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J Jassem

Publications and source records attributed to J Jassem.

At least 19 recordsLinked to original sources
PubMed2006

Continuous versus intermittent tamoxifen versus intermittent/alternated tamoxifen and medroxyprogesterone acetate as first line endocrine treatment in advanced breast cancer: an EORTC phase III study (10863).

BACKGROUND: Continuous ligand depletion of endocrine responsive tumours may enhance resistance to therapy. Intermittent treatment with tamoxifen (T) was considered to mimic (incomplete) ligand depletion and reintroduction. Furthermore it was postulated that alternating tamoxifen with a non-cross resistant endocrine modality could (further) postpone hormone resistance. PATIENTS AND METHODS: Postmenopausal patients with advanced breast cancer who did not progress after 4 months of first line T therapy were randomised to continue T (40 mg daily) or to 2 monthly intermittent T or intermittent/alternated T and medroxyprogesterone acetate (MPA, 300 mg daily). At progression during break or during MPA, T should be reintroduced. Endpoints of the study were progression free survival (PFS), time to resistance to tamoxifen and overall survival (OS). RESULTS: Of 593 registered patients, 276 were randomised. After 8 years follow-up the median PFS for continuous T, intermittent T and intermittent/alternated T and MPA was 11.0 (8.1-15.2), 8.0 (6.2-12.4) and 10.8 (7.1-16.7) months, respectively (NS). Resistance to tamoxifen was established only in 84%, 70% and 55% of patients in the three treatment arms, respectively. The median times from randomisation to resistance to tamoxifen were 12.5 (9.1-21.1), 13.2 (8.8-19.8) and 24.0 (16.9-60.9) months, respectively (p<0.001), without translation in differences in survival times. CONCLUSION: Intermittent T or intermittent/alternated T and MPA had no impact on PFS or OS as compared with classical continuous T in patients with advanced breast cancer. Intermittent/alternated T and MPA resulted in prolonged time to resistance to T, but this might partly be due to bias by omittance of the proof of tamoxifen resistance in a high proportion of the patients in this treatment arm.

Adult↗
PubMed2006

Blue-dye intraoperative sentinel lymph node mapping in early non-small cell lung cancer.

AIMS: The blue-dye staining method of sentinel lymph node identification in lung cancer patients has been scarcely reported. The study was designed to assess the sensitivity, accuracy and negative predictive value (NPV) of intraoperative sentinel lymph node mapping in patients with non-small cell lung cancer by means of staining with colloid or water solution of blue dye. PATIENTS AND METHODS: One hundred and ten patients with clinically confirmed NO non-small cell lung cancer were enrolled into prospective study of intraoperative sentinel node identification. Four quadrants of the peritumoral tissue were injected with 4 ml of blue dye. After complete lymphadenectomy, all resected lymph nodes were examined with conventional hematoxylin-eosine staining. All negative sentinel nodes were searched for metastatic deposits with both serial sections and immunohistochemistry for cytokeratines. RESULTS: The blue-dye technique was characterized by unacceptably low sentinel node identification rate (IR) and low sensitivity (27% and 67% respectively). No significant differences were found in either the sensitivity or NPV among the colloid or water solutions of the blue dye applied. Although patent blue (colloid) was superior to water solution of methylene blue in identifying sentinel lymph node (identification rate 36% and 22% respectively) the sensitivity and NPV were lower (63% and 80% for patent blue and 75% and 92% for methylene blue respectively). CONCLUSION: The blue-dye staining method of sentinel node identification in non-small cell lung cancer patients is inadequate and should not be recommended for clinical use.

Adult↗
PubMed2006

Complications of breast-cancer radiotherapy.

Although the beneficial effect of postoperative radiotherapy for breast cancer is well documented, this treatment may be related to a number of complications, which may affect patient quality of life and possibly survival. Among significant long-term irradiation sequelae are cardiac and lung damage, lymphoedema, brachial plexopathy, impaired shoulder mobility and second malignancies. The risk of these complications, particularly high with old, suboptimal irradiation techniques, has decreased with the introduction of modern technologies. In this paper, we review the contemporary knowledge on the toxicity of breast-cancer radiotherapy and discuss possible preventive measures.

Arm↗
PubMed2005

Clinical significance of apoptotic index in non-small cell lung cancer: correlation with p53, mdm2, pRb and p21WAF1/CIP1 protein expression.

