Classic Hodgkin Lymphoma in Adolescents and Young Adults.

Hodgkin lymphoma (HL) represents one of the more common cancers occurring in adolescent and young adults (AYAs) age 15-39 years. Despite a generally high cure rate, age-related differences in HL biology and the optimal therapeutic approaches including supportive care and risks for long-term adverse effects in the AYA population remain understudied. After an overview of HL epidemiology and biology in the AYA population, this review will cover frontline pediatric and adult treatment approaches. Recently completed and ongoing studies will foster harmonization of risk group definition and trial eligibility criteria across the AYA spectrum, enabling more rapid progress. In addition to treatment approaches, an evolving holistic care approach to AYA HL will result in enhanced understanding of unique challenges, and continued improved short- and long-term outcome for these patients.

Is Radiation Therapy Cost-Effective in the Positron Emission Tomography/Computed Tomography Era for Early-Stage Favorable Hodgkin Lymphoma With Alternative Payment Models?

PURPOSE: Despite multiple randomized trials, variation in practice remains regarding the most effective treatment for early-stage, favorable-risk Hodgkin lymphoma. With increasing emphasis on alternative payment models, we investigate the cost-effectiveness of chemotherapy alone versus combined modality therapy (CMT). METHODS AND MATERIALS: A Markov model was formed to compared 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) to 2 cycles of ABVD followed by 20 Gy in 10 fractions involved-site radiation therapy. Modalities were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs) and evaluated with a willingness to pay a threshold of $100,000 per QALY gained. RESULTS: The base case analysis showed that CMT is cost-effective compared with ABVD alone, with an incremental cost-effectiveness ratio of $8028 per QALY gained and an incremental cost of $236 gaining 0.029 QALYs. On sensitivity analyses, the results were the most sensitive to changes in recurrence rates. If the recurrence rate differences were ≥6%, CMT was cost-effective. CONCLUSIONS: CMT is a cost-effective strategy for early-stage, favorable-risk Hodgkin lymphoma based on currently available evidence. However, small variations in recurrence-rate estimates dramatically affect strategy cost-effectiveness.

The effect of cannabis in the treatment of Hodgkin's lymphoma in a pregnant patient - extensive case report and literature review.

PURPOSE: Hodgkin lymphoma (HL) is the fourth most frequent cancer diagnosis among pregnant females. A multidisciplinary team is mandatory to obtain the best treatment and prognosis for the mother and for the baby. Here, we present the case of a patient diagnosed with HL and its evolution during 2 pregnancies. CASE PRESENTATION: Herein we present the case of a 21-year-old female Caucasian patient, with free history, diagnosed with HL stage IIB. The patient started first line chemotherapy and radiotherapy, with incomplete remission. She refused any other treatment. Five years later, the patient became pregnant and was offered chemotherapy in the 2nd trimester of pregnancy, that she refused, and delivered by C-section at 37 weeks. In the same year, the patient became pregnant again and was proposed termination of pregnancy, that she also refused. The MRI scan revealed progression of HL and she was admitted in the hospital several times for altered general condition, respiratory infections and increased need of painkillers including opioids. At 26 weeks of pregnancy, the patient began on her own a treatment with pure cannabis. Her pain and general status got better and the tumor tissue decreased. She delivered by C-section at 34 weeks a boy that presented in the first 24 h postpartum a withdrawal syndrome and intestinal invagination, requiring care in NICU and surgery with bowel resection. CONCLUSION: Therefore, we can conclude that cannabis could be part of oncological treatment. No other case like this, as far as we know, has been previously reported.

Improving outcomes after autologous transplantation in relapsed/refractory Hodgkin lymphoma: a European expert perspective.

Autologous stem cell transplantation (ASCT) is a well-established approach to treatment of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) recommended by both the European Society for Medical Oncology and the National Comprehensive Cancer Network based on the results from randomized controlled studies. However, a considerable number of patients who receive ASCT will progress/relapse and display suboptimal post-transplant outcomes. Over recent years, a number of different strategies have been assessed to improve post-ASCT outcomes and augment HL cure rates. These include use of pre- and post-ASCT salvage therapies and post-ASCT consolidative therapy, with the greatest benefits demonstrated by targeted therapies, such as brentuximab vedotin. However, adoption of these new approaches has been inconsistent across different centers and regions. In this article, we provide a European perspective on the available treatment options and likely future developments in the salvage and consolidation settings, with the aim to improve management of patients with HL who have a high risk of post-ASCT failure. CONCLUSIONS: We conclude that early intervention with post-ASCT consolidation improves outcomes in patients with R/R HL who require ASCT. Future approvals of targeted agents are expected to further improve outcomes and provide additional treatment options in the coming age of personalized medicine.

