Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.

Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial.

Background: The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pretreated patients. Preclinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multicenter study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in postmenopausal women with moderately pretreated, estrogen receptor-positive, HER2 negative advanced breast cancer. Patients and methods: Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1 : 1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary end point was clinical benefit rate (CBR); secondary end points included progression-free survival (PFS). Results: Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% [95% confidence interval (CI): 41.5-63.7] for combination therapy, and 60% (95% CI: 47.8-72.9) for monotherapy. Median PFS was 10.8 months (95% CI: 5.6-12.7) for combination therapy, and 6.5 months (95% CI: 5.4-8.5) for monotherapy [hazard ratio (HR) 0.69; 95% CI: 0.4-1.1, exploratory P-value = 0.12]. Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI: 0.3-0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months. Conclusion: Palbociclib has clinical activity as a single agent in women with moderately pretreated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET. Clinical trial information: NCT02549430.

Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

BACKGROUND: Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. DESIGN AND METHODS: We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. RESULTS: Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women <40 years at diagnosis (HR = 1.13, 95% CI 0.69-1.84) who are less likely to develop chemotherapy-induced amenorrhea. CONCLUSION: Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected. CLINICALTRIALS.GOV: NCT00066690 and NCT00066703.

Breast cancer electron intraoperative radiotherapy: assessment of preoperative selection factors from a retrospective analysis of 758 patients and review of literature.

PURPOSE: To report our experience with full-dose 21 Gy IORT in early breast cancer patients after breast-conserving surgery to define most important selection factors. METHODS: Seven hundred and fifty eight patients, subjected to conserving surgery and IORT, were retrospectively analyzed evaluating most important clinical outcomes. RESULTS: Median follow up was 5.2 years. Results from Cox analyses defined 2 groups of patients, "suitable" (age > 50 years, non lobular histology, tumour size ≤ 2 cm, pN0 or pNmic, ki67 ≤ 20%, non triple negative receptor status and G1-G2) and "unsuitable" for IORT, with a higher rate of breast related events moving from "suitable" to "unsuitable" group. The 5 year rate of IBR is 1.8% in suitable group with significant differences versus unsuitable (1.8 vs. 11.6%, p < 0.005). Same differences between two groups were evidenced in true local relapse (0.6 vs. 6.9%, p < 0.005) and in new ipsilateral BC (1.1 vs. 4.7%, p < 0.015). CONCLUSIONS: In our current practice we consider the following preoperative factors to select patients suitable for IORT: age > 50 years, absence of lobular histology, tumor size ≤ 2 cm, pN0 or pNmic, according to APBI consensus statement, including also ki67 ≤ 20%, non triple negative receptor status and G1-G2.

Breast-conservative surgery with and without radiotherapy in patients aged 55-75 years with early-stage breast cancer: a prospective, randomized, multicenter trial analysis after 108 months of median follow-up.

OBJECTIVES: Breast-conserving therapy (BCT), including postoperative whole breast irradiation (WBI), is generally accepted as the treatment of choice for most patients with early-stage breast cancer. The question whether WBI is mandatory in all patients remains one of the most controversial issues in BCT. To answer this question, a randomized, prospective, multicentre study was launched in January 2001. Primary endpoints of the study were to assess the cumulative incidence of in-breast-recurrences (IBR) and overall survival (OAS) after conservative surgery (BCS) with or without WBI. METHODS: From January 2001 until December 2005, 749 patients with unifocal infiltrating breast cancer up to 25 mm, 0-3 positive axillary lymph nodes, no extensive intraductal component or lymphvascular invasion from 11 centres in Italy, were randomly assigned to BCS+WBI (arm 1:373 patients) or BCS alone (arm 2:376 patients). Treatment arms were well balanced in terms of baseline characteristics. Systemic adjuvant therapy was administered according to the institutional policies. Kaplan-Meier method was used for survival analysis and log-rank test to evaluate the difference between the two arms. RESULTS (Last analysis 31.12.2012): After median follow-up of 108 months, 12 (3.4%) IBR were observed in arm 1 and 16 (4.4%) in arm 2. OAS was 81.4% in arm 1 and 83.7% in arm 2. There was no statistically significant difference regarding IBR and death in the two treatment groups. CONCLUSIONS: These data are promising and suggest that WBI after BCS can be omitted in selected patients with early stage breast cancer without exposing them to an increased risk of local recurrence and death. Longer follow-up is needed to further consolidate these results.

