Search

Purpose: The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Patients and methods: Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Results: Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiationinduced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients

A panel of 28 monoclonal antibodies against Piscirickettsia salmonis was produced using a purified fraction of the bacterium. To determine their specificity to the pathogen, the antibodies were assayed by ELISA and indirect immunofluorescence microscopy. Six monoclonal antibodies were selected based on their strong reaction against P. salmonis and absence of cross-reactivity with other common fish pathogens. Western blot analysis showed that the antibodies reacted to several antigens of P. salmonis. Immunofluorescence assays revealed that these antibodies reacted with the same specificity to different isolates of P. salmonis obtained from the south of Chile. This panel of monoclonal antibodies represents an important tool to develop simple, rapid, sensitive and highly specific methods for the detection of the pathogen and diagnosis of the disease.

The rate and equilibrium retention of potassium dicyano aurate(I), K[Au(CN) 2 ] and bisthiourea-gold(I) chloride, [Au(CS(NH 2 ) 2 ) 2 ]Cl, in aqueous media on two series of lignocellulosic activated carbons were studied. Activated carbons with different burn-off were obtained by steam activation of carbonized peach stones and Eucalyptus globulus charcoal. Textural and chemical properties of the adsorbents were used to explain the gold retention of both complexes. From the study of the influence of some process variables on the gold retention rate, a pore diffusional control was confirmed. Thus, Eucalyptus activated carbons, with an important higher macroporosity, showed a higher gold retention rate. The equilibrium gold retention was mainly a function of both the pore distribution and the chemical properties of the activated carbon surfaces. The gold retention rate in all cases was higher for cyanide than for the thiourea complex but the equilibrium retention was higher for the thiourea complex.

Two-hundred two patients with limited small cell lung cancer were tested by four consecutive alternating radiotherapy and chemotherapy protocols. The alternating schedule consisted of six cycles of chemotherapy (doxorubicin, etoposide, and cyclophosphamide, plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65 and 61 Gy in the four consecutive protocols, respectively. A 1-week rest followed each chemotherapy cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. Overall results showed a 2-year cumulative incidence rate of failure of 75%. The first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. Overall survival rate at 5 years was 16%. No significant differences were observed between the four treatment groups. Alternating radio-chemotherapy approaches are feasible and currently included in Phase III trials.

In patients with the clinical diagnosis of Alzheimer disease (AD), we searched for systemic changes in components of the blood as a diagnostic tool. The acetylcholine-related enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were measured in plasma, erythrocytes, platelets and lymphocytes. Results did not show a general effect; notwithstanding, specific cell types presented alterations either in AChE or BuChE but not in both enzymatic activities. In AD patients, AChE of lymphocytes was reduced by 60% compared with the age-matched controls. However, when patients were divided, the sporadic but not the familial subgroup exhibited a significant reduction. In erythrocytes the BuChE activity was reduced by 45% in sporadic AD. The molecular forms of the lymphocyte AChE were characterized by velocity sedimentation. Both globular forms were subnormal, more so the tetrameric G4 AChE form than the G2 form.

Sulphonamides separated on a C18 LC column were detected at lower levels using amperometric detection at a glassy carbon electrode in comparison with UV detection at 258 nm. Whereas sulphonamides are detectable at a potential of +1.00 V, their N 4 -acetyl-metabolites required a potential of +1.25 V to be detected after their separation by LC. An interference commonly present in serum and urine, which co-eluted with one of the analytes, was detected at 1.25 V. This was overcome with an appropriate sample preparation in which 150 μl of serum or 75 μl of urine were first diluted to 1.5 ml with phosphate buffer (pH 3.0; 0.2 M). A 1.0 ml volume of this solution was then passed through an Extrelut® 1 column. The analytes were eluted with dichloromethane, which was evaporated under vacuum, and redissolving the analytes in an appropriate volume of mobile phase, i.e. methanol—phosphate buffer (pH 6.7; 0.067 M) (25:75, v/v). For sulphamethoxazole (SMX) and sulphamethoxypyridazine (SMP) and their N 4 -acetyl-metabolites the calibration curves were linear between 1.5 × 10 −7 and 8 × 10 −6 M. The recovery ranged between 92.6 and 97.6% in serum and between 80.5 and 99.4% in urine. Detection limits were 10 times lower with amperometric detection than with UV detection. The method has been applied to the quantitation of SMX and SMP and their N 4 -acetyl-metabolites in serum and urine after their oral administration.

