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C Kolotas

Publications and source records attributed to C Kolotas.

33 records · Page 2Linked to original sources

CT-based software for 3-D localization and reconstruction in stepping source brachytherapy.

This paper describes innovative software for catheter localization and three-dimensional (3-D) reconstruction in stepping source brachytherapy applications. Patient information is a set of computed tomography (CT) slices scanned during the implantation of brachytherapy catheters. Catheter geometry and patient anatomy are exported for use with dose calculation software modules. The errors produced by the system are also encouragingly low. Time saving was achieved, in terms of other traditional reconstruction techniques. Various automated procedures, 3-D graphics and a user-friendly GUI, have contributed to providing a powerful, comprehensive software tool, directly useable in the clinical practice.

Brachytherapy↗

Simultaneous paclitaxel and radiotherapy: initial clinical experience in lung cancer and other malignancies.

This report summarizes results from a series of pilot trials using combined-modality chemoradiotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a radiosensitizing agent in patients with cancers of the lung, cervix, and bladder. In a phase I study of paclitaxel/radiotherapy in patients with locally advanced non-small cell lung cancer, five paclitaxel dose levels were evaluated in conjunction with simultaneous radiation (total dose, 59.4 Gy). A minimum of five patients were treated at each dose level; paclitaxel doses ranged from 45 mg/m2 over 3 weeks (level 1) to 65 mg/m2 for 7 weeks. Of 34 enrolled patients, 25 are evaluable for toxicity and response. Side effects were generally moderate for this combined-modality therapy, although two patients at level 5 developed dose-limiting toxicities (grade 4 esophagitis and grade 3 pneumonitis). Among 25 evaluable patients, complete and partial response rates were 4% (one patient) and 64% (16 patients), respectively; eight patients had a minor response. Median survival was 6 months (range, 1 to 20 months). Therapy was well tolerated, suggesting that the combined modalities offer a practical, effective therapy for patients with non-small cell disease. A paclitaxel dose of 55 mg/m2 is recommended for further study of combined-modality chemoradiotherapy in this clinical setting. In another trial, 33 women with inoperable, locally advanced cervical cancer received carboplatin 50 mg/m2 via intravenous infusion simultaneously with external-beam radiation therapy and vaginal brachytherapy, to define the regimen's toxicity and safety. Among the 33 women, 78% achieved a complete response to therapy. The investigators next conducted a trial of paclitaxel 50 mg/m2 given weekly over 3 hours with the previous carboplatin/radiotherapy regimen in four women and documented two partial responses, one near-complete response, and one minor response, with moderate, manageable toxicity. In a final case report on a patient with recurrent bladder cancer, simultaneous radiotherapy and weekly paclitaxel 50 mg/m2 intravenously over 3 hours yielded a partial remission, prompting the investigators to plan a phase I study to confirm the regimen's efficacy and safety. Additional planned studies include a phase I trial of simultaneous chemoradiotherapy in patients with cancer of the head and neck.

Adult↗

Effect of recombinant human granulocyte colony stimulating factor (R-metHuG-CSF) as an adjunct to large-field radiotherapy: a phase I study.

PURPOSE: To test the feasibility of recombinant human granulocyte colony stimulating factor application during large-field radiotherapy. METHODS AND MATERIALS: Fifteen patients with clinically and histologically proven malignancy who received large-field radiotherapy entered this study. Administration of recombinant granulocyte colony stimulating factor (G-CSF) at a dose of 300 microgram subcutaneously was started on Friday and was continued on Saturday and Sunday after the first radiotherapy treatment, which began on the Monday before. In this way four courses of G-CSF were applied every Friday, Saturday, and Sunday during the radiotherapy period. Absolute neutrophil cell (ANC) and blood counts were monitored twice a week and compared to a second group of 15 patients who received large-field radiotherapy without G-CSF. Before and at the end of every cycle of G-CSF, ANC, blood counts, and biochemistry were measured. We compared the myelotoxicity of the patients treated with G-CSF with 15 patients without G-CSF treated at the same period with large-field radiotherapy, in match pair technique. RESULTS: G-CSF increased the ANC throughout the period of irradiation, and the treatment time needed for competing radiotherapy was shorter in the group who received G-CSF. Fourteen of 15 patients who received G-CSF treatment completed large-field radiotherapy without pause. Only 1 of 15 patients not receiving G-CSF was able to receive radiation treatment on schedule. Patients receiving G-CSF completed treatment with the mantle-field technique in 24 days and those with the abdominal bath technique in 26.5 days. Conversely, patients treated without G-CSF completed treatment with the mantle-field technique in 30.5 days and those with the abdominal bath technique in 36 days. The most frequent side effect was musculoskeletal pain. CONCLUSION: The prophylactic application of G-CSF during large-field radiotherapy before the onset of neutropenia was feasible in this schedule. Whether or not this shortening of treatment duration will translate into an improvement in efficacy is not clear.

