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Biomedical subjects

Jacek Jassem

Publications and source records attributed to Jacek Jassem.

At least 19 recordsLinked to original sources
PubMed2006

(CA)n microsatellite polymorphism of ERBB-1 in breast cancer.

The aim of this study was to determine polymorphism of repeated sequences (CA)(n) in the ERBB-1 gene. The study group included 197 breast cancer patients and 180 healthy women. DNA was isolated from fresh-frozen tumour tissue and from peripheral blood. ERBB-1 (CA)(n) microsatellite polymorphism was examined by polymerase chain reaction (PCR). A polymorphic simple sequence repeat region of 9-23 CA repeats was detected in both groups. Homozygotes comprised 22% and 34% of breast cancer patients and controls, respectively (P=0.009). An allelic imbalance (AI), mostly in the shorter allele, was found in 27% of breast cancer patients. AI occurrence was associated with the lack of oestrogen receptors in tumour cells (P=0.05); otherwise, there were no correlations between histoclinical features and (CA)(n) microsatellite polymorphism of ERBB-1. It was concluded that an allelic imbalance is a common feature in breast cancer patients and may coincide with the lack of oestrogen receptors in tumour cells. The clinical relevance of ERBB-1 microsatellite polymorphism in breast cancer remains to be established.

Allelic Imbalance↗
PubMed2006

Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial.

PURPOSE: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy. PATIENTS AND METHODS: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm). RESULTS: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities. CONCLUSION: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.

Adult↗
PubMed2006

EPR/alanine dosimetry in LDR brachytherapy--a feasibility study.

In this study, we present the results of in vivo dosimetry, using electron paramagnetic resonance in l-alanine, performed on 13 patients treated for gynaecological cancers. The doses from (137)Cs (12 samples) and (192)Ir (one sample) brachytherapy sources were determined inside vagina. The detectors had a form of small cellulose capsules tightly filled with crystalline alanine. The positions of the detectors were reconstructed from two orthogonal radiographs. The planned doses were calculated with a computer planning system (PLATO, Nucletron). The relative deviations between planned and measured doses ranged from -23 to +14%. The mean deviation from the prescribed dose was relatively low (-5%) with SD of 10%. The main sources of differences between the measured and calculated doses were attributed to uncertainty in the determination of the detector position inside the patient's body and to uncontrolled changes in the detector position during the treatment.

Alanine↗
PubMed2006

Increased risk of non-small cell lung cancer and frequency of somatic TP53 gene mutations in Pro72 carriers of TP53 Arg72Pro polymorphism.

The aim of this study was to assess whether the TP53 Arg72Pro polymorphism is associated with an increased risk of non-small cell lung cancer (NSCLC). Additionally, in NSCLC patients, we investigated a potential association between this polymorphism and somatic TP53 gene mutations in tumour cells. The study group included 240 NSCLC patients who underwent curative pulmonary resection. The control group (576 healthy subjects) was matched for sex and cigarette smoking. TP53 Arg72Pro polymorphism was determined by denaturing high-performance liquid chromatography. Tumours from 157 NSCLC patients were analysed for mutation in TP53 exons 5-8 by single strand conformation polymorphism, followed by sequencing of samples with different band pattern. Tumours from the remaining 83 patients were subjected to a direct sequencing of TP53 exons 5-8. The proportion of Pro homo/heterozygotes versus Arg homozygotes was significantly higher in NSCLC patients (54%) than in controls (46%, p = 0.034). The crude odds ratio for NSCLC development in Pro72 allele carriers was 1.39 (95% CI: 1.03-1.88). When adjusted for sex, age and smoking status in the multivariate logistic regression model, odds ratio for NSCLC development was 1.28 (95% CI: 0.91-1.80). Somatic TP53 mutations were found in 62 out of 240 NSCLC patients (26%), more frequently in Pro carriers (31%) than in Arg homozygotes (20%, p = 0.06). These results indicate that the TP53 codon 72 Pro allele may increase the risk of NSCLC. Additionally, the correlation between Pro72 and somatic TP53 mutations suggests that Pro72 allele carriers may be predisposed to tumour development along a p53 associated form of NSCLC, a finding that warrants further investigations.

Adenocarcinoma↗
PubMed2006

Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.

BACKGROUND: We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS: Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS: The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P=0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P=0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P=0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS: Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

Adult↗
PubMed2006

Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell lung cancer patients.

