Brentuximab vedotin and chemotherapy in relapsed/refractory Hodgkin lymphoma: a propensity score-matched analysis.

ABSTRACT: Several single-arm studies have explored the inclusion of brentuximab vedotin (BV) in salvage chemotherapy followed by autologous stem cell transplantation (ASCT) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, no head-to-head comparisons with standard salvage chemotherapy have been performed. This study presents a propensity score-matched analysis encompassing individual patient data from 10 clinical trials to evaluate the impact of BV in transplant-eligible patients with R/R cHL. We included 768 patients, of whom 386 were treated with BV with or without chemotherapy (BV cohort), whereas 382 received chemotherapy alone (chemotherapy cohort). Propensity score matching resulted in balanced cohorts of 240 patients each. No significant differences were observed in pre-ASCT complete metabolic response (CMR) rates (P = .69) or progression free survival (PFS; P = .14) between the BV and chemotherapy cohorts. However, in the BV vs chemotherapy cohort, patients with relapsed disease had a significantly better 3-year PFS of 80% vs 70%, respectively (P = .02), whereas there was no difference for patients with primary refractory disease (56% vs 62%, respectively; P = .67). Patients with stage IV disease achieved a significantly better 3-year PFS in the BV cohort (P = .015). Post-ASCT PFS was comparable for patients achieving a CMR after BV monotherapy and those receiving BV followed by sequential chemotherapy (P = .24). Although 3-year overall survival was higher in the BV cohort (92% vs 80%, respectively; P < .001), this is likely attributed to the use of other novel therapies in later lines for patients experiencing progression, given that studies in the BV cohort were conducted more recently. In conclusion, BV with or without salvage chemotherapy appears to enhance PFS in patients with relapsed disease but not in those with primary refractory cHL.

High-Frequency Language Therapy with Semantic Feature Analysis (SFA) and Transcranial Direct Current Stimulation (tDCS): A Longitudinal Single-Case Report of Semantic Variant of Primary Progressive Aphasia (svPPA).

BACKGROUND: The goal of this study was to investigate whether the combination of semantic feature analysis (SFA) and transcranial direct current stimulation (tDCS) is effective in treating word retrieval in the semantic variant of primary progressive aphasia (svPPA) and how long the potential effects last. METHODS: A 56-year-old woman diagnosed with frontotemporal dementia (FTD) and svPPA participated in this longitudinal single-subject design. A total of four 2-week stimulation phases were conducted over a 14-month period, each of which was started depending on the participant's language performance. Follow-up testing was conducted shortly after the stimulation period, approximately 2 weeks, and approximately 4 weeks thereafter. RESULTS: Significant improvement in word retrieval occurred after SFA and tDCS therapy. Two weeks after the end of each stimulation phase, approx. 80% of the trained words could be named correctly. For the untrained words, also significantly more words were correctly named at follow-ups compared to the baseline. Furthermore, the Boston Naming Test (BNT) demonstrated a significant increase in naming performance and showed that phonological cues facilitated word retrieval compared to semantic cues. CONCLUSION: The combination of SFA and tDCS was able to counteract the expected language deterioration of a participant with svPPA. This effect increased until approximately 2 weeks after each intervention. In addition, a generalization of the effect to untrained words was shown.

Sentence completion in progressive supranuclear palsy following transcranial direct current stimulation.

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian disorder which results in deterioration of motor and cognitive skills, including language disorders such as impaired word retrieval. While there is evidence of successful use of tDCS to improve word fluency in PSP, little is known about the effectiveness of brain stimulation for word retrieval in sentence context. Therefore, we investigated whether tDCS reduces sentence completion time in PSP patients. In this sham-controlled, triple-blinded crossover study, anodal tDCS (atDCS) was applied over the left Broca's area at 2 mA for 20 min (n = 23). In contrast to patients with multiple system atrophy (MSA), also an atypical Parkinsonian disorder, and healthy elderlies, sentence completion improved in PSP patients when tDCS was applied. The improvement in word fluency reported in previous studies using other electrode positions was not replicated. By using atDCS of the left Broca's area, we were able to demonstrate a difference between the two movement disorders. The obtained insight could be helpful to improve language therapy of these disorders.

Prognostic value of baseline metabolic tumor volume (MTV) for forecasting chemotherapy outcome in early-stage unfavorable Hodgkin lymphoma: Data from the phase III HD17 trial.