Assessment of Radiation Doses Delivered to Organs at Risk Among Patients With Early-Stage Favorable Hodgkin Lymphoma Treated With Contemporary Radiation Therapy.

Importance: Response-adapted randomized trials have used positron emission tomography-computed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. Objective: To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. Design, Setting, and Participants: This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography-computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. Exposures: 2 cycles of chemotherapy followed by 20-Gy involved-site RT. Main Outcomes and Measures: The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. Results: The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). Conclusions and Relevance: In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

A Comparison of the BEAM and MITO/MEL Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma: An Analysis of Efficiency and Treatment-Related Toxicity.

BACKGROUND: Approximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol. PATIENTS AND METHODS: In this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM. RESULTS: The median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P < .001). CONCLUSION: The MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.

Near-field infrared nanospectroscopy and super-resolution fluorescence microscopy enable complementary nanoscale analyses of lymphocyte nuclei.

Recent super-resolution fluorescence microscopy (3D-Structured Illumination Microscopy, 3D-SIM) studies have revealed significantly altered nuclear organization between normal lymphocyte nuclei and those of classical Hodgkin's Lymphoma. Similar changes have been found in Multiple Myeloma (MM) nuclei, as well as in a premalignant condition, Monoclonal Gammopathy of Unknown Significance (MGUS). Using 3D-SIM, an increase in DNA-poor and DNA-free voids was evident in reconstructed 3D-SIM images of diseased nuclei at 40 nm pixel resolution (x,y: 40 nm, z: 80 nm). At best, far-field FTIR imaging yields spatially resolved images at ∼500 nm spatial resolution; however, near-field infrared imaging breaks the diffraction limit at a scale comparable to that of 3D-SIM, providing details on the order of 30 nm spatial resolution. We report here the first near-field IR imaging of lymphocyte nuclei, and far-field IR imaging results of whole lymphocytes and nuclei from normal human blood. Cells and nuclei were mounted on infrared-compatible substrates, including CaF2, undoped silicon wafers, and gold-coated silicon wafers. Thermal source far-field FTIR images were obtained with an Agilent-Cary 620 microscope, 15× objective, 0.62 NA and 64 × 64 array Focal Plane Array detector (University of Manitoba), or with a similar microscope equipped with both 15× and 25× (0.81 NA) objectives, 128 × 128 FPA and either thermal source or synchrotron source (single beam) infrared light at the Advanced Light Source (ALS), LBNL, Berkeley CA. Near-field IR spectra were acquired at the ALS, on the in-house SINS equipment, as well as with a Neaspec system, both illuminated with synchrotron light. Finally, some near-field IR spectra and images were acquired at Neaspec GmbH, Germany. Far-field IR spectra of normal cells and nuclei showed the characteristic bands of DNA and proteins. Near-field IR spectra of nuclei showed variations in bands assigned to protein and nucleic acids including single and double-stranded DNA. Near-field IR images of nuclei enabled visualization of protein and DNA distribution in spatially-resolved chromosome territories and nuclear pores.

Medical Cannabis Use by Hodgkin Lymphoma Patients: Experience of a Single Center.

Hodgkin lymphoma (HL) is one of the most curable malignancies. Despite its effectiveness, chemotherapy is often associated with adverse events (AEs) such as nausea, anorexia, and impairment of general well-being. Our objective was to assess the extent of medical cannabis use among HL patients and evaluate its efficacy in controlling chemotherapy-related AEs. Patterns of medical cannabis use and efficacy were evaluated using physician-completed application forms, medical files, and patient-completed questionnaires, for all consecutive adult HL patients treated at the Tel-Aviv Medical Center between June 2010 and November 2016. One-hundred and thirty-three patients met the inclusion criteria. The median age of the cohort was 37 years, 53% were male, 46% were diagnosed at an early stage, and 88% achieved a complete response to treatment. Fifty-one patients (38%) used medical cannabis. There were no significant differences in baseline characteristics between cannabis users and nonusers. Cannabis users reported improvement in pain, general well-being, appetite, and nausea in 94, 87, 82, and 79% of cases, respectively. Importantly, 81.5% reported a high overall efficacy of cannabis in relieving symptoms. AEs related to cannabis use itself were mild. Thus, medical cannabis use is prevalent in this HL cohort, and appears to be effective in ameliorating chemotherapy-related AEs.

Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial.

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS (P < .0001) and OS (P = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm3) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm3). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d'Etude des Lymphomes de l'Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well.

Whole-Body Diffusion-weighted MR Imaging of Iron Deposits in Hodgkin, Follicular, and Diffuse Large B-Cell Lymphoma.

Purpose To analyze the frequency and distribution of low-signal-intensity regions (LSIRs) in lymphoma lesions and to compare these to fluorodeoxyglucose (FDG) uptake and biologic markers of inflammation. Materials and Methods The authors analyzed 61 untreated patients with a bulky lymphoma (at least one tumor mass ≥7 cm in diameter). When a LSIR within tumor lesions was detected on diffusion-weighted images obtained with a b value of 50 sec/mm2, a T2-weighted gradient-echo (GRE) sequence was performed and calcifications were searched for with computed tomography (CT). In two patients, Perls staining was performed on tissue samples from the LSIR. LSIRs were compared with biologic inflammatory parameters and baseline FDG positon emission tomography (PET)/CT parameters (maximum standardized uptake value [SUVmax], total metabolic tumor volume [TMTV]). Results LSIRs were detected in 22 patients and corresponded to signal void on GRE images; one LSIR was due to calcifications, and three LSIRS were due to a recent biopsy. In 18 patients, LSIRs appeared to be related to focal iron deposits; this was proven with Perls staining in two patients. The LSIRs presumed to be due to iron deposits were found mostly in patients with aggressive lymphoma (nine of 26 patients with Hodgkin lymphoma and eight of 20 patients with diffuse large B-cell lymphoma vs one of 15 patients with follicular lymphoma; P = .047) and with advanced stage disease (15 of 18 patients). LSIRS were observed in spleen (n = 14), liver (n = 3), and nodal (n = 8) lesions and corresponded to foci FDG uptake, with mean SUVmax of 9.8, 6.7, and 16.2, respectively. These patients had significantly higher serum levels of C-reactive protein, α1-globulin, and α2-globulin and more frequently had microcytic anemia than those without such deposits (P = .0072, P = .003, P = .0068, and P < .0001, respectively). They also had a significantly higher TMTV (P = .0055) and higher levels of spleen involvement (P < .0001). Conclusion LSIRs due to focal iron deposits are detected in lymphoma lesions and are associated with a more pronounced biologic inflammatory syndrome. © RSNA, 2017 Online supplemental material is available for this article.

[Treatment of indolent cutaneous B­cell lymphoma]. / Therapie indolenter kutaner B­Zell-Lymphome.

Primary cutaneous B­cell lymphomas are rarely encountered and represent 25% of all cutaneous lymphomas. Follicular B­cell lymphoma and marginal zone lymphoma belong to indolent subtypes which as a rule have no systemic dissemination and, thus, a mostly unchanged life expectancy. Therefore, skin-directed treatment options such as excision or radiotherapy are usually sufficient to control the disease. In contrast, cutaneous diffuse large B­cell lymphoma and EBV-associated B­cell lymphomas of the skin belong to more aggressive entities which demand a systemic first-line upfront therapy with R­CHOP. Nevertheless, mortality is still high and comparable to that of systemic/nodal large B­cell lymphomas so that the identification of pathogenetic driver mutations or novel therapeutic targets may pave the way to better target-oriented therapies.

Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment.

We investigated the prognostic value of interim F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis.Thirty pHL patients (age ≤16) underwent serial F-FDG PET/CT: at baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (ΔΣSUVmax0-2, ΔΣSUVmean0-2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3-78).Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan-Meier method.Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for ΔΣSUVmax0-2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between ΔΣSUVmax0-2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P = 0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P = 0.005).Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (ΔΣSUVmax0-2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies.

Clinicoepidemiological profiles, clinical practices, and the impact of holistic care interventions on outcomes of pediatric hematolymphoid malignancies - A 7-year audit of the pediatric hematolymphoid disease management group at Tata Memorial Hospital.

