[Coronary CT angiography using prospective ECG triggering: high diagnostic accuracy with low radiation dose]. / CT-Angiographie der Koronarien mit prospektivem EKG-Triggering: Hohe diagnostische Genauigkeit bei niedriger Strahlendosis.

BACKGROUND: The purpose of this study was to evaluate the diagnostic performance of coronary CT angiography (coronary CTA) using prospective ECG triggering (PT) for the detection of significant coronary artery stenosis compared to invasive coronary angiography (ICA). METHODS: A total of 20 patients underwent coronary CTA with PT using a 128-slice CT scanner (Definition AS+, Siemens) and ICA. All coronary CTA studies were evaluated for significant coronary artery stenoses (>or=50% luminal narrowing) by 2 observers in consensus using the AHA-15-segment model. Findings in CTA were compared to those in ICA. RESULTS: Coronary CTA using PT had 88% sensitivity in comparison to 100% with ICA, 95% to 88% specificity, 80% to 92% positive predictive value and 97% to 100% negative predictive value for diagnosing significant coronary artery stenosis on per segment per patient analysis, respectively. Mean effective radiation dose-equivalent of CTA was 2.6+/-1 mSv. CONCLUSION: Coronary CTA using PT enables non-invasive diagnosis of significant coronary artery stenosis with high diagnostic accuracy in comparison to ICA and is associated with comparably low radiation exposure.

5-year results of cisplatin-epirubicin-vinorelbine (PEV) combination as primary chemotherapy in T2-3, N0-2 breast cancer patients: a multicentre phase II study.

UNLABELLED: The aim this study was to assess the efficacy of cisplatin-epirubicin-vinorelbine, as primary chemotherapy, in reducing the tumour burden in T2-3 N0-2 breast carcinomas. Breast conservative surgery (BCS) rate, clinical and pathological complete response (pCR), toxicity and 5-year disease-free survival (DFS) and overall survival (OS) were evaluated. PATIENTS AND METHODS: Eighty-eight women with tumours > or =2.5 cm were treated with cisplatin (P) 50 mg/m2, epirubicin (E) 100 mg/m2 and vinorelbine (V) 25 mg/m2, every 3 weeks. RESULTS: Fifty-six out of the 88 patients (63.6%) underwent BCS, notably including 12/23 patients with initial tumours >5 cm. The overall clinical response was 72.8% (cCR=11.4%), pCR 20.5% and pTO+pNO 17%. No cardiac toxicity was observed. Grade 3/4 adverse events were leukopenia (9.4%), neutropenia (7.9%), nausea and vomiting (7.3%). After a median follow-up of 5 years, 24 patients (27.3%) had developed local or distant metastases. The mean DFS and OS were 51.7 (SE 2.38) and 57.02 (SE 1.98) months, respectively, and were significantly higher in pCR patients in comparison to the others (63.05 vs. 48.76, p<0.01 and 64.59 vs. 55.04, p<0.05, respectively). CONCLUSION: The PEV regimen was highly effective in reducing the tumour burden, especially for large tumours. The rate of pCR was similar to that obtained by other, including taxane-based regimens, and was well-tolerated. The study demonstrated the feasibility of such a regimen even in small centres, and being of low cost this combination could be of value in the application of primary therapy.

Successful validation of the palliative prognostic score in terminally ill cancer patients. Italian Multicenter Study Group on Palliative Care.

The aim of this work was to validate a previously constructed prognostic score for terminally ill cancer patients in order to determine its value in clinical practice. The Palliative Prognostic Score (PaP Score) was tested on a population of 451 evaluable patients consecutively entered in the hospice programs of 14 Italian Palliative Care Centers. The score subdivided patients into three specific risk classes based on the following six predictive factors of death: dyspnea, anorexia, Karnofsky Performance Status (KPS), Clinical Prediction of Survival (CPS), total white blood count (WBC), and lymphocyte percentage. The performance of the PaP Score index in the training and testing sets was evaluated by comparing mortality rates in the 3 prognostic risk categories. The score was able to subdivide the validation-independent case series into three risk groups. Median survival was 76 days in group A (with a 86.6% probability of 30-day survival), 32 days in group B (with a 51.6% probability of 30-day survival), and 14 days in group C (with a 16.9% probability of 30-day survival). Survival medians were remarkably similar to those of the training set (64 days in group A, 32 days in group B, and 11 days in group C). In the complex process of staging terminally ill patients, the PaP Score is a simple instrument which permits a more accurate quantification of expected survival. It has been validated on an independent case series and is thus suitable for use in clinical practice.