The purpose of this study was to determine the predictive value of breast cancer molecular subclassification regarding the benefit of adjuvant anthracycline-based chemotherapy.Tumor samples from 823 patients included in two randomized trials that compared an anthracycline-based chemotherapy with no treatment were used to construct a tissue array. Estrogen receptor (ER), Her2, epidermal growth factor receptor, cytokeratine 5/6 expressions were determined by immunohistochemistry (IHC). The potential predictive factors of treatment effect on disease-free survival (DFS) were assessed by interaction tests and multivariate analysis.Sixty-four (8%), 98 (12%), 109 (14%) and 527 (66%) patients presented a Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like breast cancer. ER expression, when assessed by IHC, was an independent predictive factor for the benefit of chemotherapy on DFS (test for interaction, P = 0.0015). The molecular subclassification significantly predicted the efficacy of chemotherapy (test for interaction, P = 0.01), but had no significant added value (P = 0.32) as compared to the ER by treatment interaction. Adjuvant chemotherapy was associated with an adjusted hazard ratio for relapse or death of 0.42 [95% confidence interval (CI): 0.17-1.05], 0.54 (95% CI: 0.27-1.08), 0.35 (95% CI: 0.18-0.68), 1.07 (95% CI: 0.81-1.41) for patients with Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like tumors, respectively.The breast cancer molecular subclassification was predictive for chemotherapy efficacy in adjuvant setting, but did not provide significant additional information to ER.

Background We studied whether dermal lymphatic emboli (DLE) add independent prognostic information to the clinical definition of inflammatory breast cancer (IBC). Patients and Methods The study was performed in 2 centers, one each in France and Tunisia. For every patient with IBC, 1-3 patients with noninflammatory breast cancer (non-IBC) were included. All patients were to have a surgical tumor biopsy, including a sample of the skin surrounding the tumor. The endpoint was the risk of a relapse at 2 years, which was estimated using univariate and multivariate Cox models. Results Three hundred thirty-seven patients were included (150 in France and 187 in Tunisia). The IBC status was divided into 2 clinical categories according to the extent of inflammation in the breast (localized IBC, which was defined as clinical inflammation in the tumor area, vs. diffuse IBC, which was defined as inflammation of at least two thirds of the breast). In total, 57 patients presented with localized IBC, 71 with diffuse IBC, and 209 with non-IBC. Dermal lymphatic emboli were found in 7% of non-IBC cases, in 25% of localized IBC cases, and in 45% of diffuse IBC cases. We found a significant interaction between the presence of DLE and diffuse IBC (P = 0.01). In patients with diffuse IBC, the presence of DLE increased the risk of relapse 3-fold. Conversely, DLE were not associated with the risk of relapse in patients with non-IBC, nor in patients with localized IBC. In patients with diffuse IBC and no DLE, the risk of relapse was similar to that of patients with localized IBC. Conclusion A DLE status might be a useful prognostic indicator exclusively in patients with diffuse IBC. However, because all patients with localized and diffuse IBC generally receive similar types of treatment, additional information on the presence or absence of DLE will not have an impact on treatment practice.

Summary Purpose The aim of the study was to compare reproductive factors in patients with inflammatory breast cancer (IBC), and with non-inflammatory breast cancer (non-IBC). The study was performed in two centers: one French including 49 IBC patients and 140 non-IBC and another Tunisian including 97 IBC and 139 non-IBC. Unconditional logistic regression was used for the analyses. Patients and methods The French IBC patients had a lower educational level, a higher body mass index and a longer cumulative duration of breast-feeding, and they included a greater proportion of non-European women, than the non-IBC patients. In the multivariate analysis, only breast-feeding duration remained associated with the IBC status ( P = 1 0 - 3 ). These results could not be verified in the Tunisian series, because the duration of breast-feeding was unavailable in this center. Results This study suggests that the etiology of IBC might be different of that of non-IBC.

Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival.We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival.The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P= 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy.Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.

