A PET-radiomics diagnostic signature to differentiate Hodgkin lymphoma from aggressive non-Hodgkin lymphomas.

We investigated the correlation between the apparent diffusion coefficient (ADC) and Ki-67 index using diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), and their utility in evaluating malignant lymphoma cell proliferation. Seventy-four patients with malignant lymphoma underwent DWIBS within 1 week before pathological confirmation. The ADC value was measured at the site of the pathological examination, and specimens were also stained with Ki-67. The ADC values and Ki-67 indices in aggressive non-Hodgkin's lymphoma (NHL), indolent NHL, and Hodgkin's lymphoma (HL) were compared using Spearman's rank correlation coefficient and the Kruskal-Wallis test. The Ki-67 indices and ADC values were inversely correlated (r = -0.289, p = 0.0125); the differences in the Ki-67 index between aggressive NHL, indolent NHL, and HL were significant (p < 0.001); this was confirmed by the Nemenyi test except for indolent NHL vs. HL. The ADC values were significantly different between the types of lymphoma (p = 0.013); the Nemenyi test showed a significant difference only between aggressive NHL and HL. The Ki-67 indices and ADC values are inversely correlated in patients with lymphoma, combining DWIBS and ADC values can evaluate the proliferation level of malignant lymphoma cells noninvasively. • By using DWIBS, malignant lymphoma cell proliferation can be assessed noninvasively. • The ADC value and Ki-67 index are significantly and inversely correlated. • The ADC values were lower in aggressive NHL than in HL. • The ADC values of aggressive and indolent NHL were not significantly different.

Are We Ready for Positron Emission Tomography/Computed Tomography-based Target Volume Definition in Lymphoma Radiation Therapy?

Late Effects after Autologous Hematopoietic Cell Transplantation

Although studies have shown that (18)F-FDG PET, when used to assess the response of malignant lymphoma after treatment, has a strong ability to predict relapse, its diagnostic accuracy in clinical practice remains unclear. The aim of this study was to systematically review the diagnostic accuracy of (18)F-FDG PET in detecting residual disease at the completion of first-line therapy of Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL). We searched relevant articles from 1966 to July 2006 using MEDLINE, EMBASE, SCOPUS, Biological Abstracts, bibliographies, review articles, and textbooks without language restriction. One assessor (for non-English-language studies) or 2 assessors (for English-language studies) independently reviewed each article to abstract relevant study characteristics and results. Relevant individual patient data or subgroup data were provided by the investigators if they were unavailable from the publications. We estimated summary receiver operating characteristic curves and confidence regions for summary sensitivity and specificity. Nineteen studies consisting of 474 HD and 254 aggressive NHL patients were included. These studies had heterogeneity and suboptimal methodologic quality and reporting. Reported ranges for the sensitivity and specificity of (18)F-FDG PET in predicting disease relapse were 0.50-1.00 and 0.67-1.00, respectively, for HD and 0.33-0.77 and 0.82-1.00, respectively, for NHL. These estimates were similar when conventional imaging tests showed a residual mass. For HD studies, the summary receiver operating characteristic curves were similar irrespective of whether a residual mass was detected by conventional tests. Factors explaining the variability of diagnostic estimates were not identified. Although currently available evidence is still limited, (18)F-FDG PET seems to have good diagnostic accuracy for assessing residual HD at the completion of first-line treatment. Clinical data on this use of (18)F-FDG PET for aggressive NHL are more limited. Prospective studies with a more rigorous research design, conduct, and reporting would more reliably reveal the clinical diagnostic accuracy of this imaging modality.