Type and trends in outcomes research in breast cancer between 2000 and 2007.

BACKGROUND: Interest in outcomes research (OR) derives from the need to know the value and the effectiveness of health interventions, especially for oncology. We focused our research on OR in breast cancer, providing an overview of the trend of publications. PATIENTS AND METHODS: We carried out a Medline search to retrieve all articles in English published from 2000 through 2007. The abstracts were reviewed and classified according to the research topics and the primary design of the trial. RESULTS: We selected 405 articles: their number remained constant until 2003, rose during 2004-2005 and decreased during the last 2 years. The most common topic was surgery (n = 234), alone or in association with other interventions. The category more investigated was the process. Clinical outcomes, and among them disease-free survival, were more frequent than other outcomes. The median value of 2007 Impact Factor of the journals publishing the selected references was 2.466 (range 0.272-25.547) and the median value of Citation Index was 8 (range 0-143). CONCLUSIONS: Our research showed a decreasing interest in OR during the more recent years. We are hopeful that it will regenerate interest, particularly by the light of the funds allocated to the comparative effectiveness research in the United States.

Acquired and inherited risk factors for developing venous thromboembolism in cancer patients receiving adjuvant chemotherapy: a prospective trial.

BACKGROUND: Acquired and inherited risk factors for venous thromboembolism (VTE) and the incidence of symptomatic VTE were investigated in patients on adjuvant chemotherapy for breast or gastrointestinal cancer (GI). PATIENTS AND METHODS: In a prospective observational study (January 2003 and February 2006), 199 GI (82 women/117 men; age range, 26-84 years) and 182 breast (180 women/2 men; age range, 29-85 years) cancer patients were enrolled and followed-up for symptomatic VTE during adjuvant chemotherapy. The effect of acquired (i.e. age, chemotherapy, tumour histotype, history of thrombosis, body mass index and smoking) and inherited risk factors [i.e. antithrombin, protein C (PC), protein S, homocysteine, activated PC resistance, factor V Leiden (FVL) and prothrombin (PT) mutations) was prospectively evaluated. RESULTS: Overall, 30 VTE events (7.87%) were recorded: 28 (7.35%) during treatment and 2 (0.52%) during the subsequent follow-up. Among all the 381 cancer patients, FVL was detected in 14 cases (3.67%) and PT mutation in 10 cases (2.62%). Multivariate analysis showed a significant association between the development of VTE and both thrombocytosis [hazard ratio (HR) 1.65; 95% confidence interval (CI), 1.04-2.637, P <0.0341] and a prior episode of thrombosis (HR 7.6; 95% CI, 1.77-33.1, P <0.006). FVL and PT mutations were not associated with the risk for VTE. CONCLUSION: The present data indicate thrombocytosis and history of thrombosis as risk factors for development of a thrombotic event during adjuvant chemotherapy in patients with malignant diseases.

Ontology-Driven Real World Evidence Extraction from Clinical Narratives.

Unstructured clinical notes contain a huge amount of information. We investigated the possibility of harvesting such information through an NLP-based approach. A manually curated ontology is the only resource required to handle all the steps of the process leading from clinical narrative to a structured data warehouse (i2b2). We have tested our approach at the Papa Giovanni XXIII hospital in Bergamo (Italy) on pathology reports collected since 2008.