Postoperative radiotherapy is commonly used to treat patients with completely resected nonsmall cell lung carcinoma, but its effect on overall survival has not been established.After undergoing complete surgical resection, 728 patients with non-small cell lung carcinoma (221 Stage I, 180 Stage II, and 327 Stage III) were randomized to receive either postoperative radiotherapy at a total dose of 60 gray or observation only . The main end point was overall survival.At the reference date, 218 of 355 patients in the control group had died and 262 of 373 in the radiotherapy group had died. Five-year overall survival was 43% for the control group and 30% for the radiotherapy group (P = 0.002, log rank test; relative risk [RR]: 1.33; 95% confidence interval [CI]: 1.11-1.59). This result was not modified by adjustment for potential prognostic factors. The excess mortality rate for the radiotherapy group was due to an excess of intercurrent deaths (P = 0.0001; RR: 3.47; the 5-year intercurrent death rate was 8% for the control group and 31% for the radiotherapy group). Radiotherapy had no significant effect on local recurrence (RR: 0.85; 95% CI: 0.64-1.14) and no effect on metastasis (RR: 1.06; 95% CI: 0.85-1.31). The rate of non-cancer-related death increased with the dose per fraction delivered.

Tamoxifen administered in patients after breast cancer surgery is one of the most effective adjuvant treatments in this pathology. A large number of randomized studies including thousands of patients allowed to quantify the treatment benefits in terms of recurrence, contralateral breast cancer and overall survival rates. The treatment is generally given for more than 2 years. However, the optimal treatment duration is unknown. Uncertainties appeared when adverse effects were described after some years of treatment (e.g. a higher incidence of endometrial adenocarcinoma). New ongoing multicentric trials will clearly define in the next years the optimal duration of this adjuvant treatment.

The yellow (y) mutation of Drosophila melanogaster affects the development of behavior and morphology. We have analyzed some behavioral and morphological parameters during the development of y mutants. Wild-type third instar larvae move in straighter paths than larvae of the same age homozygous for the y mutation. At 96 h of age, the tracks of y larvae have 10 times as many loops as tracks of wild-type larvae, and at 120 h of age, y larvae show bending behavior about 2.5 times more frequently than do wild-type. Consequently, they do not disperse as much as wild-type larvae. Concomitant with the behavioral changes, the larvae present a defect in the morphology of large chaetae in the larval denticle belts, particularly of 2nd and 3rd instars, both with light and scanning electron microscopes. These results suggest that a cuticular defect is probably involved in the abnormal locomotor activity observed in y larvae of Drosophila melanogaster.

Breast conservation is now established treatment for patients with small breast cancers. The authors reviewed a large series of patients with long term follow-up who underwent conservative treatment. Clinical and pathologic factors were analyzed to identify patients at an increased risk of relapse in the breast (local relapse) or development of a contralateral tumor.Seven hundred fifty-seven patients with unilateral invasive breast cancer (T0-2, N0-1, M0) were treated conservatively (wide local excision and radiotherapy) at the Institut Gustave-Roussy between 1970 and 1982. The median follow-up was 9 years. The risk of local relapse or development of a contralateral tumor (as first event) was studied by univariate analysis for the main clinical, pathologic, and treatment factors. Those found to be significant were entered into a Cox proportional regression analysis.Fifty-one patients relapsed in the treated breast (actuarial local relapse rates at 5 and 10 years were 5% and 8%, respectively) and 34 in the contralateral breast (actuarial contralateral tumor rates at 5 and 10 years were 3% and 6%, respectively). Multivariate analysis of the risk factors for local relapse showed that only age younger than 40 years (P0.02) or inadequate surgical excisioin (P0.02) were significant. No particular risk factors for contralateral tumor development were identified.Overall, for most patients, the risk of local relapse or of developing a contralateral tumor was low. A small number of young patients with inadequately excised tumors are at higher risk of local relapse, need more meticulous surgery, and may merit higher dose radiotherapy.

