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Branislav Jeremic

Publications and source records attributed to Branislav Jeremic.

At least 37 records · Page 2Linked to original sources
PubMed2004

Concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer.

Current evidence suggests that concurrent RT/CHT is the standard of treatment in patients with locally advanced, inoperable NSCLC. This treatment approach, however, bears risk of increased toxicity and, therefore, must be carefully balanced regarding the choice of patients suitable for such an intervention. Newer RT technologies, third-generation CHT drugs, and widely used radioprotectors represent the current framework for numerous clinical studies that ultimately will help optimize the treatment of this disease.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Treatment of locally advanced and metastatic non-small cell lung cancer in the elderly.

In locally advanced NSCLC, RT/CHT can be used in fit elderly patients. In cases in which CHT is prohibitive, RT can be used alone. Advanced IIIB stage may be treated with palliative RT or CHT, each given alone. In metastatic NSCLC, platinum-containing regimens are feasible when elderly patients have good renal/cardiac function, but a third-generation drug may be a viable option, the choice depending on its toxicity profile. Short-course, palliative RT given in addition to CHT may play an important role in the treatment of symptomatic intra- and extrathoracic disease. Many questions concerning the optimal treatment for elderly patients with NSCLC remain unanswered and more trials designed for the elderly are urgently needed in the future.

Aged↗
PubMed2004

Radiation therapy.

RT is an indispensable part of current treatment approaches of locally advanced and metastatic NSCLC. It can be used alone or in combination with surgery or CHT. Because RT can potentially cure some patients, prolong the life of others, and reduce symptoms in the majority of them, it is a unique treatment modality in this disease. Radiation oncologists have learned how to deal with RT-induced toxicities and how to improve quality of life of lung cancer patients. Although recent technologic advances made sophisticated RT somewhat more expensive than before (demanding more manpower and being more time-consuming), it is still an inexpensive treatment modality, which is important in the era of focusing on cost-effectiveness. Although newer RT technologies are used to enable effective dose-escalation-a clear must for the community of radiation oncologists--optimization of RT must also include clear identification of various pretreatment, patient, and tumor-related characteristics that may influence treatment outcome. Regardless of the current therapeutic/technologic potential, we still lack some basic knowledge to better understand the process of, for example, combining RT and CHT. There is recognized need for better translational research that ultimately should be seen as a "two-way road," from laboratory to clinic and vice versa, preferably in a continuous way. The National Cancer Institute in the United States recently organized a workshop on translational research in radiation oncology, which has identified RT-CHT interactions as one of its major areas of research. Research topics include development of the methods of imaging the results of RT/ CHT interactions (confirmed by biopsy), development of new radiation modifiers, and identification of factors other than genetic ones that may influence the response of tumors to RT/CHT interactions. Tumor microenvironment was also clearly addressed as one of the targets for research, indicating as special tasks the development of new, microenvironmentally activated cytotoxic or cytostatic drugs, development and validation of more user-friendly methods for determining tumor oxygenation, and answering whether hypoxia predicts for radioresistance to CHT in treatment and whether it causes increased tumor aggression and metastasis. The future may, therefore, be quite simple: technology meets biology.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Biologic premises of combined radiation therapy and chemotherapy in lung cancer.

When radiation is combined with concurrent chemotherapy, independent cell kill and enhancement of tumor response may be expected. On the other hand, spatial cooperation may be the main rationale for sequential combination of the two modalities. Among many new agents being investigated, radiation-activated antitumor prodrugs have a therapeutic potential as a new method to effectively combine radiation and concurrent chemotherapy.

Combined Modality Therapy↗
PubMed2004

Clinical prognostic factors in patients with malignant glioma treated with combined modality approach.

The impact of various clinical pretreatment prognostic factors in patients with malignant glioma treated with a combined modality approach was investigated in 229 patients treated on four consecutive prospective phase II studies. The median survival time for all 229 patients is 14 months, and 2- and 5-year survival rates are 34%, and 9%, respectively. The median time to tumor progression is 14 months, and 2- and 5-year progression-free survival rates are 32%, and 9%, respectively. Females did better than males, while patients 55 years or less did better than those more than 55 years. Patients with Karnofsky performance status (KPS) 80 to 100 did better than those with KPS 50 to 70 as well as did patients having preoperative tumor sizes 4 cm or less when compared to those with larger tumors. Frontal tumor location as well as more extensive surgery favorably influenced survival. Patients harboring anaplastic astrocytoma fared significantly better than those with glioblastoma multiforme. Both univariate and multivariate Cox analyses confirmed independent influence of these prognosticators. When progression-free survival was used as an endpoint, all seven variables remained independent prognosticators. This study showed that sex, age, KPS, tumor size, tumor location, histology, and extent of surgery are independent prognosticators in patients with malignant glioma treated with combined modality approach.

