the two treatment groups, but patients treated with the weekend CHT had significantly more high-grade (> or = 3) hematologic toxicity (p = 0.0046). Late high-grade toxicity was not different between the two treatment groups. CONCLUSION: The addition of weekend carboplatin/etoposide did not improve results over those obtained with Hfx RT and concurrent low-dose, daily carboplatin/etoposide, but it led to a higher incidence of acute high-grade hematologic toxicity.
PURPOSE: To investigate the incidence of second cancers occurring in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with radiation therapy (RT) alone. PATIENTS AND METHODS: Seventy-eight patients had been treated with conventionally fractionated (CF) RT (1982 to 1987), and 116 patients had been treated with hyperfractionated (Hfx) RT (1988 to 1993). Tumor doses were 60 Gy for CF and 69.6 Gy (1.2 Gy bid) for Hfx. RESULTS: A total of 26 patients developed second cancers. The cumulative incidence of second cancer was 21.8% (SE, 4.7%) at 5 years and 34.8% (SE, 6.7%) at 10 years. For second lung cancers, it was 6.0% (SE, 2.8%) at 5 years and 14.2% (SE, 5.2%) at 10 years, and for second nonlung cancers, it was 16.3% (SE, 4.2%) at 5 years and 22.2% (SE, 5.7%) at 10 years. The rate of developing second cancer per patient per year was 4.3% (95% confidence intervals [CI], 2.7% to 5.9%), with the rates being 1.4% (CI, 0.5% to 2.3%) for the second lung cancers and 2.8% (CI, 1.5% to 4.1%) for second nonlung cancers. The rate of developing second cancers during the first and second 5-year period after RT (0 to 5 and 5 to 10 years) was 4.3% (CI, 2.4% to 6.2%) and 4.2% (CI, 0.6% to 7.8%), respectively, for all cancers. These rates were 1.0% (CI, 0.1% to 1.9%) and 2.2% (CI, 0% to 4.6%), respectively, for second lung cancers, and 3.2% (CI, 1.6% to 4.8%) and 1.5% (CI, 0% to 3.6%), respectively, for second nonlung cancers. CONCLUSION: Long-term survivors after RT alone for early stage NSCLC carry the same risk of developing second cancer, either lung or nonlung, as their counterparts treated surgically when the results of this study are compared with those of the published literature.
PURPOSE: To evaluate the risk of developing radiation myelitis after a cervical spinal cord dose of 50.6 Gy given via 1.1 Gy b.i.d. fractionation during a prospective, randomised trial of hyperfractionated radiation therapy (HFX RT) to a total dose of 77 Gy given in 70 fractions of 1.1 Gy b.i.d., with and without concurrent low-dose, daily cisplatin (CDDP) for head and neck cancer. METHODS: Of 130 patients with locally advanced, unresectable, nonmetastatic squamous cell carcinoma of the head and neck (SCC H&N) who entered a prospective, randomised trial, 101 patients received 50.6 Gy to a portion of their spinal cord and survived > 1 year following the beginning of therapy. Forty-five patients were treated with HFX RT alone and fifty-six patients also received CDDP. RESULTS: None of these 101 patients developed cervical radiation myelitis. Therefore, it was not possible to investigate the influence of potentially contributing factors on the occurrence of radiation myelitis, such as interfraction interval, cord length, and administration of concurrent CDDP. CONCLUSIONS: Given the increasing number of studies with both altered fractionated regimens and concurrent radio-chemotherapy in SCC H&N, new studies with more patients are needed to gain better insight into the risks of developing cervical radiation myelitis.
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Bone metastases are a frequent complication of cancer, and frequently cause pain. Indications for radiotherapy for bone metastases include pain, risk for pathologic fracture, and neurological complications arising from spinal cord compression, nerve root pain or cranial nerve involvement. There are numerous fractionation patterns of external beam radiation therapy for painful bone metastasis, both fractionated schedules and single fraction regimens. All prospective randomized trials that evaluated differences in the outcomes associated with various fractionated regimens versus single fraction regimens unequivocally showed that single fraction regimens (mostly 8 Gy) are at least equal with various fractionated regimens. The single fraction regimens have an additional advantage of being more convenient to both patients and hospitals. However, there are still numerous questions that are left unanswered in these trials, such as the "optimal" single fraction that should be used, the possibility for retreatment, and prognostic factors that may help identify those patients more likely to respond to a single fraction radiation therapy in the treatment of painful bone metastasis.