BACKGROUND: Sentinel lymph node identification has been tested in lung cancer patients with conflicting results. The present study was designed to assess the sensitivity, negative predictive value, and accuracy of intraoperative sentinel lymph node mapping by means of a radio-guided method in patients with nonsmall cell lung cancer to find the most appropriate definition of sentinel lymph node and to evaluate the usefulness of different particle sizes of radiocolloid. METHODS: One hundred ten patients with clinically N0 nonsmall cell lung cancer were enrolled in the pilot study of intraoperative sentinel node identification. Four quadrants of the peritumoral tissue were injected with 2 mL of 0.5 mCi technetium-99m suspension. Four radiocolloids of different particle size were used. After complete lymphadenectomy, all resected lymph nodes were examined with hematoxylin-eosin staining. All sentinel nodes negative for metastases by routine staining were searched further for metastatic deposits with both serial sections and immunohistochemistry for cytokeratins. RESULTS: The radio-guided method had a high identification rate, a high sensitivity, and a high negative predictive value (100%, 87%, and 93%, respectively) when immunohistochemistry was considered. When standard hematoxylin and eosin staining was applied, sensitivity and negative predictive value of sentinel lymph node labeling was lower (74% and 89%, respectively). No significant differences were found in either the sensitivity or negative predictive value among the colloid solutions of different particle size used in radio labeling, although smaller particles have shown a tendency to produce better results. CONCLUSIONS: The radio-guided technique provides efficient sentinel lymph node identification in lung cancer. Further studies are warranted to confirm the clinical utility of this strategy.

Adult↗
PubMed2006

Changes in lateral dimensions of irradiated volume and their impact on the accuracy of dose delivery during radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: To assess changes in lateral dimensions of irradiated volume during head and neck cancer radiotherapy and to determine their impact on the accuracy of dose delivery. PATIENTS AND METHODS: Lateral dimensions of irradiated volumes were measured in five predefined points prior to treatment and then bi-weekly. For each measurement, midline dose was calculated and verified using in vivo dosimetry. Early radiation reactions, patient weight changes and the need to modify radiotherapy accessories were also recorded. The study included 33 head and neck cancer patients irradiated using parallel opposed megavoltage fields. RESULTS: Body mass changes during radiotherapy ranged from -18 to +4 kg (median -5). Lateral dimension changes >5 mm (range -37 to +16) occurred in 32 patients (97%). For axis measurements, the degree of lateral dimension changes were correlated with treatment field size (P = 0.022) and degree of mucositis (P = 0.017). Axis doses calculated for changed dimensions varied from those prescribed by -2.5 to +6% (median +2%). Differences larger than 5% were present in 4.8% of calculations. In 17 patients (52%), radiotherapy accessories had to be modified during treatment. The need to modify radiotherapy accessories correlated with larger treatment portals (P = 0.004), more weight loss during treatment (P = 0.01) and higher initial N stage (P = 0.04). CONCLUSIONS: Changes of irradiated volume lateral dimensions during head and neck cancer radiotherapy may lead to considerable dose delivery inaccuracies. Watchful monitoring, corrections to calculated dose when changes observed are significant and radiotherapy accessories modification during the course of treatment are strongly recommended.

Adult↗
PubMed2006

Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial.

BACKGROUND: Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer (NSCLC) is not known. We aimed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC. METHODS: 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were randomly assigned to observation (n=433) or to 30 mg/m(2) vinorelbine plus 100 mg/m(2) cisplatin (n=407). Postoperative radiotherapy was not mandatory and was undertaken according to every centre's policy. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN95053737. FINDINGS: 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%); seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin than with vinorelbine (median dose intensity 89% [range 17-108] vs 59% [17-100]). After a median follow-up of 76 months (range 43-116), median survival was 65.7 months (95% CI 47.9-88.5) in the chemotherapy group and 43.7 (35.7-52.3) months in the observation group. Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls (hazard ratio 0.80 [95% CI 0.66-0.96]; p=0.017). Overall survival at 5 years with chemotherapy improved by 8.6%, which was maintained at 7 years (8.4%). INTERPRETATION: Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC, better defining indication of adjuvant chemotherapy.

Adolescent↗
PubMed2006

Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy.

The prognostic impact of pretreatment hemoglobin (Hb) level and its changes during definitive radiotherapy was evaluated by univariate and multivariate analysis in the group of 453 FIGO IB-IIIB cervical cancer patients. Pretreatment anemia (Hb < 12 g/dl) was present in 148 patients (33%), and anemia at the end of irradiation in 48%; in 64% Hb level declined during therapy. Median overall survival in patients with initial Hb >or=12 g/dl was 66 months compared to 22 months in those with lower baseline Hb levels (p = 0.0001). This difference was mainly due to increased risk of distant spread in anemic patients (40% compared to 25% in subjects with pretreatment Hb >or=12 g/dl; p = 0.001). Baseline Hb >or=12 g/dl was also associated with longer disease-free survival and improved local control. Declining Hb level during radiotherapy predicted for impaired 5-year disease-free survival and local control probability. In multivariate analysis, low pretreatment Hb level remained associated with worse overall and disease-free survival, whereas adverse impact of declining Hb level on outcome was not observed. With regard to other clinical factors, stage and tumor extension (uni- or bilateral parametrium involvement for Stage III) were the only independent determinants of prognosis.