Brain Neoplasms↗
PubMed2004

Stage III non-small-cell lung cancer treated with high-dose hyperfractionated radiation therapy and concurrent low-dose daily chemotherapy with or without weekend chemotherapy: retrospective analysis of 301 patients.

We investigated the outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with high-dose hyperfractionated radiation therapy (Hfx RT) and concurrent chemotherapy (CHT) consisting of carboplatin (C) and etoposide (E). During three prospective randomized phase III and one prospective phase II study enrolling a total of 536 patients, 301 patients were treated with high-dose Hfx RT (69.6 Gy) and either low-dose daily CE (50 mg each) (n = 163) or daily CE (30 mg each) accompanied by "weekend" CE (100 mg of each on Saturdays and Sundays) (n = 138). The median survival time for all 301 patients is 22 months and 5-year survival is 24%. Median local recurrence-free survival (LRFS) time is 21 months and 5-year local recurrence-free survival is 32%. The median time to distant metastasis is 25 months, and 5-year distant metastasis-free survival (DMFS) is 35%. Only the type/schedule of CHT administration did not influence overall survival, LRFS, and DMFS. On multivariate analyses using these three endpoints, age stage, interfraction interval, and type/schedule of CHT administration did not predict survival, LRFS, and DMFS, while gender, KPS, and weight loss did. Only high grade hematologic toxicity was more frequent in weekend CHT group. High dose Hfx RT and concurrent low-dose daily CE with or without weekend CE is an active treatment approach in stage III NSCLC that led to high overall survival, LRFS, and DMFS rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Interfraction interval in patients with stage III non-small-cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy: final results in 536 patients.

We investigated the influence of interfraction interval (IFI) on treatment outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT). During 3 randomized phase III and 1 phase II study, a total of 536 patients were treated with Hfx RT alone or with concurrent carboplatin/etoposide. Two hundred eighty-five patients were treated with IFI of 4.5-5.0 hours, while 251 patients were treated with IFI of 5.5-6.0 hours. "Shorter" (4.5-5.0 hours) IFI led to better overall survival (OS) (P = 0.0000) and local recurrence-free survival (LRFS) (P = 0.0000). Multivariate analyses showed IFI to be an independent prognosticator of both OS and LRFS. These results were confirmed when we separated all patients (n = 536) into those treated with Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409). Various RT-related high-grade acute toxicity was not different between the 2 IFI, but patients treated with shorter IFI had a significantly higher incidence of hematological toxicity (P = 0.002). None of the late high-grade toxicities were different between the 2 interfraction intervals. Using regression analysis, it was shown that IFI was not a significant predictor of any of acute or late high-grade (> or =3) toxicity. IFI is an important prognosticator of OS and LRFS in patients with stage III NSCLC treated with Hfx RT with or without concurrent carboplatin/etoposide. IFI led to higher incidence only of hematological toxicity, but was not predictive of any acute or late high-grade (> or =3) toxicity. A carefully designed randomized trial seems necessary to give better insight into the issue of optimal IFI in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Hyperfractionated radiation therapy for incompletely resected supratentorial low-grade glioma: a 10-year update of a phase II study.

PURPOSE: To provide a 10-year update of hyperfractionated radiation therapy (Hfx RT) in adults with incompletely resected supratentorial low-grade glioma. METHODS AND MATERIALS: A total of 37 patients were treated with 55 Gy in 50 fractions in 25 treatment days in 5 weeks to tumor plus 2 cm, and additional 17.6 Gy given in 16 fractions in 8 treatment days in 1.5 weeks to tumor plus 1 cm, (1.1 Gy twice daily). Total dose was 72.6 Gy in 66 fractions in 33 treatment days in 6.5 weeks. RESULTS: After a median follow-up time of 121 months for all patients, the median survival time (MST) for all 37 patients was 145 months, whereas 10-year survival rate was 67%. Median time to tumor progression (MTP) has not yet been attained, but 10-year progression-free survival (PFS) rate was 62%. There was no difference in survival or PFS regarding gender, age, location, site, size, CT enhancement, and histology; whereas lower KPS, higher neurologic status, and lesser extent of surgery had an adverse influence. Infield progression occurred in 15 (88%), whereas in only 2 (12%) patients, tumor progression was described as marginal. Brain necrosis has not been observed so far. Autopsy findings confirmed recurrent glioma and excluded post-RT necrosis in 14 (38%) patients. Of those, 7 (50%) patients had either Grade 3 (n = 4) or Grade 4 (n = 3) glioma. CONCLUSION: High-dose HFX RT is effective with mild to moderate toxicity. Further studies are warranted with more patients before testing it against standard fractionation RT in this patient population.

