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J Jassem

Publications and source records attributed to J Jassem.

At least 19 recordsLinked to original sources
PubMed2002

Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer.

Prognostic value of p53 and PCNA expression in non-small cell lung cancer (NSCLC) remains controversial. In this study we determined the relevance of these abnormalities in terms of overall survival and disease-free survival in 95 NSCLC patients who underwent curative pulmonary resection. Expression of p53 was found in 44 samples (45%), expression of PCNA-in 79 samples (83%), and expression of both markers-in 35 samples (36%). There was no relationship between expression of either protein and major clinicopathological characteristics. Median survival for patients with and without p53 expression was 36 and 33 months, respectively and 5-year survival probability-29 and 37%, respectively (P=0.73). Median survival for patients with and without PCNA expression was 36 and 27 months, respectively and 5-year survival probability-35 and 25%, respectively (P=0.60). There was no significant difference in overall survival between particular groups of patients with tumors carrying four possible p53/PCNA phenotypes. In multivariate analysis including patient age, sex, tumor stage, tumor type and differentiation, p53 and PCNA expression, the only variable important for survival was stage of disease. These results suggest the lack of prognostic relevance of p53 and PCNA expression in surgically treated NSCLC patients.

Adenocarcinoma↗
PubMed2002

The EORTC Breast Cancer Group: 40 years of research contributing to improve breast cancer management.

The EORTC Breast Cancer Group (EBCG) is a multidisciplinary international group created in 1962 in conjunction with the EORTC. This group has always focused its activities on the development of new cancer treatments and strategies for all categories of breast cancer. It has been active both in drug development, as well as in the development of new radiotherapy and surgical techniques to attempt to improve cure rates and loco-regional control. Over 40 years, the EBCG has performed dozens of clinical studies including several thousands of patients. Many of these studies have contributed to the clinical knowledge on the treatment of breast cancer and have influenced the standard management of this tumour. Beside its clinical research activities, the Group has also been very active in developing guidelines for breast cancer research, promoting high standards of care in conferences, as well as in fellowships and quality assurance programmes. EBCG is a founding member of the Breast InterGroup (BIG).

Breast Neoplasms↗
PubMed2001

Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial.

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m(2) followed 24 hours later by paclitaxel 220 mg/m(2)) or FAC (5-fluorouracil 500 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2)), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non-anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P =.032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P =.034]; overall survival 23.3 months v 18.3 months [P =.013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P <.001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

Adult↗
PubMed2001

Rectal doses in intracavitary brachytherapy of gynecological malignancies: comparison of two dosimetric methods.

PURPOSE: To compare calculated rectal doses obtained by two dosimetric methods in intracavitary brachytherapy of gynecological malignancies. MATERIALS AND METHODS: This analysis included 124 intracavitary applications performed in 102 patients with cervical or endometrial cancer. The pelvic dose distribution based on orthogonal intracavitary placement films was calculated with the computer planning system. In each application the rectal dose was defined in the specific rectal point determined by both the use of a wire marker inserted into the rectum (R1) and by packing the vagina with radio-opaque gauze - the method recommended by the ICRU Report 38 (R2). The comparison included R1 and R2 doses as well as the respective radiobiological equivalent doses determined by the linear-quadratic model (r1 and r2). RESULTS: In 83% of applications the absolute value of R1 was lower than R2. The mean difference between R1 and R2 was 3.7 Gy (95% CI 3.03-4.41 Gy) and between r1 and r2 7.2 Gy (95% CI 5.77-8.56 Gy). These differences were significant (P<0.001 for both comparisons). The difference between the doses was not influenced by the type of applicator and remained significant even when a systemic+/-10% error of method was assumed. CONCLUSION: The rectal point dose determined with the use of rectal wire marker may be underestimated, therefore this method should be discouraged in gynecological brachytherapy.

Brachytherapy↗
PubMed2001

The feasibility study on continuous 7-day-a-week external beam irradiation in locally advanced cervical cancer: a report on acute toxicity.