Patients with primary progressive or refractory Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL) have a particularly poor prognosis. Here we report the results of autologous tandem transplantation in these patients. Patients aged 18-55 years with primary progressive or refractory relapsed HD and aggressive NHL were included. Patients received high-dose etoposide (2000 mg/m(2)) followed by peripheral blood stem cell harvest (PBSC). The first high-dose chemotherapy (TMC) consisted of thiotepa (750 mg/m(2)), mitoxantrone (40 mg/m(2)), and carboplatin (990 mg/m(2)). Patients with no change (NC), partial remission (PR), or complete remission (CR) after TMC then received BEAM with carmustine (300 mg/m(2)), etoposide (1200 mg/m(2)), cytarabine (1600 mg/m(2)), and melphalan (140 mg/m(2)). Patients with bulky disease (>5 cm) or residual lymphoma received involved field radiotherapy. Twenty-five patients were included (HD=10, NHL=15, median age 34 years). Two patients with HD achieved a CR and five patients a PR [response rate (RR) 70%]. Three patients (30%) experienced treatment failure including two deaths due to peritransplant complications. Five patients with aggressive NHL were in CR and two patients in PR (RR 46%). Of the eight patients (56%) with treatment failure, three had progressive disease and five died from peritransplant complications. Freedom from treatment failure (FFTF) and overall survival (OS) for all patients after 12 months was 28% and 40%, respectively. Tandem HDCT followed by autologous stem cell transplantation (ASCT) offers a chance of cure in these poor prognostic patients, but is associated with risks.

The aim of this study was to evaluate the role of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the staging of Hodgkin's and aggressive non-Hodgkin's lymphoma (HL and NHL), comparing it with conventional diagnostic methods, i.e. contrast-enhanced CT and bone marrow biopsy. Sixty-five consecutive patients (30 HL and 35 NHL) who underwent conventional disease staging and FDG-PET/CT were included. Concordance between conventional methods and PET was established when both procedures identified the same disease stage. Discordant findings were investigated further by using other diagnostic techniques (ultrasonography or magnetic resonance imaging) and/or clinical follow-up. PET correctly staged 93.8% of enrolled patients (61/65), whereas conventional techniques correctly staged 89.2% (58/65; p=NS, Chi(2) test). There was complete concordance in 54/65 patients (83.1%); among the remaining 11 cases, PET upstaged eight patients (seven true positive and one false positive), and downstaged three (all false negative). In 5/65 patients, chemotherapy treatment was modified on the basis of PET findings. Our data confirm the high accuracy of FDG-PET/CT in staging HL and NHL. FDG-PET/CT should therefore be used routinely in the initial evaluation of both patient subgroups.

Although Hodgkin lymphoma (HL) is not considered an AIDSdefining malignancy, population-based studies have demonstrated an increased incidence of this disease in the setting of HIV infection. In a prospective cohort study of 11,112 individuals who were positive for HIV, with 71,687 patient-years of follow-up, the incidence of HL was 14 times higher than in the general population. In contrast to other HIV-associated malignancies that occur more commonly with severe immunocompromise, HL is associated with moderate immunologic impairment and the incidence actually seems to decline at CD4 lymphocyte counts of less than 200/ L. Although incidence rates for the AIDS-defining malignancies (Kaposi’s sarcoma, aggressive B-cell non-Hodgkin lymphoma [NHL]) have fallen, the incidence of HL may actually be increasing since the advent of combination antiretroviral therapy (cART), perhaps as a consequence of improvement in the level of immune function. However, the increased relative risk of HL is substantially lower than that observed for aggressive B-cell lymphoma. As a result of the small number of cases, studies investigating approaches to management of HIV-associated HL have been largely retrospective in design. For the more common AIDS-defining lymphomas, diffuse large B-cell lymphoma and Burkitt lymphoma, outcomes have improved dramatically in the 16 years since the introduction of active antiretroviral therapies, which have transformed HIV disease into a survivable chronic illness. Prospective studies in the pre-cART era demonstrated 2-year overall survival (OS) in the 10% to 20% range with complete remission (CR) rates of 35% to 50%, far inferior to those observed in non-HIV–associated lymphomas. Prognosis at that time was largely dependent on the severity of immunosuppression rather than on features of the lymphoma. This experience changed with the advent of cART such that now treatment outcomes using standard regimens such as rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab approach those observed in the non-HIV–infected population, with CR rates of 65% to 77% and 2-year OS rates of more than 60%. The International Prognostic Index (IPI) score seems to be a significant prognostic factor in patients treated with chemotherapy and concurrent cART. On the basis of the age-adjusted IPI score, the survival of patients in one trial using rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone was similar to that achieved by patients with aggressive lymphomas who were not infected with HIV. HL in the HIV-seropositive population is more likely to have mixed cellularity or lymphocyte-depleted histology and is almost always Epstein-Barr virus–associated. The majority of patients present with advanced-stage disease. Before the introduction of cART, treatment outcomes for HIV-HL were poor. In an Italian retrospective study of 114 patients with HIV-associated HL who received various standard chemotherapeutic regimens, the median OS was 15 months. Sixty percent died, 35% of those from opportunistic infection, 33% from HL, and 12% from both. As has been the case for aggressive B-cell lymphomas in patients with HIV infection, small retrospective and prospective studies have suggested improvement in outcome with the advent of cART. A retrospective study of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with cART in 62 patients with advanced-stage HIVassociated HL demonstrated a CR rate of 87% and 5-year OS of 76%. A prospective trial reported a CR rate of 81% and 2-year OS of 51% in 59 patients treated with the Stanford V regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) administered with antiretroviral therapy. The fact that only 10% of these patients received radiotherapy suggests that the regimen was either not delivered as designed or that the inclusion of patients with early-stage and low-bulk disease (factors associated with inferior outcome with this regimen) resulted in relatively disappointing outcomes. In the article that accompanies this editorial, the German HIV-Related Lymphoma Study Group presents data from the largest prospective trial ever conducted in patients with HIV-associated HL. In this study, 112 patients were allocated to treatment on the basis of stage and risk category. Those with early-stage favorable disease (IA/B or IIA/B) received two to four cycles of ABVD plus 30 Gy of involved-field radiotherapy. Patients with early-stage unfavorable disease received four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) at baseline or four cycles of ABVD followed by 30 Gy of involved-field radiotherapy if disease was 5 cm or residual disease was 2 cm. Those with advanced disease received eight cycles of BEACOPP with or without radiotherapy to sites 2.5 cm. Patients with advanced HIV disease, including Eastern Cooperative Oncology Group performance score 2, received ABVD. There were five toxic deaths: 4% with early favorable, 0% with early unfavorable, and 7% with advanced disease. CR rates were 96%, 100%, and 86% for these three groups, respectively, and 2-year PFS JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 33 NOVEMBER 2