OBJECTIVES: The prognostic relevance of metabolic tumor volume (MTV) having recently been demonstrated in patients with early-stage favorable and advanced-stage Hodgkin lymphoma. The current study aimed to assess the potential prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in early-stage unfavorable Hodgkin lymphoma patients treated within the German Hodgkin Study Group HD17 trial. METHODS: 18 F-FDG PET/CT images were available for MTV analysis in 154 cases. We used three different threshold methods (SUV2.5 , SUV4.0 , and SUV41% ) to calculate MTV. Receiver-operating-characteristic analysis was performed to describe the value of these parameters in predicting an adequate therapy response. Therapy response was evaluated as PET negativity after 2 cycles of eBEACOPP followed by 2 cycles of ABVD. RESULTS: All three threshold methods analyzed for MTV showed a positive correlation with the PET response after chemotherapy. Areas under the curve (AUC) were 0.70 (95% CI 0.53-0.87) and 0.65 (0.50-0.80) using the fixed thresholds of SUV4.0 and SUV2.5 , respectively, for MTV- calculation. The calculation of MTV using a relative threshold of SUV41% showed an AUC of 0.63 (0.47-0.79). CONCLUSIONS: MTV does have predictive value after chemotherapy in early-stage unfavorable Hodgkin lymphoma, particularly when the fixed threshold of SUV4.0 is used for MTV calculation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01356680.

Web-Based Cognitive-Behavioral Therapy to Reduce Severe Cancer-Related Fatigue Among Survivors of Hodgkin Lymphoma: A Feasibility Study.

We investigated the feasibility of a web-based cognitive-behavioral therapy to reduce cancer-related fatigue (CRF) among survivors of Hodgkin lymphoma. In this before-and-after trial, patients were primarily recruited via the German Hodgkin Study Group (GHSG). We assessed feasibility (response and drop-out rate) and preliminary efficacy including CRF, quality of life (QoL), and depressive symptomatology. T tests compared baseline levels with t1 (post treatment) and t2 (3 months of follow-up). Among 79 patients contacted via the GHSG, 33 provided interest (42%). Among the seventeen participants, four were treated face-to-face (pilot patients), 13 underwent the web-based version. Ten patients completed the treatment (41%). Among all participants, CRF, depressive symptomatology, and QoL improved at t1 (p ≤ .03). The effect in one of the CRF measures remained at t2 (p = .03). Except for QoL, post-treatment effects were replicated among the completers of the web-based version (p ≤ .04). The potential for this program has been demonstrated, but needs to be re-assessed after identified issues on feasibility have been resolved.Trial registration: The study was registered at ClinicalTrials.gov (Number: NCT03968250).

Anodal transcranial direct current stimulation (atDCS) and functional transcranial Doppler sonography (fTCD) in healthy elderly and patients with MCI: modulation of age-related changes in word fluency and language lateralization.

Introduction: In addition to age-related changes in language, hemispheric lateralization of language functions steadily declines with age. Also, performance on word fluency tasks declines and is sensitive to the expression of dementia-related changes. The aim of this study is to evaluate the effect of anodal tDCS combined with a word fluency training on language lateralization and word fluency performance in healthy elderly subjects and in persons with mild cognitive impairment (MCI). Methods: The effect of anodal tDCS over the left inferio frontal gyrus (IFG) was measured in a group of healthy elderly up to the age of 67 years (YG, Ø = 63.9 ± 3.02), a group of healthy elderly aged 68 years and older (OG, Ø = 78.1, ± 4.85), and a group of patients with MCI (Ø = 81.18, ± 7.35) by comparing performance in phonological and semantic word fluency tasks before and after 3 days of tDCS. Half of the experimental participants received sham stimulation. In addition, language lateralization was determined using a lateralization index (LI) measured with functional transcranial Doppler sonography (fTCD) before and after the stimulation period. Results: Anodal tDCS was associated with significantly higher scores in phonological but not semantic word fluency in both YG and OG. In MCI patients, no difference was measured between the tDCS and sham groups in either word fluency task. fTCD showed significantly increased left lateralization in all three groups after the training phase. However, this effect was independent of tDCS and the degree of lateralization could not be predicted by word fluency performance in any of the groups. Discussion: Phonological word fluency can be increased with atDCS in healthy elderly people by stimulating the IFG in a 3-day training. When cognitive decline has reached a certain stage, as is the case with MCI, this paradigm does not seem to be effective enough.

Predictive value of baseline metabolic tumor volume in early-stage favorable Hodgkin Lymphoma - Data from the prospective, multicenter phase III HD16 trial.

