ALBERT

Description: Abstract 880 On behalf of the German Low-Grade Lymphoma Study Group (GLSG) and the European MCL Network Background: In younger patients with mantle cell lymphoma (MCL), autologous stem cell transplantation (ASCT) significantly prolonged response duration with a trend towards improved overall survival in a randomized trial of the European MCL Network (Dreyling et al., ASH 2008). A recently updated clinical trial of the German Low-Grade Lymphoma Study Group (GLSG) also reported a significantly prolonged response duration by the addition of Rituximab to first-line CHOP (Hoster et al., ASH 2008). By pooled analysis of these trials we investigated whether Rituximab and ASCT independently prolong response duration. Methods: The analysis included all advanced stage MCL patients of the trials “CHOP vs. MCP” (Nickenig et al., Cancer 2006), “CHOP vs. R-CHOP” (Lenz et al., JCO 2005) and European MCL trial 1 (Dreyling et al., Blood 2005) with complete or partial remission to either CHOP or R-CHOP first-line induction and randomization between ASCT and Interferon-α maintenance. Response duration was defined as time from the end of successful induction chemotherapy to relapse or death from any cause, overall survival from the end of successful induction chemotherapy to death from any cause. Stratified Kaplan-Meier curves for response duration and overall survival were calculated for the four treatment groups (CHOP without ASCT, CHOP with ASCT, R-CHOP without ASCT and R-CHOP with ASCT). By multiple Cox regression we tested whether the impact of Rituximab (R) and ASCT was independent and additive. Results: One-hundred and eighty patients with MCL were evaluable, 80 treated with R-CHOP, 78 with ASCT (CHOP without ASCT: 56, CHOP with ASCT: 46, R-CHOP without ASCT: 44 and R-CHOP with ASCT: 34). Median age was 55 years (range 34-65), the MIPI classified 71% as low risk, 22% as intermediate risk, and 6% as high risk, and baseline characteristics were comparable between treatment groups. With a median follow-up of 63 months, median response duration was 16 months after CHOP without ASCT, 26 months after R-CHOP without ASCT, 39 months after CHOP with ASCT, and 41 months after R-CHOP with ASCT. In multiple Cox regression including R and ASCT, the hazard ratios of R (0.60, 95% CI 0.42-0.86, p = 0.0056) and ASCT (0.50, 95% CI 0.35-0.70, p = 0.0001) were independently significant. There was no interaction between R and ASCT (p=0.43). Median overall survival was 54 months after CHOP without ASCT, 66 months after R-CHOP without ASCT, 90 months after CHOP with ASCT, and not reached after R-CHOP with ASCT. The hazard ratios for OS were 0.70 (95% CI 0.44-1.12, p = 0.14) for R and 0.63 (95% CI 0.41-0.97, p = 0.0379) for ASCT. Conclusions: Our results indicate an additive effect of ASCT and Rituximab in combination with CHOP on response duration in advanced stage MCL patients and support strategies of several study groups to combine Rituximab-containing induction therapies with ASCT in younger MCL patients. However, even after combined treatment approaches, delayed relapses have been observed, supporting the use of maintenance therapy and the introduction of molecular targeted therapeutical strategies. Disclosures: Hoster: Roche: Travel Support. Off Label Use: Rituximab in Mantle Cell Lymphoma. Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees. Dührsen:Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Gisselbrecht:Roche: Research Funding, Speakers Bureau. Unterhalt:Roche: Travel Support. Dreyling:Roche: Honoraria, Research Funding.

Description: We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoptosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c-Flip) and numbers of active caspase 3-positive lymphoma cells were used to determine the status of the caspase 8-mediated pathway. Expression levels of Bcl-2 and X-linked inhibitor of apoptosis (XIAP) were used to determine the status of the caspase 9-mediated pathway. Expression of c-Flip, XIAP, Bcl-2, and caspase 3 activity all provided prognostic information. According to these immunohistochemical parameters, inhibition of either or both caspase signaling pathways was detected in all patients. Three groups of patients were identified, one with a caspase 8 inhibition profile, one with caspase 8 and 9 inhibition profiles, and one with a caspase 9 inhibition profile. Caspase 9 inhibition was strongly associated with poor response to chemotherapy and usually with fatal outcome, whereas caspase 8 inhibition was associated with excellent clinical outcome. Thus, our data strongly suggest that inhibition of the caspase 9-mediated pathway, but not the caspase 8-mediated pathway, is a major cause for therapy resistance in patients with nodal DLBCL.

