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Patients with asymptomatic follicular lymphoma (AFL) are candidates for observation or immunotherapy. Given the effectiveness of radiation therapy in FL, another option is 90Yttrium-ibritumomab tiuxetan radioimmunotherapy (RIT). We conducted a trial where untreated AFL patients were randomized to rituximab 375 mg/m2 weekly × 4 or rituximab 250 mg/m 2 days 1, 8, and 0.4 mCi/kg (maximum 32 mCi) of RIT day 8. Twenty patients were enrolled before the study was halted due to unavailability of RIT. The ORR for rituximab and RIT were 90% and 80%, respectively; the CR rate at 6 months was 30% and 60%, respectively. After a median follow-up of 67 months, eight patients have progressed-three in the rituximab arm and five in the RIT arm and five have required systemic therapy. All patients remain alive. Both agents are highly active for AFL. The 1-week treatment with RIT and sparing of T-cells make combination therapy with newer agents attractive.

Introduction: Yttrium-90 ibritumomab tiuxetan [(90)Y-IT] is a CD20-targeted radio-immuno conjugate. Clinical trials of (90)Y-IT as a first-line stand-alone treatment in follicular lymphoma (FL) and/or marginal zone lymphoma (MZL) showed high efficacy. However, long-term survival outcomes and toxicities are not well-defined., Methods: We report a retrospective single-institution, multi-center study of (90)Y-IT in previously untreated low grade (LG)-FL and MZL at Mayo Clinic Cancer Center between January 2000 and October 2019. We selected patients with LG-FL and MZL who received standard-dose (90)Y-IT as a single agent in the first line setting., Results: The cohort (n = 51) consists of previously untreated LG-FL (n = 41) or MZL (n = 10). Median follow-up was 5.3 years (95% CI; 4.2, 6.2). Overall response rate (ORR) was 100% with complete response rate (CR) of 94%. Continuous CR was observed in 59% patients who had more than 2 years of follow-up. Long-term CR (>7 years) was seen in 25% of patients. Median progression free survival (mPFS) for the whole cohort was not reached (NR) (95% CI; 4.9, NR). Bulky disease was associated with shorter median PFS of 3.5 years (CI 95%; 0.8, 4.9) compared to non-bulky disease NR (CI 95%; 5.8, NR), P = .02. The incidence of grade 3 or higher thrombocytopenia, neutropenia and anemia were 47%, 37%, and 4% respectively. No therapy-related myelodysplasia or acute myeloid leukemia were observed., Conclusion: Long real-life follow-up showed that single-agent (90)Y-IT is highly efficacious with durable long-term survival in previously untreated LG-FL and MZL without significant risk for secondary malignancies., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence (TR) rate after bilateral lobar resection (BLR)., Patients and Methods: There were 2952 low-risk adult papillary thyroid cancer (LRAPTC) patients (with MACIS scores <6) who underwent potentially curative BLR during 1955-2014. During 1955-1974, 1975-1994, and 1995-2014, RRA was administered in 3%, 49%, and 28%. Statistical analyses were performed using SAS software., Results: During 1955-1974, the 20-year CSM and TR rates after BLR alone were 1.0% and 6.8%; rates after BLR+RRA were 0% (P=.63) and 5.9% (P=.82). During 1975-1994, post-BLR 20-year rates for CSM and TR were 0.3% and 7.5%; after BLR+RRA, rates were higher at 0.9% (P=.31) and 12.8% (P=.01). When TR rates were examined separately for 448 node-negative and 317 node-positive patients, differences were nonsignificant. In 1995-2014, post-BLR 20-year CSM and TR rates were 0% and 9.2%; rates after BLR+RRA were higher at 1.4% (P=.19) and 21.0% (P<.001). In 890 pN0 cases, 15-year locoregional recurrence rates were 3.4% after BLR and 3.7% after BLR+RRA (P=.99). In 740 pN1 patients, 15-year locoregional recurrence rates were 10% higher after BLR+RRA compared with BLR alone (P=.01). However, this difference became nonsignificant when stratified by numbers of metastatic nodes., Conclusion: RRA administered to LRAPTC patients during 1955-2014 did not reduce either the CSM or TR rate. We would therefore not recommend RRA in LRAPTC patients undergoing BLR with curative intent., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: Yttrium-90 transarterial radioembolization (TARE) is a safe, effective modality of locoregional therapy for intermediate and advanced-stage hepatocellular carcinoma (HCC). We aim to identify novel predictors of important outcomes of TARE therapy., Methods: A single-center retrospective study of 166 patients treated with TARE for HCC at Mayo Clinic Rochester between 2005-2015 and followed until December 2017. Multivariate logistic and stepwise regression analysis models were used to identify variables associated with overall survival (OS) and progression-free survival (PFS)., Results: The median OS and the median PFS were12.9  (95% CI: 11.0-17.3), and 8 months (95% CI: 6-11), respectively. Macrovascular invasion (HR: 1.9 [1.3-2.8]), Child-Pugh score (CPS) B or C vs. A (HR: 1.8 [1.2-2.7]), Eastern Cooperative Oncology Group Performance status (ECOG-PS) 2 or 1 vs. 0 (HR: 1.6 [1.1-2.4]) and activity (A) of administered radiation dose (HR: 1.005[1.00-1.010), independently correlated with poorer OS. Infiltrative HCC (HR: 2.4 [1.3-4.5), macrovascular invasion (HR: 1.6 [1.1-2.7]), and high activity of administered radiation dose (HR: 1.005 [1.00-1.010) were associated with worse PFS., Conclusion: In HCC patients treated with TARE; macrovascular invasion, the activity of radiation dose, CPS, ECOG-PS, and infiltrative HCC predict OS and PFS.