BACKGROUND: 18F -fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the staging and response assessment of lymphoma patients. Our aim was to explore the predictive relevance of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with early stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD16 trial. METHODS: 18F-FDG PET/CT images were available for MTV and TLG analysis in 107 cases from the HD16 trial. We calculated MTV and TLG using three different threshold methods (SUV4.0, SUV41% and SUV140%L), and then performed receiver-operating-characteristic analysis to assess the predictive impact of these parameters in predicting an adequate therapy response with PET negativity after 2 cycles of chemotherapy. RESULTS: All three threshold methods analyzed for MTV and TLG calculation showed a positive correlation with the PET response after 2 cycles chemotherapy. The largest area under the curve (AUC) was observed using the fixed threshold of SUV4.0 for MTV- calculation (AUC 0.69 [95% CI 0.55-0.83]) and for TLG-calculation (AUC 0.69 [0.55-0.82]). The calculations for MTV and TLG with a relative threshold showed a lower AUC: using SUV140%L AUCs of 0.66 [0.53-0.80] for MTV and 0.67 for TLG [0.54-0.81]) were observed, while with SUV41% an AUC of 0.61 [0.45-0.76] for MTV, and an AUC 0.64 [0.49-0.80]) for TLG were seen. CONCLUSIONS: MTV and TLG do have a predictive value after two cycles ABVD in early stage Hodgkin lymphoma, particularly when using the fixed threshold of SUV4.0 for MTV and TLG calculation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00736320 .

Reproducibility of hemispheric lateralization over several days using functional transcranial Doppler sonography (fTCD): a pilot single-case study of word fluency.

Functional transcranial Doppler sonography (fTCD) is a time- and cost-effective, non-invasive approach to determining real time hemispheric lateralization and is well-suited for repetitive study designs comprising multiple days. To date, no study has examined the reproducibility of the direction and degree (strength) of lateralization during word fluency (WF) over multiple, consecutive sessions within a single person, although there are many studies of lateralization during language processing. Moreover, there is conflicting evidence as to whether there is a relationship between the degree of laterality and the word fluency performance. In this study, one right-handed male (aged 24 years) completed a total of seven examination sessions in the time span of 10 days. Each session comprised multiple phonological and semantic WF tasks. The maximum difference of relative cerebral blood flow velocity (CBFV) changes between the left and right middle cerebral artery (MCA) during WF was defined as the Lateralization Index (LI). The word-fluency performance and the LIs were used in a linear regression model to detect relative changes in the direction and degree of lateralization during repetitive WF tasks. The reproducibility of the direction of language-related lateralization is very stable over multiple sessions within this single person and the processed LIs were left-lateralized in every session for both WF tasks. In addition, performance during phonological WF could significantly predict the variability in the degree of lateralization. This result could not be confirmed for the semantic WF task. The results of this pilot study support the usage of fTCD as a reliable method for examining lateralization patterns, especially in longitudinal study designs. They also provide evidence for the notion that performance in WF tasks can be related to the degree of lateralization, at least intra-individually.

Clinical outcomes of relapsed and refractory Hodgkin lymphoma patients after contemporary first-line treatment: a German Hodgkin Study Group analysis.

To evaluate patterns of rrHL after contemporary first-line treatment we studied 409 patients with first rrHL (HD13: n = 87, HD14: n = 118, HD15: n = 188, HDR3i: n = 51) at a median age of 37.4 years (18.4-76.8) from the GHSG database. Time to first relapse was ≤12 months in 49% and stage III/IV rrHL present in 52% of patients. In total, 291 patients received high-dose chemotherapy and autologous stem-cell transplantation (ASCT) and intended ASCT failed in 38 patients. ASCT was primarily not intended in 80 patients largely due to low risk disease or age/comorbidities. Overall, 10-year progression-free (PFS) and overall survival (OS) rates after first relapse were 48.2% (95% CI 41.9-54.2%) and 59.4% (95% CI 53.0-65.2%), respectively, with significant differences between subgroups. Inferior survival was observed with no ASCT due to advanced age/comorbidities (five-year PFS 36.2%, 95% CI 17.7-55.0%) or failure of salvage therapy (five-year PFS 36.3%, 95% CI 19.7-53.2%). Similarly, presence of primary refractory disease or stage IV at rrHL conferred inferior survival. In patients with low-risk disease, however, survival appeared favorable even without ASCT (10 y PFS 72.6%, 95% CI 53.7-84.8%). We herein confirm the curative potential of current rrHL treatments providing a robust benchmark to evaluate novel therapeutic strategies in rrHL. Approximately 50% of rrHL patients experienced a consecutive relapse.

