Summary
The epidemiology, outcome and targeted immunotherapy in adolescent and young adult non‐Hodgkin and Hodgkin lymphoma were discussed during the 6th International Symposium on Childhood, ...Adolescent and Young Adult Non‐Hodgkin Lymphoma September 26th–29th 2018 in Rotterdam, the Netherlands. This review summarizes some of those presentations, as well as other current and novel antibody therapy, immune check‐point inhibitors, chimeric antigen receptor T cells, cancer vaccines and cytotoxic T lymphocyte therapy.
The automatic classification of lymphoma lesions in PET is a main topic of ongoing research. An automatic algorithm would enable the swift evaluation of PET parameters, like texture and heterogeneity ...markers, concerning their prognostic value for patients outcome in large datasets. Moreover, the determination of the metabolic tumor volume would be facilitated. The aim of our study was the development and evaluation of an automatic algorithm for segmentation and classification of lymphoma lesions in PET.
Pre-treatment PET scans from 60 Hodgkin lymphoma patients from the EuroNet-PHL-C1 trial were evaluated. A watershed algorithm was used for segmentation. For standardization of the scan length, an automatic cropping algorithm was developed. All segmented volumes were manually classified into one of 14 categories. The random forest method and a nested cross-validation was used for automatic classification and evaluation.
Overall, 853 volumes were segmented and classified. 203/246 tumor lesions and 554/607 non-tumor volumes were classified correctly by the automatic algorithm, corresponding to a sensitivity, a specificity, a positive and a negative predictive value of 83%, 91%, 79% and 93%. In 44/60 (73%) patients, all tumor lesions were correctly classified. In ten out of the 16 patients with misclassified tumor lesions, only one false-negative tumor lesion occurred. The automatic classification of focal gastrointestinal uptake, brown fat tissue and composed volumes consisting of more than one tissue was challenging.
Our algorithm, trained on a small number of patients and on PET information only, showed a good performance and is suitable for automatic lymphoma classification.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. ...Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum.
Methods
After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy‐proven LR, an additional fluorodeoxyglucose (FDG)‐positron emission tomography (PET)‐CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated.
Results
After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth.
Conclusion
Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH.
Background
The International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH) seeks to provide a universally acceptable definition of cortical bone involvement in the ...staging of newly diagnosed pediatric Hodgkin lymphoma.
Procedure
A comprehensive literature search was performed using PubMed and Google Scholar with the search terms “Hodgkin lymphoma,” “osseous lesions,” “bony involvement,” and “pediatric.” Publications reviewed included case reports, retrospective analyses, and literature reviews. Each was evaluated for study design, number of participants, median age and age range at diagnosis, percentage of pediatric patients, criteria of interest definition, diagnostic tools, study objectives, and level of evidence. The final definition was based on the available data and consensus of the SEARCH working group.
Results
Twenty‐five papers specifically addressing cortical bone involvement in Hodgkin lymphoma met the inclusion criteria. Eighteen papers were case reports with literature reviews; the remainder were observational cohort studies. Of these, 14 included pediatric patients (aged 0‐21 years). The criteria for cortical bone involvement were not clearly defined in any paper, often varied within a study, and were inconsistent between publications.
Conclusions
The SEARCH group for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (CAYAHL) proposes the following criteria as defining cortical bone involvement: any cortical bone biopsy‐proven lesion; a positive bony window lesion on computer tomography (CT), with an FDG‐PET positive correlate in a patient with biopsy‐proven Hodgkin lymphoma, if there is no other typical skeletal pathology; auspicious skeletal lesions on FDG‐PET or magnetic resonance imaging should be confirmed by CT or Tc‐99m scan to distinguish cortical lesions from bone marrow involvement. Nodal masses that extend into bone with bony destruction are considered extranodal extension or “E” lesions and do not represent metastatic or stage IV disease.
The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin ...lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non‐transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus‐based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments.
Summary Background Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce ...the incidence of veno-occlusive disease in this setting. Methods In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov , number NCT00272948. Findings Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference −7·7%, 95% CI −15·3 to −0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Interpretation Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Funding Gentium SpA, European Group for Blood and Marrow Transplantation.
Background
In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet‐PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or ...nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross‐sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging.
Patients, materials, and methods
The EuroNet‐PHL‐C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross‐sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re‐assessed by applying an imaging‐based algorithm considering information from 18F‐fluorodeoxyglucose positron emission tomography, contrast‐enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging‐based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment.
Results
The imaging‐based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging‐based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient.
Conclusions
The imaging‐based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future.
Vincristine, etoposide, prednisone, and doxorubicin (OEPA)-cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) is derived from standard vincristine, procarbazine, prednisone, and ...doxorubicin (OPPA)-cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) chemotherapy by replacing procarbazine with etoposide and dacarbazine for a potentially less gonadotoxic regimen for boys with Hodgkin's lymphoma (HL).
Five hundred seventy-three pediatric patients with classical HL were enrolled onto the German Society of Pediatric Oncology and Hematology-Hodgkin's Disease (GPOH-HD) -2002 study between November 2002 and December 2005. Boys received two courses of OEPA and girls received two courses of OPPA for induction. Treatment group (TG) -2 (intermediate stages) and TG-3 (advanced stages) patients received further two or four cycles COPP (girls) or COPDAC (boys), respectively. After chemotherapy all patients received involved-field irradiation with 19.8 Gy, except for patients with early-stage disease (TG-1) in complete remission.
Five hundred seventy-three patients (287 males and 286 females) were less than 18 years old and fulfilled all inclusion criteria; 195 patients (34.0%) were allocated to TG-1, 139 (24.3%) were allocated to TG-2, and 239 (41.7%) were allocated to TG-3. Toxicity of OEPA-COPDAC was tolerable overall. Hematotoxicity was more pronounced with OEPA than OPPA, whereas it was less pronounced with COPDAC compared with COPP. The median observation time was 58.6 months. Overall survival and event-free survival (EFS) rates (+/- SE) at 5 years were 97.4% +/- 0.7% and 89.0% +/- 1.4%, respectively. In TG-1, overall EFS was 92.0% +/- 2.0%. EFS of patients without irradiation (93.2% +/- 3.3%) was similar to that of irradiated patients (91.7% +/- 2.5%), confirming results of the previous GPOH-HD-95 study. In TG-2+3, EFS did not significantly differ between boys and girls (90.2% +/- 2.3 v 84.7% +/- 2.7, respectively; P = .12).
In TG-2+3, results in boys and girls are superimposable. OPPA-COPP and OEPA-COPDAC seem to be exchangeable regimens in intermediate- and advanced-stage classical HL in pediatric patients.
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