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Branislav Jeremic

Publications and source records attributed to Branislav Jeremic.

At least 55 records · Page 3Linked to original sources
PubMed2003

Radiochemotherapy of malignant glioma in adults. Clinical experiences.

BACKGROUND: Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy. MATERIAL AND METHODS: Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed. RESULTS: 3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome. CONCLUSIONS: Therefore, search for newer and more effective drugs continues, as well as for "optimal" administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation.

Adult↗
PubMed2003

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II: Treatment-related late toxicity.

BACKGROUND: For more than 60 years, radiation therapy has been an integral part in the management of childhood low-grade glioma. As this tumor carries an excellent long-term prognosis, the risk of late effects is of particular clinical importance and impinges upon radiotherapeutic treatment strategies. MATERIAL AND METHODS: Studies on the use of radiation therapy in children with low-grade glioma were systematically reviewed for data on radiotherapy-induced side effects on brain parenchyma, endocrine dysfunction, growth retardation, neurocognitive dysfunction, vasculopathy, and secondary neoplasms. RESULTS: Data on late effects are scarce and heterogeneous. Past reports included only retrospective series from the 1930s to present days, a time during which treatment policies and radiation techniques widely varied and considerably changed in recent years. Often, considerable uncertainty existed regarding pretreatment health status and radiotherapy-related factors (e.g., total dose, dose per fraction, treatment fields). In spite of these shortcomings and often conflicting observations, it appears that especially younger children and children with neurofibromatosis (NF) are at risk of endocrinopathies in terms of growth retardation and developmental abnormalities, as well as neurocognitive dysfunction expressed as problems in the psychosocial environment such as in education and occupation. However, both observations may be attributed to the higher proportion of NF in the very young who frequently develop large tumors spreading along the entire supratentorial midline. The risk of radiation-induced disturbances in visual function is low (no case reported). Young children with NF appear to have an increased risk of vasculopathies. 33 cases of moyamoya disease were found (preferably in the very young), 18 of whom were NF-positive. Other cerebrovascular accidents (24 cases, of whom 14 were NF-positive) and secondary neoplasms (15 cases, of whom only five occurred in field--four were high-grade astrocytomas) are a rare condition. The latter cannot be distinguished from late relapses with malignant transformation. Modern treatment techniques appear to reduce the risk of radiation-induced late effects. CONCLUSIONS: More studies and clear definitions of clinical endpoints such as neurocognitive and endocrinological outcome are needed in order to clarify the impact of radiation therapy on the risk of late sequelae. Presently, the strategy to postpone radiotherapy in the younger children, especially with NF, is justified to reduce the risk of late effects. These information and the contribution of tumor, surgery and chemotherapy will help to define the role of radiation therapy in the future management of childhood low-grade glioma and whether the use of highly sophisticated and expensive treatment techniques is justifiable. The recently initiated prospective study of the APRO (Pediatric Radiooncology Working Party) on documentation of dose prescription to organs at risk and the network of the GPOH to explore late effects as well as the forthcoming prospective SIOP/GPOH (International Society of Pediatric Oncology/German Society of Pediatric Oncology and Hematology) LGG 2003 trial are addressing these issues.

Adolescent↗
PubMed2003

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part I: Treatment modalities of radiation therapy.

BACKGROUND: Treatment of childhood low-grade gliomas is a challenging issue owing to their low incidence and the lack of consensus about "optimal" treatment approach. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy, including orthovoltage, megavoltage and recently modern high-precision treatments, were reviewed with respect to visual function, survival, prognostic factors, dose prescriptions, target volumes, and treatment techniques. Based on these experiences, future strategies in the management of childhood low-grade glioma are presented. RESULTS: Evaluation of published reports is difficult because of inconsistencies in data presentation, relatively short follow-up in some series and failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature, primarily concerning indications, age at treatment, dose response, timing and use of "optimal" treatment fields, radiation therapy continues to play an important role in the management of these tumors achieving long-term survival rates up to 80% or more. Particularly in gliomas of the visual pathway, high local tumor control and improved or stable visual function is achieved in approximately 90% of cases. Data on dose-response relationships recommend dose prescriptions between 45 and 54 Gy with standard fractionation. There is consensus now to employ radiation therapy in older children in case of progressive disease only, regardless of tumor location and histologic subtype. In younger children, the role of radiotherapy is unclear. Recent advances in treatment techniques, such as 3-D treatment planning and various "high-precision" treatments achieved promising initial outcome, however with limited patient numbers and short follow-ups. CONCLUSIONS: Radiation therapy is an effective treatment modality in children with low-grade glioma regarding tumor control and improvement and/or preservation of neurologic function or vision, respectively. More prospective studies are needed to address the impact of modern radiation therapy technologies (including intensity-modulated radiotherapy) on outcome especially in the very young and to define the role of radiation therapy as a part of a comprehensive treatment approach. The forthcoming prospective trial SIOP/GPOH LGG RT 2003 is addressing this issue.