Early in the course of immunotherapy there is frequently a transient enlargement of tumor masses (pseudo-progression) due to tumor infiltration by TILs. Current clinical imaging modalities are not able to distinguished pseudo-progression from true tumor progression. Thus, patients often remain on treatment 4-8 weeks longer to confirm disease progression. Nuclear medicine offers the possibility to image immune cells and potentially discriminate pseudo-progression and progression. We conducted a pilot study in patients with metastatic melanoma receiving ipilimumab (IPI) or pembrolizumab (PEMBRO) to assess safety and feasibility of SPECT/CT imaging with 99m Tc- interleukin-2 ( 99m Tc-HYNIC-IL2) to detect TILs and distinguish between true progression from pseudo- progression. Scans were performed prior to and after 12w treatment. After labelling, 99m Tc-HYNIC-IL2 was purified and diluted in 10 mL of 5% glucose with 0.1% human serum albumin. Of the 5 patients (2 treated with IPI and 3 with PEMBRO) enrolled, two failed to complete the second scan as they discontinued IPI due grade 3 colitis (1 patient) or patient refusal after developing multiple toxicities attributed to IPI (1 patient). Following the first scan, one patient reported to have a grade 1 pruritus with grade 1 pain. No other toxicities attributed to the radiopharmaceutical infusion were reported. Metastatic lesions could be visualized by 99m Tc-IL2 imaging and there was positive correlation between size and 99m Tc-HYNIC-IL2 uptake, both before and after 12 weeks of therapy. The results of this pilot study demonstrate the safety and feasibility of 99m Tc-IL2 imaging and has led to a number of hypotheses to be tested in future studies., Competing Interests: CONFLICTS OF INTEREST None.

Staging of peripheral T-cell non-Hodgkin lymphoma (PTCL) is determined by 18-F FDG PET scan and bone marrow biopsy. This study addressed the accuracy of PET at detecting bone marrow (BM) involvement at restaging in patients with known involvement pretreatment. We identified patients with biopsy proven BM PTCL at diagnosis and concomitant BM and PET at the end of therapy. Pre-treatment PET demonstrated 50% (8/16) had a false-negative PET scan of the BM. After induction, repeat biopsy revealed 62.5% (10/16) with BM involvement. Of these 10, two had a positive PET; eight were false negative by PET. Of the six patients with a negative posttherapy BM biopsy, four were PET negative and two false positive. The sensitivity of PET at end of treatment was 20% (2/10) with a specificity of 66.7% (4/6). PET/CT is not an accurate predictor of BM involvement in patients with known PTCL in the marrow.

Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively (P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (tMDS/AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/AML in non-fludarabine treated patients (n = 90) versus fludarabine treated (n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT., (© 2017 John Wiley & Sons Ltd.)

Chronic lymphocytic leukemia (CLL) patients progressed early on ibrutinib often develop Richter transformation (RT) with a short survival of about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled, and 60% received prior ibrutinib. Objective responses were observed in 4 out of 9 RT patients (44%) and in 0 out of 16 CLL patients (0%). All responses were observed in RT patients who had progression after prior therapy with ibrutinib. After a median follow-up time of 11 months, the median overall survival in the RT cohort was 10.7 months, but was not reached in RT patients who progressed after prior ibrutinib. Treatment-related grade 3 or above adverse events were reported in 15 (60%) patients and were manageable. Analyses of pretreatment tumor specimens from available patients revealed increased expression of PD-ligand 1 (PD-L1) and a trend of increased expression in PD-1 in the tumor microenvironment in patients who had confirmed responses. Overall, pembrolizumab exhibited selective efficacy in CLL patients with RT. The results of this study are the first to demonstrate the benefit of PD-1 blockade in CLL patients with RT, and could change the landscape of therapy for RT patients if further validated. This trial was registered at www.clinicaltrials.gov as #NCT02332980., (© 2017 by The American Society of Hematology.)

Background: Clinical data that support stereotactic body radiation therapy (SBRT) metastatic malignant melanoma (MM) are limited. Furthermore, functional imaging with 18F-fludeoxyglucose positron emission tomography (PET) may offer a more accurate post-SBRT assessment. Therefore, we assessed the clinical outcomes and metabolic response of metastatic MM after SBRT., Methods and Materials: Patients with MM who were treated with SBRT and had pre- and post-PET scans (>1) were included in this study. A total of 390 pre- and post-SBRT PET/computed tomography (CT) scans for 80 metastases were analyzed. The PET metabolic response was evaluated per the PET Response Criteria in Solid Tumors (PERCIST), version 1.0, criteria. Single-fraction equivalent dose (SFED) was calculated as per the standard. The Kaplan-Meier method was used for estimates of overall survival (OS) and progression-free survival. The cumulative incidence method was used to estimate metastasis control (MC). A Wilcoxon test was used to compare survival estimates. The prognostic factors for MC and OS were assessed using the Cox proportional hazards model, and the Likelihood Ratio was also used for comparisons between groups., Results: A median of 6 PET scans (range, 2-6 scans) was evaluated for each metastasis. The median SFED was 42.8 Gy (range, 18-56.4 Gy) and the median biologically effective dose was 254.4 Gy 2.5 (range, 100.8-540 Gy 2.5 ). Twenty percent of patients received chemotherapy and 59% received immunotherapy: granulocyte-macrophage colony-stimulating factor (64%) and ipilimumab (34%). MC was 94% and 90% at 1 year and 3 years, respectively. The OS was 74% and 27% and 1 year and 3 years, respectively. Complete response was achieved in 90% at a median of 2.8 months (range, 0.4-25.2 months). SFED >24 Gy correlated with improved MC (93% vs 75%, P = .01). Acute and late grade 3+ toxicities were 4% and 11%, respectively, with no grade 5 toxicity., Conclusions: Post-SBRT PET/CT for extracranial metastatic MM resulted in high rates of complete response at a median of 2.8 months, and durable MC was achieved with SFED >24 Gy. SBRT, in addition to surgery and ablation, should be discussed with patients with MM, especially those with oligometastases.

Patients with diffuse large B-cell lymphoma (DLBCL) and pre-treatment bone marrow (BM) involvement require a restaging BM biopsy to document complete remission (CR). We investigated whether BM assessment by restaging PET-CT could obviate the need for a repeat BM biopsy. Patients with DLBCL and a positive BM biopsy at diagnosis were identified from the Mayo Clinic Lymphoma Data Base. The concordance of BM status on restaging histopathology and PET-CT reports and the positive (PPV) and negative predictive value (NPV) of PET-CT were determined. One thousand eighty patients with DLBCL were evaluated and 69 patients (6%) had DLBCL involving the BM at diagnosis. Of 46 patients who completed frontline chemoimmunotherapy, 34 had a restaging PET-CT and BM biopsy and were included in the analysis. Thirty-three patients had a negative BM by both PET-CT and BM biopsy; one patient had persistent BM involvement by biopsy and PET-CT. Thus, restaging PET-CT had 100% PPV and 100% NPV for assessing residual BM disease. The findings were validated in a prospective cohort of 68 DLBCL patients treated on a phase II clinical trial where four patients (6%) had DLBCL involving the BM at diagnosis. All had a negative BM by both restaging BM biopsy and PET-CT. Compared with the gold standard of BM biopsy, PET-CT had a 100% NPV to exclude residual BM disease after frontline therapy. If further validated, DLBCL practice guidelines and response criteria could be modified so that BM biopsy is no longer required to document CR if the restaging PET-CT is negative., (© 2014 Wiley Periodicals, Inc.)

