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Biomedical subjects

A Kramar

Publications and source records attributed to A Kramar.

At least 55 records · Page 3Linked to original sources
PubMed1994

Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma.

PURPOSE: The analysis of complications in a prospective randomized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented. METHODS AND MATERIALS: Between 1985 and 1988, 204 patients with Stage I and limited Stage II cervical cancer were randomized to receive one of two preoperative brachytherapy low-dose rates (0.4 and 0.8 Gy/hr). The objective of this trial was to determine the benefits, if any, of the higher-dose rate within the therapeutic arsenal for this patient population, in terms of survival, local control, and complications. The type and severity of all complications were evaluated according to a common glossary and a strict follow-up schedule was established given that the treatment of cervical cancer is multidisciplinary, involving gynecologists, surgeons, and radiotherapists. RESULTS: Overall survival: 85% at 2 years and local control: 93% at 2 years, were similarly distributed between the two groups. Regardless of their nature and severity, 139 and 175 complications were observed among 63% and 75% of patients, in the 0.4 and 0.8 Gy/h dose rate groups respectively. Gynecologic and urinary complications were the most frequent (38% and 28% of all complications), followed by vascular (15%), digestive (10%), nervous (5%) and cutaneous (5%). A total of 14 and 17 severe complications (Grade 3) were observed in 7% and 13% of patients, respectively in the 0.4 and 0.8 Gy/h dose rate groups (p = 0.12). Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups: 62% and 72% at 2 years (p = 0.27). When the first complication and its evolution were considered (early complications), the prevalence of complications was not significantly different between the two groups: 28% vs. 34% at 2 years (p = 0.31). In this prospective trial, patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up. When successive complications and their evolution were taken into account, the prevalence of complications was significantly greater in the higher-dose rate group: 30% vs. 45% at 2 years (p = 0.03). CONCLUSION: The results of this trial showed that long-term effects of treatment, when represented by prevalence of complications over time, were more frequent in the higher dose rate group. This underlines the importance of the regular follow-up of patients and of coding, not only the occurrence of all complications, but also their evolution over time.

Brachytherapy↗
PubMed1994

Acute tumor lysis syndrome in poor-risk germ cell tumors: does it exist?

Acute tumor lysis syndrome (ATLS) is a well-known adverse event described after effective chemotherapy for extensive, highly proliferative, and chemosensitive tumors. While its occurrence with hematological malignancies is frequently described, there have been scattered case reports documenting ATLS in solid tumors. However, such events have not been reported in poor-risk germ cell tumors. We reviewed retrospectively 46 cases of such tumors treated in our department between 1988 and 1993 by aggressive cisplatin-based chemotherapy. All patients received systematically 6 l/24 h hydration according to the cisplatin- protocol administration. Blood chemistry data for potassium, phosphorus, calcium, alkaline reserve, uric acid, creatinine and lactate dehydrogenase were obtained before treatment and during the 7 days of the induction chemotherapy. No metabolic abnormalities suggestive of ATLS were observed. Nevertheless, 2 patients with bulky disease of the chest experienced early death from respiratory distress complicated by multiorgan failure. ATLS seems to be an unlikely event in poor-risk germ cell tumors and therefore special prophylactic therapy may be unnecessary.

Acute Disease↗
PubMed1994

Prognostic factors and survival in patients with metastatic renal cell carcinoma treated with chemotherapy or interferon-alpha.

Prognostic factors and survival were analysed in 295 patients with metastatic renal cell carcinoma (MRCC), treated with either chemotherapy (1975-1990) or interferon (IFN) (1983-1990). The 3-year survival was 8 and 24% in the chemotherapy and IFN groups, respectively (P < 0.001). In the univariate analysis, age < or = 60 years, prior nephrectomy, more than 1 year since initial diagnosis and treatment for metastatic disease, ECOG performance status 0 or 1, absence of liver metastases, lower erythrocyte sedimentation rate (first hour), and < or = 10% weight loss, within the past 6 months, were correlated with improved survival. Sedimentation rate, performance status and weight loss remained independent prognostic factors from the results of a Cox regression analysis. Three prognostic groups were identified from a combination of these factors. In the poor and intermediate risk groups, no significant survival difference was observed between patients treated with chemotherapy and those treated with IFN. The 3-year survival estimates for good risk patients were 15 and 48% in the chemotherapy and IFN groups, respectively. Therefore, in MRCC, sedimentation rate, performance status and weight loss are easily assessable and reproducible prognostic variables for the identification of risk groups. We hypothesise that IFN may increase survival in good risk patients, but is as ineffective as chemotherapy in poor risk patients with MRCC.

