Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab. RESULTS: After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT. CONCLUSION: Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.     

Feasibility and diagnostic performance of hybrid PET/MRI compared with PET/CT for gynecological malignancies: a prospective pilot study

Purpose

The purpose of the study was to assess the feasibility and diagnostic performance of FDG-PET/MR imaging compared to PET/CT for staging of patients with a gynecological malignancy.

Methods

25 patients with a gynecological malignancy were prospectively enrolled into this pilot study. Patients underwent sequential full-body PET/CT and PET/MR of the abdomen and pelvis after administration of a single dose of F-18 FDG. PET/MRI and PET/CT images were independently reviewed by two expert radiologists. Readers were blinded to the results of the other imaging procedures. Clinical and pathologic information was abstracted from medical charts.

Results

18 patients were included in the final analysis with a median age of 62 years (range 31–88). 61% of patients (11/18) had cervical cancer, while the remaining patients had endometrial cancer. PET/MRI as compared to PET/CT detected all primary tumors, 7/7 patients with regional lymph nodes, and 1/1 patient with an abdominal metastasis. Two patients had additional lymph nodes outside of the abdominopelvic cavity detected on PET/CT that were not seen on PET/MRI, whereas 6 patients had parametrial invasion and one patient had invasion of the bladder seen on PET/MRI not detected on PET/CT. Five cervical cancer patients had discordant clinical vs. radiographic staging based on PET/MRI detection of soft tissue involvement. Management changed for two patients who had clinical stage IB1 and radiographic stage IIB cervical cancer.

Conclusions

PET/MRI is feasible and has at least comparable diagnostic ability to PET/CT for identification of primary cervical and endometrial tumors and regional metastases. PET/MRI may be superior to PET/CT for initial radiographic assessment of cervical cancers.

     

Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and Ga-67 scintigraphy in evaluation of lymphoma

BACKGROUND: The accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET; dual-head camera with attenuation correction) and Ga-67 scintigraphy was compared to identify disease sites in patients with Hodgkin disease (HD) and intermediate and high-grade non-Hodgkin lymphoma (NHL) at initial diagnosis or clinical recurrence. METHODS: Fifty-one contemporaneous FDG-PET and Ga-67 scintigraphies were performed on patients with NHL (35 intermediate grade, 3 high grade) or HD (13 patients). Sites of disease were correlated on a site-by-site basis on FDG-PET and Ga-67 images. Tumor-to-background (T/B) ratios were obtained for both techniques. Discordant FDG-PET and Ga-67 findings were correlated with computed tomography findings or clinical evaluation including repeat FDG-PET scans obtained after therapy. RESULTS: Fluorodeoxyglucose positron emission tomography was positive at all 158 sites in 51 patients compared with 113 sites in 41 positive studies with Ga-67 scintigraphy (single positron emission computed tomography [SPECT] and/or planar images). In 44 patients who had complete Ga-67 SPECT data on all tumor sites, FDG-PET was positive at 126 sites and Ga-67 SPECT was positive at 81 sites. Ga-67 SPECT failed to demonstrate disease at 45 sites (35.7%). In 10 of 44 patients, Ga-67 SPECT completely failed to detect any disease at 22 of 45 sites (17.5%) and partially identified disease sites at 23 of 45 sites (18.2%) in 11 patients regardless of the tumor site and histology. In these patients, the lesions measured between 0.6 and 14.0 cm by CT. Fluorodeoxyglucose positron emission tomography revealed higher stage disease in 13 patients compared with Ga-67 imaging. Tumor-to-background ratios were statistically different between the two techniques with higher ratios obtained with FDG-PET (P < 0.0001). CONCLUSIONS: In imaging aggressive lymphoma and HD before therapy, FDG-PET has significantly higher site and patient sensitivity than Ga-67 scintigraphy (100% vs. 71.5% and 100% vs. 80.3%, respectively). The change in disease stage by FDG-PET may result in a change in therapy strategy.     

X-linked recessive inheritance of radial ray deficiencies in a family with four affected males

Radial ray deficiencies are frequently associated with additional clinical anomalies and have a heterogeneous aetiology. X-linked forms are extremely rare. We report a family in which four male relatives show bilateral absence of the radius with presence of the thumbs and associated anomalies. The segregation of the phenotype is suggestive for X-linked recessive inheritance. This is confirmed by performing linkage analysis using 24 markers spanning the X chromosome in which a maximum lod score of 1.93 for DXS8067 and DXS1001 is obtained. We defined a critical region of maximal 16.2 cM on the X chromosome with haplotype analysis.     