Confirmed activity of FAM polychemotherapy in advanced gastric carcinoma.

During a 3-year period at our hospital, 54 consecutively observed patients with parametric, locally advanced, metastatic gastric carcinoma were treated with fluorouracil + adriamycin + mitomycin C. Of 47 evaluable patients, 44.6% had an objective response (complete + partial response) and 29.7% had stabilized disease. The median duration of response was 7.5 months. The median survival was 8.9 months for all patients. In particular, the survival of responders (greater than 12 months) and of patients with stabilized disease (8.6 months) was significantly longer than that of patients with progressive disease (4.5 months). Toxicity was limited and reversible, which allowed treatment also of patients in poor general condition (PS 3-4 of the Zubrod scale).

Endometrioid carcinoma in pelvic endometriosis in a postmenopausal woman with tamoxifen adjuvant therapy for breast cancer. A case report.

This concerns a 57 year old woman operated on in 1988 for a left radical mastectomy due to ductal breast carcinoma and subsequently treated with chemotherapy and Tamoxifen adjuvant. In 1990 a laparo-hystero-oophorectomy was carried out due to uterine fibromas. The woman continued taking Tamoxifen. Two years later a pelvic regeneration appeared, resulting in endometriosis, site of adenomatose hyperplasia and of endometrioid carcinoma GI. This furthermore confirms the importance of a gynecological follow-up for all women treated with Tamoxifen adjuvant therapy.

Oral idarubicin and cyclophosphamide for metastatic breast cancer in elderly patients.

The authors treated 39 heavily pretreated breast cancer patients, median age 72, with a combined oral regimen featuring idarubicin and cyclophosphamide, administered without hospitalization in cycles repeated every 4 weeks for a total not to exceed idarubicin 400 mg/m2. Treatment was remarkably well tolerated, with generally mild hematological toxicity and only one discontinuation caused by severe neutropenia; non-hematologic toxicity consisted mainly of moderate nausea and vomiting in fewer than half the cycles, and hair loss of various severity in the majority of patients. Therapeutic results were graded as partial responses (13 cases), no change (NC; 11 cases) or progressive disease (11 cases) for a response rate of 37.2% (95% CI: 21.1-53.1%). The authors single out the NC issue as being of special interest, its mere occurrence being rewarding in the circumstance and its duration in excess of 5 months (seen in six cases) almost equivalent to therapeutic success.

Impact of delirium on the short term prognosis of advanced cancer patients. Italian Multicenter Study Group on Palliative Care.

BACKGROUND: The objective of this study was to evaluate the impact of delirium on the survival of advanced cancer patients also assessed with a validated prognostic score (the palliative prognostic [PaP] score). METHODS: The study population was a prospective multicenter consecutive case series of advanced cancer patients for whom chemotherapy was no longer considered viable and who were referred to palliative care programs. Clinical and biologic prognostic factors included in the PaP score were assessed at study entry. The Confusion Assessment Method criteria were applied to screen patients presenting with delirium. Survival times were measured from time of enrollment and death taken as an outcome. Survival curves were traced with the Kaplan-Meier method and comparison were based on log rank tests. RESULTS: Delirium was found in 109 cases among 393 consecutive patients (27.7%). The diagnosis of delirium was independently associated with male gender, central nervous system metastases, lower performance status, worse clinical prediction of survival, and progestational treatment. The survival curve of patients with delirium was significantly different from the nondelirious patients curve (log rank, 31.6, P < 0.0001). The median survival time was 21 days (95% confidence interval [CI], 16-27) for the delirious patients and 39 days (95% CI 33-49) for the others. Multivariate analysis showed that the diagnosis of delirium and PaP score were independently associated with prognosis. CONCLUSIONS: The diagnosis of delirium significantly worsens life expectancy prognosticated with the PaP score. By using the PaP score together with the assessment of cognitive status, physicians can correctly predict patients 30-day survival in greater than 70% of cases.