Adult↗
PubMed1994

A comparison of early effects with two dose rates in brachytherapy of cervix carcinoma in a prospective randomised trial.

This phase III randomised trial examined the early effects of two low dose rates (0.38 and 0.73 Gy/h) in brachytherapy of stage I and IIp cervical cancer patients. A total of 204 patients were included between January 1985 and September 1988. Since the main analysis of this paper concerned surgical difficulties, only the 155 patients (76%) on whom surgery was performed at the Institut Gustave-Roussy were retained in this analysis. Treatment consisted of uterovaginal 137Cs irradiation followed by immediate or deferred surgery. The two groups were similar for pretreatment characteristics except for endocervix involvement. Their brachytherapy parameters were also similar (60 Gy pear dimensions, doses to critical organs, total kerma, etc.). The factors with a poor prognosis were, for surgical difficulties, older age, stage II and a small irradiated pear volume; for difficulties with haemostasis, immediate surgery, stage II and previous surgery; and for difficulties in dissection, lymph node involvement. The dose rate significantly influenced surgical difficulties for the stage IIp patients operated on by deferred surgery. Those treated with the higher dose rate showed a 2-fold increase in surgical difficulties compared to those irradiated at the lower dose rate (P = 0.03). The independent prognostic factors for sterilisation of the surgical specimen were small tumour size and absence of lymph node involvement. An inverse dose rate effect was observed for medium size tumours, with significantly more sterilisations observed in stage IIp patients in the lower dose rate group (P < 0.01).

Adult↗
PubMed1994

[Prognostic factors for extratesticular involvement in stage I testicular cancer. Apropos of 58 cases].

To assess prognostic factors for extratesticular involvement in patients with testicular stage I non seminomatous germ cell tumors, we retrospectively studied the clinical and histological features of 58 patients treated at Institut Gustave-Roussy. Twenty-four patients were followed after orchiectomy alone, and 34 patients underwent an initial subsequent retroperitoneal lymphadenectomy. Nineteen patients (33%) experienced an extratesticular involvement after a mean follow-up period of 40 months. All relapses occurred during the first year of follow-up. Disease-free survival at one year was 64% and overall survival was 100%. The clinical and histological features studied were: age, AFP and HCG serum levels before orchiectomy, tumor size, TNM stage, histologic type with the corresponding percentage, venous and lymphatic involvement. The detection of metastasis at lymphadenectomy or during the follow-up after orchiectomy was the single criteria for prognostic factor research. Venous and/or lymphatic involvement as well as a high percentage of embryonal carcinoma component turned out to be the two independent significant prognostic factors which predict extratesticular involvement.

Adult↗
PubMed1994

[Method for evaluating long term complications. A study from a phase III trial comparing two low dose rates in gynecologic brachytherapy].

When treatment complications are the main criteria of a study, the simplest way for estimating the complication rate over time is to use the Kaplan-Meier method. The failure is the onset of the first complication. A new way is proposed here which takes into account the time to an eventual second, and third complication, and their duration as well. Results from a phase III randomized trial comparing two preoperative brachytherapy low dose rates in localized stage cervix carcinoma patients are used to illustrate both methods. The new method showed a greater long term complication rate in the higher dose rate group.

Brachytherapy↗
PubMed1993

Prognostic factors in metastatic melanoma.