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) cells typically have low 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) avidity, and patients with CLL have an increased risk of developing FDG-avid aggressive lymphomas, second malignancies and infections. We hypothesized that FDG positron emission tomography-computed tomography (PET-CT) of the trunk is a sensitive method of detecting these complications in patients with CLL. Of the of 2299 patients with CLL seen in the Division of Hematology at Mayo Clinic Rochester between 1 January 2006 and 31 December 2011, 272 (11.8%) had 526 PET-CT scans and 472 (89.7%) of these were reported as abnormal. Among the 293 (55.7%) PET-CT scans used for routine evaluation of CLL, the PET component was of clinical value in only one instance. In contrast, in 83 (30.5%) patients, PET-CT scans used to evaluate new clinical complications localized high FDG-avidity lesions for biopsies. This resulted in clinically relevant new diagnoses in 32 patients, including those with more aggressive lymphoma (n = 16), non-hematological malignancies (n = 8) and opportunistic infections (n = 3). Twenty-seven patients had high FDG-avidity CLL, which was associated with prominent lymph node proliferation centers, an increased frequency of poor prognostic factors (17p13 deletion, unmutated immunoglobulin heavy chain variable gene [IGHV], expression of ZAP-70 and CD38) and a shorter overall survival. We conclude that FDG PET scans should not be used for routine surveillance of patients with CLL. However PET-CT scans are sensitive, but not specific, for detection of aggressive lymphomas, other cancers and systemic infections in patients with CLL.

Background: Since atrial fibrillation (AF) impacts the measurement and interpretation of left ventricular ejection fraction (LVEF), we hypothesized that the outcome in heart failure (HF) with AF and LVEF ≤ 35% would be more strongly associated with neurohormonal measures than LVEF., Methods and Results: Cardiac adverse events [CAE; HF progression (HFP), life-threatening arrhythmia (ARR), and cardiac death (CD)] and all-cause mortality (ACM) were recorded prospectively in 954 patients with HF and LVEF ≤ 35%: 852 in sinus rhythm (SR) and 102 in AF. Cox proportional hazard models found that the univariate hazard ratios (HR) for LVEF and the first CAE (primary outcome), HFP, ARR, CD, and ACM were significant in SR (0.933, P < .001, 0.933, P < .001, 0.929, P < .001, 0.916, P < .001, 0.945, P = .001, respectively), but not in AF (1.002, P = .95, 1.060, P = .24, 0.922, P = .15, 0.885, P = .09, 0.932, P = .25). HRs for CAEs and ACM and one or more neurohormonal measures (iodine 123 m-iodobenzylguanidine cardiac parameters, B-type natriuretic peptide, and plasma norepinephrine) were significant in SR and AF. The multivariate models for the first CAE and HFP included neurohormonal measures and LVEF in SR and neurohormonal measures in AF., Conclusions: In HF with LVEF ≤ 35% with AF, neurohormonal measures, but not LVEF, were related to outcomes.

Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial, we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m(2) days 1,8, and 15; (111) In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of (90) Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hr without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: Intermediate-stage hepatocellular carcinoma (HCC) is usually treated with locoregional therapy using transarterial chemoembolization (TACE). Transarterial radioembolization (TARE) using β-emitting yttrium-90 integral to the glass matrix of the microspheres is an alternative to TACE. This retrospective case-control study compared the outcomes and safety of TARE versus TACE in patients with unresectable HCC., Materials and Methods: Patients with unresectable HCC without portal vein thrombosis treated with TARE between 2005 and 2008 (n = 61) were retrospectively frequency-matched by age, sex, and liver dysfunction with TACE-treated patients (n = 55) in the Mayo Clinic Hepatobiliary Neoplasia Registry. Imaging studies were reviewed, and clinical and safety outcomes were abstracted from the medical records., Results: Complete tumor response was more common after TARE (12 %) than after TACE (4 %) (p = 0.17). When complete response was combined with partial response and stable disease, there was no difference between TARE and TACE. Median survival did not differ between the two groups (15.0 months for TARE and 14.4 months for TACE; p = 0.47). Two-year survival rates were 30 % for TARE and 24 % for TACE. TARE patients received fewer treatments (p < 0.001). Fifty-nine (97 %) TARE patients received outpatient treatment. In contrast, 53 (98 %) TACE patients were hospitalized for ≥1 day (p < 0.001). Compared with TACE, TARE was more likely to induce fatigue (p = 0.003) but less likely to cause fever (p = 0.02)., Conclusion: There was no significant difference in efficacy between TARE and TACE. TARE patients reported more fatigue but had less fever than TACE patients. Treatment with TARE required less hospitalization than treatment with TACE. These findings require confirmation in randomized trials.

Background: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine malignancy with high potential for nodal or distant metastatic spread. Little information exists on sensitivity and specificity of various imaging techniques when compared with the gold standard of histopathologic evaluation of the lymph node basin., Objective: We sought to further understand the value of various imaging modalities in the staging and initial workup of patients with MCC., Methods: Of 240 patients with primary MCC evaluated between 1981 and 2008, 99 had diagnostic imaging at initial presentation with biopsy-proven cutaneous MCC and had histopathologic nodal evaluation within 4 weeks of the initial scan. We conducted a retrospective chart review of these identified patients., Results: Computed tomography (n = 69) demonstrated a sensitivity of 47%, specificity of 97%, positive predictive value of 94%, and negative predictive value of 68% in detecting nodal basin involvement. Fluorine-18-fluorodeoxyglucose positron emission tomography scan (n = 33) demonstrated a sensitivity of 83%, specificity of 95%, positive predictive value of 91%, and negative predictive value of 91% in detecting nodal basin involvement. Magnetic resonance imaging (n = 10) demonstrated a sensitivity of 0%, specificity of 86%, positive predictive value of 0%, and negative predictive value of 67% in detecting nodal basin involvement., Limitations: This was a retrospective study with small sample size., Conclusion: Use of fluorine-18-fluorodeoxyglucose positron emission tomography in the evaluation of a regional lymph node basin in primary MCC is significantly more sensitive and equally specific when compared with traditional computed tomography. Both fluorine-18-fluorodeoxyglucose positron emission tomography and computed tomography are more sensitive than clinical examination alone., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