Improved Outcomes of Autologous (Auto) Hematopoeitic Stem Cell Transplantation (HSCT) for Intermediate and High Risk (I/HR) Aggressive (AG) Non Hodgkin Lymphoma (NHL) with IV vs PO Busulfan (Bu) in a Bu, Cyclophosphamide (Cy) and Etoposide (E) Preparative Regimen.

Whole-body diffusion-weighted MRI and 18F-FDG PET/CT can discriminate between different lymphoma subtypes

The Role of Surveillance Imaging for the Detection of Relapsed Lymphoma.

Limited PET-CT May Be Adequate for Interim and End of Therapy Response Assessment in Patients with Early Stage Hodgkin and Aggressive Non-Hodgkin Lymphoma - A Retrospective Single Center Study

CT or CT/PET Surveillance in Asymptomatic Adult and Pediatric Patients Following Curative Intent Therapy for Hodgkin Lymphoma and Aggressive Non-Hodgkin Lymphoma: A Systematic Review

Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY) in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16) and methotrexate (MTX) in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC) transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65) affected by aggressive non-Hodgkin's lymphoma (NHL) (60.6%) or persistent or relapsed Hodgkin's disease (39.4%) were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease) followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233). Thirty-one patients underwent autografting and received a median of 6.19 x 10(6)/kg (1.07-29.3) CD34+ cells. Patients who were chemosensitive to HDCY (N = 22) and patients who were chemoresistant (N = 11) presented an overall survival of 96 and 15%, respectively (P<0.0001). Overall survival was 92% for chemosensitive patients and 0% for patients who were still chemoresistant before transplantation (P<0.0001). Toxicity-related mortality was 12% (four patients), related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment.

It is well known that localized cancers, including aggressive non-Hodgkin's lymphoma, have a better prognosis than cancers that have spread. When the results of treatment for aggressive non-Hodgkin's lymphoma are reported, the results for Ann Arbor stage I disease (involvement of a single lymph-node region) are typically reported separately from those for stage III (involvement of lymph nodes on both sides of the diaphragm) and stage IV (stage III plus extranodal involvement). The results of treatment for stage II disease (involvement of two or more lymph nodes on the same side of the diaphragm) may be included in either group. . . .

Long-Term Outcome of Gemcitabine, Vinorelbine, Liposomal-Doxorubicin (GVD) As Salvage Regimen for Patients with Previously Heavily Treated Hodgkin Lymphoma and Aggressive Non-Hodgkin Lymphoma