INTRODUCTION: The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) at a tertiary cancer care hospital developed extensive patient support programs to improve retention and outcomes while focusing on protocols adapted to meet patient needs. An audit of measures and outcomes was done for a 7-year period from January 2010 to December 2016. MATERIALS AND METHODS: DMG protocols and patient support activities over the study period were documented and audited. Data was retrieved from internal databases and records. Measures taken and their impact were assessed by descriptive analytical tools. Survival outcomes were calculated using Kaplan-Meier method on SPSS v. 24™ software. RESULTS: Holistic patient support measures were undertaken through a charitable foundation entirely under pediatric oncology. Activities included infrastructure growth, socioeconomic support, provision of accommodation, nutrition, education, and multiple blood component donation drives. Patient registrations increased from 502 in 2009 to 874 in 2016, with the steepest rise in acute lymphoblastic leukemia (ALL) - 330 (2009) to 547 (2016). Treatment refusal and abandonment rates decreased from 32% to 3.4% over the same period, and male to female ratio decreased from 2.56 to 2.28:1. Early mortality in acute myeloid leukemia (AML) fell within 2 years from 26.7% in 2009 to 7%. Five-year overall survival (OS) was 69.5% for all patients registered in 2010, whereas disease-specific 5-year OS was ALL 67.1%, AML 49.3%, chronic myeloid leukemia 100%, Hodgkin lymphoma 90.4%, and non-Hodgkin lymphoma 74.2%. CONCLUSIONS: Holistic patient support-specific activities and adapted protocols made a measurable impact on patient outcomes. High survival outcomes of patients have been achieved despite relatively few receiving salvage therapies or stem cell transplant.

Augmented efficacy of brentuximab vedotin combined with ruxolitinib and/or Navitoclax in a murine model of human Hodgkin's lymphoma.

Despite relative success of therapy for Hodgkin's lymphoma (HL), novel therapeutic agents are needed for patients with refractory or relapsed disease. Recently, anti-PD1 immunotherapy or treatment with the anti-CD30 toxin conjugate brentuximab vedotin (BV) have been associated with remissions; however, the median responses of complete responses (CRs) with the latter were only 6.7 mo. To obtain curative therapy, other effective agents, based on HL biology, would have to be given in combination with BV. Hodgkin's Reed-Sternberg (HRS) cells secrete cytokines including IL-6 and -13, leading to constitutive activation of JAK/STAT signaling. In the present study the JAK1/2 inhibitor ruxolitinib reduced phosphorylation of STAT3 and STAT6 and expression of c-Myc in the HL cell line HDLM-2. These changes were enhanced when, on the basis of a matrix screen of drug combinations, ruxolitinib was combined with the Bcl-2/Bcl-xL inhibitor Navitoclax. The combination augmented expression of Bik, Puma, and Bax, and attenuated Bcl-xL expression and the phosphorylation of Bad. The use of the two-agent combination of either ruxolitinib or Navitoclax with BV or the three-agent combination strongly activated Bax and increased activities of cytochrome c and caspase-9 and -3 that, in turn, led to cleavage of poly(ADP ribose) polymerase and Mcl-1. Either ruxolitinib combined with Navitoclax or BV alone prolonged survival but did not cure HDLM-2 tumor-bearing mice, whereas BV combined with ruxolitinib and/or with Navitoclax resulted in a sustained, complete elimination of the HDLM-2 HL. These studies provide scientific support for a clinical trial to evaluate BV combined with ruxolitinib in select patients with HL.

Acquisition of CD30 and CD15 accompanied with simultaneous loss of all pan-T-cell antigens in a case of histological transformation of mycosis fungoides with involvement of regional lymph node: an immunophenotypic alteration resembling classical Hodgkin lymphoma.

: Acquired expression of CD30 is frequently noted in histological transformation of mycosis fungoides (MF), but simultaneous gain of CD15 accompanied with loss of pan-T-cell antigens are extremely rare. We report an unusual case of transformed MF with such an immunophenotypic alteration resembling classical Hodgkin lymphoma. The patient was an 81-year-old male with MF, who was initially treated with topical steroids and phototherapy. Despite the initial response, the patient developed a tumor-like skin lesion that was confirmed to be CD30-positive large T-cell lymphoma and was subsequently found to have a regional lymph node involvement by pleomorphic large cell lymphoma. Besides CD30, pleomorphic large cells were positive for CD15 but negative for all B cell- and T cell-specific antigens. Epstein-Barr virus was negative. Polymerase chain reaction-based assays demonstrated a clonal rearrangement of T-cell receptor gamma gene but detected no B-cell clone. The mechanism and clinical significance of this phenotypic conversion remains to be elucidated.

Impact of risk factors on outcomes in early-stage Hodgkin's lymphoma: an analysis of international staging definitions.