Adolescent↗
PubMed2003

Treatment of lung cancer in the elderly. Part I: non-small cell lung cancer.

There is a general trend worldwide of an increasing incidence of elderly population. Age is the greatest risk factor for cancer; therefore, this demographic shift is the main reason for an increase of cancer incidence. Lung cancer is a typical disease of the elderly patients. This review summarizes the issues of treatment of non-small cell lung cancer (NSCLC) in the elderly. Early stage NSCLC is usually treated with radical surgery, locally advanced NSCLC with radiotherapy (RT) and/or chemotherapy (CHT) and metastatic disease with CHT, but the evidence for these approaches is based on studies which are usually performed with highly selected patients while elderly patients are under-represented. We used the data from studies addressing particularly elderly or providing subgroup information on age to analyse the feasibility of current standard approaches for elderly and discuss alternative approaches. Surgery is an effective method in elderly patients with early stage NSCLC although some approaches bear a somewhat higher risk of operative morbidity and mortality. RT for early stage may be an alternative with curative potential. For locally advanced stage RT alone, or combined radiochemotherapy in selected cases, is feasible for elderly patients with locally advanced NSCLC when a careful assessment of pre-therapeutic status is made and appropriate drugs are selected. Advanced age alone also should not preclude CHT, although the risk of adverse effect may be higher in certain cases. New generation drugs seem to be particularly feasible and efficient in elderly patients. In general, age itself does not seem to preclude patients from standard treatments although in some cases co-morbidity forces to alternative approaches. Currently, single-agent CHT should be considered as the standard treatment of advanced NSCLC elderly patients.

Age Factors↗
PubMed2003

Treatment of lung cancer in elderly part II: small cell lung cancer.

There is a general trend worldwide of an increasing incidence of elderly population. Age is the greatest risk factor for cancer; therefore, this demographic shift is a main reason for an increase of cancer incidence. Lung cancer is a typical disease of the elderly patients. Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancer cases. This review summarises the issues of treatment of SCLC in elderly. The number of randomised phase III trials concerning treatment of SCLC in elderly patients are very limited. Although currently most treatment decisions are based on lower grades of evidence, some conclusions can be drawn from the current studies. Age alone is a very uncertain prognostic criteria for outcome or tolerability of treatment. Much more important is the geriatric assessment of each individual patient. Current treatment standards for limited disease (LD)-SCLC (polychemotherapy plus local thoracic irradiation and additional prophylactic cranial irradiation in case of complete remission) seems to be also feasible for 'fit' elderly (>70 years) LD-SCLC patients with a good performance and full functional capacities. There are preliminary data indicating that a similar outcome in elderly patients can probably be achieved a with reduced number of treatment schedules (e.g. 2 instead of 4 cycles in combination with radiotherapy. Surgical resection is also feasible in selected elderly patients with very early stage SCLC, where this maybe an appropriate approach, although no phase III data are available, which demonstrated the benefit of additional surgery compared to chemotherapy alone in early stage SCLC. In patients with extensive disease-SCLC age alone does not necessarily restrict the use of multiagent regimen, although the risk of haematological toxicity seems to be higher than in the younger patients. When standard treatment is not feasible due to co-morbidity or loss of functional capacity, several alternative combination regimens are available, which appear to be slightly superior to single agent treatment, although randomised data for elderly on that issue are sparse. Carboplatin and etoposide seems currently the most appropriate two-drug combination in elderly patients, but there are a variety of active and low toxic third generation agents like taxanes, gemcitabine and vinorelbine which are active in both, non-small cell lung cancer and SCLC. For the comparison of trials in elderly patients it will be of key importance to include a comprehensive and standardised geriatric assessment in such studies.

Aged↗
PubMed2003

Impact of treatment interruptions due to toxicity on outcome of patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone.