A total of 22 women with fibroadenomas had preoperative dynamic MR study (T1-weighted images every 47 s after injection of Gd-DOTA). Their age, hormonal status, breast MR studies and histopathological slides were retrospectively reviewed. Eleven pre- (n = 2) or post-menopausal (n = 9) women showed no early contrast enhancement. The absence of early contrast enhancement correlated with hyalin stromal component. Eleven pre- (n = 7) or post-menopausal (n = 4) women showed focal (n = 9) or diffuse (n = 2) early contrast enhancement. Early focal contrast enhancement correlated with myxoid (n = 9), mixed hyalin/myxoid (n = 1) or hyalin (n = 1) fibroadenomas. Early diffuse contrast enhancement of the breast correlated with myxoid (n = 1) or hyalin (n = 1) stromal component associated with proliferative fibrocystic disease of the breast parenchyma. The presence of contrast enhancement correlated with myxoid fibroadenomas, whereas absence of contrast enhancement correlated with hyalin fibroadenomas. As hyalin fibroadenomas occurs in post-menopausal women, the diagnostic accuracy of dynamic MRI may be improved in this age group.

The effect of adjuvant chemotherapy after resection of nonsmall cell lung cancer (NSCLC) remains an unresolved question.From October, 1982, to November, 1986, 267 patients with resected NSCLC were included in a randomized trial. The adjuvant allocated treatments were either postoperative radiotherapy, 60 Gy in 6 weeks (radiotherapy group = 129 patients), or three courses of postoperative COPAC (cyclophosphamide, doxorubicin, cisplatin, vincristine, lomustine) chemotherapy followed by a similar radiotherapy schedule (chemotherapy/radiotherapy group = 138 patients).The sex ratio (M:F) was 19/1; mean age was 57 +/- 9 years. According to postoperative staging, 8 patients were Stage I, 70 were Stage II, and 189 were Stage III. The histologic type was squamous cell carcinoma in 175 patients, adenocarcinoma in 57, and large cell carcinoma in 35. The minimum follow-up was 6 years. Four patients were lost to follow-up. Death was recorded in 233 patients. No significant difference was observed in terms of disease free interval (P = 0.47, log-rank test), or overall survival (P = 0.68, log-rank test). With respect to the first site of relapse, distant metastasis occurred more frequently in the radiotherapy group (P = 0.09, log-rank test) whereas local relapse occurred similarly in both groups (P = 0.27). An interaction was observed between lymph node involvement and treatment in terms of overall survival.The COPAC chemotherapy as postoperative treatment failed to improve overall survival in patients with resected NSCLC receiving postoperative radiotherapy but decreased the pattern of metastatic progression, mainly in the N2 patients.

Two-hundred two patients with limited small cell lung cancer were tested by four consecutive alternating radiotherapy and chemotherapy protocols. The alternating schedule consisted of six cycles of chemotherapy (doxorubicin, etoposide, and cyclophosphamide, plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65 and 61 Gy in the four consecutive protocols, respectively. A 1-week rest followed each chemotherapy cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. Overall results showed a 2-year cumulative incidence rate of failure of 75%. The first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. Overall survival rate at 5 years was 16%. No significant differences were observed between the four treatment groups. Alternating radio-chemotherapy approaches are feasible and currently included in Phase III trials.

113 Background: Preoperative radiotherapy (PreopRT) in locally advanced breast cancer patients (LABC) has been rarely reported. The purpose of this study was to determine if pathological response to PreopRT could have prognostic value on locoregional control and survival. Methods: From 1970 to 1984, 203 LABC patients were treated by PreopRT, delivering 45Gy in 25 fractions to the breast, supraclavicular fossa, axilla and ipsilateral internal mammary chain. After a median interval of 38 days (range: 5-121 days), radical mastectomy and axillary dissection was performed independently of radiation response. Chemotherapy or endocrine therapy was prescribed according to physician discretion in 28% and 11% of patients, respectively. Premenopausal patients underwent ovarian ablation. Median follow-up was 26 years. Locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method, the comparison of survival between groups was performed using the log-rank test, multivariate analysis was performed using the Cox model. Results: Thirty-three patients (16.2%) had a pathologic complete response (pCR) in the breast. The 10- and 20-year Kaplan-Meier LC were 90% (95% confidence interval CI: 85-94%) and 84% (95% CI: 77-89%), respectively. The 10 and 20-years DFS were 49% (CI: 42-55%) and 35% (CI: 29-42%), and the 10 and 20-years OS, 56% (CI: 49-63%) and 41% (CI: 35-48%), in that order. Patients with pCR tended to have better DFS (p=0.06) and OS (p=0.07) when compared to patients with partial response or stable/progressive disease. Having a pCR did not significantly influenced LRC (p=0.44). Multivariate analysis showed that a lower number of positive nodes on axillary dissection and younger age were associated with better DFS (p Conclusions: LCR achieved by PreopRT followed by radical mastectomy in LABC was excellent in this study, despite few patients having adjuvant systemic therapy. Complete pathologic response defined a subgroup of women with a trend toward better DFS and OS. Older patients and those with a higher number of involved axillary nodes had a worse prognosis.