BACKGROUND: In early-stage Hodgkin's lymphoma (HL), treatment according to the early favorable or unfavorable subgroup is guided by staging definitions, which differ between various study groups worldwide. We analyzed risk factors used in different international staging systems and their impact on the outcome of early-stage HL patients. PATIENTS AND METHODS: In 1173 early-stage HL patients treated homogenously within the German Hodgkin Study Group (GHSG) trials HD10 and HD11, the impact of three staging systems developed and used by the GHSG, the European Organization for Research and Treatment of Cancer (EORTC), and the National Comprehensive Cancer Network (NCCN) in discriminating risk groups for progression-free survival (PFS) and overall survival (OS) was assessed and the relevance of their single risk factors was investigated. RESULTS: All the three staging systems defined an unfavorable risk group out of early-stage patients of comparable size (56%, 55%, and 57%), having a significantly poorer PFS and OS as compared with the corresponding favorable group; 5-year differences between early favorable and early unfavorable in terms of PFS were 9.4% (HR 2.61, 95% CI 1.74-3.91), 6.7% (HR 2.10, 95% CI 1.41-3.13), and 8.6% (HR 2.14, 95% CI 1.45-3.16) with the GHSG, EORTC, and NCCN definition, respectively. Sensitivity was high for all systems (84%, 79%, and 83%); however, there was a low specificity with high rates of false-positive results (1-specificity 54%, 53%, and 55%, respectively). Models of high sensitivity included risk factors associated with large tumor burden and high tumor activity. Most risk factors for tumor-specific end points were also predictive of OS. CONCLUSIONS: Differentiating between a favorable and an unfavorable risk group has significant impact on PFS and OS in early-stage HL patients in the modern treatment era. Risk-adapted treatment strategies using new risk factors with higher specificity are needed.

Lymphocyte-predominant Hodgkin disease: a comprehensive overview.

Lymphocyte-predominant Hodgkin disease is a rare form of Hodgkin lymphoma that is recognized as a separate histopathological entity. This disease tends to have multiple relapses, but has an overall good prognosis. Owing to its rarity, and the prolonged time period between recurrence and transformation events, there is no consensus regarding optimal management. However, the National Comprehensive Cancer Network guidelines indicate that for early stages, appropriate treatment is radiotherapy. Several management options have been reported including observation, radiation, chemotherapy, combined chemoradiotherapy, and anti-CD20 antibody therapy. Salvage therapy remains effective in inducing prolonged remission in patients with relapsed/refractory disease.

Involved node radiation therapy: an effective alternative in early-stage hodgkin lymphoma.

PURPOSE: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. METHODS AND MATERIALS: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. RESULTS: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. CONCLUSIONS: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL.

Anti-CD30-targeted gold nanoparticles for photothermal therapy of L-428 Hodgkin's cell.

PURPOSE: Due to the efficient bioconjugation and highly photothermal effect, gold nanoparticles can stain receptor-overexpressing cancer cells through specific targeting of ligands to receptors, strongly absorb specific light and efficiently convert it into heat based on the property of surface plasmon resonance, and then induce the localized protein denaturation and cell death. METHODS: Two gold nanoparticle-antibody conjugates, gold-BerH2 antibody (anti-CD30 receptor) and gold-ACT1 antibody (anti-CD25-receptor), were synthesized. Gold-BerH2 conjugates can specifically bind to the surface of L-428 Hodgkin's cells, and gold-ACT1 conjugates were used for the control. The gold nanoparticle-induced L-428 cell-killing experiments were implemented with different experimental parameters. RESULTS: At a relatively low concentration of gold and short incubation time, the influence of cytotoxicity of gold on cell viability can be overlooked. Under laser irradiation at suitable power, the high killing efficiency of gold-targeted L-428 cells was achieved, but little damage was done to nontargeted cancer cells. CONCLUSION: Gold nanoparticle-mediated photothermal therapy provides a relatively safe therapeutic technique for cancer treatment.

The dermatology hospitalist: creating value by rapid clinical pathologic correlation in a patient-centered care model.

BACKGROUND: The active and continuous presence of dermatologists in hospitals has undergone continued involution over the past two decades. Our patient-centered, value-based dermatology hospitalist model describes an efficient system for the integration of the dermatologist in the hospital treatment team. METHODS: We describe five difficult inpatient cases to illustrate the value of dermatology intervention and clinical pathologic correlation in facilitating timely diagnosis and treatment. RESULTS: Prompt specialty evaluation and clinicopathologic correlation by hospital dermatologists led to decreased morbidity and the avoidance of delay in initiating definitive treatment. CONCLUSIONS: Efficient evaluation and clinicopathologic correlation by dermatology hospitalists are essential to hospitals that provide comprehensive care. This value-based model has the potential to produce better patient outcomes and greater satisfaction in both patients and other health care providers.