Prediction of survival of patients terminally ill with cancer. Results of an Italian prospective multicentric study.

BACKGROUND: The individualization of prognostic factors in the various stages of cancer facilitates the planning of a therapeutic assistance program aimed at various subsets of patients. The prognostic factors for survival in patients terminally ill with cancer have been investigated in case studies that are often retrospective, monocentric and/or include a mixture of patients in advanced disease stages. The aim of this prospective multicentric study was to verify those clinical factors predictive of survival in a population of patients with terminal cancer. METHODS: This prospective and multicentric study was performed on 540 patients with solid tumors in the disseminated phase, no longer subject to specific therapy. Patients were evaluated at study entry and every 4 weeks thereafter. The analysis was performed for 23 clinical parameters. RESULTS: Of 530 assessable patients with a median survival of 32 days, 15 factors were found to be statistically significant prognostic factors. By univariate analysis, 13 factors were found to be indicators of a worse survival: age older than 65 years (P = 0.05); palliative corticosteroid treatment (P < 0.001), anorexia (P < 0.001); dry mouth (P < 0.001); dysphagia (P < 0.001); hospitalization (P < 0.001); transfusion (P < 0.001); weight loss greater than or equal to 10% (P = 0.001); dyspnea (P = 0.01); pain (P = 0.006); increasing amount of pain-killer treatment (P = 0.01); increasing number of symptoms (P < 0.001); and worse clinical prediction of survival (P < 0.001). Two factors that correlated with a better survival rate were palliative progestin treatment (P = 0.03) and a higher Karnofsky performance status (P < 0.001). Multiple regression analysis revealed that only clinical prediction of survival, anorexia, dyspnea, palliative steroidal treatment, Karnofsky performance status, and hospitalization were independent predictors of survival. CONCLUSIONS: The importance of certain clinical parameters as prognostic indicators for patients with terminal cancer (clinical experience, physical activity level, clinical symptoms relating to and unrelated to nutritional state) were confirmed; some others possible factors, such as treatment with corticosteroids and hospitalization, also were noted. These may be useful factors in the therapeutic, assistance decision-making process and may eliminate overtreatment and undertreatment resulting from philosophically preconceived attitudes, rather than from considering the patient's true pathologic condition.

Stages I and II non-Hodgkin's lymphoma of the gastrointestinal tract. Retrospective analysis of 79 patients and review of the literature.

We reviewed the medical records of 79 patients with primary gastrointestinal lymphoma (GI-NHL), defined according to the criteria of Dawson et al. (without involvement of liver, spleen, peripheral or mediastinal lymph nodes, or bone marrow), observed and treated in our institution between 1973-90. The most common disease site was the stomach (70 patients), followed by the small bowel (five patients) and the large bowel (four patients). The stage was IE in 36 cases and IIE in 43. Radical surgery or surgical debulking was the main therapeutic approach (67 patients); 12 patients received only chemotherapy, eight of whom had tumors considered unresectable at laparotomy. After surgery, most of the patients received chemotherapy; radiotherapy (RT) was given to only four patients. Surgically calculated overall survival (OS) rates at 5 years for the patients treated with surgery plus chemotherapy were 64% (radical surgery) and 46% (surgical debulking with microscopic lymphoma residue). For the 12 patients treated with chemotherapy alone, OS at 5 years was 0%. Our findings, in accordance with most published data, suggest that surgery, together with stage and tumor size, remains an important prognostic factor of survival in primary GI-NHL, especially when it is radical. In patients with negative prognostic factors (bulky disease, high-grade histologic type, microscopic residue, and stage II), postoperative chemotherapy and RT decrease the risk of distant failure and local recurrence.

Schedule specific biochemical modulation of 5-fluorouracil in advanced colorectal cancer: a randomized study. GISCAD, IOR and collaborating centers.