Approximately 60% of patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) are curable with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemoimmunotherapy. Epratuzumab (E) is an unlabeled anti-CD22 monoclonal antibody with efficacy in relapsed DLBCL. This phase 2 trial tested the safety and efficacy of combining E with R-CHOP (ER-CHOP) in untreated DLBCL. A secondary aim was to assess the efficacy of interim positron emission tomography (PET) to predict outcome in DLBCL. Standard R-CHOP with the addition of E 360 mg/m(2) intravenously was administered for 6 cycles. A total of 107 patients were enrolled in the study. Toxicity was similar to standard R-CHOP. Overall response rate in the 81 eligible patients was 96% (74% CR/CRu) by computed tomography scan and 88% by PET. By intention to treat analysis, at a median follow-up of 43 months, the event-free survival (EFS) and overall survival (OS) at 3 years in all 107 patients were 70% and 80%, respectively. Interim PET was not associated with EFS or OS. Comparison with a cohort of 215 patients who were treated with R-CHOP showed an improved EFS in the ER-CHOP patients. ER-CHOP is well tolerated and results appear promising as a combination therapy. This study was registered at www.clinicaltrials.gov as #NCT00301821.

Objective: To explore the prognostic value of F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in radioiodine-negative patients with differentiated follicular cell-derived thyroid carcinoma with circulating antithyroglobulin autoantibodies (TgAb)., Methods: We retrospectively reviewed cases of all patients with differentiated thyroid cancer and increased TgAb referred for FDG-PET at Mayo Clinic, Rochester, Minnesota, from August 2001 to December 2004. PET findings were compared with results of other imaging and laboratory studies. Follow-up information was recorded until 19 December 2009., Results: Of the 17 patients identified, PET results were true positive in 10 and false negative in two. In eight of these 12 patients with confirmed residual or recurrent disease, the increased TgAb level persisted and the disease progressed. In four of the 12 patients, TgAb decreased or disappeared after further treatment. In five patients, no residual or recurrent disease was found during follow-up. PET results were true negative in these five patients; TgAb disappeared spontaneously in four of these patients., Conclusions: Negative PET results were associated with the absence of active disease and disappearing TgAb over time. FDG-avid residual lesions were associated with more aggressive disease and persistently increased TgAb.

Purpose: To explore the prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) in patients with suspected residual or recurrent medullary thyroid carcinoma (MTC)., Procedures: This retrospective study included all patients with MTC examined with FDG-PET at Mayo Clinic, Rochester, Minnesota, from October 1999 to March 2008. The PET results were compared with other imaging studies and clinical findings, including carcinoembryonic antigen and calcitonin levels., Results: Twenty-nine patients with MTC were included. PET was positive in 14 patients, with follow-up information for 11; six died from metastatic disease, four had disease progression, and one remained in stable condition. PET was negative in 15 patients, with follow-up for 12; one had recurrent disease, and 11 had no evidence of clinical disease. Calcitonin doubling time was shorter for PET-positive than for PET-negative patients., Conclusion: FDG-PET has high prognostic value in patients with suspected residual or recurrent MTC.

Neuroendocrine tumors (NETs) of the distal colon and rectum are also known as hindgut carcinoids based on their common embryologic derivation. Their annual incidence in the United States is rising, primarily as a result of increased incidental detection. Symptoms of rectal NETs include hematochezia, pain, and change in bowel habits. Most rectal NETs are small, submucosal in location, and associated with a very low malignant potential. Tumors larger than 2 cm or those invading the muscularis propria are associated with a significantly higher risk of metastatic spread. Colonic NETs proximal to the rectum are rarer and tend to behave more aggressively. The incidence of rectal NETs in African Americans and Asians is substantially higher than in Caucasians. Colorectal NETs are generally not associated with a hormonal syndrome such as flushing or diarrhea. A multidisciplinary approach is recommended in diagnosing and managing hindgut NETs.

Extrapulmonary poorly differentiated neuroendocrine carcinomas can originate in the gastrointestinal tract, bladder, cervix, and prostate. These high-grade malignancies are characterized by aggressive histological features (high mitotic rate, extensive necrosis, and nuclear atypia) and a poor clinical prognosis. They are infrequently associated with secretory hormonal syndromes (such as the carcinoid syndrome) and rarely express somatostatin receptors.Most poorly differentiated neuroendocrine carcinomas are locally advanced or metastatic at presentation. First-line systemic chemotherapy with a platinum agent (cisplatin or carboplatin) and etoposide is recommended for most patients with metastatic-stage disease; however, response durations are often short. Sequential or concurrent chemoradiation is recommended for patients with loco-regional disease. In patients with localized tumors undergoing surgical resection, adjuvant treatment (chemotherapy with or without radiation) is warranted in most cases.

Multiple myeloma (MM) remains an incurable illness affecting nearly 20,000 individuals in the United States per year. High-dose melphalan (HDM) with autologous hematopoietic stem cell support (ASCT) is one of the mainstays of therapy for younger patients, but little advancement has been made with regards to conditioning regimens. We opted to combine (153)Samarium ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP), a radiopharmaceutical approved for the palliation of pain caused by metastatic bone lesions, with HDM and ASCT in a Phase II study. Individualized doses of (153)Sm were based on dosimetry and were calculated to deliver 40 Gy to the bone marrow. The therapeutic dose of (153)Sm-EDTMP was followed by HDM and ASCT. Forty-six patients with newly diagnosed or relapsed disease were treated. Study patients were compared to 102 patients contemporaneously treated with HDM and ASCT. Fifty-nine percent of study patients achieved a very good partial response (VGPR) or better. With a median follow-up of 7.1 years, the median overall survival and progression free survival (PFS) from study registration was 6.2 years (95% CI 4.6-7.5 years) and 1.5 years (1.1-2.2 years), respectively, which compared favorably to contemporaneously treated non-study patients. Addition of high-dose (153)Sm-EDTMP to melphalan conditioning appears to be safe, well tolerated, and worthy of further study in the context of novel agents and in the Phase III setting., (2010 Wiley-Liss, Inc.)