Adult↗

Simultaneous radiochemotherapy with paclitaxel in non-small cell lung cancer: a clinical phase I study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents available for the treatment of non-small cell lung cancer (NSCLC), with reported response rates of 21% to 24%. Its observed radiosensitizing effect is attributed to its interruption of cell development at the G2/M phase of the cell cycle, when cells are most sensitive to the killing effects of ionizing radiation. This phase I study of paclitaxel and simultaneous radiation therapy in patients with previously untreated, locally advanced inoperable stage IIIA/B NSCLC was designed to determine the maximum tolerated paclitaxel dose, to define the safety and toxicity of this combined modality, and to obtain preliminary data on its activity. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week, in shrinking-field technique, for a total dose of 59.4 Gy) and concomitant chemotherapy with a 3-hour infusion of paclitaxel once weekly on day 1, initially at a dose of 45 mg/m2, for 3 weeks. This dose remained constant during study levels 1 to 3, with the number of weeks of treatment increasing to 5 and 7 at levels 2 and 3, respectively. At dose level 4, the paclitaxel dose was increased to 55 mg/m2 over 7 weeks. Of 22 NSCLC patients who entered the study, 18 are evaluable for toxicity and response. Responses included one complete and 10 partial remissions; the other seven patients had minimal improvement. The therapy was well tolerated; no severe adverse events were associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment for NSCLC. The maximum tolerated paclitaxel dose has not yet been reached, and dose escalation is planned.

Adult↗

Paclitaxel and simultaneous radiation in locally advanced stage IIIA/B non-small cell lung cancer: a clinical phase I study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents for the treatment of non-small cell lung cancer, with response rates of 21% to 24%. We present a phase I study with paclitaxel and simultaneous radiation in previously untreated, locally advanced, inoperable, stage IIIA/B non-small cell lung cancer. The aims of the study were to determine the maximum tolerated dose, define the safety and toxicity, and obtain preliminary data about the activity of the combined modality. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week for 6.5 weeks, for a total dose of 59.4 Gy) and concomitant chemotherapy with paclitaxel 45 mg/m2 days 1, 8, and 15 in level 1; days 1, 8, 15, 22, and 29 in level 2; and days 1, 8, 15, 22, 29, 36, and 43 in level 3. The paclitaxel dosage was increased to 55 mg/m2 on days 1, 8, 15, 22, 29, 36, and 43 in level 4. Paclitaxel was administered as a 3-hour continuous intravenous infusion. Dexamethasone, clemastine, and ranitidine were given for hypersensitivity prophylaxis. Twenty-two patients (18 men and four women) entered the study; their median age was 66.5 years (age range, 38 to 74 years). Disease stage was IIIA in six of 22 patients and stage IIIB in 16. Six patients were treated at level 1, five at level 2, five at level 3, and six at level 4. There were 18 patients evaluable for toxicity and response. Side effects generally were moderate during the treatment period. One patient withdrew by request after the first course, one patient died of tumor bleeding after five courses, one patient died of progressive disease (lymphangiosis carcinomatosa of both lungs) after the sixth course, and one patient is too early for evaluation. Among the 18 patients evaluable for response, there were one complete and 10 partial remissions; seven patients reached a minor response. It is concluded that the therapy was well tolerated in these patients. Importantly, no severe adverse events were observed that could be associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment of non-small cell lung cancer. The maximum tolerated dose has not yet been reached, and dose escalation is planned.

Adult↗

Carboplatin and radiotherapy in the treatment of head and neck cancer: six years' experience.