PURPOSE: To evaluate the feasibility and toxicity of continuous 7-day-a-week pelvic irradiation with no breaks between external beam irradiation and intracavitary applications. MATERIAL AND METHODS: Between November 1998 and December 1999, 30 patients with FIGO Stage IIB or IIIB cervical cancer were treated with continuous 7-day-a-week pelvic irradiation, to the total Manchester point B dose of 40.0-57.6 Gy. The first 13 patients (group A) were applied a daily tumor dose of 1.6 Gy and the remaining 17 patients (group B)-10.8 Gy. One or two immediate brachytherapy applications (point A dose 10-20 Gy, each) were performed in 28 cases. RESULTS: Two patients did not complete the irradiation due to apparent early progression of disease during the irradiation. Of the remaining 28 evaluable patients 11 (39%) completed treatment within the prescribed overall treatment time and 17 had unplanned treatment breaks. For the latter group overall treatment time ranged from 103 to 122% (mean 114%) and from 103 to 197% (mean 138%) of the planned treatment time for group A and B, respectively. The majority of patients experienced acute toxicity. Severe toxicity (EORTC/RTOG grade 3 and 4), predominantly gastrointestinal, occurred in 5 of the 13 patients in group A, and in 7 of 17 patients in group B. CONCLUSION: The studied regimen was accompanied by considerable toxicity, hindering delivery of irradiation within planned treatment time.

Adult↗
PubMed2001

Serum p53 antibodies in small cell lung cancer: the lack of prognostic relevance.

Prognostic relevance of serum p53 antibodies was assessed in 96 patients with microscopically proven small cell lung cancer (SCLC). The study group included 67 males and 29 females; mean age 58 years; range 35--86 years; 60 with limited disease (LD), and 36 with extensive disease (ED). The control group consisted of 41 patients with non-malignant diseases. The presence of p53 antibodies was assayed by the immunoenzymatic method (P53 ELISA kit, PharmaCell, France). Antibodies were present in 26 SCLC cases (27%); 15 (25%) in LD and 11 (31%) in ED. Antibodies were also found in one out of 41 control subjects (2%). There was no correlation between the level of antibodies and clinical characteristics of SCLC patients including age, gender and extent of disease. The median follow-up for the entire group was 30 months (range: 11--39 months). By the time of analysis, 78 patients (82%) had deceased. Median survival in SCLC patients with and without antibodies was 42 and 39 weeks, respectively (log rank, P=0.81). These results indicate the lack of clinical relevance of serum p53 antibodies in SCLC.

Adult↗
PubMed2001

Types and localisation of p53 gene mutations: a report on 332 non-small cell lung cancer patients.

Mutations of p53 suppressor gene are among the most common molecular abnormalities in human malignancies. We demonstrated earlier significant differences in mutational profiles between NSCLC patients from Poland and Spain. These differences were most probably related to ethnic and/or geographical factors. In the present study we analyzed the types and location of p53 gene mutations in a large group of 332 operated NSCLC patients from two institutions in Northern Poland. Within the last decades this region has been characterized by the highest incidence of lung cancer in Poland. We used both frozen and paraffin-embedded tumor samples and the screened region included exons from 5 to 8. A total of 96 samples (29%) were positive for p53 gene mutation. The proportion of mutations in particular exons was as follows: exon 5-33%, exon 6-22%, exon 7-16%, and exon 8-29%. Three 'hot spots' were located in codons 176,245 and 248. Evolutionary conserved domains were much more frequently affected than the regions outside domains. The majority of mutations (73%) were missense type, followed by null and silent mutations (21 and 6%, respectively). In all six silent mutations substituted was the third base in codon. There were no major differences in the types and locations of mutations between patients from the two institutions. This homogeneity, together with our earlier findings, may confirm the impact of ethnic and geographical factors on the mutational profile of p53 gene in NSCLC.

Aged↗
PubMed2001

Radiotherapy for non-small cell lung cancer.