Description: There is no generally established prognostic index for patients with mantle cell lymphoma (MCL), because the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) have been developed for diffuse large cell and follicular lymphoma patients, respectively. Using data of 455 advanced stage MCL patients treated within 3 clinical trials, we examined the prognostic relevance of IPI and FLIPI and derived a new prognostic index (MCL international prognostic index, MIPI) of overall survival (OS). Statistical methods included Kaplan-Meier estimates and the log-rank test for evaluating IPI and FLIPI and multiple Cox regression for developing the MIPI. IPI and FLIPI showed poor separation of survival curves. According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the 4 independent prognostic factors: age, performance status, lactate dehydrogenase (LDH), and leukocyte count. Cell proliferation (Ki-67) was exploratively analyzed as an important biologic marker and showed strong additional prognostic relevance. The MIPI is the first prognostic index particularly suited for MCL patients and may serve as an important tool to facilitate risk-adapted treatment decisions in patients with advanced stage MCL.

Description: Abstract 25 Introduction: Accumulating evidence shows that venous and arterial thrombosis may be viewed as two diseases with similar pathophysiological entities. Both high factor VIII and low free protein S levels are risk factors for venous thrombosis, but if, and in what way, these thrombophilic factors also increase the risk of arterial thrombosis is unknown. Patients and Methods: In a single-center retrospective cohort study of families with thrombophilia, we performed a post-hoc analysis to identify if relatives with high factor VIII or low free protein S levels were at risk of arterial thrombosis. Clinical data were collected before laboratory testing. To avoid bias, all probands were excluded from the analyses. In addition, relatives with protein S deficiency type I were excluded from analysis when analyzing effects of free protein S. Factor VIII:C levels were measured by one-stage clotting assays and were considered increased at levels above 150 IU/dL. Free protein S antigen levels were measured by enzyme-linked immunosorbent assay after precipitation of protein S complexed with C4b-binding protein with polyethylene glycol. Free protein S antigen levels were considered decreased at levels below the normal range (〈 65 IU/dL). Coronary and peripheral arterial disease had to be symptomatic and angiographically proven, whereas myocardial infarction was diagnosed according to clinical, enzymatic and electrocardiographic criteria. Known risk factors for arterial thrombosis were recorded and included: hypertension, hyperlipidemia, the presence of diabetes mellitus, smoking habits or obesity. Absolute risks of first arterial thrombosis in relatives with high factor VIII or low free protein S levels were calculated. Linear regression was used to determine the relation between factor VIII levels and free protein S levels, respectively, combined with traditional arterial thrombotic risk factors. Adjustments were made for age and sex. Cumulative distribution functions were constructed to visualize a possible relationship between factor VIII and free protein S levels, respectively, and BMI Results: Of 1468 relatives tested for thrombophilia, 1399 were analyzed on factor VIII and 1143 on free protein S. Forty-six percent were male. Mean age at enrollment was 45 years. Mean factor VIII level was 146 IU/dL and mean free protein S level 80 IU/dL. High factor VIII levels were observed in 39% of relatives and low free protein S levels in 23% of relatives. First arterial thrombotic events were documented in 86 relatives at a mean age of 57 years. Annual incidence of arterial thrombosis in relatives with high factor VIII levels was 0.29% (95%CI, 0.22-0.38) compared to 0.13% (95%CI, 0.09-0.19) in relatives with normal factor VIII levels. In relatives with low free protein S levels, this risk was 0.26% (95%CI, 0.16-0.40), compared to 0.14% (95%CI, 0.10-0.20) in relatives with normal free protein S levels. Relatives with hypertension, diabetes mellitus, and obesity had mean factor VIII levels (age and sex adjusted) that were 11 IU/dL, 18 IU/dL, and 21 IU/dL higher than relatives without these arterial thrombotic risk factors, which were statitically significant findings. In addition, a dose response relation could be demonstrated between increasing factor VIII and body mass index (Figure). None of these associations were shown for free protein S. Conclusions: Both high factor VIII and low free protein S levels were a risk factor for arterial thrombosis in thrombophilic families. High factor VIII levels were particularly observed in relatives with traditional arterial thrombotic risk factors, suggesting that increase of these levels were acquired. Free protein S levels were not influenced by these arterial thrombotic risk factors which assumes that low free protein S levels were genetically determined. Disclosures: No relevant conflicts of interest to declare.