Reinduction therapy with everolimus in combination with dexamethasone, high-dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD-R3i).

Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18-60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0-13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.

Physiological Correlates of Processing Health-Related Information: An Idea for the Adoption of a Foreign Field.

Measuring health may refer to the measurement of general health status through measures of physical function, pain, social health, psychological aspects, and specific disease. Almost no evidence is available on the possible interaction of physiological measures and correlating emotional-affective states that are triggered by dealing with individual health-relevant issues and their specific processing modes. Public health research has long been concerned with the processing of health-related information. However, it is not yet clear which factors influence access and the handling of health-related information in detail. One way to close this research gap could be adopting methods from neurocognitive experiments to add psychophysiological data to existing approaches in health-related research. In this article, we present some of these methods and give a narrative overview and description of their usefulness for enlarged research in public health.

Abstract Action Language Processing in Eleven-Year-Old Children: Influence of Upper Limb Movement on Sentence Comprehension.

Regarding the embodiment of language processing in adults, there is evidence of a close connection between sensorimotor brain areas and brain areas relevant to the processing of action verbs. This thesis is hotly debated and has therefore been thoroughly studied in adults. However, there are still questions concerning its development in children. The present study deals with the processing of action verbs in concrete and abstract sentences in 60 eleven-year-olds using a decision time paradigm. Sixty-five children mirrored arm movements or sat still and rated the semantic plausibility of sentences. The data of the current study suggest that eleven-year-olds are likely to misunderstand the meaning of action verbs in abstract contexts. Their decision times were faster and their error rates for action verbs in concrete sentences were lower. However, the gender of the children had a significant influence on the decision time and the number of errors, especially when processing abstract sentences. Females were more likely to benefit from an arm movement before the decision, while males were better if they sat still beforehand. Overall, children made quite a few errors when assessing the plausibility of sentences, but the female participants more often gave plausibility assessments that deviated from our expectations, especially when processing abstract sentences. It can be assumed that the embodiment of language processing plays some role in 11-year-old children, but is not yet as mature as it is in adults. Especially with regard to the processing of abstract language, the embodied system still has to change and mature in the course of child development.

Non-Hodgkin lymphoma after treatment for classical Hodgkin lymphoma: a report from the German Hodgkin Study Group.

Data on non-Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first-line treatment within the randomized German Hodgkin Study Group (GHSG) HD7-HD15 studies. After a median follow-up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five-year event-free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death.

Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy.

PURPOSE: We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS: We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS: A total of 174 patients' disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION: After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

Early Response to First-Line Anti-PD-1 Treatment in Hodgkin Lymphoma: A PET-Based Analysis from the Prospective, Randomized Phase II NIVAHL Trial.

PURPOSE: A primary analysis of the ongoing NIVAHL trial demonstrated unexpectedly high interim complete response rates to nivolumab-based first-line treatment in early-stage unfavorable Hodgkin lymphoma. However, biomarkers such as metabolic tumor volume (MTV) or total lesion glycolysis (TLG) and their change under treatment (ΔMTV and ΔTLG), measured on PET, might provide additional relevant information for response assessment in this setting. Hence, the current analysis aimed to investigate early response to checkpoint inhibitor therapy beyond conventional criteria. PATIENTS AND METHODS: NIVAHL is a prospective, randomized phase II trial that recruited between April 2017 and October 2018. Patients in arms A and B were assessed for early treatment response after two courses of doxorubicin, vinblastine, and dacarbazine with two concomitant nivolumab infusions per cycle (2 × N-AVD) and 4 × nivolumab, respectively. In the current analysis, we included all 59 individuals with PET images available to the central review panel for quantitative analysis before April 30, 2019. RESULTS: At interim restaging, we determined a mean ΔMTV and ΔTLG of -99.8% each in arm A after 2 × N-AVD, compared with -91.4% and -91.9%, respectively, for treatment group B undergoing 4 × nivolumab. This high decrease in MTV and TLG was observed regardless of the initial lymphoma burden. CONCLUSIONS: Our study showed that nivolumab-based first-line treatment leads to rapid, near-complete reduction of tumor metabolism in early-stage unfavorable Hodgkin lymphoma. Thus, PET-derived biomarkers might allow reduction or even omission of chemotherapy and radiotherapy. Furthermore, MTV and TLG could be also used to optimize immune checkpoint-targeting treatments in other cancers.