This article shortly reviews the role of external-beam radiotherapy in the management of NSCLC with the focus on novel therapeutic approaches. The following applications of radiotherapy are addressed: definitive treatment in localized inoperable disease, radiotherapy as an adjunct to surgery (preoperative and postoperative), and palliative chest irradiation.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients.

PURPOSE: A randomized phase II trial of oral vs. intravenous (i.v.) vinorelbine was designed to determine the efficacy and safety of oral vinorelbine with an intrapatient dose escalation in previously untreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between December 1997 and April 1999, 115 patients with stage IIIB or IV NSCLC were randomized (2 to 1) to receive either oral vinorelbine at a dose of 60 mg/m2/week for the first three administrations and then increased to 80 mg/m2/week in the absence of severe neutropenia, or i.v. vinorelbine at 30 mg/m2/week. RESULTS: One hundred and fourteen patients (76 in the oral arm and 38 in the i.v. arm) were treated. Ninety-eight patients (86%) were eligible and assessable. The two treatment arms were well-balanced for demographic and prognostic features. After external panel review, the response rates in evaluable patients were 14%, in the oral arm and 12% in the i.v. arm. The median progression-free survival with oral and i.v. vinorelbine was 3.2 months and 2.1 months, respectively, and the median survival 9.3 and 7.9 months, respectively. The most common hematological toxicity was neutropenia, which was severe (grade 3-4) in 46% of patients and for 7% of administrations in the oral arm, and in 62% of patients and for 25% of administrations in the i.v. arm. Non-hematological toxicities including nausea, vomiting, anorexia, weight loss, diarrhea .and constipation were generally mild to moderate. CONCLUSION: The activity of oral and i.v. vinorelbine in advanced NSCLC appears to be comparable. The safety profiles of both formulations look qualitatively similar. Oral vinorelbine can therefore be considered a good alternative to i.v. administration.

Administration, Oral↗
PubMed2001

Oral vinorelbine: feasibility and safety profile.

BACKGROUND: Patient preference as well as concerns and difficulties with intravenous access and pharmaco-economic issues have driven the development of oral vinorelbine. PATIENTS AND METHODS: Four phase II studies were conducted in chemotherapy-naive non-small-cell lung cancer (NSCLC) and as first-line chemotherapy of advanced breast cancer (ABC). As recommended in the phase I dose-finding study, the first step used a weekly dose of 80 mg/m2. This regimen was associated with an excessive rate of early deaths (10%) due to complicated neutropenia and led to discontinuation of the first two studies. In a second step, the dose of 60 mg/m2/week was given for the first three courses and subsequently increased to 80 mg/m2/week, in the absence of severe neutropenia. RESULTS: One hundred and thirty eight patients (76 with NSCLC and 62 with ABC) received this regimen, of whom only five were unable to undergo dose escalation. The incidence of febrile neutropenia and neutropenic sepsis were low (2.9 and 3.6%, respectively). Although severe events were uncommon, nausea/vomiting and diarrhoea were frequent and primary prophylaxis with antiemetics should be recommended. CONCLUSIONS: Overall, the safety profile of oral vinorelbine at 60 mg/m2/week for the first three courses with escalation to 80 mg/m2 is qualitatively comparable to that of i.v. vinorelbine at standard doses. Similarly to i.v. chemotherapy, close haematological monitoring is necessary.

Administration, Oral↗
PubMed2001

Expression of vascular endothelial growth factor (VEGF) and its receptor FLK-1 in non-small cell lung cancer (NSCLC)--a preliminary report.