Description: The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m2 or 1000 mg/m2 days 1-7) in conjunction with imatinib (200 mg, 400 mg, 600 mg, or 800 mg), according to predefined, successive dose levels. All dose levels proved feasible. Seven dose-limiting toxicities (DLTs) were observed in 302 cycles of chemotherapy, which were caused by streptococcal bacteremia in 5 cases. Intermediate-dose cytarabine (1000 mg/m2) prolonged time to neutrophil recovery and platelet recovery compared with a standard dose (200 mg/m2). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery compared with a standard dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3 or 4 were observed after intermediate-dose cytarabine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete cytogenetic response in 48% and a major molecular response in 30% of patients, which increased to 46% major molecular responses at 1 year, including 13% complete molecular responses. We conclude that combination therapy of escalating dosages of imatinib and cytarabine is feasible. This study was registered at www.kankerbestrijding.nl as no. CKTO-2001-03.

Description: Abstract 138 Background: The Mantle Cell Lymphoma (MCL) International Prognostic Index (MIPI) has been recently developed as first prognostic index especially designed for patients with advanced stage MCL (Hoster et al., Blood 2008). The MIPI is based on four easily available prognostic factors (age, ECOG performance status, leukocyte count, and LDH). It was internally validated using a bootstrap strategy, and several authors reported its validity on larger patient cohorts (Salek et al., ASH 2008, Geisler et al., EHA 2009). We evaluated the prognostic relevance of the MIPI using the pooled data of two currently recruiting randomized trials (MCL Younger and MCL Elderly) of the European MCL Network (Dreyling et al., ASH 2007). Methods: Outcome parameters were primarily overall survival (OS) and secondarily time to treatment failure (TTF). Kaplan-Meier curves according to the MIPI prognostic groups were compared by means of the log rank test and univariate Cox regression. We checked the value of the MIPI prognostic factors within multiple Cox regression. We also evaluated the simplified MIPI and exploratively included patients with stage II into the analyses. Since randomization is ongoing, all analyses were blinded for treatment arms. Results: Currently, 606 patients with advanced stage MCL were evaluable, 317 in MCL Younger and 289 in MCL Elderly. Median age was 63 years (range 32 – 87), 6% had an ECOG performance status 〉 1, median LDH/ULN ratio was 0.95 (0.29 – 12.2), and median leukocyte count 7,600/μl (1,075/μl – 396,000/μl). The MIPI classified 220 patients (36%) into the low risk (LR), 187 (31%) into the intermediate risk (IR) and 199 (33%) into the high risk (HR) group. With a median follow-up of 19 months and 116 events, the probability for OS at 24 months was 91%, 77%, and 58% for LR, IR, and HR (medians not reached in LR, IR vs. 28 months in HR patients, p 〈 0.0001), corresponding to a hazard ratio of 2.7 for IR vs. LR (95% CI, 1.5 – 4.9, p = 0.001) and 2.6 for HR vs. IR (95% CI, 1.7 – 4.0, p 〈 0.0001). The four MIPI prognostic factors were independently prognostic for OS (p 〈 0.0001 each). In MCL Younger, the distribution to LR, IR, and HR groups was 61%, 23%, and 16%, as compared to 9%, 40%, and 51% in MCL Elderly, the difference reflecting the strong prognostic impact of age. According to preliminary subgroup analyses, 2-years OS rates were 92%, 76%, and 58% (p 〈 0.0001) in MCL Younger, and 85%, 78%, and 58% (p 〈 0.0001) in MCL Elderly. The MIPI also separated LR, IR, and HR group with respect to TTF, with medians of 49, 36, and 20 months (p 〈 0.0001) and a hazard ratio of 2.2 for IR vs. LR (95% CI, 1.4 – 3.4, p = 0.0004) and 2.0 for HR vs. IR (95% CI, 1.4 – 2.8, p = 0.0001). The simplified MIPI classified 36%, 32%, and 33% to LR, IR, and HR groups with high concordance to the MIPI (weighted kappa 0.82). Two-years OS rates were 90%, 79%, 58% for LR, IR, HR according to the simplified MIPI (p 〈 0.0001) with a hazard ratio of 2.4 for IR vs. LR (95% CI, 1.3 – 4.2, p = 0.003) and 2.5 for HR vs. IR (95% CI, 1.7 – 3.8, p 〈 