PURPOSE: The aim of this study was to assess the prognostic relevance of apoptotic index (AI), considered alone or together with expression of several proteins controlling G1 check point (p53, mdm2, pRb and p21WAF1/CIP1) in non-small cell lung cancer (NSCLC) patients. METHODS: Study group included 50 NSCLC patients who underwent curative pulmonary resection. Apoptosis was detected with the use of TUNEL technique and AI was defined as the number of apoptotic cells per 1,000 tumor cells. The expression of p53, mdm2, pRb and p21WAF1/CIP1 was assessed immunohistochemically. RESULTS: The mean and median AI calculated for all 50 patients was 14 and 9, respectively. Patients with lower (<14) and higher (> or =14) AI constituted 35 (70%) and 15 (30%) of cases, respectively. AI was not correlated with patient clinical characteristics, and expression of p53, pRb and p21WAF1/CIP1 . However, lower AI was correlated with over-expression of mdm2 protein (P=0.04). Median survival for patients with lower and higher AI was 43 months and 22 months, respectively, and 5-year survival probability-60 and 25%, respectively (P=0.03). In multivariate analysis, the only variable associated with shortened survival was AI (P=0.03, HR=2.9, 95% CI 1.95-3.86). CONCLUSIONS: These results suggest that AI correlates with mdm2 protein expression and influences survival in NSCLC.

Aged↗
PubMed2005

First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study.

BACKGROUND: This randomized, phase III study compared the efficacy and safety of first-line gemcitabine versus epirubicin in the treatment of postmenopausal women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients aged > or = 60 years (median 68 years) with clinically measurable MBC received either gemcitabine 1200 mg/m(2) or epirubicin 35 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. RESULTS: Of 410 patients entered, 397 (198 gemcitabine and 199 epirubicin) were randomized and qualified for the time to progressive disease (TTP) and survival analyses. Total cycles administered in 185 gemcitabine and 192 epirubicin patients, respectively, were 699 (mean 3.5, range 0-12) and 917 (mean 4.6, range 0-10). Epirubicin demonstrated statistically significant superiority in TTP (6.1 and 3.4 months, P=0.0001), overall survival (19.1 and 11.8 months, P=0.0004), and independently assessed response rate (40.3% and 16.4% in 186 and 183 evaluable patients, P <0.001). For gemcitabine (n=190) and epirubicin (n=192), respectively, common WHO grade 3/4 toxicities were neutropenia (25.3% and 17.9%) and leukopenia (14.3% and 19.3%). Of the 28 on-study deaths (17 gemcitabine, 11 epirubicin), three were considered possibly or probably related to treatment (gemcitabine). CONCLUSIONS: Postmenopausal women > or =60 years of age with MBC tolerate chemotherapy well. In this study, epirubicin was superior to gemcitabine in the treatment of MBC in women age > or =60, confirming that anthracyclines remain important drugs for first-line treatment of MBC.

Aged↗
PubMed2005

A prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC).

A prospective randomised study compared two palliative radiotherapy schedules for inoperable symptomatic non-small-cell lung cancer (NSCLC). After stratification, 100 patients were randomly assigned to 20 Gy/5 fractions (fr)/5 days (arm A) or 16 Gy/2 fr/day 1 and 8 (arm B). There were 90 men and 10 women aged 47-81 years (mean 66), performance status 1-4 (median 2). The major clinical characteristics and incidence and degree of initial disease-related symptoms were similar in both groups. Treatment effects were assessed using patient's chart, doctor's scoring of symptomatic change and chest X-ray. Study end points included degree and duration of symptomatic relief, treatment side effects, objective response rates and overall survival. A total of 55 patients were assigned to arm A and 45 to arm B. In all, 98 patients received assigned treatment, whereas two patients died before its termination. Treatment tolerance was good and did not differ between study arms. No significant differences between study arms were observed in the degree of relief of all analysed symptoms. Overall survival time differed significantly in favour of arm B (median 8.0 vs 5.3 months; P=0.016). Both irradiation schedules provided comparable, effective palliation of tumour-related symptoms. The improved overall survival and treatment convenience of 2-fraction schedule suggest its usefulness in the routine management of symptomatic inoperable NSCLC.

Adult↗
PubMed2005

Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).

BACKGROUND: In 2004, level I evidence was established for the postoperative adjuvant treatment of patients with selected high-risk locally advanced head and neck cancers, with the publication of the results of two trials conducted in Europe (European Organization Research and Treatment of Cancer; EORTC) and the United States (Radiation Therapy Oncology Group; RTOG). Adjuvant chemotherapy-enhanced radiation therapy (CERT) was shown to be more efficacious than postoperative radiotherapy for these tumors in terms of locoregional control and disease-free survival. However, additional studies were needed to identify precisely which patients were most suitable for such intense treatment. METHODS: Both studies compared the addition of concomitant relatively high doses of cisplatin (on days 1, 22, and 43) to radiotherapy vs radiotherapy alone given after surgery in patients with high-risk cancers of the oral cavity, oropharynx, larynx, or hypopharynx. A comparative analysis of the selection criteria, clinical and pathologic risk factors, and treatment outcomes was carried out using data pooled from these two trials. RESULTS: Extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of CERT was significant in both trials. There was also a trend in favor of CERT in the group of patients who had stage III-IV disease, perineural infiltration, vascular embolisms, and/or clinically enlarged level IV-V lymph nodes secondary to tumors arising in the oral cavity or oropharynx. Patients who had two or more histopathologically involved lymph nodes without ECE as their only risk factor did not seem to benefit from the addition of chemotherapy in this analysis. CONCLUSIONS: Subject to the usual caveats of retrospective subgroup analysis, our data suggest that in locally advanced head and neck cancer, microscopically involved resection margins and extracapsular spread of tumor from neck nodes are the most significant prognostic factors for poor outcome. The addition of concomitant cisplatin to postoperative radiotherapy improves outcome in patients with one or both of these risk factors who are medically fit to receive chemotherapy.