Axillary recurrence in sentinel lymph node-negative breast cancer patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) was developed to axillary lymph node dissection (ALND) in the treatment of breast cancer. SLNB is predictive of axillary node status. Major concern is the occurrence of a false-negative SLN. Purpose of this study is to determine the rate of axillary recurrence in our series of unselected patients. PATIENTS AND METHODS: All patients with a negative SLNB from November 1999 to December 2006 have been treated and followed at our unit. Information on patients' characteristics, treatment and follow-up has been collected. RESULTS: Eight-hundred and four patients with negative SLNB did not receive ALND. After a median follow-up of 38.8 months, 21 patients had distant metastases, four had axillary relapse, nine had an in-breast recurrence and two had both. All patients with axillary recurrence received axillary dissection and systemic adjuvant therapy. They are all presently alive and free from disease. CONCLUSION: Data from this series, the largest from a general hospital, showed that isolated axillary node recurrence after negative SLNB is rare (<1%) and comparable with those reported from referral cancer institutions. We confirm that SLNB for the treatment of early breast cancer patients of a community-based hospital is safe and reliable.

Comparison of CA15-3 and carcinoembryonic antigen in monitoring the clinical course of patients with metastatic breast cancer.

Fifty-three women with metastatic breast cancer and serial plasma samples were selected to study the correlation between disease course and variations in circulating CA15-3 and carcinoembryonic antigen (CEA) levels. Forty-nine patients had their first sample drawn at the beginning of therapy, while four patients did not receive any treatment during the period of study. Clinical course was scored as progressive disease (PD), responsive disease (RD), and stable disease on the basis of radiological and physical evaluations. The percentage of variation in antigen level between the initial sample and samples drawn at the time of the clinical evaluation was correlated with clinical course. CA15-3 levels above 22.0 units/ml and CEA levels above 3.0 ng/ml were considered elevated values. Antigen levels that increased greater than or equal to 25% and decreased greater than or equal to 25% from the initial value were considered to correlate with PD and RD, respectively. Variations in antigen levels +/- 25% from the initial value were considered to correlate with stable disease. Significantly more patients had elevated circulating levels of CA15-3 than CEA (96.2 versus 69.8%; P less than 0.01) at some point in the course of disease. Overall, CA15-3 correlated with disease progression, regression, or stability in a higher number of patients than CEA (60.3 versus 39.6%; P = 0.02). CA15-3 increased greater than or equal to 25% more often than CEA in patients with PD (75.0 versus 58.3%) and decreased greater than or equal to 25% more often than CEA in patients with RD (38.1 versus 23.8%). In a logistic regression model, changes in CA15-3 levels correlated significantly with both PD (P = 0.0004) and RD (P = 0.02), while changes in CEA levels did not (PD, P = 0.34; RD, P = 0.92). Furthermore, correlations obtained when using both antigens together failed to improve the results obtained with CA15-3 alone. The present study thus demonstrates that CA15-3 is more useful than CEA in monitoring the clinical course of patients with metastatic breast cancer.

Evaluation of monoclonal antibody DF3 conjugated with ricin as a specific immunotoxin for in vitro purging of human bone marrow.

DF3 is an IgG1 monoclonal antibody (MAb) generated against a Mr 350,000-400,000 glycoprotein expressed by approximately 80% of human breast cancers. We have coupled MAb DF3 to ricin. Purification of the immunotoxin (DF3-IT) was obtained by affinity and size exclusion chromatography. DF3 antigen-positive breast cancer cell lines (ZR-75-1, BT-20, and MCF-7) and DF3 antigen-negative lung cancer cell lines (A549 and CALU6) were tested for cytotoxicity with metabolic labeling and clonogenic assays. The cells were exposed for 3 h to different concentrations of DF3-IT, MAb DF3, ricin, and a combination of unconjugated MAb DF3 and ricin. In the presence of 100 mM lactose, DF3-IT specifically inhibited protein synthesis of lines expressing DF3 antigen on their cell surface. Moreover, clonogenic survival experiments demonstrated that DF3-IT at a concentration of 1 x 10(-9) M specifically kills 2.6-2.8 log of ZR-75-1 and BT-20 cells and 1.6 log of MCF-7 cells. At the same concentration, nonspecific toxicity of DF3-IT resulted in a 30% reduction of bone marrow granulocyte and macrophage colony formation. In bone marrow-purging experiments, tumor cells were mixed with an excess of bone marrow cells and treated with DF3-IT or ricin. Tumor cell clonogenic survival assays demonstrated that the presence of bone marrow cells had no detectable effect on activity or specificity of the DF3-IT. These results thus indicate that MAb DF3 is an effective vehicle to specifically deliver toxins to cancer cells which express DF3 antigen on their surface and that DF3-IT may be useful for in vitro purging of bone marrow.