0.0001). Inclusion of 32 patients with stage II MCL did not essentially change the results. Discussion: We could confirm the prognostic relevance of the MIPI in a large independent patient cohort treated within current randomized trials. Therefore, the MIPI may be used for risk stratification in future clinical trials, for the comparative interpretation of the results of different trials, for the evaluation of new biological prognostic factors, and may finally lead to risk-adapted treatment decisions in advanced stage MCL. Disclosures: Hoster: Roche: travel support. Trneny:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dreyling:Roche: Honoraria, Research Funding. Unterhalt:Roche: travel support.

Description: Abstract 2313 Poster Board II-290 BACKGROUND: The ability to receive an autologous stem cell transplant (ASCT) is the main factor determining outcome in patients with refractory or relapsed aggressive non-Hodgkin lymphoma (NHL). Final eligibility for ASCT is mainly dependent on response to salvage therapy. The secondary age-adjusted international prognostic index (saa-IPI) at relapse can predict for response to salvage therapy and outcome after transplantation. In allogeneic settings, comorbidity according to the stem cell transplant comorbidity index (HCT-CI) has shown to be an independent predictor for survival in hematologic malignancies. The aim of the current analysis is to assess the additional prognostic value of comorbidity at time of relapse (R-HCT-CI) for ASCT eligibility and outcome after autologous transplant. PATIENTS AND METHODS: We retrospectively analyzed 156 consecutive patients with refractory or relapsed NHL, referred to our center for salvage chemo-immunotherapy between 1999 and 2007. Patients responding to salvage treatment and able to receive further treatment were considered eligible for subsequent high-dose chemotherapy and ASCT. Comorbidity according to the hematopoietic stem cell transplant comorbidity index (Sorror et al; Blood 2005) was scored twice: i at relapse (R-HCT-CI), before start of salvage re-induction and ii. at start of high-dose chemotherapy (BEAM) before ASCT (HCT-CI). Primary endpoints were receipt of actual transplantation and overall survival (OS). RESULTS: R-HCT-CI scores of 0, 1-2 and ≥3 were found among 64 (41%), 62 (40%) and 30 (19%) patients, respectively at relapse. Comorbidity at transplantation (HCT-CI) did not substantially differ from scores at time of relapse. 108/156 patients achieved at least PR after salvage chemo-immunotherapy. All responsive patients were considered eligible to receive ASCT. Of these responsive patients, 13 did not receive ASCT mainly because of progressive lymphoma just before starting BEAM. Ultimately 95 patients received ASCT. Higher R-HCT-CI scores were associated with significant less chance on receiving ASCT with odds ratios of 2.9 and 4.3 for R-HCT-CI scores of 1-2 and ≥3 respectively (p〈 .01). However, in multivariate analysis together with saa-IPI scores, comorbidity did not retain significance (p= .08). Comorbidity at relapse could predict for overall survival independent from saa-IPI scores: hazard ratios of 2.5 and 1.7 for R-HCT-CI scores of 1-2 and ≥3 respectively (p= .02). Overall survival rates at 5 years for transplanted patients were 62%, 30% and 17% for R-HCT-CI scores of 0, 1-2 and ≥3 respectively (Figure). CONCLUSION: In patients with relapsed aggressive NHL, comorbidity at relapse can predict for ASCT eligibility and, after transplantation, for subsequent survival independently from saa-IPI. Both indices can therefore contribute to a more accurate selection of patients who may benefit most from intensive salvage treatment and subsequent ASCT. Overall survival according to Comorbidity score at relapse for patients receiving ASCT. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2469 Poster Board II-446 Background: Use of clinical decision rules have been validated in secondary care setting to safely rule out deep vein thrombosis (DVT) without using compression ultra sound (CUS). Clinical decision rules are now also used in primary care in the Netherlands (Thromb Haemost. 