BACKGROUND: We have recently suggested that bolus 5-fluorouracil (5-FU) may work via a RNA directed mechanism while continuous infusion 5-FU may kill cells via a thymidylate synthase related pathway. It may thus be possible to selectively modulate each schedule biochemically. We have compared an alternating regimen of bolus and continuous infusion 5-FU, selectively modulated for the schedule of administration, with modulated bolus 5-FU in advanced colorectal cancer patients. PATIENTS AND METHODS: Two hundred fourteen patients from nineteen Italian centers were randomized to the control arm consisting of biweekly cycles of MTX, 200 mg/m2 on day 1, followed by bolus 5-FU 600 mg/m2 on day 2 and 6-S-leucovorin rescue, or to the experimental arm consisting of two biweekly cycles of the same regimen as in the control arm alternated to three weeks of continuous infusion 5-FU (200 mg/m2 day) + weekly bolus 6-S-leucovorin, 20 mg/m2. RESULTS: Nine CR and twenty-seven PR were obtained on one hundred eleven evaluable patients treated in experimental arm (RR = 32%, 95% confidence interval (95% CI): 24%-42%), while two CR and eleven PR were observed among one hundred three evaluable patients in control arm (RR = 13%, 95% CI: 7%-21%). WHO grade 3-4 toxicity occurred in 13% of cycles of experimental arm and in 8% of cycles in control arm. The PFS was significantly longer in experimental arm (6.2 vs. 4.3 months, odds ratio 0.66, P = 0.003), while the overall survival was similar in both arms (14.8 months in experimental arm vs. 14.1 months in control arm); quality of life was similar as well. Eighty percent of patients receiving second-line chemotherapy in control arm were treated with continuous infusion 5-FU. CONCLUSIONS: Alternating, schedule-specific biochemical modulation of FU is more active than MTX --> 5-FU as first-line treatment of advanced colorectal cancer. However, the overall survival was similar suggesting that alternating bolus and infusional 5-FU upfront may be as effective as giving them in sequence as first- and second-line treatment.

High-versus low-dose levo-leucovorin as a modulator of 5-fluorouracil in advanced colorectal cancer: a 'GISCAD' phase III study. Italian Group for the Study of Digestive Tract Cancer.

BACKGROUND: Although leucovorin (LV) + 5-fluorouracil (5-FU) is considered the treatment of choice for advanced colorectal cancer in most countries, the optimal schedule of this combination has not yet been established. Low-dose LV appears to be as active as high-dose LV in the daily-times-five regimen, but no randomized study of the levorotatory stereoisomer (6S-LV) given at two different dose levels has been published. PATIENTS AND METHODS: Between November 1991 and June 1994, 422 patients (all with measurable disease previously untreated with chemotherapy) were randomized to 6S-LV (100 mg/sqm/i.v.) + 5-FU (370 mg sqm/15 min i.v. infusion), both administered for 5 days every 28 days (arm A), or to 6S-LV (10 mg/sqm/i.v./5-FU (doses as above), also given for 5 days every 28 days (arm B). The primary endpoint of the study was the comparison of response rates (WHO criteria): the secondary endpoint was the assessment of survival and tolerability. No evaluation of the quality of life or the symptomatic effect of treatment was planned. RESULTS: The response rate was 9.3% in arm A (95% CI: 5.4-13.1), with 2 CR and 18 PR, and 10.7% in arm B (95% CI: 6.5-14.9), with 3 CR + 19 PR, without any significant difference (P = 0.78). The median time to progression was eight months in both groups and overall survival was 11 months, with no difference between treatments. Toxicity mainly consisted of gastrointestinal side effects (mucositis and diarrhoea), which were rarely severe (grade 3-4: 5%-10% of patients) and similar in the two groups. CONCLUSIONS: In this large-scale multicentre trial, the low and high doses of 6S-LV appeared to be equivalent in terms of the biochemical modulation of 5-FU in advanced colorectal cancer although, for several reasons (including the timing and the strict criteria of response evaluation, the high number of patients with unfavourable prognostic factors, the multi-institutional nature of the study, the dose and modality of 5-FU administration), the response rate was lower than that reported in some of the other published studies. Given the considerable difference in economic cost between the two dosages, the use of high-dose 6S-LV in the daily-times-five regimen is not recommended in clinical practice.