This retrospective analysis was conducted on breast cancer patients treated by radiotherapy alone at The Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients had either operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Previous results showed that a radiation dose increase of 15 Gy can decrease the relative risk of tumor or lymph node recurrence twofold. In this third report, the same data were analyzed to determine the treatment-related complication rates and to correlate these to the radiation dose levels. Overall results were analyzed on 453 patients, but detailed analyses on complications were conducted on 372 patients not developing local recurrence in the first 6 months of follow-up. Each complication was graded on a 3-level previously defined scale. Most frequent complications were skin changes of different degrees, which were usually asymptomatic. More disabling complications were arm edema, impaired shoulder mobility, rib fractures and brachial plexopathy. The incidence of disabling complications was low. The only factor significantly increasing the risk of complications was the radiation dose level to the tumor and axilla. Technical factors such as overlapping fields should also be taken into account. As the more effective control of tumor and lymph nodes obtained in patients treated with higher radiation doses is counterbalanced by an increase in the complication rate, the dose to be delivered for each patient should be carefully chosen according to individual risk factors.

638 Background: IBC is the most aggressive form of locally advanced breast cancer with a poor clinical outcome. The locoregional treatment is crucial because local relapses are commonly associated ...

This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules.

Most patients with locally advanced non small cell lung carcinoma are treated with external thoracic radiotherapy. Because of the high incidence of distant metastasis the addition of chemotherapy has been proposed. The present randomized study was conducted from June 1983 to February 1989 and included 353 patients. The trial compared arm A, thoracic megavoltage radiotherapy alone at a total dose of 65 Gy in 26 fractions and 45 days, to arm B that comprised the same radiotherapy preceded and followed by 3 monthly cycles of VCPC (vindesine 1.5 mg/m2 d 1-2, cyclophosphamide 200 mg/m2 d 2-4, cisplatinum 100 mg/m2 d 2 and lomustine 75 mg/m2 d 3). Disease was deemed unresectable but non-metastatic after bronchoscopic, radiologic, CAT, and nuclear scans and physical examinations. Only patients in clinical, radiological, endoscopic, and histological complete remission were considered as locally controlled; these patients were monitored by fiberoptic bronchoscopy and systematic biopsies to the primary site. One hundred seventy-seven patients received thoracic radiotherapy alone and 176 received the combined modality. Twenty-seven percent of arm B patients had an objective response after 2 VCPC cycles. At the time of final assessment, performed 3 months after the end of thoracic radiotherapy in both arms, there were 20% of complete responders in arm A versus 16% in arm B. The two-year survival rate was 14% in arm A versus 21% in arm B (p = 0.08, logrank test). The distant metastasis rate was 67% in arm A versus 45% in arm B (p less than 0.001). Local control at 1 year was poor in both groups (17% and 15%, respectively). The striking effect of VCPC chemotherapy on the incidence of distant metastasis did not have a significant impact on overall survival. We conclude that thoracic tumor control remains a significant problem in unresectable non small cell lung cancer.

616 Background: The identification of predictive biomarkers for the efficacy of adjuvant treatments could allow to better tailor adjuvant treatments. We evaluated the predictive value of MRP2, bcl2, topoisomerase IIα (Topo IIα) expression and p53 status for the efficacy of adjuvant anthracyclines (A)-based chemotherapy. Methods: Tumor samples from 823 patients included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no treatment were used to perform a tissue-array. Chemotherapy consisted of 5FU (500mg/m2), farmorubicine (90% of patients) or doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) (D1=D28) for 6 cycles. Immunostainings (cut-off: >10% stained cells) were performed for MRP2 (M2III-6; 1:300; Alexis), p53 ( DO-7; 1:50; Dako), bcl2 (124; 1:50; Dako), and Topo IIα (KI-S1; 1:5000; Chemicon). We previously reported predictive values of ER, HER2 expression and molecular subclassification using the same tissue-array (Conforti, Annals of Oncology, 2007)...