We investigated the effect of treatment interruptions due to high-grade (> or =3) toxicity on outcome of patients with early stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy (Hfx RT). Of 116 patients treated with total tumour doses of 69.6 Gy, 1.2 Gy b.i.d. fractionation, 44 patients refused surgery while 72 patients were medically inoperable due to existing co-morbid states. Patients who were medically inoperable had worse KPS (P=0.0059) and more pronounced weight loss (P=0.0005). Among them, 12 patients experienced high-grade toxicity and 11 of them with either acute (n=6) or "consequential" late (n=5) high-grade toxicity requested interruption in the Hfx RT course (range, 12-25 days; median, 17 days). Superior survival (OS) was observed in patients who refused surgery when compared to those who were medically inoperable (P=0.0041), as well as superior local recurrence-free survival (LRFS) (P=0.011), but not different distant metastasis-free survival (P=0.14). Cause-specific survival (CSS) also favoured patients who refused surgery (P=0.004). Multivariate analysis showed independent influence of the reason for not undergoing surgery on OS (P=0.035), but not on LRFS (P=0.084) or CSS (P=0.068). Patients who refused surgery did not experience high-grade toxicity (0/44), whereas 11 of 72 patients with medical inoperability and co-morbid states experienced high-grade toxicity and had treatment interruptions to manage toxicity (P=0.0064). Patients without treatment interruptions had significantly better OS (P=0.00000), LRFS (P=0.00000) and CSS (P=0.00000) than those with treatment interruptions. When corrected for treatment interruptions, the reason for not undergoing surgery independently influenced OS (P=0.040), but not LRFS (P=0.092) or CSS (P=0.068). In contrast to this, treatment interruption was independent prognosticator of all three endpoints used (P=0.00031, P=0.0075 and P=0.00033, respectively). When 11 patients with treatment interruptions were excluded, the reason for not undergoing surgery still affected OS (P=0.037) and CSS (P=0.039) but not LRFS (P=0.11). Multivariate analyses using OS, CSS and LRFS showed that the reason for not undergoing surgery affected OS (P=0.0436), but neither CSS (P=0.083) nor LRFS (P=0.080).

Adult↗
PubMed2002

Stereotactic fractionated radiotherapy in patients with optic nerve sheath meningioma.

PURPOSE: To evaluate the effectiveness of stereotactic fractionated radiotherapy (SFRT) in the treatment of optic nerve sheath meningioma (ONSM). METHODS AND MARERIALS: Between 1994 and 2000, a total of 39 patients with either primary (n = 15) or secondary (n = 24) ONSM were treated with SFRT and received a median total tumor dose of 54 Gy using 1.8 Gy/fraction. RESULTS: The radiographic response to SFRT was documented in all patients as stable disease (no change) except for 1 patient with a partial response. After a median follow-up of 35.5 months, all patients with ONSM were alive without recurrence. The visual fields and visual acuity were improved in 6 of 15 and 1 of 16 examined eyes in patients with primary ONSM, respectively, and in 6 of 24 and 7 of 26 examined eyes in patients with secondary ONSM, respectively. Stable visual fields and visual acuity was observed in 8 of 14 and 15 of 16 patients with primary ONSM, respectively, and in 17 of 24 and 19 of 26 patients with secondary ONSM, respectively. Except for reversible alopecia and erythema, no other SFRT-related toxicity was observed. CONCLUSION: SFRT represents a very effective and low-toxic treatment modality for ONSM. Despite a median follow-up of 3 years, this series of primary ONSM holds promise for future studies. It adds substantial evidence that SFRT may definitely become a standard treatment approach in selected cases of ONSM.

Adolescent↗
PubMed2002

Radiotherapy alone in technically operable, medically inoperable, early-stage (I/II) non-small-cell lung cancer.

PURPOSE: To investigate the effectiveness of high-dose, curative radiotherapy (RT) given alone in technically operable, but medically inoperable, patients with early-stage (I-II) non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Computerized and manual searches were done to identify published reports dealing with curative RT for NSCLC. Relevant studies were identified and the information provided therein was extracted regarding patient and treatment characteristics, treatment outcome, and various pretreatment and treatment-related factors influencing outcome, as well as toxicity and quality-of-life issues. RESULTS: Although a large variation of pretreatment and treatment characteristics was noted in the available studies, a median survival time of >30 months and a 5-year survival rate of up to 30% had been achieved. Accumulated experience seems to suggest that doses of at least 65 Gy with standard fractionation, or its equivalent when altered fractionation is used, are necessary for control of NSCLC. Smaller tumors seem to have a favorable prognosis, and the issue of elective nodal RT continues to be controversial. Analyses of patterns of failure have clearly identified local failure as the predominant pattern. Although a number of potential pretreatment patient- and tumor-related prognostic factors have been examined, none has been shown to clearly influence survival. Toxicity was usually low, but very high doses (e.g., 80 Gy) given with a conventional approach may carry a risk of an excessive rate of side effects. CONCLUSION: High-dose, curative RT is an effective treatment modality in technically operable, but medically inoperable, patients with early-stage NSCLC.