2005;94:200-205, Ann Intern Med. 2009;150:229-35). Because of this referral filter, pre-test probability of diagnosing a DVT in a hospital setting could be enlarged. On the other hand, the negative outcome of a clinical decision rule may still lead to referral as primary care physicians may have an a-priori opinion on the risk for DVT in certain patients, despite a low probability of having the disease given by a clinical decision rule (i.e. Bayes theorem). Whether the excellent negative predictive values (NPV's) of these decision rules are therefore still valid in a hospital setting is doubtful. The aim of this prospective single-center university-hospital based study was to confirm whether pre-test probability of diagnosing DVT in our hospital setting was increased due to the referral pattern of primary physicians, compared to historical data (16-27%; Thromb Haemost. 2004;91:1237-46, N Engl J Med. 2003;349:1227-35). We also evaluated the NPV's of the simplified (J Intern Med. 1998;243:15-23) and revised (N Engl J Med. 2003;349:1227-35) Wells score, with and without D-dimer level. Finally, we analyzed whether CRP levels influenced predictive values of these 2 clinical decision rules. Methods: Between April 2008 and July 2009, consecutive patients suspected of DVT by their primary physician who were referred to our emergency department were included. Clinical data were collected prior to laboratory testing to avoid bias of adjudication of clinical outcome events. CUS was used in all patients to establish or rule out a diagnosis on the same day. Calf vein thrombosis or thrombophlebitis was not considered as DVT. D-dimer levels were measured at presentation with a Tina-Quant assay. Levels 〉 500 ng/ml were considered positive. CRP levels 〉 5 mg/L were considered high. For both decision rules, patients with a score of 〈 2 were considered unlikely and those with a score of ≥ 2 were considered likely to have a DVT. Predictive values were calculated for each score, with and without D-dimer or CRP results, respectively. Results: Of 227 patients, 50% were women and 115 (51%) had DVT; 55% of the thromboses were provoked. The median age at presentation was 54 years. The median duration of symptoms before presentation was 5 days. For the simplified Wells score, the NPV was 87%. Adding a negative D-dimer to the calculation increased the NPV to 96%. In patients considered likely to have a DVT, the positive predictive value (PPV) was 63%, which increased to 71% when a positive D-dimer level was included. Using the revised Wells score (which includes the item of previous DVT), the NPV was 86%, which increased to 95% with a negative D-dimer level. In patients considered likely to have a DVT, the PPV was 58% when not considering D-dimer level and 68% with a positive D-dimer level. Of note, the NPV of a negative D-dimer test alone, without considering the Wells score, was 94%. Addition of CRP level did not result in a better PPV or NPV of the simplified or revised Wells score. Interpretation: According to recent literature, we are the first in 5 years to re-validate the simplified and revised Wells score with a D-dimer test in an emergency department population. We found an absolute 24 to 35% increase in prevalence of DVT in this setting compared to historical data. The increased prevalence in our cohort could be due to the use of clinical decision rules in primary care setting, better awareness of primary care physicians for this serious and common disease, or by being a tertiary care center. Referral bias may, however, not be of great influence as a previous study of ours has shown that 50% of patients referred by their primary physician with clinically suspected venous thrombosis were sent to our hospital and the other 50% to the only other hospital in our region (Ann Intern Med. 2006;145:807-15). Decision making in primary care probably reduced the number of referrals to our hospital substantially. However, the NPV of a low Wells score and a negative D-dimer test, or a negative D-dimer test alone were 95% and 94% respectively. Although these preliminary results should be handled with caution due to small numbers, these NPVs may be too low to safely rule out deep vein thrombosis without CUS. Disclosures: No relevant conflicts of interest to declare.