Between 1987 and 1991, 103 patients with advanced head and neck carcinoma were treated with radiochemotherapy plus carboplatin. Tumors were located in the oral cavity in 33 patients, the oropharynx in eight, and the hypopharynx in seven. Four patients had a tumor of the epipharynx and three, tumor of the larynx. In 48 patients tumor involvement included two or more compartments. Radiotherapy was performed with cobalt-60 rays or 8-MeV photons in a fractionation of 5 x 2 Gy/wk to a dose of 50 Gy. Carboplatin 60 to 70 mg/m2/d was administered days 1 through 5 and 29 through 33. For inoperable patients radiotherapy was continued to a dose of 70 to 74 Gy. To date, 103 patients have entered the study and 100 have completed treatment; three patients died during the treatment period. Actuarial 1- and 2-year survival rates are 77% and 53%, respectively, for all patients; comparable figures for patients with interposed surgery are 93% and 69%, and for the patients treated with radiotherapy alone, 71% and 47%. In a pilot study conducted between 1990 and 1991, 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/d 5 days per week; total dose, 64 to 67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1 through 5 and 29 through 33). Eleven patients had T4 and four had T3 tumors. At the end of the treatment period, 12 patients had achieved a complete tumor remission and all others attained a partial tumor involution. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging. As a result of the encouraging results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy plus carboplatin or hyperfractionated accelerated irradiation plus carboplatin. As of July 1994, 178 patients have been entered in the study. Results will be evaluated after the study is completed.

Actuarial Analysis↗

Combined radiochemotherapy with carboplatin in the treatment of advanced head and neck carcinomas.

From 1987 to 1991, 100 evaluable patients with advanced head and neck carcinomas (T2-4, N0-3) were treated with radiotherapy and simultaneous carboplatin. Tumors were located in the oral cavity in 33 patients, oropharynx in 8 patients, and hypopharynx in 7 patients. Four patients had a tumor of the epipharynx, 3 of the larynx, and 45 had involvement of two or more compartments. Radiotherapy was performed in a fractionation of 5 x 2 Gy/week up to a dose of 50 Gy. Carboplatin was administered in a dose of 60 or 70 mg/m2 from days 1-5 and 29-33. After a 2-week interval, tumor involution was evaluated and a decision was made on the patients' operability. In cases of inoperability, radiotherapy was continued up to a dose of 70-74 Gy. Thirty patients underwent surgery after 50 Gy. Eight patients showed a histologically complete remission (CR), 7 showed microscopic residual tumor, and 15 showed macroscopic tumor. Seventy patients were treated with radiotherapy and concomitant carboplatin only. Thirty-nine of them achieved a CR and 30 a partial remission (PR). The residual tumor was operable in 8 of the latter patients. Only a minor response was achieved in the remaining patient. At the end of the treatment 77 patients achieved a CR with this combined modality. From 1990 to 1992, 20 patients with locally advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, 5 days per week: total dose, 64-67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1-5 and 29-33) in a pilot study. Fifteen patients had T4 and 5 had T3 tumors. Six weeks after the end of treatment, 16 patients (80%) had CR, and PR was seen in the other 4 patients (20%). Overall and disease-free survival at 1 year was 82 and 81%, respectively. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial CR rate of 80% is encouraging. Because of the results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy with carboplatin or hyerfractionated accelerated irradiation with carboplatin. Results will be forthcoming.

Actuarial Analysis↗

[Radiotherapy following a breast-preserving operation in breast carcinoma].

Between 1980 and 1988, 116 patients with invasive breast cancer were treated by limited surgery with axillary node dissection followed by radiation therapy. Radiotherapy was performed by individually computerized treatment planning. The target volume dose was 50 Gy to the whole breast followed by an electron boost of 10 Gy to the tumor bed. The median follow-up period was 59 months. The actuarial overall survival rate is 93%, and the disease-free survival 75.2%. Ten (8.6%) breast recurrences occurred. Analysis of clinical and pathological prognostic factors revealed that local control was impaired by young age, negative hormone receptors, G3-4 tumors and intraductal growth. The recurrence rate for T3- and T4-tumors was 12.5%.

Adult↗

Simultaneous radiotherapy and chemotherapy with carboplatin in inoperable squamous cell carcinoma of the head and neck: a phase II study.