Aged↗
PubMed2002

Elective neck irradiation in locally advanced squamous cell carcinoma of the maxillary sinus: a review.

This review has been undertaken to evaluate the impact of elective nodal irradiation (ENI) in locally advanced squamous cell carcinoma (SCC) of the maxillary sinus. The indications for radiotherapy (RT) including the dose, the volume to be covered, as well as possible toxicities encountered in the reports available are discussed. A total dose of 50 Gy standard fractionation appears to be efficient in achieving locoregional control in about 95% of all cases with low toxicity. The lymphatic drainage that needs to be covered remains to be defined more clearly, but it seems that there is no need for irradiation of the low neck. Bilateral upper neck irradiation remains controversial. Pattern of nodal failure in patients who received ENI and in those without ENI seem to suggest ipsilateral neck irradiation confined to submandibular and subdigastric/jugulodigastric areas. Finally, matching of the primary (maxillary sinus) tumor fields and neck field(s) must be carefully performed so as not to leave regions of possible under/overdosage of these neck areas. The authors believe that ENI is justified in these patients. However, given the background of only a few studies addressing this issue and anticipated better local control with the newer technologies, this issue needs to be properly studied in the future.

Carcinoma, Squamous Cell↗
PubMed2002

Radiation therapy in the multimodal treatment approach of pituitary adenoma.

BACKGROUND: Pituitary tumors are relatively uncommon, comprising 10-12% of all intracranial tumors. The treatment consisting of surgery, radiotherapy and drug therapy or a combination of these modalities is aimed at the control of tumor cell proliferation and--in endocrine active tumors--the reduction of hormone secretion. However, the slow proliferation characteristics of pituitary tumors necessitate long-term studies for the evaluation of the treatment results. In the last decade there has been continuous improvement in surgical procedures, radiotherapy techniques and drug generation. In this paper, literature will be reviewed to assess the role of modern radiotherapy and radiosurgery in the management of pituitary adenomas. MATERIAL AND METHODS: Nowadays, magnetic resonance imaging for the definition of the target volume and a real three-dimensional (3-D) treatment planning with field conformation and the possibility for non-coplanar irradiation has to be recommended. Most groups irradiate these benign tumors with single doses of 1.8-2.0 Gy up to a total dose of 45 Gy or 50.4 Gy in extensive parasellar adenomas. Adenomas are mostly small, well circumscribed lesions, and have, therefore, attracted the use of stereotactically guided high-precision irradiation techniques which allow extreme focussing and provide steep dose gradients with selective treatment of the target and optimal protection of the surrounding brain tissue. RESULTS: Radiation therapy controls tumor growth in 80-98% of patients with non-secreting adenomas and 67-89% for endocrine active tumors. Reviewing the recent literature including endocrine active and non-secreting adenomas, irradiated postoperatively or in case of recurrence the 5-, 10- and 15-year local control rates amount 92%, 89% and 79%. In cases of microprolactinoma primary therapy consists of dopamine agonists. Irradiation should be preferred in patients with macroprolactinomas, when drug therapy and/or surgery failed or for patients medically unsuitable for surgery. Reduction and control of prolactin secretion can be achieved in 44-70% of patients. After radiotherapy in acromegaly patients somatomedin-C and growth hormone concentrations decrease to normal levels in 70-90%, with a decrease rate of 10-30% per year. Hypercortisolism is controlled in 50-83% of adults and 80% of children with Cushing's disease, generally in less than 9 months. Hypopituitarism is the most common side effect of pituitary irradiation with an incidence of 13-56%. Long-term overall risk for brain necrosis in a total of 1,388 analyzed patients was estimated to be 0.2%. Other side effects are rare too, and do also depend on the damage produced by tumor itself or preceding surgery. They include deterioration of vision in 1.7% of all cases, vascular changes in 6.3%, neuropsychological disorders such as dementia in 0.7% and secondary malignancies in 0.8%, if single doses of 2.0 Gy and total doses of 50 Gy are not exceeded. CONCLUSION: Conventional radiation therapy of pituitary adenoma is highly effective. It is recommended after subtotal resection of primary tumors such as macroadenomas, after gross total resection from endocrine active adenomas with postsurgical hormone secretion and for recurrent tumors. Radiosurgery seems to be a possible treatment alternative in experienced centers, and only in patients with adenomas smaller than 25-30 mm with a minimum distance of 2-3 mm to the chiasm.