BACKGROUND: Each year, 6000 people die in the United States from metastatic melanoma. Further study of factors affecting the prognosis of patients with this disease is needed. METHODS: The authors analyzed response and survival data from 635 patients who had entered three Eastern Cooperative Oncology Group trials for metastatic melanoma. RESULTS: Factors associated with poorer survival after study entry included poor performance status and the presence of symptoms, such as reduced appetite, fever, or nausea/vomiting. Male patients had poor survival, as did patients entering the study less than 1 year after a documented recurrence to study entry. As expected, characteristics of the initial primary disease (treatment and symptoms) had little association with survival after entering the advanced disease protocol. Two summary measures of the extent of metastatic involvement had a strong influence on survival. These were the number of nonbone metastases and the clinician's assessment as to the most significant metastatic site. Patients with the liver as their clinically most significant metastatic site had a poorer prognosis than those otherwise classified, including those with central nervous system metastases. The prognosis also worsened with an increasing number of sites of nonbone metastases, including skin and soft tissue. Tumor response occurred in only 11% of the patients. Patients with poor performance status and those with lung involvement had a significantly lower response rate than did others. Although the frequency of response was low, patients with objective responses survived significantly longer than did the nonresponders (based on an analysis appropriately adjusted for the time of response using a time-dependent proportional-hazards model). CONCLUSIONS: These results provide useful guidelines for the design and analysis of clinical trials in metastatic melanoma.

Adult↗
PubMed1993

Phase III trial comparing two low dose rates in brachytherapy of cervix carcinoma: report at two years.

This Phase III randomized trial examined the effect of two low dose rates (0.73 or 0.38 Gy.h-1) on the local control, survival, relapse-free survival, complications, and secondary effects in the treatment of cervical cancers. A total of 204 Stage Ib or II cervical carcinoma patients were included between January 1985 and September 1988. Treatment consisted of uterovaginal 137Cs irradiation followed by surgery. The two groups were similar for age, tumor stage and medical or surgical history. Their brachytherapy parameters were also similar (60 Gy pear dimensions, dose to critical organs, total kerma, etc....) There were no differences in the short-term effects or therapeutic outcome. However, overall complications and side effects observed after 6 months were significantly more frequent (p < 0.01) in the higher dose rate group.

Adenocarcinoma↗
PubMed1993

High failure rate of carboplatin-etoposide combination in good risk non-seminomatous germ cell tumours.

24 patients with good risk non-seminomatous germ cell tumours (GR-NSGCT) were enrolled in a phase II trial combining carboplatin (C) and etoposide (E). Carboplatin was given at a fixed dose of 450 mg/m2 at d2, and E 120 mg/m2, dl-3, every 4 weeks x 4 cycles (cy). Myelosuppression was the major toxicity with neutropenia grade 4 in 18 cy (19%) and grade 3 in 26 cy (27%). Thrombocytopenia grade 3 and 4 occurred in 7 and 1 cy, respectively. Responses included: 20 complete responses (CR) (83%) with 16 clinical CR and 4 pathological CR; 3 additional patients had complete surgical removal of residual disease (SRRD) with viable tumour (surgical CR); 1 patient progressed during C+E therapy. 5 of the 16 clinical CR relapsed, and all the 3 surgical CR progressed despite post-operative salvage chemotherapy. Adverse events occurred in 9 patients (37.5%; 95% C.I., 19-59%). After a median follow-up of 24 m (range 14 to 38) 4 patients had died [3 progressive disease (PD), 1 suicide while in CR], 3 were alive with PD, and 17 had no evidence of disease. No significant correlation between area under the curve values of carboplatin, overall treatment failure and the platelet nadirs was observed. We conclude that the efficacy of the C+E regimen as given in our protocol is inferior to the standard cisplatin-containing regimens. The low dose-density (D/I) of carboplatin could be responsible for the high failure rate.

Adolescent↗
PubMed1993

Prediction of long-term response after high-dose chemotherapy with autologous bone marrow transplantation in the salvage treatment of non-seminomatous germ cell tumours.