The assessment of tumour angiogenesis in NSCLC is presently a subject of intensive research with potential clinical applications. In this study, the expression of VEGF and FLK-1 was examined by immunohistochemistry in 67 archival tumour samples obtained from NSCLC patients treated by radical resection. Distribution of age, sex, tumour stage and histology was typical for patient population in Poland. VEGF expression (more than 25% of positive cells) was noted in 65% of tumour cells. FLK-1 expression was observed in 91% of tumour cells. Neither the number of positive cells nor the staining intensity correlated with the clinical variables (all p values >0.05, chi-square test). No correlation was noted between the expression of VEGF and FLK-1 (p=0.35, chi-square test). In survival analysis, neither the number of positive cells nor the staining intensity of both molecules was of prognostic significance. The expression of VEGF and FLK-1 in NSCLC cells was confirmed in this study. The relation to clinical variables and survival will be further assessed in a larger group of patients.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Recurrent endometrial cancer after surgery alone: results of salvage radiotherapy.

PURPOSE: Postoperative irradiation of endometrial cancer patients decreases the risk of local recurrence but is associated with a number of long-term sequelae. In a proportion of patients, no immediate postoperative radiotherapy is applied and this treatment is introduced only at relapse. The aim of our study was to assess the long-term results of salvage radiotherapy in previously nonirradiated endometrial cancer patients who developed local recurrence, and to evaluate the impact of patient- and treatment-related factors on treatment efficacy. METHODS AND MATERIALS: We performed a detailed retrospective analysis of 73 endometrial cancer patients given radiotherapy for local recurrence after the initial surgery only. The mean age at diagnosis of the recurrence was 63 years (range, 39-78 years). Median time to recurrence was 11 months (range, 1-19 months). All recurrences were staged with the use of Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma. There were five (7%) Stage I patients, 43 (59%) Stage II patients, and 25 (34%) Stage III patients. Forty-four patients (60%) received both external beam irradiation (EBRT) and endovaginal brachytherapy (BRT), 17 (23%) received only BRT, and 12 (17%) received only EBRT. The mean total physical radiation dose was 75.9 Gy (range, 8-130 Gy), and the mean normalized total dose (NTD) calculated on the base of the linear-quadratic model was 86.6 Gy (range, 8.5-171.9 Gy). Median follow-up for alive patients was 8.8 years (range, 3-21 years). The impact of patient-, tumor-, and therapy-related factors on the treatment outcome was evaluated with the use of uni- and multivariate analyses. RESULTS: Three- and 5-year overall survival rates were 33% and 25%, respectively. In the univariate analysis, lower stage of recurrent disease (p < 0.0005), combined EBRT and BRT (p = 0.027), higher total radiation dose (p = 0.031), and higher NTD (p = 0.006) were significantly correlated with better survival. In the multivariate analysis, only stage of recurrent disease (p < 0.005) and high total dose (p = 0.047) were independently correlated with better survival. Lower FIGO stage of recurrence (p = 0.023) and higher total dose (p = 0.005) were also independently correlated with longer time to progression, whereas higher radiotherapy dose was the only factor correlated with better local control (p = 0.029). CONCLUSIONS: The efficacy of salvage radiotherapy in endometrial cancer patients with local failure after previous surgery is limited. Factors determining treatment outcome include advancement of the tumor at relapse and radiotherapy dose.

Adult↗
PubMed2000

Combined treatment with buserelin and tamoxifen in premenopausal metastatic breast cancer: a randomized study.