Acromegaly↗
PubMed2002

Radiosurgery for brain metastases: the Tuebingen experience.

PURPOSE: To retrospectively investigate the effectiveness of linear accelerator based radiosurgery (RS) in the treatment of brain metastases (BM). MATERIAL AND METHODS: Of 55 patients with a total of 72 BM, 41 patients had a single brain metastasis and 14 patients had two or three metastases. Median tumour dose of 15Gy (range 8-20Gy) was prescribed to a median isodose surface of 90% (range 70-100%) encompassing the target volume. RESULTS: The median survival time (MST) for all 55 patients was 7 months [95% confidence interval (CI), 5-10 months] and 2-year survival is 18%. There was no significant difference between patients who had one brain metastasis and those with either two or three metastases (log rank P=0.7565). Multivariate analysis in patients with a single BM showed that interval between primary diagnosis (PD) to BM, maximum size of metastasis, and histology (renal cell carcinoma and melanoma versus others) were independent prognostic factors influencing survival. Local control was obtained in 66/72 (92%) metastases. Actuarial local control at 24 months was 52%. Only age ( 50 years) and histology (renal cell versus others) influenced local control in the univariate analysis in patients with a single BM. In multivariate analysis, size, histology (renal cell and melanoma versus others), activity of extracranial metastatic disease, age, interval from PD to BM and location (midline versus other) independently influenced local control, while the dose was not significant for our patient group. Only one patient developed radiographically suspected RS-induced necrosis after previous whole brain RT. CONCLUSION: RS was effective and little toxic in BM. Identification of prognostic factors must be performed to gain knowledge on patients most likely to benefit from this procedure.

Adult↗
PubMed2002

External beam radiation therapy for bronchial stump recurrence of non-small-cell lung cancer after complete resection.

BACKGROUND AND PURPOSE: External beam radiation therapy (EBRT) is occasionally used in the treatment of bronchial stump recurrences after complete surgical resection in patients with non-small-cell lung cancer (NSCLC), but no prospective study exists, so far. The objective of this review is to determine effectiveness of high-dose EBRT in this disease. METHODS: A systematic review was undertaken using electronic databases, reference lists and hand searching of journals to identify potentially eligible studies. Selection criteria included studies that provided outcome after high-dose EBRT in this disease. Six retrospective studies were reviewed, including a total of 54 patients. RESULTS AND CONCLUSION: High-dose EBRT appears to be an effective treatment modality for recurrent NSCLC confined to the bronchial stump after curative resection with a median survival time of approximately 30 months and 5-year survival of approximately 30%. Although small patient numbers and unclear indications for radical versus palliative EBRT may obscure the overall conclusions, among patients with intrathoracic recurrence those with bronchial stump recurrence only do better than those with non-stump recurrence. It seems there is a dose-response effect in this patient population and a predominantly local pattern of failure, both observations having an implication for future studies. The optimal dose/fractionation pattern or treatment fields must be further investigated in the future. Identification of an unfavourable subset of patients may help optimize treatment in the future by omitting high-dose, curative RT in those patients who may be best treated with palliative RT. Prospective studies on EBRT in both bronchial stump and other post-surgical recurrences are urgently needed.

Bronchi↗
PubMed2002

No thoracic radiation myelitis after spinal cord dose > or = 50.4 Gy using 1.2. Gy b.i.d. fractionation in patients with Stage III non-small cell lung cancer treated with hyperfractionated radiation therapy with and without concurrent chemotherapy.

We investigated a risk of developing radiation myelitis during four prospective studies using hyperfractionated radiation therapy (HFX RT) with and without concurrent chemotherapy (CHT) during which a portion of thoracic spinal cord received a dose > or = 50.4 Gy given via 1.2 Gy b.i.d. fractionation. Of 536 patients with Stage III non-small cell lung cancer (NSCLC) which were treated on three prospective randomised Phase III studies and one Phase II study, 336 patients received irradiation dose > or = 50.4 Gy to a portion of their spinal cord and survived >1 year after the beginning of therapy. None of these 336 patients developed thoracic radiation myelitis. Therefore, the influence of potentially contributing factors on the occurrence of radiation myelitis, such as cord length, interfraction interval, or administration of concurrent CHT was not possible to investigate. These results give new insight about the influence of total dose/dose per fraction/interfraction interval with or without concurrent CHT on the thoracic spinal cord toxicity.

Adult↗