Adult↗
PubMed2006

Intraocular malignant teratoid medulloepithelioma in an adult: clinicopathological case report and review of the literature.

PURPOSE: To report a case of intraocular medulloepithelioma, an embryonal tumour with extremely rare presentation in adults. METHOD: The case of a 44-year-old man with intraocular malignant teratoid medulloepithelioma, primarily diagnosed as intraocular teratoma, is described and the literature on this subject is reviewed. RESULTS: The patient presented with progressive proptosis caused by a tumour in the left eyeball. He had a 28-year history of loss of vision in the left eye. Histopathological examination of the enucleated eye demonstrated an intraocular teratoma. No adjuvant treatment was given. Six months later the patient presented with massive progression in the left orbit and intracranial invasion. Cisplatin-based chemotherapy was administered, but discontinued after two cycles due to poor tolerance and lack of response. At subsequent pathology review, a final diagnosis of malignant teratoid medulloepithelioma was made. Salvage radiotherapy (60 Gy in 30 fractions) resulted in partial response of the intracranial lesion. However, the patient died 6 months later due to intracranial tumour progression. CONCLUSION: Medulloepithelioma should be considered in the differential diagnosis of intraocular tumours in adults, especially in the case of coexisting, long-standing ocular symptoms. In some cases this disease is very aggressive.

Adult↗
PubMed2005

Epoetin beta therapy in patients with solid tumours.

Anaemia is a common occurrence in patients with cancer, resulting in symptoms such as fatigue that have a profound impact on quality of life. Anaemia is also associated with poor treatment outcome and overall survival. Epoetin beta, a recombinant human erythropoietin that has the same structure and function as the endogenous hormone, is an effective and safe treatment of cancer-related anaemia. Various studies in patients with solid tumours have shown that this agent effectively increases haemoglobin levels and reduces the need for emergency blood transfusions regardless of the type of concomitantly administered chemotherapy. Epoetin beta also improves the quality of life of anaemic patients with cancer, decreasing fatigue and improving the ability to perform usual daily activities. In addition, epoetin beta prevents severe anaemia and reduces transfusion requirements in patients with a high-risk of developing anaemia during chemotherapy, such as those receiving platinum-based regimens. A meta-analysis of epoetin beta trials showed that epoetin beta has no negative impact on survival or thrombosis-related survival and may reduce the risk of tumour progression in patients with solid or lymphoid malignancies. Another study has shown epoetin beta to be equally effective when administered once weekly or three times weekly. Therefore, epoetin beta offers an effective, safe and convenient therapy for the management of anaemia in patients with cancer.

Anemia↗
PubMed2005

Prognostic impact of BRCA1 pathogenic and BRCA1/BRCA2 unclassified variant mutations in patients with ovarian carcinoma.

BACKGROUND: The clinical relevance of BRCA1/2 alterations in ovarian carcinoma patients is debatable. Our aim was to determine factors influencing the risk of recurrence and death in ovarian carcinoma patients with BRCA pathogenic and unclassified variant mutations. METHODS: A consecutive series of 205 women with primary ovarian carcinoma were screened for mutations in BRCA1 and BRCA2 genes using a conformational sensitive gel electrophoresis and direct sequencing. Data regarding medical and familial history were collected using questionnaires. Clinical and pathologic data were extracted from medical records. RESULTS: Unclassified variant mutations in BRCA1 or BRCA2 genes were found in 16 (8%) patients, and BRCA1 pathogenic mutations were found in 18 (9%) patients. No pathogenic mutation was found in BRCA2 gene. Multivariate analysis showed that BRCA1 pathogenic mutation was an independent predictor of reduced risk of relapse and death (Hazard ratios [HR] 0.52 [confidence interval {CI} 0.28-0.98] and 0.38 [CI 0.10-0.96], respectively). Unclassified variant mutation did not affect recurrence and survival (HR 0.84 [CI 0.43-1.66] and 0.94 [CI 0.48-1.82], respectively). Other factors associated with reduced risk of relapse and death were complete pathologic remission at second-look laparotomy and family history of breast and ovarian carcinoma, respectively. Recurrence and death outcomes among unclassified variant mutation carriers did not differ significantly from those in sporadic cases. CONCLUSIONS: Patients with BRCA1 pathogenic mutation seem to have reduced risk of recurrence and death. These results should be interpreted with caution as they may be influenced by more intensive treatment, better response to cisplatin, and younger age of mutation carriers. Clinical relevance of BRCA1/2 unclassified variant mutations warrants further studies.