Antineoplastic Agents↗
PubMed2005

Prevalence and clinical correlations of BRCA1/BRCA2 unclassified variant carriers among unselected primary ovarian cancer cases - preliminary report.

The objective of this study was to determine the prevalence of BRCA1 and BRCA2 gene mutations in unselected ovarian cancer patients, and to analyse clinical and pathological features of ovarian cancer unclassified variant mutation carriers in comparison with BRCA1 pathogenic mutation carriers and sporadic cases. A consecutive sample of 205 women with primary ovarian cancer was screened for mutations in the BRCA1 and BRCA2 genes using a direct test for small deletions and insertions, conformational sensitive gel electrophoresis and direct sequencing. Data regarding medical and familial history were collected using questionnaires. Clinical and pathological data were extracted from medical records. Unclassified variants and polymorphic mutations accounted for 8% (n = 16) and 6% (n = 13) of all cases, respectively. BRCA1 pathogenic mutations were found in 18 (9%) patients. None were found in BRCA2. The mean age of onset for BRCA1-associated tumours was 43.1 years (standard deviation (SD: 7.3) whereas in the patients with an unclassified variant, polymorphism, or no detectable gene changes, the mean age of onset ranged from 49.5-56.4 years. The most significant predictors for pathogenic or unclassified variant changes in BRCA1 in ovarian cancer patients were a younger age of onset and a history of hyperthyroidism and infertility. Except for infertility and hyperthyroidism, unclassified variant-linked ovarian tumours share features with sporadic tumours rather than with BRCA1 pathogenic mutations.

Adult↗
PubMed2005

Diagnosis and management of neck metastases from an unknown primary.

Neck lymph node metastases from occult primary constitute about 5%-10% of all patients with carcinoma of unknown primary site. Metastases in the upper and middle neck (levels I-II-III-V) are generally attributed to head and neck cancers, whereas the lower neck (level IV) involvement is often associated with primaries below the clavicles. Diagnostic procedures include a careful clinical evaluation and a fiberoptic endoscopic examination of the head and neck mucosa, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computerized tomography scan, and magnetic resonance. The most frequent histological finding is Squamous Cell Carcinoma, particularly when the upper neck is involved. In these cases, a systematic tonsillectomy in the absence of suspicious lesions is discussed since up to 25% of primary tumours can be detected in this site. Thoracic, and abdominal primaries (especially from lung, oesophagus, stomach, ovary or pancreas) should be sought in the case of adenocarcinoma and involvement of the lower neck. Positron emission tomography with fluoro-2-deoxy-D-glucose allows detection of primary tumour in about 25% of cases, but this procedure is still considered investigational. Therapeutic approaches include surgery (neck dissection), with or without post-operative radiotherapy, radiotherapy alone and radiotherapy followed by surgery as reported by several guide-lines. In early stages (N1), neck dissection and radiotherapy seem to have similar efficacy, whereas more advanced cases (N2, N3) require combined approaches. The extent of radiotherapy (irradiation of bilateral neck and mucosa versus ipsilateral neck radiotherapy) remains debatable. A potential benefit from extensive radiotherapy should be weighed against its acute and late morbidity and difficulties in re-irradiation in the case of subsequent primary emergence. The role of other methods, such as chemotherapy and hyperthermia, remains to be determined.

Aged↗
PubMed2004

Long-term survival of a patient with primarily chemo-resistant metastatic breast cancer treated with medroxyprogesterone acetate.

The prognosis of breast cancer patients with liver metastases is extremely poor. Here we present the case of a 66-year-old female breast cancer patient with multiple liver metastases diagnosed 2 years after a radical modified mastectomy followed by adjuvant tamoxifen. At progression, anthracycline-based chemotherapy was administered, but a CT scan following two cycles of FEC (5-fluorouracil, epirubicin, cyclophosphamide) showed progression of the liver metastases. Chemotherapy was therefore switched to medroxyprogesterone acetate (MPA). After 3 months the patient's general status improved, and disease stabilization was observed at the next CT scan. A further 4 months of MPA treatment resulted in complete response of all liver lesions. Treatment with oral MPA was continued for 4 years. At present, 11 years after the diagnosis of metastatic liver involvement, the patient is alive, free of cancer, and fully ambulatory. Despite bulky visceral disease and chemoresistance, hormonal treatment with MPA resulted in a spectacular and long-lasting response.