Fifty-six untreated patients with inoperable squamous cell carcinoma of the head and neck were treated with carboplatin 70 mg/m2 i.v. daily on days 1-5 and 29-33 in combination with simultaneous conventional radiation up to a target volume dose of 50 Gy. Depending on tumor response and upon recommendation of surgeons, 21 of 56 patients underwent surgery after a radiation dose of 50 Gy and two courses of carboplatin. Patients who showed pCR after surgery received no further radiotherapy. In all other patients radiotherapy was continued using a shrinking field technique up to a target absorbed dose of 70-74 Gy. Combined modality induced 66% complete remission (CR) and an overall response rate of 98%. After completion of the whole treatment program (combined modality +/- surgery) 53 (94%) of the 56 patients were disease free. The median survival for all patients is 25+ months and the percentage of two-year survivors is 53%. Myelosuppression was the most frequent toxicity, but rarely was severe; leukopenia and thrombocytopenia of WHO grade 3 occurred in 21% of the patients. No other toxicities above WHO grade 2 occurred. Nephrotoxicity, neurotoxicity and ototoxicity were not seen. The addition of carboplatin did not increase the rate of surgical complication over that expected for preoperative radiotherapy. Two patients died of pulmonary embolism after surgery. Combined modality with carboplatin and simultaneous radiation is a highly active and well-tolerated regimen for untreated patients with inoperable squamous cell carcinoma of the head and neck.

Adult↗

Intraarterial 5-FU-infusion and simultaneous radiotherapy as palliative treatment of recurrent rectal cancer.

Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer.

Adult↗

Phase I study of hyperfractionated accelerated radiation and simultaneous Carboplatin therapy for advanced head and neck carcinomas.

From 1990 to 1991 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, five days/week, total dose 64.0 to 67.2 Gy) and simultaneous intravenous application of Carboplatin (60 mg/m2, days 1 to 5 and 29 to 33) in a pilot study. Eleven patients had T4 and four had T3 tumours. At the end of treatment twelve patients had a complete tumour remission and in the others a partial tumour involution was seen. Although acute side-effects were more pronounced compared to conventional irradiation this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging.

Adult↗

Cyclophosphamide, mitoxantrone, fluorouracil versus conventional CMF as adjuvant treatment in node-positive breast cancer patients. A Hellenic Cooperative Oncology Group Study.

362 evaluable node-positive patients with stage II breast cancer were randomized, receiving either 6 cycles of conventional CMF or 6 cycles of the combination of cyclophosphamide (500 mg/m2), mitoxantrone (Novantrone 10 mg/m2), and fluorouracil (500 mg/m2; CNF). After a median follow-up of 51 months, 64 (36%) patients relapsed in the CMF group and 60 (33%) in the CNF group (p=0.8276). By Cox multivariate analysis, tumor size, menopausal status and number of involved nodes were retained as independently significant variables. Toxicities were remarkably similar in both groups. It appears that after a median follow-up of 51 months there is no significant difference in relapse-free survival between node-positive patients with breast cancer who received either 6 cycles of the conventional CMF or the CNF combination as adjuvant treatment.

Adult↗

Clinical relevance of tumor ploidy and micronucleus formation for oral cavity cancer.

AIMS AND BACKGROUND: To study the clinical relevance of tumor ploidy and micronucleus formation as prognostic factors. METHODS AND STUDY DESIGN: Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with primary radiochemotherapy consisting of irradiation up to 70 Gy in combination with cisplatin. Cell cycle distribution, micronucleus formation and ploidy were evaluated by flow cytometry of biopsies taken before treatment and after irradiation to 10 Gy (5x2 Gy). Sexteen out of 28 patients relapsed after a minimum follow-up period of two years. RESULTS: Flow cytometry of the recurrence biopsy showed hyperpentaploid (5c exceeding) cells in 13/16 (81%) of the relapsed patients. In 7 patients the hyperploid clone was not present in the flow cytometry of the primary tumors. Ploidy could retrospectively be determined also by image cytometry in archival tumor material of the pretreatment specimens. Patients with a level below 100 5c cells per 10,000 cell nuclei were shown to have a significantly better prognosis than patients with more than 100 hyperpentaploid tumor cells. The micronucleus formation was 2-5 times higher in tumors showing a good response to treatment than in carcinomas relapsing within two years. CONCLUSIONS: The 5c-exceeding ratio measured by image cytometry and micronucleus formation proved to be good prognostic parameters for the clinical outcome of patients with locally advanced head and neck carcinomas.

Chemotherapy, Adjuvant↗