BACKGROUND: Surgical or medical castration and antiestrogenic treatment with tamoxifen are common endocrine treatments for premenopausal women with breast cancer. However, tamoxifen therapy induces high levels of plasma estradiol, with unknown long-term effects. In this study, we investigated the effect of combining estrogen suppression with the luteinizing hormone-releasing hormone agonist buserelin and estradiol receptor blockade with tamoxifen to determine whether the high estradiol levels induced by tamoxifen could be reduced and whether the antitumor effects would be better. METHODS: In a three-arm, randomized, prospective trial, from 1988 through 1995, a total of 161 premenopausal patients with advanced breast cancer were randomly assigned to treatment with buserelin, tamoxifen, or both. Patients with steroid receptor-negative tumors or with tumors of unknown receptor status who had a disease-free interval of less than 2 years were excluded. The median follow-up was 7.3 years, during which 76% of the patients died, all of breast cancer. Patient and tumor characteristics were well balanced among treatment groups. All P values are from two-sided tests. RESULTS: Combined treatment with buserelin and tamoxifen was superior to treatment with buserelin or tamoxifen alone by objective response rate (48%, 34%, and 28% of patients who could be evaluated, respectively; P =.11 [chi(2) test]), median progression-free survival (9.7 months, 6.3 months, and 5.6 months; P =.03), and overall survival (3.7 years, 2.5 years, and 2.9 years; P =.01). Actuarial 5-year survival percentages were 34.2% (95% confidence interval [CI] = 20.4%-48.0%), 14.9% (95% CI = 3.9%-25.9%), and 18.4% (95% CI = 7.0%-29.8%), respectively. No differences in antitumor effects were observed between single-agent treatment groups. During combined treatment or treatment with buserelin alone, plasma estradiol levels were suppressed equally; in contrast, during treatment with tamoxifen alone, plasma estradiol levels increased threefold to fourfold over pretreatment levels. CONCLUSION: Combined treatment with buserelin and tamoxifen was more effective and resulted in longer overall survival than treatment with either drug alone.

Adult↗
PubMed2000

Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland.

Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.

Adult↗
PubMed2000

Results of surgical treatment of non-small cell lung cancer: validation of the new postoperative pathologic TNM classification.

OBJECTIVE: Prognostic relevance of the current TNM stage grouping for lung cancer is still a matter of debate. METHODS: To validate the new pathologic TNM classification for non-small cell lung cancer, we analyzed the survival data of 586 patients who underwent complete pulmonary resection and pathologic staging at one institution. RESULTS: The current TNM stage grouping well reflected the long-term prognostic hierarchy. There was a good distinction between new substages IA and IB (5-year survivals of 66% and 53%, respectively). The subdivision of stage II led to an under-representation of stage IIA (6 patients [1.0%]), and therefore the appropriateness of this modification could not be verified. Five-year survival in the T3 N0 category (30%) was significantly better than that found in the new stage IIIA (15%). No difference was found between T3 N0 and T2 N1, the categories constituting new stage IIB. Within stage IIIA there was a significant survival difference between T3 N2 (6%) and the remaining T and N designations (18%). Moreover, the 5-year survival in the T3 N1 category (35%) was similar to that found in the new stage IIB (27%) and better than in any T N2 tumors (12%). CONCLUSION: Most of our findings confirmed prognostic relevance of the current pTNM stage grouping in patients with resectable non-small cell lung cancer. However, despite recent modifications, there is still a significant heterogeneity that flaws stage IIIA.

Adult↗
PubMed2000

Second lower genital tract squamous cell carcinoma following cervical cancer. A clinical study of 46 patients.

BACKGROUND: Patients after treatment for cervical cancer have increased risk of developing second squamous cell malignancy of the lower genital tract. MATERIAL AND METHODS: A retrospective study of 46 patients with second lower genital tract epidermoid cancers following previous treatment for invasive cervical carcinoma. RESULTS: Patient age at diagnosis of cervical cancer was 27 to 68 years (median 44 years) and at diagnosis of the second malignancy - 43 to 72 years (median 63 years). There were four cases (9%) of synchronous cancers. Time span between metachronous malignancies ranged from 66 to 406 months (median 206 months). In 32 cases (70%) second lesion was located in the vagina and in 14 (30%) - in the vulva. Out of 35 previously irradiated patients, in 24 (69%) second tumor was located within the high dose volume and in 11 (31%) - outside it. Treatment of second cancer consisted of surgery in 12 patients (26%), radiotherapy in 23 (50%), combined surgery and radiotherapy--in five (11%), chemotherapy in four (9%) and surgery plus chemotherapy - in one case. Median survival was 52 months and five-year survival from the diagnosis of second malignancy - 47.5%. No prognostic factors for survival were identified. CONCLUSION: Treatment outcome in patients with second lower genital tract carcinoma is unsatisfactory due to poor feasibility of another definite treatment after previous radical surgery and/or radiotherapy.

Adult↗