Aged↗
PubMed2003

Continuing chemotherapy or not after the induction treatment in advanced breast cancer patients. clinical outcomes and oncologists' preferences.

The optimal duration of cytostatic treatment for metastatic breast cancer is still a matter of debate. Possible gain in the duration of remission has to be weighed against the side-effects of treatment. Our aim was to define the optimal duration of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) treatment by studying the time to treatment failure, overall survival and using a Q-TWiST analysis. The treating physician's opinion was asked. The European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Group conducted a randomised trial in 204 non-progressing metastatic breast cancer patients after induction chemotherapy (CMF) to stop or continue treatment. Progression-free (PFS) and overall survival (OS) were studied. To gain more insight into the burden of treatment-related side-effects, Q-TWiST was analysed. In addition, we asked for oncologists' preferences as patients are likely to be influenced by their physicians' opinion. Continuation of CMF had a significantly longer time to treatment failure (TTF) 5.2 versus 3.5 months (P=0.011). There was no overall survival (OS) difference 14.0 versus 14.4 months (P=0.77). Mean quality-adjusted survival time was equal to 8.4 months for no further treatment and decreased to 7.9 months for continuation of CMF (95% Confidence Interval (CI) of difference equals 0.5+/-2.5 months). Almost half of the oncologists said they would favour continuous treatment for a 3-month gain in time to progression-a difference which was not found in this study. Based on these data, an interruption of chemotherapy (CMF), if this is the wish of the patient, is justified.

Adult↗
PubMed2003

Oral vinorelbine in combination with cisplatin: a novel active regimen in advanced non-small-cell lung cancer.

BACKGROUND: A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-six chemotherapy-naïve patients received cisplatin 100 mg/m(2) and i.v. vinorelbine 25 mg/m(2) on day 1, followed by oral vinorelbine 60 mg/m(2) on days 8, 15 and 22, every 28 days. RESULTS: After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7-6.4) and 8.9 months (95% CI 8.8-11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3-4 in 73% of patients) and anemia (grade 3-4 in 11% of patients). Grade 3-4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved. CONCLUSIONS: The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.

Administration, Oral↗
PubMed2003

Conservative treatment for carcinoma of the anus--a report of 35 patients.

Conservative treatment for carcinoma of the anus has become the standard care for this malignancy. In this study we report on our experience with this method with particular emphasis on treatment outcome and acute toxicity. Between April 1991 and February 2002, 35 patients (male/female ratio 0.35) with UICC T(1-i) N(0-3) M(0) squamous cell carcinoma of the anal canal or anal margin were treated with chemo-radiation (31 patients) or radiotherapy alone (4 patients). Three patients had previously undergone local tumor excision with anus preservation. The total tumor dose of 48 to 60 Gy was delivered either by split-course or continuous radiation therapy to the pelvis, followed by a local boost to the primary tumor. Chemotherapy included one or two cycles of mitomycin C (10-15 mg/m(2) day 1) and 5-fluorouracil (450-750 mg/m(2) day 1 to 4 or 5) given during the first and the last part of irradiation. Complete tumor remission was obtained in 26 (76%) out of 34 evaluable patients. Clinically persistent disease was found in five (17%) and three (7%) patients treated with chemo- radiation and radiation alone, respectively. In four of these cases salvage surgery was performed. With a median follow-up of 49 months (range 2-131 months) local recurrence occurred in four patients (12%), and distant metastases - in two (6%). Overall, local treatment failure was observed in twelve patients (35%) including eight with T3 and one with T4 tumor. Local control was maintained until the last follow-up or death in 22 patients (65%). An actuarial 5-year overall and colostomy-free survival rates were 63% (CI, 45-81%) and 45% (CI, 25-64%), respectively. Nineteen patients (54%) experienced acute toxicity, predominantly hematologic and gastrointestinal, and severe effects including one death occurred in 11 patients (31%). Late sequelae including chronic diarrhea, edema of genitalia and legs, impaired sexual activity, and bone fractures were observed in eight patients (24%). Moderate anal stool incontinence occurred in three patients (9%). In conclusion, conservative management of anal carcinoma allows durable colostomy-free survival in a proportion of patients. However, the risk of local failure is relatively high in patients with large primary tumors. Combined chemo-radiation is associated with relatively high rate of acute toxicity.

Adult↗
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↗