PURPOSE: Feasibility, antitumor activity and toxicity of accelerated hyperfractionated radiation therapy (Acc Hfx RT) and concurrent carboplatin/etoposide (CBDCA/VP 16) chemotherapy were investigated in patients with malignant glioma. MATERIAL AND METHODS: Seventy-nine patients with either glioblastoma multiforme (GBM) (n = 61) or anaplastic astrocytome (AA) (n = 18) entered into a phase II study on the use of Acc Hfx RT with 60 Gy in 40 fractions in 20 treatment days over 4 weeks and concurrent CBDCA, 200 mg/m2, and VP 16, 200 mg/m2, both given once weekly during the RT course. RESULTS: The median survival time for all 79 patients was 14 months (11 and 44 months for GBM and AA patients, respectively), while the 2- and 4-year survival was respectively 33% and 11% for all patients, 13% and 1.6% for GBM patients, and 100% and 44% for AA patients (p < 0.0001). The median time to progression for all patients was 12 months (9 and 40 months for GBM and AA, respectively), while the 2- and 4-year progression-free survival (PFS) was respectively 28% and 10% (all patients), 10% and 1.7% (GBM) and 89% and 39% (AA) (p < 0.0001). Multivariate analysis showed that age, performance status, and preoperative size of tumor influenced survival in GBM. Only 5 (6%) patients experienced grade 3 leukopenia and 6 (8%) patients experienced grade 3 thrombocytopenia. No late RT-induced toxicity was observed to date. CONCLUSIONS: Although Acc Hfx RT/CBDCA + VP 16 was feasible and little toxic, it failed to improve survival/progression-free survival over that obtained with other currently used regimens. These results do not justify the investigation of this regimen in a phase III trial.
In this review on current concepts in radiation therapy in the treatment of incompletely resected supratentorial low-grade glioma, a number of important issues are discussed. They include indication for radiation therapy, timing (early vs delayed), dose response issue, impact of modern neuroimaging, 'optimal' treatment fields, impact of histology, new and promising approaches as well as quality of life in this disease are also discussed. This disease remains a focus of investigations in neuro-oncology owing to the fact that a number of questions discussed in the text are still far from being optimally addressed and answers are, therefore, lacking. New studies and more patients are needed to get more insight into this disease.
BACKGROUND: The current study was conducted to investigate retrospectively whether elective ipsilateral neck irradiation (EINI) is effective in controlling subclinical neck disease in patients with locally advanced (T3 and T4) nonmetastatic (N0, M0) squamous cell carcinoma (SCC) of the maxilla. METHODS: Between 1987 and 1993 a total of 44 patients were treated with EINI. The primary tumor bed was treated with 60 grays (Gy) in patients undergoing radical maxillectomy or with 66 Gy in patients undergoing partial maxillectomy. The ipsilateral upper and lower neck (down to the clavicle) was treated with either opposing anteroposterior-posteroanterior fields or appositional electron fields. The dose of elective neck radiotherapy was 50 Gy in 25 daily fractions. RESULTS: The 5-year and 10-year survival rates (with standard error [SE]) were 66% (SE 7%) and 60% (SE 8%), respectively, whereas the 5-year and 10-year recurrence free survival rates both were 64% (SE 7%). The 10-year local recurrence free survival rate was 69% (SE 7%), whereas the 10-year regional recurrence free survival rate was 94% (SE 4%). Of the 2 patients who developed a recurrence in the neck, 1 was salvaged successfully by surgery, producing an ultimate 10-year regional recurrence free survival rate of 97%. The 10-year distant metastasis free survival rate was 91% (SE 4%). CONCLUSIONS: The findings of the current study appear to suggest the potential efficacy of EINI in patients with locally advanced, nonmetastatic SCC of the maxilla and that the high rate of control of cervical lymph nodes may lead to better overall survival than that reported in the majority of the recent series.