Diffuse large-cell lymphoma of the testis.

PURPOSE: To evaluate clinical outcome of patients with testicular diffuse large-cell lymphoma treated with conventional-dose systemic chemotherapy. PATIENTS AND METHODS: This study is a retrospective analysis of adult patients with testicular diffuse large-cell lymphoma who were treated with a doxorubicin-based chemotherapy regimen at our institution, the Istituto Nazionale Tumori of Milan. Twenty-nine assessable patients, with a median age of 61 years, were identified. Sixteen patients had limited stage (Ann Arbor stage I/II) disease, whereas 13 patients had a testicular mass and distant organ involvement (Ann Arbor stage IV). Patients were retrospectively classified according to the International Prognostic Index. RESULTS: After a median follow-up of 82 months, 22 patients presented disease progression and 22 patients had died. Actuarial median time to treatment failure and overall survival were 44 and 41 months for patients with limited stage and 9 and 16 months for patients with advanced stage, respectively. Eight patients failed initial treatment, and 14 patients relapsed from clinical remission after a median disease-free time of 17 months (range, 6 to 98 months). Median survival time after progression of lymphoma was 5 months (range, 0 to 22 months). In nine (41%) of the 22 failing patients, the initial site of relapse was either the CNS or the contralateral testis; the remaining patients experienced relapse in multiple extranodal sites. CONCLUSION: Poor prognosis of patients with diffuse large-cell lymphoma calls for more effective treatment strategies, such as high-dose chemotherapy programs for younger patients or specifically designed chemotherapy regimens for patients not suitable for high-dose treatment, with the purpose to provide control of both systemic disease and disease of the CNS and contralateral testis. The potential benefit of contralateral testicular irradiation has to be taken into account in the treatment planning.

Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas.

PURPOSE: A single-center, prospective, nonrandomized trial was conducted to evaluate therapeutic results of a short-term program of chemotherapy followed by locoregional radiotherapy in stage I or II intermediate/aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1985 to 1990, 183 consecutive patients with a diagnosis of NHL (Working Formulation [WF] E through J excluding Burkitt's type), Ann Arbor stage I or II, and no more than three sites of disease involvement were treated with four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (six cycles in partial responders). Radiation therapy to initial sites of disease involvement (40 to 44 Gy) and to proximal uninvolved nodal region (36 Gy) was delivered shortly after completion of the chemotherapy program. RESULTS: The complete remission (CR) rate was 98% at the end of combined therapy. Diagnostic excision of all measurable disease was performed in 33% of patients. In the remaining patients, 87% achieved CR with chemotherapy and 11% with radiation therapy, while three patients failed to achieve CR. After a median follow-up of 51 months, 26 patients have relapsed and 25 have died. The 5-year relapse-free and total survival rates were 83%. Aside from age older than 60 years, no other factor such as histology, stage, extranodal disease, bulky lymphoma, or abnormal lactic dehydrogenase (LDH) could predict for treatment outcome. There was a trend toward higher relapse rate for patients achieving CR at the time of radiation therapy (31%) as opposed to patients achieving CR with chemotherapy (15%) or with initial surgery (10%). Treatment was well tolerated and no deaths due to acute toxicity were observed. CONCLUSION: For patients who present with limited-stage, aggressive NHL, a short course of CHOP chemotherapy followed by locoregional irradiation is safe, highly effective, and curative for most. Therefore, at the present time this approach can be regarded as standard therapy for these patients.