The role of FDG-PET imaging in the management of lymphoma

Positron emission tomography (PET) imaging using [F-18]fluorodeoxyglucose (FDG) has become a useful imaging modality in the staging and treatment evaluation algorithm for lymphoma, providing unique metabolic information. Increased FDG uptake in lymphoma tumor masses is a function of increased anaerobic metabolism and longer residence time of FDG in malignant cells relative to most normal tissues. The information provided by FDG-PET appears to result in greater sensitivity compared to anatomic imaging modalities, particularly computed tomography (CT). Over several decades CT has been the principal imaging modality for the staging and restaging of lymphoma, although it can have significant shortcomings stemming from its sized-based criteria, particularly in the post-therapy setting. Gallium-67 (Ga-67) scintigraphy has played an important role in monitoring response to therapy; however, the sensitivity of Ga-67 depends on histologic subtype of lymphoma, size, and location of disease. Published results suggest that FDG-PET is superior to Ga-67 imaging and equal or superior to CT for the detection of nodal and extranodal lymphoma at initial staging. Furthermore, persistent FDG uptake during and after chemotherapy has a high sensitivity and specificity for prediction of subsequent relapse. While in some cases FDG-PET imaging can yield findings that prompt a change in treatment strategy, prospective studies are necessary to better establish the ability of routine FDG-PET imaging to impact therapeutic outcomes for patients with lymphoma.     

PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease.

Early identification of chemotherapy-refractory lymphoma patients provides a basis for alternative treatment strategies. Metabolic imaging with (18)F-FDG PET offers functional tissue characterization that is useful for assessing response to therapy. Our objective was to determine the predictive value of (18)F-FDG PET early during chemotherapy (after 1 cycle) and at the completion of chemotherapy for subsequent progression-free survival (PFS) in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). METHODS: (18)F-FDG PET (dual-head coincidence camera with attenuation correction) was performed before and after 1 cycle of chemotherapy on 30 patients (17 NHL, 13 HD; mean age, 52.3 +/- 16.0 y). For 23 of the 30 patients, (18)F-FDG PET data were also obtained after the completion of chemotherapy. The patients had a median follow-up of 19 mo (range, 18-24 mo). Follow-up of PFS was compared between patients with positive and negative (18)F-FDG PET results obtained after the first cycle of chemotherapy and at the completion of chemotherapy. RESULTS: Positive (18)F-FDG PET results obtained both after the first cycle and at the completion of therapy were associated with a shorter PFS (median, 5 and 0 mo, respectively) than were negative (18)F-FDG PET results (PFS medians not reached). A statistically significant difference in PFS between positive and negative (18)F-FDG PET results was obtained both after the first cycle and at the completion of chemotherapy (P < or = 0.001). The PFS and (18)F-FDG PET results obtained after the first cycle correlated better than those obtained after the completion of chemotherapy (r(2) = 0.45 vs. 0.17). (18)F-FDG PET had more false-negative results after the last cycle (6/17 cases, or 35%) than after the first cycle (2/13 cases, or 15%). Thus, (18)F-FDG PET had greater sensitivity and positive predictive values after the first cycle (82% vs. 45.5% and 90% vs. 83%, respectively) than after the last cycle. CONCLUSION: (18)F-FDG PET after 1 cycle of chemotherapy is predictive of 18-mo outcome in patients with aggressive NHL and HD and may earlier identify patients who would benefit from more intensive treatment programs.     

Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin's disease in the mediastinum.

In a retrospective study of a series of 30 adult patients during restaging of Hodgkin's disease after therapy, computed tomography (CT) and biopsy results were correlated with 67Ga SPECT in order to determine the value of SPECT imaging in monitoring recurrent mediastinal Hodgkin's disease. SPECT had an overall accuracy of 93% (28/30) and correctly identified active disease in 24 of 25, 96% of histopathologically proven recurrent Hodgkin's disease. Thus in this post-therapy setting, we have confirmed the high sensitivity of 67GA SPECT scans in patients selected for biopsy. Gallium-67 may prove particularly useful in detecting residual disease activity in patients in whom biopsy was positive but the interpretations of the CT scans were uncertain in regard to presence of tumors [8/30 (27%)]. In this group of patients, we found SPECT particularly helpful. A larger prospective series is under way to assess this possibility.     

Early 18F-labeled fluoro-2-deoxy-D-glucose positron emission tomography scanning in the lymphomas: changing the paradigms of treatments?