Description: Chemotherapy with alemtuzumab and the combination of cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP) has become experimental trial therapy for aggressive T-cell lymphoma. Several multicenter phase 3 trials will incorporate this scheme. As part of an ongoing phase 2 trial in which we recently treated 20 patients with 8 cycles of CHOP every 2 weeks with 3 additional doses of 30 mg alemtuzumab per cycle, we observed the development of Epstein-Barr virus (EBV)-positive lymphoproliferative disease, after completion of the immunochemotherapy in 3 patients with peripheral T-cell lymphoma. Because the occurrence of EBV-positive lymphoproliferative disease is rare after alemtuzumab monotherapy, such as is given for chronic lymphocytic leukemia, we think that early reporting of this potential side effect is warranted. It may be caused by intrinsic T-cell defects in patients with T-cell lymphoma, or by the combination of alemtuzumab with CHOP chemotherapy.

Description: Posttransplant lymphoproliferative disease (PTLD) is a serious complication that may arise after solid organ transplantation. PTLD may involve nodal as well as extranodal sites, with frequent involvement of the allograft and digestive tract. Extranodal localizations of PTLD may not always be visualized with routine conventional diagnostic methods such as computer tomography (CT) or magnetic resonance imaging (MRI). Our aim was to evaluate the value of 2-[18F] fluoro-2-deoxy-D-glucose (FDG)-PET in the staging and treatment evaluation of histologically confirmed PTLD (patient #3 confirmed by ascites cytology) in 10 kidney transplant recipients transplanted between January 2000 and June 2004. At time of PTLD diagnosis patients were fully staged by standard conventional diagnostic methods according to lymphoma protocols, including at least whole body CT scanning and bone marrow biopsy. In addition, whole body-mode PET studies were performed. All patients had their scans prior to therapy. In addition, four had repeated PET-scans during and after therapy. To compare CT with FDG-PET, all scans were re-evaluated (blinded) by a radiologist and an expert in nuclear medicine, respectively. All PET-scans at initial diagnosis could readily be interpreted and showed high FDG uptake in the primary sites of histological confirmed PTLD. This was true for monomorphic as well as polymorphic PTLD. The large majority of other sites of involvement as detected by conventional diagnostic methods at diagnosis were also PET positive. However, additional extranodal sites were detected by FDG-PET not readily visualized by CT scanning (table 1). After treatment with Rituximab, a decline or disappearance of FDG-uptake coincided with clinical response as detected by conventional diagnostic methods. These findings suggest that FDG-PET is suitable in visualization of (different histological subtypes of) PTLD and useful for both staging and response to treatment evaluation. The ability of FDG-PET to visualize extranodal localizations of PTLD, often present but not readily detectable by routine conventional diagnostic methods, is of additional value. Sites of PTLD involvement at diagnosis: CT and PET compared Patient Site of Biopsy Ann Arbor Stage Diagnosis* PET CT *Disconcordant lesions are bolded, **confirmed by MRI 1 liver IV jugular, supraclavicular, axillar, mediastinum, lung hili, liver , spleen, para-aortal, paracaval, bone marrow spleen, para-aortal, para-caval 2 ascites IV no abnormal foci No abnormalities 3 colon IV multiple foci abdomen ventral No abnormalities 4 cerebrum IE cerebrum cerebrum** 5 pancreas IE pancreas pancreas 6 lymph node jugular IV lymph node jugular , small pelvic, rectum, surrounding allograft small pelvic, right groin 7 lymph node axillar IV jugular, axillar, liver, rectum, bone marrow jugular, axillar, mediastinum, para-caval , 8 stomach IV supraclavicular, infraclavicular, mediastinum, multiple foci retroperitoneal, stomach, multiple foci abdomen supraclavicular, infraclavicular, mediastinum, para-caval, para-aortal, stomach, central abdomen 9 cerebrum IE cerebrum cerebrum** 10 skin left leg IE skin left leg no other sites involved