Gallium-67 scintigraphy evaluation of therapy in non-Hodgkin's lymphoma.

UNLABELLED: Patients with diffuse large cell lymphoma may achieve complete remission (CR) after chemotherapy, and the time to reach CR may be predictive of treatment outcome. Partial remission, or recurrence from CR, is associated with poor survival. Gallium-67 imaging has proven to be useful in evaluating lymphoma patients. In tumor models, this radiotracer is an indicator of tumor viability. Gallium-67 uptake is seen only in avid and viable lymphoma tissue, not in fibrotic or necrotic tissue. In this study, we prospectively assessed the ability of this radiotracer to define residual disease. In addition, we evaluated the possibility of predicting the clinical outcome in patients with diffuse cell lymphoma on the basis of scan positivity during chemotherapy. METHODS: Thirty-three consecutive patients with histologically proven diffuse large cell lymphoma were investigated with 67Ga scintigraphy 48-72 hr after injection of 185-259 MBq 67Ga-citrate for staging and during follow-up after four to six cycles of intensive chemotherapy. Patients were monitored for a mean of 56.0 mo (range 7-90 mo), and they were restaged using physical examination, CT and all necessary imaging modalities. RESULTS: Patients were divided into two groups according to the positivity or negativity of 67Ga scan after four to six cycles of chemotherapy. Of the 33 patients studied, 14 (42.4%) showed persistent abnormal uptake of 67Ga-citrate after four to six cycles of chemotherapy. In this group, 9 patients (64.2%) died of lymphoma at a mean of 24.3 mo from presentation with the diagnosis (range 7-71 mo). Four patients had no evidence of disease at an average of 71.7 mo after diagnosis, and 1 patient was considered to be in partial remission. In the second group of 19 67Ga-negative patients, after four to six cycles of chemotherapy, 4 died and 15 are alive and considered to be in CR. A statistical analysis of the association between 67Ga scan results after four to six cycles of chemotherapy and survival was performed using the log-rank test; there was a statistically significant association between scan results and survival (p=0.00125). CONCLUSION: We conclude that 67Ga scintigraphy is an excellent predictor of residual tumor viability in lymphoma patients and that persistent positivity of the scan predicts poor outcome and may justify a change in treatment.

Circulating tumor markers in breast cancer.

A list of tumor markers evaluated in breast cancer patients is included as well as their relative value for a patient with metastatic breast cancer. Variations in the levels of circulating markers correlated well with disease course; however, the accuracy of these variations is not total.

Sentinel node biopsy in the surgical management of breast cancer: experience in a general hospital with a dedicated surgical team.

The aims of this study were to analyse the feasibility and accuracy of the sentinel lymph node biopsy (SLNB) procedure as performed in a general hospital compared with the literature results; to report on the organizational aspects of planning surgical time with higher accuracy of pathological analysis; and to verify that there is a real advantage of SLNB in the surgical management of breast cancer. From October 1999 to September 2000, 371 consecutive patients with T1-2N0 breast lesions underwent SLNB. The immunoscintigraphic method of sentinel node identification was the main one used, the blue dye method being used only when the lymphoscintigraphic method was unsuccessful in identifying sentinel nodes. SLNB was done under either general or local anaesthesia, depending on how the surgical procedure was organized and clinically planned. SLNB was successful in 99% of these T1-2N0 breast cancer cases, and in 71% no metastases were found in the sentinel node. In 47% of cases with axillary metastasis only the sentinel node was involved. Nodal involvement was not present in any case of microinvasive or in situ carcinoma. In T1 cancers nodal involvement was present in 21%; in T2 cases the corresponding rate reached 51%. The results obtained with the SLNB procedure at Bergamo Hospital are similar to the literature data. When a dedicated surgical team, the nuclear medicine department and the pathology department work together, a general hospital can provide breast cancer patients with appropriate surgical treatment.