Unlabelled: To determine whether the therapeutic effect of (90)Y-ibritumomab might be enhanced by a full course of rituximab followed by single dose of (90)Y-ibritumomab, the trial included pre- and post-rituximab treatment imaging with (111)In-ibritumomab and blood pharmacokinetics. Comparison of the pre- and post-rituximab imaging and blood data allowed for the assessment of impact of rituximab on (90)Y-ibritumomab dosimetry., Methods: Seventeen patients with relapsed B cell non-Hodgkin lymphoma first received 250 mg/m(2) of rituximab plus 185 MBq of (111)In-ibritumomab for initial dosimetry evaluation. In weeks 2-4, patients received 3 weekly 375 mg/m(2) doses of rituximab. In week 6, patients received a 250 mg/m(2) dose of rituximab plus 185 MBq of (111)In-ibritumomab for a second dosimetry evaluation. Five sequential, whole-body gamma-camera images were acquired after the (111)In-ibritumomab injection. Calculated radiation doses were based on patient-specific organ masses. For each patient, paired comparison of radiation doses before and after rituximab treatment was performed. Paired comparison of residence times for spleen and tumor was also performed., Results: Before rituximab treatment, the median radiation dose (mGy/MBq) was 0.48 (range, 0.24-0.86) for total body, 3.7 (range, 2.1-11.6) for liver, 6.1 (range, 1.8-17.8) for spleen, 3.3 (range, 2.0-4.7) for kidneys, 2.4 (range, 1.3-3.7) for heart wall, 1.1 (range, 0.4-2.3) for lungs, 0.79 (range, 0.32-1.22) for marrow from blood, and 18.1 (range, 4.7-98.9) for tumor. Paired comparisons were performed in 16 patients only because human antimurine antibody developed in 1 patient. The median change was 0.007 mGy/MBq for body, -0.14 mGy/MBq for liver, -0.31 mGy/MBq for kidneys, 0.38 mGy/MBq for heart wall, -0.17 mGy/MBq for lungs, and 0.046 mGy/MBq for marrow from blood. The median change in residence time was -0.92 h for spleen and -0.24 h for tumor. The changes were statistically insignificant for total body, liver, kidneys, lungs, and marrow from blood. The median residence times, or mGy/MBq if there were no volume changes, decreased 24% for spleen (P = 0.0005) and 28% for tumor (P = 0.005). The median radiation dose to heart wall increased 16%, which was statistically significant (P = 0.002)., Conclusion: Changes in (90)Y-ibritumomab dosimetry after 4 wk of rituximab treatment were not significant for most organs, except for the heart wall. The reduction of spleen and tumor residence times is more likely to be due to the therapeutic effects of rituximab.

Purpose: To evaluate the impact of identifiable hepatic vein tumor thrombus on the ability to safely deliver TheraSphere (yttrium 90-containing glass microspheres) for the treatment of hepatocellular carcinoma (HCC)., Materials and Methods: A retrospective review was performed of 87 patients (71 men, 16 women; mean age, 64.5 years; age range, 25-83 y) referred for TheraSphere therapy for HCC during a 2-year period between April 2005 and May 2007. Evaluation included contrast-enhanced computed tomography or magnetic resonance imaging, selective mesenteric angiography, and radionuclide perfusion scintigraphy to measure the arteriovenous shunting through the tumor., Results: Of the 87 patients, 83 underwent angiography and perfusion scintigraphy; 53 were ultimately treated with 65 glass microsphere infusions. Twelve of 83 were identified as having tumor thrombus in a hepatic vein or extending into the inferior vena cava. The mean lung shunt for the patients with hepatic vein tumor thrombus was 30% (range, 11%-60%), compared with 8.2% (range, 3%-23%) for patients without identifiable tumor thrombus. Two of the 12 patients were treated with reduced doses of glass microspheres, and the remaining 10 were offered alternative therapies., Conclusions: The presence of hepatic vein tumor thrombus is a risk factor for an increased lung shunt that may prohibit delivery of a therapeutic dose of TheraSphere to hepatic tumor.

Background: A 58-year-old white man who was being followed by his hepatologist for nonalcoholic steatohepatitis-related liver cirrhosis and portal hypertension and who had been found to have a biopsy-proven hepatocellular carcinoma (HCC) on routine screening, self-referred to our center for a second opinion on the management of his HCC., Investigations: Laboratory investigations, CT scan of the abdomen and chest, bone scan and technetium macroaggregated albumin scan., Diagnosis: The patient had unresectable HCC., Management: The patient underwent two treatments with Yttrium-90 glass microspheres, which were performed as outpatient procedures 1 month and 3 months after diagnosis. He underwent orthotopic liver transplantation (OLT) 1 year after the initial diagnosis of HCC. The post-OLT immunoregimen included OKT3 plus rituximab and high-dose steroids. On discharge from hospital he was on immunosuppressive treatment with tacrolimus. He had de novo autoimmune hepatitis 6 months post-OLT, which was treated with a short course of low-dose steroids and addition of mycophenolate mofetil.

Unlabelled: Although (123)I-MIBG has been in clinical use for the imaging of pheochromocytoma for many years, a large multicenter evaluation of this agent has never been performed. The present study was designed to provide a prospective confirmation of the performance of (123)I-MIBG scintigraphy for the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma., Methods: A total of 81 patients with a prior history of primary or metastatic pheochromocytoma or paraganglioma and 69 with suspected pheochromocytoma or paraganglioma based on symptoms of catecholamine excess, CT or MRI findings, or elevated catecholamine or metanephrine levels underwent whole-body planar and selected SPECT 24 h after the administration of (123)I-MIBG. Images were independently interpreted by 3 masked readers, with consensus requiring agreement of at least 2 readers. Final diagnoses were based on histopathology, correlative imaging, catecholamine or metanephrine measurements, and clinical follow-up., Results: Among 140 patients with definitive diagnoses (91, disease present; 49, disease absent), (123)I-MIBG planar scintigraphy had a sensitivity and specificity of 82%. For patients evaluated for suspected disease, sensitivity and specificity were 88% and 84%, respectively. For the subpopulations of adrenal (pheochromocytoma) and extraadrenal (paraganglioma) tumors, sensitivities were 88% and 67%, respectively. The addition of SPECT increased reader confidence but minimally affected sensitivity and specificity., Conclusion: This prospective study demonstrated a sensitivity of 82%-88% and specificity of 82%-84% for (123)I-MIBG imaging used in the diagnostic assessment of primary or metastatic pheochromocytoma or paraganglioma.

Metastatic malignant melanoma is an incurable malignancy with extremely poor prognosis. Patients bearing this diagnosis face a median survival time of approximately 9 months with a probability of surviving 5 years after initial presentation at less than 5%. This is contrasted by the curative nature of surgical resection of early melanoma detected in the skin. To date, no systemic therapy has consistently and predictably impacted the overall survival of patients with metastatic melanoma. However, in recent years, a resurgence of innovative diagnostic and therapeutic developments have broadened our understanding of the natural history of melanoma and identified rational therapeutic targets/strategies that seem poised to significantly change the clinical outcomes in these patients. Herein we review the state-of-the-art in metastatic melanoma diagnostics and therapeutics with particular emphasis on multi-disciplinary clinical management.

Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. The use of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in ATC has not been studied, and only a few case reports have been published. The objective of this study was to investigate the potential contribution of 18F-FDG PET to the clinical management of patients with ATC., Methods: All patients with ATC studied with 18F-FDG PET from August 2001 through March 2007 were included. The PET results were correlated with computed tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake value. Any change in the treatment plan as a direct result of the PET findings as documented in the clinical notes was recorded., Results: Sixteen patients were included. True-positive PET findings were seen for all primary tumors, in all nine patients with lymph node metastases, in five out of eight patients with lung metastases, and in two patients with distant metastases other than lung metastases. In 8 of the 16 patients, the medical records reported a direct impact of the PET findings on the clinical management., Conclusions: ATC demonstrates intense uptake on 18F-FDG PET images. In 8 of the 16 patients (50%), the medical records reported a direct impact of the PET findings on the management of the patient. PET may improve disease detection and have an impact on the management of patients with ATC relative to other imaging modalities.

Positron emission tomography (PET) utilizing fluorodeoxyglucose (FDG) has an ever-increasing role in the management of numerous malignancies. FDG PET in lymphoma is being incorporated into the response assessment in lymphoma as published by the Imaging Subcommittee of International Harmonization Project in Lymphoma. The exact role of FDG PET in non-Hodgkin's lymphoma (NHL) associated with autologous stem cell transplant (ASCT) is unclear. Numerous studies have identified pretransplant PET scans as being highly prognostic with regard to overall and PFS after ASCT. Many included a wide range of histologies, including Hodgkin's lymphoma and NHL. In studies with mixed histologies, PFS at 2 years has been improved by as much as 82% in patients with negative pre-ASCT PET scans. In studies incorporating only patients with NHL, improvements in failure-free survival have been reported as high as 43% for patients with negative pre-ASCT PET imaging. Limitations have included inclusion of many histologies, different reported time points, small retrospective studies and variation in the interpretation of a positive PET. Validation is ongoing in larger prospective trials. Future directions include the potential incorporation of post-ASCT therapy, such as radiation therapy or maintenance antibody therapy, for patients with positive pre-ASCT PET scans.

Objective: To determine the value of F-FDG PET/CT in the different manifestations of primary central nervous system lymphoma (PCNSL) in HIV-negative patients., Methods: All PCNSL and HIV-negative patients referred for PET/CT in our institution from July 2001 to June 2006 were retrospectively studied. PET/CT examinations were reviewed by two experienced readers and evaluated for each possible anatomical site of nervous system involvement: cerebral, spinal/nerve and ocular. PET/CT results were characterized as true positive or negative and false positive or negative according to the status of the disease, which was determined after the evaluation of biopsies, laboratory, clinical and imaging examinations, and follow-up., Results: Forty-two PET/CT examinations were carried out in 25 PCNSL patients. For intracerebral disease, PET/CT was true positive in 13 cases, true negative in 27 and false negative in two. For disease involving spinal cord and/or nerves, PET/CT was true positive in four cases, true negative in 37 and false negative in one. For ocular disease, PET was true positive in only one case and false negative in four. The sensitivity of PET/CT in detecting active disease in the brain was 87% (13/15), in the spine/nerves 80% (4/5), and in the eyes only 20% (1/5)., Conclusion: PET/CT seems to be sensitive for the detection of viable intracerebral as well as for spinal and peripheral nerve disease, but not for the detection of ocular involvement.

Objective: Treatment-related complications are more common in older patients with non-Hodgkin's lymphoma (NHL), often leading to chemotherapy modifications that can compromise efficacy. We analyzed data from clinical trials of yttrium-90-ibritumomab tiuxetan (Zevalin); Biogen Idec, Cambridge, MA) to determine its safety and efficacy in older patients with NHL., Design and Methods: Data on safety and efficacy from four clinical trials of (90)Y-ibritumomab tiuxetan in 211 patients with NHL were pooled and analyzed by ages of <60, 60-69, and > or =70 years., Results: Patients > or =70 years had a similar incidence of grade 3 or 4 neutropenia (68% vs. 66%), thrombocytopenia (68% vs. 70%), anemia (8% vs. 22%), and nonhematologic adverse events (23% vs. 19%) as that observed in patients <60 years. Response rates (range, 71%-80%) and the durations of response (median of 9.9, 11.0, and 9.4 months) were similar in the three groups., Conclusions: Yttrium-90-ibritumomab tiuxetan produces high rates of clinical response (up to 80%) and durable remissions in patients with NHL, and can be given at standard doses in older patients. The favorable safety profile of the regimen makes it an effective treatment for older patients, who may not otherwise tolerate the adverse events associated with chemotherapy.

Objective: To demonstrate 3 cases of artifactual focal F-18 fluoro-deoxy-glucose accumulation in the lung parenchyma in the absence of any computed tomographic (CT) abnormality., Materials and Methods: Three patients were examined: a 30-year-old man who had a positron emission tomography (PET)/computed tomography for restaging a biopsy-proven recurrence of head and neck cancer, a 68-year-old woman who was referred for initial staging of esophageal carcinoma, and a 57-year-old man who had a PET/computed tomography for initial staging of melanoma. In each case, there was intense focal activity in the lung parenchyma with no corresponding CT abnormality. Each patient was further evaluated with a repeat PET scan in days 1 and 3 in the first 2 cases and with a delayed repeat acquisition in the third case. Patients were followed for 24, 10, and 1 month, respectively., Results: In the first 2 cases, the abnormal focal activity in the lungs had resolved in the repeat study. In the third case, the focus of increased activity in the lung had moved more peripherally in the delayed acquisition. Clinical follow-up was negative for disease in the corresponding pulmonary parenchymal sites., Conclusions: The finding of significant focal accumulation of fluoro-deoxy-glucose in the lung parenchyma in the absence of corresponding CT abnormality was artifactual. This was likely due to injection technique and the creation of particulate embolus. Positron emission tomography/Computed tomographic readers should be aware of this type of artifact to avoid misinterpretation.