The identification of refractory or nonresponding tumors at an early period during therapy may lead to abbreviation of the current therapy regimen or timely institution of an alternative therapy protocol. Nevertheless, evaluation of treatment response is consequential clinically if the tumor potentially is curable and if effective treatment alternatives exist, so that change in treatment ultimately may increase the probability of response and survival. Hodgkin disease (HD) and diffuse large cell lymphoma (LCL) fit in this model well. However, a subset of patients is either refractory to first-line treatment or develops recurrent disease after an initial remission. Improvements in the treatment of these diseases rely not only on new therapy modalities and accurate assessment of disease extent but also on the assessment of disease extent and on timely and accurate therapy response to enable a more effective management plan. Although the International Prognostic Score for HD and International Prognostic Index for LCL have proved valuable for the stratification of patients in clinical trials, there is variability in outcome within the individual risk groups. Recently, positron emission tomography using (18)F-labeled fluoro-2-deoxy-D-glucose (FDG-PET) imaging has been suggested as a sensitive and relatively more specific means to reflect tumor biologic changes after therapy. With increasingly compelling evidence, early FDG-PET provides a reliable means to assess tumor response accurately that may lead to better management with an effective therapeutic approach.     

FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease

BACKGROUND: Early prediction of response to therapy may offer the potential to identify patients who will benefit from standard conventional therapy. The objective of this study was to determine the predictive value of FDG-PET as an early response indicator after 1 cycle of chemotherapy for progression-free survival (PFS) in diffuse large cell lymphoma (DLCL) and classic Hodgkin disease (HD). METHODS: FDG-PET was performed before, after 1 cycle, and after completion of chemotherapy in 47 patients. The patients were followed with a median follow-up of 21 months (range, 3-47 months). PFS was compared between PET-positive and PET-negative patients after 1 cycle and after completion of therapy. RESULTS: All PET-negative patients after 1 cycle (n = 31) had sustained complete remission with a median follow-up of 28 months. Fourteen of 16 PET-positive patients after 1 cycle had refractory disease or relapsed (median PFS, 5.5 months). There were 2 false-positive results, 1 with an active infection at the biopsy site and the other in a patient who had been in remission after radiation therapy. There was good agreement between the results obtained after 1 cycle and at completion of therapy (kappa, 0.80); however, the negative predictive value was higher for FDG-PET after 1 cycle than after completion of chemotherapy (100% vs 91.4%), although not statistically different (P = .40). CONCLUSIONS: FDG-PET had a high prognostic value after 1 cycle of chemotherapy, thus it can be a valid alternative for posttreatment evaluation of DLCL and HD and may offer the potential for change in treatment paradigms.     

Subsequent therapy can be administered after tositumomab and iodine I-131 tositumomab for non-Hodgkin lymphoma

BACKGROUND: Iodine I-131 tositumomab is a well tolerated and effective therapy for recurrent low-grade and transformed low-grade non-Hodgkin lymphoma (NHL). Hematologic reserve after radioimmunotherapy (RIT) is an important consideration when subsequent therapy is required. METHODS: One hundred fifty-five patients who received treatment with I-131 tositumomab were assessed, and 68 patients had progressive disease after RIT. The median age (n=68 patients) was 59 years (range,18-82 yrs), and patients received a median of 2 pre-RIT regimens (range,1-8 regimens), including 66% who received anthracycline, 19% who received platinum, and 50% who received fludarabine. RESULTS: The median time to disease progression (among progressors) was 168 days (range, 19-771 days). At the time they developed recurrent disease, patients had median white blood cell count (WBC) of 4.9 K cells/microL (range, 1.1-21.4 K cells/microL), a median absolute neutrophil count (ANC) of 3.25 K cells/microL (range, 0.59-8.20 K cells/microL), a median platelet count of 130 K cells/microL (range, 9-440 K cells/microL), and there was no significant difference between pre-RIT and recurrence values except for the platelet count (P<0.05). No patient demonstrated a WBC<1.0 K cells/microL or an ANC<0.5 K cells/microL, although 1 patient had a platelet count<10 K cells/microL. Twenty-four patients subsequently received no further chemotherapy; and, in 21 patients (88%), hematologic parameters appeared to allow subsequent chemotherapy if necessary (blood counts: National Cancer Institute Grade 0-2). Among 44 patients (65%) who received further chemotherapy (median, 2 regimens; range, 1-4 regimens), 19 patients (43%) were treated with anthracyclines, 17 patients (39%) were treated with platinum, 10 patients (23%) were treated with fludarabine, and 13 patients (30%) underwent stem cell transplantation. Disease improvement occurred in most patients, although 18 patients died (40%) after further chemotherapy, predominantly from refractory lymphoma. CONCLUSIONS: Most patients with progressive disease after treatment with iodine I-131 tositumomab were able to receive subsequent therapy, including cytotoxic chemotherapy and stem cell transplantation.