1085 Background: Until recently, patients (pts) with stage IV breast cancer at diagnosis (BC) were generally treated with exclusive systemic therapy. There is recent retrospective evidence of the potential benefits of local surgery as part of the treatment plan. We attempted to evaluate, in a large retrospective series, local control (LC) rates achieved by loco-regional radiation therapy (LRRT) alone or in combination with surgery. Methods: We retrospectively reviewed the prospectively registered data of all pts treated at the Institut Gustave Roussy since 1990, for BC with evidence of distant metastases at diagnosis and who have received a loco-regional treatment. Survival curves were determined by the Kaplan-Meier method and Cox models were used for adjusted comparisons. Results: Between 1990 and 2003, 239 BC pts met the inclusion criteria. Median follow-up 6.5 years, median age: 55 years; ER-positive 68%, visceral metastases 51%. Primary chemotherapy was given in 86% of pts. Pts were categorized for lo...

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

623 Background: The benefit provided by chemotherapy (CT) for breast cancer patients is based on the risk of recurrence at a population level and not on an individual benefit. Pathologic complete response (pCR) to primary chemotherapy (PC) has been demonstrtated to be a surrogate marker of survival, demonstrtaing that patients that achieve a pCR are the most likely to benefit from CT. We hypothesized that individuals who benefit from adjuvant CT share the same clinico-pathologic characteristics as patients with pCR after PC and therefore that the same nomogram can be used to evaluate the probability of pCR and the benefit from receiving adjuvant CT after initial surgery. Methods: Two cohorts of patients treated at the IGR were studied. The first cohort (n=502) has received anthracycline-based PC. The second cohort (n=788) has been treated with initial surgery and has been randomized to receive either an adjuvant anthracycline-based CT or no CT. This trial demonstrated a disease-free survival benefit in th...

810 Background: The routine use of CA 15.3 for monitoring breast cancer is controversial. The aim of this study was to evaluate the prognosis of metastatic breast cancer patients included in a randomised trial according to the circumstances of diagnosis. Methods: Among a cohort of 926 patients included in a randomised trial comparing ovarian function suppression versus not after surgery and chemotherapy, 217 patients who have presented a distant recurrence and who were treated at the Institut Gustave Roussy comprised the study population. Survival was evaluated according to the circumstances of diagnosis (group 1: elevation of CA 15.3 (n=55, including 25 patients without initial clinical or radiological evidence of metastasis), group 2: symptoms (n=95), group 3: clinical examination (n=34), group 4: radiological test (n=33)). Results: The 4 groups did not differ in terms of clinico-pathological characteristics, treatments received and metastasis sites. Median interval between initial treatment and metasta...

The interocular transfer of the extinction of visual pattern discriminations was studied in cats with either section of optic chiasm (split-chiasm cats) or combined sections of chiasm and forebrain commissures (split-brain cats). Visual pattern discriminations were monocularly learned and their interocular transfer was assessed through the opposite eye. Then, learning was unilaterally extinguished and interocular transfer of extinction was tested on the other side. In split-chiasm cats, the total number of trials to extinction criterion (EC) was significantly lower with the second eye than with the first eye, indicating a successful interocular transfer. In split-brain cats, EC with the second eye was attained faster than with the first in some performances; it was similar with both eyes in other tasks, and with the second eye was higher than with the first in still other tasks. Statistical analysis applied to this group of split-brain cats pointed out that extinction performances with the two eyes were not significantly different. These findings suggest that interocular transfer of extinction was abolished in split-brain cats and that memory for extinction was unilaterally established in the absence of forebrain commissures.

A review of 20 patients with malignant thymic tumors is presented. A simplified classification is used avoiding the term thymoma, which is considered misleading. Most of the patients were treated by a combination of surgery and radiation therapy while 7 were treated by irradiation alone. Postoperative radiation therapy is indicated when the tumor is incompletely removed. This is also advised in invasive tumors even when they are considered completely resected. Irradiation alone of inoperable tumors should be carried out with high doses (55 to 60 Gy) to decrease the risk of local recurrence.