High-dose chemotherapy (HDCT) and autologous bone-marrow transplantation (ABMT) are widely used in the salvage treatment of non-seminomatous germ cell tumours (NSGCT). We compiled 10 published series with NSGCT patients treated by HDCT and ABMT. Several prognostic factors for long-term non-evolutive disease (NED) were studied: dose of etoposide (ETO), oxazaphosphorine derivative (OXA) (expressed in cyclophosphamide equivalents using a cyclophosphamide/ifosfamide ratio of 1:3), platin-derivate (PLAT) (expressed in cisplatin equivalents using a cisplatin/carboplatin ratio of 1:4), disease status (refractory or responder), OXA and PLAT compounds. Strong interactions were shown between disease status and PLAT and ETO. In refractory patients, logistic regression analysis showed that the doses of OXA and PLAT increase the probability of NED. Conversely, in responder patients only ETO and OXA dosages increase the probability of NED. It is concluded that the status of the disease is the most important prognostic factor for long-term NED after HDCT + ABMT in NSGCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Prognostic factors in non-seminomatous germ cell tumours of the testis. Experience at the Institut Gustave-Roussy.

The original prognostic model in non-seminomatous germ cell tumours of the testis at the Institut Gustave-Roussy was updated in a larger patient population. As in the former model human chorionic gonadotrophin (hCG) and alpha-feto-protein (AFP) serum concentrations attained prognostic significance in the multivariate analysis. We studied two important issues in this patient population: the impact of expressing hCG values in mass units and of the introduction of etoposide-containing chemotherapy. Etoposide has a major impact on the determination of the prognostic group limits which are considerably increased. It is, thus, suggested to reevaluate prognostic models in patient populations treated by modern chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Early intensified chemotherapy with autologous bone marrow transplantation in first line treatment of poor risk non-seminomatous germ cell tumours. Preliminary results of a French randomized trial.

UNLABELLED: For 30 months we have treated 115 non-pretreated non-seminomatous germ cell tumour (NSGCT) patients with poor risk characteristics. Patients were allocated randomly to either arm A: NCI regimen with vinblastine, etoposide (E), bleomycin and double dose cisplatin (P2) (PVeBV) 3 or 4 cycles Q3W, or arm B: modified PVeBV protocol (bleomycin in continuous infusion) Q4W than a cycle of high-dose E + cyclophosphamide + P2 (PEC) and autologous bone marrow transplantation (ABMT). 114 patients are evaluable: 81 testicular, 18 mediastinal and 15 retroperitoneal primaries. RESULTS: Arm A 57 patients: 7 patients did not complete the treatment. There were 15 failures, 9 PR, 33 CR. Seven patients relapsed. The 2-year survival is 82%. Arm B 57 patients: 16 patients did not complete the treatment. There were 26 failures, 7 PR and 24 CR. Nine patients relapsed. The 2-year survival is 60%. Both CR rates and survival are not statistically different. This trial fails to show any benefit of early intensified chemotherapy + ABMT to increase the CR and survival rates in poor risk NSGCT.

Adult↗
PubMed1993

Role of autologous bone marrow transplantation in germ-cell cancer.

The results of high-dose chemotherapy and autologous bone marrow transplantation in 388 patients with germ-cell tumors have been reported. It is clear that one or two cycles of various combinations of etoposide, cyclophosphamide, ifosfamide, cisplatin, and carboplatin can be administered with acceptable toxicity, and it appears that high doses of etoposide and oxazophosphorine derivatives increase the cure rate. Cyclophosphamide may be preferable to ifosfamide, because it seems less toxic. The need for and the dose and mode of administration of carboplatin remain in question. In patients with refractory disease, the long-term results of high-dose therapy and marrow transplantation are poor, with cure rates of 8% to 20%, but there is no clear alternative. As consolidation treatment after conventional salvage chemotherapy, early results suggest benefit, but randomized trials are needed. As first-line treatment in patients with high-risk disease, the results to date demonstrate no benefit over available therapy.

Bone Marrow Transplantation↗
PubMed1992

[Therapeutic strategy in metastatic renal cancer].

Prognostic factors have been described in metastatic renal cell cancer: performance status, weight loss, elevated erythrocyte sedimentation rate, presence of liver metastases. The treatment for a patient with good prognosis consists of: surgical exeresis of solitary metastasis, immunotherapy by either interferon or interleukin 2. Treatment in case of a rom prognosis is a combination of supportive care, orthopedic surgery for pathologic fracture or medullar compression, antalgic radiotherapy, embolization, nephrectomy for hematuria, and analgesic treatments.