Adult↗
PubMed2005

Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18.

PURPOSE: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. RESULTS: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). CONCLUSION: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.

Administration, Oral↗
PubMed2005

Prognostic value of cyclin D1 overexpression in correlation with pRb and p53 status in non-small cell lung cancer (NSCLC).

PURPOSE: The aim of this study was to assess the impact of cyclin D1 overexpression (considered separately or jointly with previously assessed p53 and pRb statuses) on survival in a group of 111 surgically treated non-small cell lung cancer patients (NSCLC). METHODS: Cyclin D1 accumulation was assessed immunohistochemically, with the use of monoclonal antibody (DCS-6, DakoCytomation) and the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. RESULTS: Overexpression of cyclin D1 was found in 55 samples (49%), whereas the altered phenotypes cyclin D1+/p53+ or cyclin D1+/pRb- were found in 23 (22%) and 9 samples (9%), respectively. Statistical analysis was performed for different cut-off values and the only significant differences were found if samples with some expression of each protein were considered positive. There was no relationship between cyclin D1 overexpression and major clinicopathological factors, including p53 expression; however, there was a direct correlation between cyclin D1 and pRb protein expression (p=0.007). Cyclin D1 accumulation did not influence patients' survival. Of all possible cyclin D1/p53, cyclin D1/pRb and cyclin D1/p53/pRb phenotypes, patients with cyclin D1-/p53+ phenotype had shortened overall survival compared to other patients (p=0.027, HR=1.8). In the multivariate analysis, the only variable associated with shortened overall and disease-free survival was the stage of disease (p<0.001). CONCLUSIONS: These results suggest the lack of prognostic value of cyclin D1 overexpression in NSCLC patients.

Biomarkers, Tumor↗
PubMed2005

Chemotherapy in the primary treatment of cervical carcinoma.

Two major treatment modalities in cervical cancer include radiotherapy and surgery. In an attempt to improve the outcome, these modalities have been increasingly supplemented by chemotherapy. Chemotherapy can be combined with local therapies in various sequences. Of the two possible strategies using chemotherapy and radiotherapy (sequential or concomitant), the latter seems to be more effective. Platinum-based regimens applied concurrently with both definitive and post-operative radiation therapy were demonstrated to provide survival benefit in five of the six recently published randomised trials. The positive impact of chemotherapy added to radiotherapy has also been shown in a meta-analysis including 1894 patients in 19 randomised studies. This strategy, however, is accompanied by increased early toxicity. The benefit of chemotherapy applied prior to surgery remains debatable. The role of new cytotoxic and biological substances, as well as agents combating tumour hypoxia, warrants further clinical investigation.

Antineoplastic Agents↗
PubMed2005

Branchiogenic carcinoma--conceptual or true clinico-pathological entity?

The existence of branchiogenic carcinoma remains controversial. According to some authors, this malignancy is more conceptual than a true clinicopathologic entity. The originally proposed diagnostic criteria of branchiogenic carcinoma have been subsequently challenged. Many reports regarding primary branchiogenic carcinoma have failed to provide sufficient evidence to distinguish this entity from nodal metastases arising from unrecognized primary tumours. There is growing evidence that the majority of branchiogenic carcinomas are in fact cystic metastases from oropharyngeal carcinoma, most commonly originating in the tonsils, and not true carcinomas arising in a branchial cleft cyst. The missing link between branchial cyst and branchiogenic squamous cell carcinoma could be fulfilled by the occurrence of in situ branchial cyst carcinomas, yet such cases are extremely rare. Isolated cystic neck lesions, necessitate a thorough search for a primary tumour, similarly to other occult primaries presenting with cervical metastases. The treatment of cervical cyst with dysplasia or carcinoma in situ includes complete surgical excision. The true branchiogenic carcinomas should be approached with postoperative irradiation to the half neck. A cervical metastatic cystic squamous carcinoma of unknown origin should be treated as for other cases of occult primaries, i.e. with surgery and radiotherapy. The data on the prognosis of branchiogenic carcinoma are scarce, though long-term survival has been reported. Further histopathologic and clinical studies are warranted in order to better understand the biology and natural history of cervical cystic lesions. The existence of true branchiogenic carcinoma remains to be verified with new clinical and molecular criteria.

Biopsy↗