1. Urinary kallikrein excreted by normal rats is significantly increased (P < 0·001) 2 h after: (a) water loading, (b) water loading plus frusemide, 0·27 mmol (10 mg) per rat, (c) salt loading. In water-loaded rats, 5 i.u. of renin strikingly reduced kallikrein excretion (P < 0·01) but considerably increased sodium excretion (P < 0·001). 2. Renal kallikrein, measured by its kininogenase activity within 2 h of water loading, was significantly increased (P < 0·05); after water loading and frusemide it was 40% decreased (P < 0·001) and after salt loading it was reduced by approximately 50% (P < 0·02). Renin did not change renal kallikrein. 3. Severely hypertensive (one-kidney) rats (blood pressure >150 mmHg) showed no increase of urinary kallikrein after water loading, although there was a marked natriuresis; in moderately hypertensive rats (blood pressure

1. In normally hydrated rats prostaglandin F2α (PGF2α) in doses of 5 μg/100 g body weight given subcutaneously every 2 h (three times) induced a significant increase in urinary kallikrein activity, and in sodium, potassium and water excretion for 8 h after the first injection. In moderately hyperhydrated rats loaded 2·5% of body wt. with 0·5% NaCl solution, PGF2α produced similar changes in kallikrein activity and electrolyte excretion. 2. In normally hydrated rats prostaglandin E2 (PGE2) in the same conditions and doses as in 1 had no effect on kallikrein activity, showing a tendency to decrease potassium and water excretion. 3. PGE2 in doses of 5, 12·5 and 25 μg/100 g body wt. in overhydrated rats given 2·5% and 0·5% NaCl and 5% of tap water/100 g body wt. 1 h later, significantly increased kallikrein activity in the urine collected for 120 min after the injections. A significant decrease in potassium and water excretion was observed with the highest dose. 4. PGF2α, had no effect on kallikrein activity in overhydrated rats, but an increase in sodium and a decrease in potassium excretion was seen at the highest dose. 5. The different actions of PGE2 and PGF2α may be part of a regulatory mechanism associated with the kallikrein—kinin system which contributes maintainance of extracellular fluid homeostasis.

While the effect of chemotherapy dose on tumor response in small cell lung cancer has been fairly well established, the effect on survival has been retrospectively analyzed only in some series. This particular point was studied in a series of 52 consecutive patients with limited small cell lung cancer treated by an alternating radiotherapy-chemotherapy schedule. The induction treatment consisted of 6 chemotherapy cycles (the planned doses were: doxorubicin 40 mg/m2 day 1, VP16213 75 mg/m2 days 1-3, cyclophosphamide 300 mg/m2 days 3-6, and cisplatinum 100 mg/m2 day 2) alternated after the first 2 cycles with 3 courses of thoracic radiotherapy delivering a total dose of 55 Gy. Eighty-one percent of patients went into complete remission and the 3-year relapse-free survival was 24%. A multivariate analysis of prognostic factors took into account age, sex, T stage, performance status, delayed hematological toxicity to the first course of chemotherapy, actual dose/m2 of each drug during the first course and mean dose/course delivered during the induction treatment after the first cycle of chemotherapy. It was possible to identify 3 independent factors influencing overall survival and relapse-free survival: actual initial dose of cisplatinum, actual initial dose of cyclophosphamide and the T stage. The effect of the initial dose of cisplatinum and cyclophosphamide proved to be linear on relapse-free survival. The results of this analysis show a possible effect of initial doses of chemotherapy in the management of limited small cell lung cancer in terms of both distant metastasis and overall survival rates.

Small cell carcinoma do not have specific features, because bronchi can present either with a tumoral obstruction (42%) or with an infiltration (41%) or a compression (14%) or normal (3%) pattern. The improvement of the endoscopic technology, the more frequent changes in biopsy forceps, the increasing ways in performing these biopsies are expected to decrease the number of false negative results. But, if were the case, more sophisticated diagnosis tests under fluoroscopy are needed. The transthoracic needle aspiration-biopsy because of its better sensitivity and less fatal complications seems to be preferred to the transbronchial biopsy. Using such approach it can be expected that small cell carcinoma, which chimio sensitivity is known, will be diagnosed accurately.