Information about prognostic factors influencing survival have been only occasionally reported in studies on the use of radiosurgery in the treatment of patients with brain metastasis. To answer the question of whether activity of extracranial metastases is an independent prognostic factor influencing survival in radiosurgery of brain metastases, a review of the literature was performed. Fourteen studies were identified in the English language literature that dealt with this topic. Only three studies showed borderline insignificance of the influence of activity of extracranial metastases when analysed by univariate methods. When multivariate analysis was used to test for the independent influence of this factor on survival, of nine studies that used that statistical approach eight showed that it is an independent prognosticator influencing survival, most often being the strongest one. This review of literature supports the view that the "activity of extracranial metastases" is an independent prognostic factor influencing survival of these patients as documented in published reports. However, prospective randomised trials are necessary to definitely establish the independent influence of this prognostic factor.
PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m(2)) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P =.0075). It also offered higher progression-free survival (46% v 25% at 5 years; P =.0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P =.041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P =.0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.
PURPOSE: To investigate feasibility, toxicity, and efficacy of accelerated hyperfractionated radiation therapy and concurrent carboplastin/oral etoposide in elderly (> 70 years) patients with stage III non-small-cell lung cancer. METHODS AND MATERIALS: Between January 1988 and June 1993, a total of 58 patients entered a phase II study. Carboplatin (400 mg/m(2)) was given intravenously on days 1 and 29, and etoposide (50 mg/m(2)) was given orally on days 1-21 and 29-42. Accelerated hyperfractionated radiotherapy was administered starting on day 1, with a total dose of 51 Gy in 34 fractions over 3.5 weeks. RESULTS: In 55 evaluable patients, the complete response rate was 27% and the overall response rate was 65%. For the 55 patients, the median survival time was 10 months, and the 1-, 2-, and 5-year survival rates were 45%, 24%, and 9.1%, respectively. The median time until relapse was 8 months and the 1-, 2-, and 5-year relapse-free survival rates were 45%, 20%, and 9.1%, respectively. The median time to local recurrence was 14 months and the 5-year local control rate was 13%; the median time to distant metastasis was 18 months and the 5-year distant metastasis-free rate was 15%. Hematological, esophageal, and bronchopulmonary acute grade 3 or 4 toxicities were observed in 22%, 7%, and 4% of the patients, respectively. There was no grade 5 toxicity or late grade > or = 3 toxicity. CONCLUSION: Concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide produced relatively low and acceptable toxicity. The survival results appeared to be comparable to those obtained in nonelderly patients with stage III non-small-cell lung cancer treated by full-dose radiation.
PURPOSE: To investigate feasibility, activity and toxicity of pre-irradiation chemotherapy (CHT) in patients with newly diagnosed high-grade astrocytoma. MATERIAL AND METHODS: Thirty-five patients with glioblastoma multiform (GBM) and ten patients with anaplastic astrocytoma (AA) entered into this study. Three weeks after surgery patients started their CHT consisting of two cycles of carboplatin (CBDCA) (C) 400 mg/m2, day 1 and etoposide (VP 16) (E) 120 mg/m2, days 1-3, given in a 3-week interval. One week after the second cycle of CE, accelerated hyperfractionated radiation therapy (ACC HFX RT) was introduced with tumor dose of 60 Gy in 40 fractions in 20 treatment days in 4 weeks, 1.5 Gy b.i.d. fractionation. RESULTS: Responses to two cycles of CE could be evaluated in 29 (67%) of 43 patients who received it. Fourteen patients were found impossible to determine radiographic response due to an absence of post-operative contrast enhancement because they were all grossly totally resected. There were 7, 24% (95% confidence intervals - CI, 9-40%), PR (2 AA and 5 GBM), 19 SD, and 3 PD. After RT, of those 29 patients, there were 3 CR and 11 PR (overall objective response rate was 48% (95% CI, 30-67%)), 12 SD, and 3 PD. Median survival time (MST) for all 45 patients is 14 months (95% CI, 11-20 months, while median time to progression (MTP) for all patients is 12 months (95% CI, 8-16 months). Toxicities of this combined modality approach were mild to moderate, with the incidences of CHT-induced grade 3 leukopenia, being 5% (95% CI, 0-11%), and grade 3 thrombocytopenia being 7% (95% CI, 0-15%). Of RT-induced toxicity, grade 1 external otitis was observed in 26% (95% CI, 13-39%), while nausea, vomiting and somnolence were each observed in 5% (95% CI, 0-11%) patients. CONCLUSION: Pre-irradiation CE and ACC HFX RT was a feasible treatment regimen with mild to moderate toxicity, but failed to improve results over what usually would be obtained with 'standard' approach in this patient population.