The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear cell renal cell carcinomas (RCCs). We performed a phase I clinical trial to evaluate the safety, blood pharmacokinetics (PK), and biodistribution of repeated doses of cG250. The primary endpoint was toxicity. Secondary endpoints were cG250 biodistribution and PK; measurement of human anti-chimeric-antibodies (HACA); and tumour response rates. Eligible patients had unresectable or metastatic clear cell RCC. Doses of 5, 10, 25, or 50 mg/m(2) were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace (131)I-labelled cG250 was administered on weeks 1 and 5. Thirteen patients participated and were evaluable. One patient developed brain metastases and was replaced. No grade 3 or 4 toxicities and no dose-limiting toxicity occurred. One patient died due to progressive disease within 30 days of receiving the study drug. One patient developed HACA during the second six-week cycle. PK analysis showed mean whole body and blood alpha and beta half-lives of cG250 of 18.99 +/- 6.84 and 180.19 +/- 86.68 hours, respectively. All patients had cG250 tumour localization by gamma camera imaging in week 1 and 5. One patient had a complete response, nine patients had stable disease, and three had progressive disease. One patient received 11 six-week cycles of treatment with no toxicity or HACA. In conclusion, repeated intravenous doses of up to 50 mg/m(2) of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively.

Unlabelled: Our purpose was to determine the clinical significance of diffusely increased (18)F-FDG uptake in the thyroid gland as an incidental finding on PET/CT., Methods: All patients who were found to have diffuse thyroid uptake on (18)F-FDG PET/CT in our institution between November 2004 and June 2006 were investigated and compared with an age- and sex-matched control group. The (18)F-FDG uptake in the thyroid was semiquantified using maximum standardized uptake value and correlated to the available serum thyroid-stimulating hormone (TSH) and thyroid peroxidase (TPO) antibody levels using regression analysis., Results: Of the 4,732 patients, 138 (2.9%) had diffuse thyroid uptake. Clinical information was available for 133 of the 138 patients. Sixty-three (47.4%) had a prior diagnosis of hypothyroidism or autoimmune thyroiditis, of whom 56 were receiving thyroxine therapy. In the control group, consisting of 133 patients with no thyroid uptake, there were 13 (9.8%) with a prior diagnosis of hypothyroidism, 11 of whom were receiving thyroxine therapy. In the study group, 38 (28.6%) of 133 patients did not undergo any further investigation for thyroid disease, whereas 32 (24.1%) of 133 patients were examined for thyroid disease after PET. Nineteen were found with autoimmune thyroiditis or hypothyroidism, and replacement therapy was initiated in 12. No significant correlation was found between maximum standardized uptake value and TSH (P = 0.09) or TPO antibody (P = 0.68) levels., Conclusion: The incidental finding of increased (18)F-FDG uptake in the thyroid gland is associated with chronic lymphocytic (Hashimoto's) thyroiditis and does not seem to be affected by thyroid hormone therapy. SUV correlated neither with the degree of hypothyroidism nor with the titer of TPO antibodies.

Background: Radioimmunotherapy with radiolabeled monoclonal antibodies to CD20 produces a high response rate in patients with recurring non-Hodgkin lymphoma (NHL), but the durability of those remissions is not well defined., Methods: Data on patients with recurring NHL treated with yttrium Y 90 ibritumomab tiuxetan in 4 clinical trials were reviewed to identify patients with a long-term response, defined as a time to progression of 12 months or longer., Results: Long-term responses were seen in 37% (78/211) of patients. At a median follow-up of 53.5 months (range, 12.7-88.9) the median duration of response was 28.1 months and the median time to progression was 29.3 months. A third of these patients had been treated with at least 3 previous therapies, and 37% of them had not responded to their last therapy. The findings in patients with follicular lymphoma (n=59) were similar to those in the overall population of long-term responders. The estimated overall survival at 5 years was 53% for all patients treated with 90Y ibritumomab tiuxetan and 81% for long-term responders., Conclusions: A single dose of 90Y ibritumomab tiuxetan can produce durable responses and prolonged overall survival in a substantial number of patients in whom previous therapies have failed., (Copyright (c) 2007 American Cancer Society)

Objective: To determine if quantification of [18F]fluorodeoxyglucose (18F-FDG) uptake in a thyroid nodule found incidentally on whole-body 18F-FDG positron emission tomography-computed tomography (PET-CT) can be used to discriminate between malignant and benign aetiology., Methods: A retrospective review of all patients with focally high uptake in the thyroid as an incidental finding on 18F-FDG PET-CT from May 2003 through May 2006. The uptake in the nodules was quantified using the maximum standardized uptake value (SUVmax). The aetiology was determined by cytology and/or ultrasound, or on histopathology., Results: Incidental focally high uptake was found in 79/7347 patients (1.1%). In 31/48 patients with adequate follow-up, a benign aetiology was determined. Median SUVmax for the benign group was 5.6, range 2.5-53. Malignancy was confirmed in 15/48 patients. The malignancies were papillary thyroid carcinoma in 12, metastasis from squamous cell carcinoma in one, and lymphoma in two. Median SUVmax for the malignant lesions was 6.4, range 3.5-16. Cytology suspicious for follicular carcinoma was found in 2/48 patients. No statistical difference (P=0.12) was found among the SUVmax between the benign and malignant groups., Conclusion: Focally high uptake of 18F-FDG in the thyroid as an incidental finding occurred in 1.1% of the patients. Malignancy was confirmed or was suspicious in 17/48 (35%) of the patients that had adequate follow-up. There was no significant difference in the SUVmax between benign and malignant nodules.

Purpose: Primary central nervous system lymphoma (PCNSL) accounts for approximately 3% of all primary brain tumors and 1% of all non-Hodgkin lymphomas. Detection of systemic spread of PCNSL, although rare (4%), is very important since therapy is usually modified. Contrast-enhanced computed tomography (CT) is commonly used for systemic staging of PCNSL. No previous case report is available in the published literature elaborating the potential contribution of F-18 FDG PET in systemic staging of PCNSL. The purpose of this case report was to document the potential usefulness of F-18 FDG-PET in the detection of occult systemic involvement in PCNSL., Materials and Methods: A 50-year-old, immunocompetent, male patient completed successful treatment of PCNSL. As part of a routine pretransplant evaluation he had an F-18 FDG PET coregistered with CT (PET-CT). The PET-CT results were then compared with those of contrast-enhanced CT of the chest, abdomen, and pelvis., Results: The PET-CT examination detected multiple sites of extranodal systemic disease that were not seen in the contrast-enhanced CT of the chest, abdomen, and pelvis (both studies were performed within 24 hours of each other). Percutaneous ultrasound guided biopsy confirmed the presence of systemic spread of PCNSL. The patient's subsequent therapy was modified to include rituximab with cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). A follow up PET-CT confirmed resolution of systemic spread., Conclusion: F-18 FDG PET coregistered to CT may be a useful examination in the detection and monitoring for systemic spread of the disease in PCNSL patients.