Population-based sentinel lymph node biopsy in early invasive breast cancer.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has been proposed as a reliable method for staging of early invasive breast cancer (EIBC). In the present study we analyse the impact of this procedure when systematically applied to all unselected women of a community-based Breast Cancer Unit (BCU). METHODS: All consecutive women with unifocal cT1-2 (

Continuous cisplatin infusion in combination with vincristine and high-dose methotrexate for advanced osteogenic sarcoma.

Fifteen patients with metastatic osteogenic sarcoma (OS) were treated with a combination of Vincristine (1.4 mg/m2), high-dose Methotrexate (8 g/m2), and Cisplatin (120 mg/m2 as a 72-h continuous infusion). The overall response rate was 66% [5 complete response (CR) and 5 partial response (PR)]. Four of the six patients not previously treated had a CR. Toxicity from this regimen was moderate and never life-threatening. In no case was impairment of the renal function observed, and the clearance of high-dose Methotrexate was never delayed.

Supporting tools for guideline development and dissemination.

This paper describes a methodology for representing clinical practice guidelines and facilitating their introduction into the medical routine. Since this methodology can be exploited in a www environment, it can represent the basis for sharing clinical guidelines both between different institutions and between human and software agents cooperating within a clinical context. In addition, the proposed guideline formalization is intended to deal with patient and organization preferences. This goal is achieved by augmenting the guideline with decision analytic models and by linking the guideline with an organizational model of the clinical setting. The designed framework allows guideline development, tailoring and implementation, real-time access to the guideline prescriptions and guideline validation.

Clinical utility of radioimmunoscintigraphy of non-Hodgkin's lymphoma with radiolabelled LL2 monoclonal antibody, LymphoSCAN: preliminary results.

AIMS AND BACKGROUND: Adequate clinical staging of non-Hodgkin's lymphoma patients is essential because only localized disease can be treated satisfactorily. Many imaging procedures are necessary to stage the disease accurately. The objective of this study was to evaluate the efficacy of an antilymphoma antibody in the Fab' fragment form, labelled with 99mTc, to detect malignant lesions. METHODS: Radioimmunodetection (RAID) with 99mTc-labelled B-cell lymphoma monoclonal antibody IMMU-LL2-Fab' (LymphoSCAN; Immunomedics, Morris Plain, NJ, USA) was investigated in 10 patients (5 females and 5 males; age range, 20-72 years) with histologically proved non-Hodgkin's lymphoma. Of the 10 lymphomas, 7 were intermediate grade and 3 were low grade. Whole body images with multiple planar views were obtained at 30 min, 4-6 and 24 h after i.v. injection of 1 mg LL2-Fab' labelled with 740-925 MBq of 99mTc. SPET of the chest or abdomen was performed in all patients 5-8 h after the immunoreagent injection. RESULTS: No adverse reactions were observed in any patient after Mab infusion, and no appreciable changes were seen in the blood counts, renal or liver function tests. A total of 18 of 21 (85.7%) lymphoma lesions were detected by RAID. All the tumor localizations were confirmed by clinical examination and with other imaging techniques, such as CT scan, MRI or gallium scan. In this series of patients no false-positive results were noted. As regards the biodistribution of the immunoreagent, no appreciable bone marrow activity was seen; splenic targeting was demonstrated in all patients; the tumor-to-non-tumor ratios ranged from 1.2 to 2.8 ad measured by the ROI technique; no difference in uptake was noted for different tumor grades. The images obtained 24 h after injection did not reveal new lesions, but areas of doubtful uptake were seen as positive focal areas in the delayed scan. CONCLUSIONS: LymphoSCAN seems to be useful for detection, staging and follow-up of non-Hodgkin's lymphoma patients.