Adult↗
PubMed2003

Multivariate analysis of clinical prognostic factors in patients with glioblastoma multiforme treated with a combined modality approach.

We investigated the influence of various clinical prognostic factors in patients with glioblastoma multiforme (GBM) treated with a combined modality approach. A total of 175 patients with GBM was treated in four consecutive prospective phase II studies using surgery, hyperfractionated or accelerated hyperfractionated radiotherapy (RT) and either adjuvant or concurrent or pre-irradiation chemotherapy (CHT) between January 1988 and December 1993. The median survival time for all 175 patients was 14 months and 1-3-year survival (OS) rates were 57%, 34% and 24%, respectively. The median time to tumour progression was 12 months, and 1-3-year progression-free survival (PFS) rates were 43%, 11% and 7%, respectively. Survival analysis showed that of all investigated prognostic factors, only gender did not influence survival. Patients </=55 years did better than those >55 years; patients with KPS 80-100 did better than those with KPS 50-70; patients with frontal tumours did better than those with tumours in other locations; patients with tumours up to 4 cm did better than those with larger tumours, as did patients with either subtotal or gross total tumour resection when compared to those undergoing biopsy only. Multivariate analysis showed that gender and tumour location did not independently influence survival. When PFS was used as the endpoint, only gender did not influence PFS, as confirmed by multivariate analysis.

Chemotherapy, Adjuvant↗
PubMed2003

Pretreatment clinical prognostic factors in patients with stage IV non-small cell lung cancer (NSCLC) treated with chemotherapy.

PURPOSE: We investigated the influence of potential pre-treatment clinical prognostic factors in stage IV non-small cell lung cancer (NSCLC). METHODS AND PATIENTS: A total of 285 patients were enrolled in two consecutive prospective randomised studies which compared (study 1) carboplatin and prolonged oral etoposide (group 1; n=58) with the same etoposide alone (group 2; n=59), and (study 2) carboplatin and prolonged oral etoposide (group 1; n=84) with the same carboplatin and high-dose intravenous etoposide (group 2; n=84). RESULTS: The median survival time for all 285 patients was 7 months, while 1- and 2-year survival rates were 29% and 8%, respectively. Age did not impact on outcome ( P=0.21), while female patients did significantly better than male patients ( P<0.0001). Patients with KPS 80-100 did significantly better than those with KPS 50-70 ( P<0.0001), as did patients with less pronounced weight loss ( P<0.0001) and those with only one metastatic site when compared to those having at least two metastatic sites ( P<0.0001). When evaluated regarding the metastatic site, only subcutaneous metastatic site did not influence survival. This was confirmed within univariate analyses, but when multivariate analyses were done gender, KPS, weight loss, number of metastatic sites, presence of liver metastases and presence of brain metastases independently influenced survival, while age and other metastatic locations did not. CONCLUSION: In this analysis, gender, KPS, weight loss, number of metastatic sites, presence of liver metastases and presence of brain metastases independently influenced survival in patients with stage IV NSCLC treated with CHT.

Aged↗
PubMed2003

Radiation therapy alone in early stage non-small cell lung cancer.

Among the patients with early stage (I/II) non-small cell lung cancer (NSCLC), there are those who, due to medical comorbidities, advanced age, or refusal, never undergo surgery. For them, exclusive radiation therapy (RT) has been the treatment of choice, achieving median survival times of 30 months and 5-year survival of up to 42%. Doses of > or =65 Gy with standard fractionation (or its radiobiological equivalent when altered fractionation is used) are necessary for long-lasting local control of the disease, with smaller tumors having a more favorable prognosis. The issue of elective nodal irradiation (ENI) remains controversial, since failure patterns identified local failure as the predominant pattern. None of the potential pretreatment patient- and tumor-related prognostic factors has been shown to clearly influence survival. Toxicity is generally mild to moderate, although high doses (e.g., 80 Gy) may carry a risk for an excessive rate of side effects. Conformal treatment and consideration of comorbidities such as altered lung function may be essential, since simultaneous supportive treatment of acute sequelae (mainly acute esophagitis) is necessary. RT is an effective treatment modality in technically operable, but medically inoperable patients with early stage NSCLC and offers a long-lasting cure.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Treatment of recurrent disease in lung cancer.