Purpose: To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials., Methods: An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted., Recommendations: PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.

In four patients, aged 15 - 20 years, with high-risk acute myeloid leukemia (AML), high-dose samarium 153-labelled ethylenediaminetetramethylenephosphonate (153Sm-EDTMP) was used for targeted marrow irradiation before preparative chemotherapy conditioning regimens and allogeneic (three patients) or autologous (one patient) hematopoietic stem cell transplantation. The dose of 153Sm-EDTMP was 703 MBq/kg (n = 1) or 1110 MBq/kg (n = 3). No side-effects occurred during the 30-min infusion of 153Sm-EDTMP. Samarium - melphalan regimens were given to three patients; one had 153Sm-EDTMP - busulfan + cyclophosphamide. Total body radioactivity was below the 133 MBq safe limit before infusion of stem cells (day 14 after 153Sm-EDTMP). No hemorrhagic cystitis, nephrotoxicity or serious infections occurred. Leukocyte engraftment (white blood cell count >0.5 x 10(9)/l) occurred between 12 and 23 days after stem cell infusion (mean of 17 days). Complete cytogenetic and morphologic remission of AML was evident on follow-up marrow aspirate and biopsy specimens from all patients. In two of the four study patients, the disease remains in complete remission and the patients have an excellent quality of life (Eastern Cooperative Oncology Group performance status 0; no medications) and no organ toxicity more than 2 years and more than 4 years, respectively, after their blood and bone marrow transplantations. Thus, in adolescents and adults, 153Sm-EDTMP may provide a relatively simple and effective means for using irradiation to eliminate AML within the marrow.

Background: Non-Hodgkin lymphomas (NHL) are radiosensitive tumors. Recent trials have demonstrated the effectiveness of beta irradiation delivered by monoclonal antibodies conjugated to radioisotopes such as yttrium-90 or iodine-131. Many patients eventually relapse after radioimmunotherapy (RIT) and require additional treatment. The goal of this study was to determine the safety and efficacy of external beam radiation therapy (EBRT) delivered after RIT., Methods: We reviewed the records of 135 patients with relapsed B-cell NHL who had received RIT with 90Y-ibritumomab tiuxetan to identify patients who subsequently received EBRT. The response rates and radiation-induced toxicity from the EBRT were assessed., Results: Nineteen of 135 (14%) patients received EBRT to a total of 39 tumor sites. Complete radiation therapy records were available for 16 patients (36 tumor sites), which formed the basis for this analysis. The median EBRT dose was 28.5 Gy (range, 10-40 Gy), with a median fraction size of 2 Gy (range, 1-5 Gy). Response data were available for 29 treated sites. The overall response rate was 90% (26/29) with 12 complete responses (41%), 7 complete clinical responses (24%), 7 partial responses (24%), and 3 stable (10%). Toxicities were generally transient, reversible, and corresponded to the anatomic regions irradiated., Conclusions: EBRT can produce tumor responses at sites of NHL that relapse after RIT with acceptable toxicity.

Yttrium 90 ((90)Y) ibritumomab tiuxetan (Zevalin), a radiolabeled monoclonal antibody against the CD20 antigen, is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), including patients with rituximab-refractory follicular NHL. Data on 211 patients treated in four clinical trials were analysed to compare the efficacy and safety of (90)Y ibritumomab tiuxetan when it was used after the first relapse of NHL and when it was used after two or more prior therapies. Sixty-three patients (30%) were treated with (90)Y ibritumomab tiuxetan after their first relapse and 148 (70%) after two or more prior therapies. Demographics, disease characteristics and the frequency of adverse events were similar in all groups, with the exception of a higher rate of marrow involvement in first-relapse patients than in patients with two or more prior therapies (57% vs. 39%; P < 0.05). The complete response rate [confirmed (CR) and unconfirmed (Cru)] was higher in first-relapse patients (49% vs. 28%; P < 0.01), and the median time to progression (TTP) was longer (12.6 vs. 7.9 months; P < 0.05). In patients with follicular NHL, the differences were even more pronounced (CR/CRu: 51% vs. 28%; P < 0.01; TTP: 15.4 vs. 9.2 months; P < 0.05). (90)Y ibritumomab tiuxetan has substantial clinical benefits as a second-line therapy, especially in patients with follicular NHL. The quality of disease remissions obtained when (90)Y ibritumomab tiuxetan is administered after first relapse appears to be comparable with that observed with most chemotherapy regimens in first-relapse patients.

Introduction: Parathyroid scintigraphy (PS) may be used to localize hyperactive parathyroid glands preoperatively. Performance of PS in the setting of secondary and tertiary hyperparathyroidism (HPT) is not well quantified. The performance of PS in secondary/tertiary HPT versus primary HPT may reflect physiologic as well as radiopharmaceutical kinetic differences between multigland hyperplasia versus adenoma. The aim of this study was to review the performance of PS in secondary/tertiary HPT with a comparison to that for primary HPT. Moreover, we evaluated (1) the sensitivity of PS in detecting enlarged glands, and (2) PS detectability as a function of gland weight., Methods: We performed a retrospective review of the Mayo Clinic database from 2000 to 2004. We identified 40 patients with secondary or tertiary HPT as well as a matched control group of 40 patients with primary HPT who had had preoperative PS and underwent parathyroid surgery., Results: Parathyroid scintigraphy correctly localized all enlarged glands in 88% of patients in the primary HPT group. PS correctly identified both the number and locations of all hyperplastic glands in only 28% of the secondary/tertiary HPT patients. PS failed to identify one enlarged gland in 23% of the patients and two or more enlarged glands in 40% of the patients. PS correctly detects the largest gland in 88% of the patients with secondary and tertiary HPT. The mean gland weight detectable by PS was 612 +/- 120 mg for primary HPT. In secondary/tertiary HPT, glands detected by PS had a mean weight of 950 +/- 109 mg, whereas the mean weight was 276 +/- 34 mg for undetected glands (P < 0.002)., Conclusions: Parathyroid scintigraphy is a sensitive study for localizing parathyroid glands preoperatively in primary HPT patients. Its sensitivity is low in secondary and tertiary HPT patients. Thus PS has limited value as a preoperative localization study in secondary/tertiary HPT patients.

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.