Blood Sedimentation↗
PubMed1992

Prognostic factors and natural history in lymph node-negative breast cancer patients.

The prognostic significance of clinical and histological factors as well as hormone receptors was analyzed in a population of 3,064 lymph node-negative breast cancer patients operated in the Stockholm region between 1976 and 1988. None of these patients received systemic adjuvant treatment. Multivariate analysis showed that only histological tumor size, number of examined axillary lymph nodes, and progesterone receptors were independent prognostic factors in terms of recurrence-free interval. An individual risk of recurrence was calculated taking into account these three factors to discriminate between three groups of patients with a risk of less than 15%, 15-25%, and more than 25% of recurrence at 5 years. Similar results were obtained taking into account only the first two factors. The prognostic information added by the knowledge of progesterone receptors only changed the recurrence rate in approximately 3%. This study showed that conventional prognostic factors permit the identification of high risk lymph node-negative breast cancer patients. Results obtained by the use of new more sophisticated factors should be compared with those obtained analyzing strong conventional prognostic factors.

Breast Neoplasms↗
PubMed1992

Competing risks determining event-free survival in early breast cancer.

To evaluate the natural history of a disease and the effects of therapeutic interventions, it is important to determine which are the causes of treatment failure and to assess the extent to which each cause contributes to the total failure rate. The paper presents a new biostatistical technique to decompose the total event-free survival of a diseased population into cause-specific failure rates. The technique was based on a competing risk approach thereby avoiding biases related to assumptions of independence between different types of event. Such assumptions are inherent in the conventional Kaplan-Meier or actuarial methods. The competing risk method was used to analyse the pattern of failure among 2,850 pre- and postmenopausal patients with early-stage breast cancer and the results were compared to those obtained using conventional methods. The following events were analysed: loco-regional recurrence, distant metastasis, contralateral breast cancer, other new primary malignancies, and intercurrent deaths. The rate of new primary malignancies was found to be significantly higher in post- than in premenopausal patients (6% vs 3% at 10 years). In low-risk, node-negative postmenopausal patients the incidence of recurrences from breast cancer were found to be no greater than other types of events. This observation highlights the significance of the effect of different adjuvant therapies not only on the disease itself but also on the risk of second primary malignancies and other intercurrent diseases. In general, it was found that the conventional statistical methods tended to overestimate the event-specific rates. In conclusion, the method based on competing risks permits an unbiased analysis of all types of events determining the total event-free survival. It is thus useful for the description of the natural history of breast cancer as well as other diseases.

Aged↗
PubMed1992

Competing events determining relapse-free survival in limited small-cell lung carcinoma. The French Cancer Centers' Lung Group.

PURPOSE: We report results in terms of relapse-free survival (RFS), obtained in patients with limited small-cell lung carcinoma (SCLC) treated by four consecutive alternating protocols, using a competing risk approach with local recurrences, distant metastases, and death unrelated to cancer as competing events. PATIENTS AND METHODS: Two hundred two patients with limited SCLC were included in four consecutive protocols alternating radiotherapy and chemotherapy (CT). The alternating schedule consisted of six cycles of CT (doxorubicin, etoposide [VP16213], and cyclophosphamide [CAVP16], plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65, and 61 Gy in the four consecutive protocols, respectively (accelerated hyperfractionation was used in the first course of the fourth protocol). A 1-week rest followed each CT cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. RFS variables were determined according to a model assuming competing risks to define the first cause of failure (local disease, distant metastasis, or intercurrent death). RESULTS: No significant differences were observed between the four treatment groups. Overall results showed a 2-year cumulative incidence rate of failure of 75%. When analyzed, the first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. CONCLUSIONS: The methodology of competing risks allowed an unequivocal description of first events in limited SCLC. The extent of the local problem has been relatively overshadowed by the use of conventional descriptive methods.

Antineoplastic Combined Chemotherapy Protocols↗