Recurrence is a common event after treatment of lung cancer. Retreatment options depend on previous therapies, location of recurrence, and physical condition of the patient. Locoregional relapse can be treated the same way as initial lung cancer, including surgery, radiotherapy (RT), and chemotherapy (CHT), or combined treatment. Approximately 1% to 2% of all recurrent lung cancer is treated with curative reoperation, with somewhat dismal results. RT has been used for either postsurgical or post-RT locoregional recurrences. In the former case, external beam RT was particularly effective in isolated bronchial stump recurrences, with median survival time of approximately 28.5 months and a 5-year survival of approximately 31.5%. In the latter case, reirradiation, generally with endobronchial brachytherapy, was successful in palliation of intrathoracic symptoms (in at least two-thirds of cases), carrying a low incidence of radiation pneumonitis (up to 5%) although cumulative doses went up to 120-150 Gy. Besides external beam RT, endobronchial RT was used to treat symptomatic intraluminal recurrences, with the vast majority of studies using high-dose rate brachytherapy. Finally, CHT has been used in relapsed/refractory advanced or metastatic non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with the major emphasis on the third-generation drugs that show good response after previously used platinum-based CHT.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Complex and controversial issues in locally advanced non-small cell lung carcinoma.

Locally advanced non-small cell lung carcinoma (NSCLC) presents enormous challenges to clinicians and researchers. Because of the absence of metastatic disease, it is a potentially curable condition, greatly differentiating it from stage IV NSCLC. The median and actuarial survival rates are poor, though clearly improved in the past decade, and clearly better than several other types of locally advanced malignancies (e.g., pancreatic cancer, glioblastoma). As demonstrated in Table I, the combination of chemotherapy and radiotherapy has earned the designation of "standard of care" for most good-performance-status patients with locally advanced NSCLC. It is likely that improvements in radiotherapy have also contributed to the enhanced survival and local control rates in this disease. With concurrent chemoradiotherapy, the majority of patients can receive a substantial local response (Fig. 1). Many achieve durable local control, only to succumb to eventual distant metastatic failure. There remains much room for improvement, and there are several avenues for clinical and translational research that offer promise. These include new systemic chemotherapy options (and newer ways of combining these drugs with radiotherapy), improvements in radiotherapy fractionation and dose intensity, methods of protection from chemoradiotherapy toxicity, specific therapies to prevent brain metastatic failure, and the integration of biologically targeted molecules into chemoradiation programs. This article summarizes the advances in the treatment of locally advanced NSCLC over the past several decades and explores some of the many remaining controversies and areas for future investigation.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Limited-disease small-cell lung cancer.

Substantial improvements in treatment outcome for limited-disease small-cell lung cancer (LD SCLC) have been achieved in the last two decades owing to the introduction of chemotherapy (CHT) consisting of cisplatin and etoposide (PE), and the understanding that thoracic radiation therapy (TRT) is an essential component in improving treatment outcome. In addition, a recent metaanalysis confirmed the importance of prophylactic cranial irradiation (PCI) in general treatment plans for patients who show a complete response to treatment. However, numerous questions remain unanswered regarding this disease. While TRT/PE/PCI is considered to be the standard treatment in the majority of centers worldwide, the emergence of new and effective drugs (e.g., topoisomerase I inhibitors and paclitaxel) for the treatment of LD SCLC will likely affect therapy strategies in the near future. Important issues regarding optimal doses and fractionation regimens, as well as the timing of TRT, remain to be resolved. While most centers currently use b.i.d. fractionation as a result of the Intergroup findings, high-dose standard TRT may also be beneficial. TRT volumes are also considered an important issue, since they likely relate to the incidence of both local failure and toxicity. Finally, the optimization of PCI (total dose, fractionation regimen, and timing) is already under way. The value of surgery is limited to peripheral tumors and poorly responding cancer, and to confirm histology or improve local control and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Curative approaches to lung cancer in the elderly.

Lung cancer is a common disease in elderly patients, and the increase in the size of the elderly population will lead to an increased proportion of elderly among lung cancer patients in the future. The prognosis of lung cancer is still poor, but curative approaches are feasible for patients with local stage NSCLC and for some patients with limited disease (LD) SCLC. The evidence for these curatively-intended approaches is derived from studies that are usually performed with highly selected patients. Elderly patients are underrepresented, and in daily clinical practice elderly patients are less likely to be treated with full standard approaches. We used the data from studies that focused particularly on the elderly, or provided subgroup information on age, to analyze the feasibility of applying current standard approaches to the elderly. We also discuss alternative approaches. Age alone is a very uncertain prognostic criterion for outcome or tolerability of treatment. It is much more important to obtain a comprehensive geriatric assessment of each individual patient. When adequate patient selection is provided, standard treatment approaches appear to be feasible for elderly (>70 years) patients with good performance status.

Age Factors↗