The interplay between cancer-related fatigue and functional health in Hodgkin lymphoma survivors.

OBJECTIVE: Cancer-related fatigue (CRF) is among the most distressing symptoms reported by cancer survivors as compromising their quality of life. This study investigates the complex interplay between CRF and functional health (FH) in survivors of Hodgkin lymphoma by using longitudinal data to clarify the etiology of CRF. METHODS: Data from N = 3596 survivors (HD13-15) from the German Hodgkin Study Group was analyzed using bivariate latent curve models with structured residuals to model how the interplay between CRF and FH unfolds over time across and within individuals. CRF and FH were measured with the EORTC QLQ-C30. Assessed FH domains were physical, cognitive, emotional, social, and role functioning. Age at diagnosis, gender, country, baseline fatigue, and cancer stage were included as covariates. RESULTS: The latent curve models with structured residuals had an adequate model fit (χ² = 416.63-548.28, df = 114, p < .001, root mean square error of approximation = .03, comparative fit index = .98-.99, Tucker-Lewis index = .97-.98). On the between-person level, CRF and all FH domains were strongly negatively correlated (r = -.72 to r = -.84). On the within-person level, earlier CRF (ρF = -.05 to ρF = -.12) and FH deviations (ρFH = -.05 to ρFH = -.13) negatively predicted subsequent deviations of the respective other variable. Time-specific within-person improvements in physical, cognitive, and emotional functioning reduced CRF more than vice versa, whereas the effect of CRF was stronger for social functioning. Role functioning had a balanced relation with CRF. CONCLUSIONS: This analysis reveals a complex reciprocal relation between CRF and FH with distinct between- and within-person effects. The results contribute to a better understanding of CRF in survivors of Hodgkin lymphoma and could inform the development of much-needed targeted interventions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Health-Related Quality of Life in Patients With Hodgkin Lymphoma: A Longitudinal Analysis of the German Hodgkin Study Group.

PURPOSE: Many important details of health-related quality of life (HRQoL) after diagnosis and treatment of Hodgkin lymphoma (HL) are still unknown because large longitudinal studies of HRQoL are rare. Therefore, we analyzed a systematically assessed, comprehensive range of HRQoL domains in patients with HL of all stages from diagnosis up to 5 years of survivorship. PATIENTS AND METHODS: We included patients with HL age 18-60 years at diagnosis from the German Hodgkin Study Group trials HD13, HD14, and HD15. We analyzed HRQoL using all functional and symptom scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 including deviations from reference values. We estimated the effect of different disease, patient, and treatment characteristics using multiple regression and repeated measures analysis and computed correlations of HRQoL scores. RESULTS: We analyzed 4,215 patients with any HRQoL assessment within 5 years after treatment. Higher tumor burden at diagnosis was associated with impaired baseline scores in many HRQoL domains. During survivorship, cognitive, emotional, role, and social functioning and fatigue, dyspnea, sleep, and financial problems were severely and persistently affected. From year 2 on, mean deviations from reference values ranged between 12 and 29 points, with 10 points being a commonly used margin of clinical relevance. In all 3 trials, HRQoL domains 2 and 5 years after therapy were significantly influenced by baseline scores and age but not by randomized treatments. Fatigue was most closely correlated with other symptoms and scales. CONCLUSION: Our results show a high and persistent amount of different HRQoL deficits in survivors of HL that are largely independent of the applied chemotherapies. Our analysis underscores the high, unmet medical need of these rather young survivors of HL regarding the psychosocial adverse effects of the cancer experience.

Symptomatic osteonecrosis as a treatment complication in Hodgkin lymphoma: an analysis of the German Hodgkin Study Group (GHSG).

The majority of patients with Hodgkin Lymphoma (HL) can be cured with stage and risk adapted treatment today. Therefore, current research focuses on reducing long-term sequelae of treatment. Osteonecrosis (ON) is a severe long-term complication of HL treatment which has so far not been systematically evaluated. Hence, we investigated incidence, risk factors and timing of symptomatic ON in HL patients. Further endpoints included localization, intervention and outcome of ON. We included all qualified HL patients of the randomized German Hodgkin Study Group trials HD10-15 and HD18, recruited between 05/1998 and 07/2014 and aged from 16 to 60 years. Among 11 330 patients, 66 developed symptomatic ON after first-line treatment, 83.3% within three years. The incidence of symptomatic ON was 0.2% in early-stage HL and 1.0% in advanced-stage HL. Logistic regression revealed the total cumulative corticosteroid dose to be a strong risk factor interacting with younger age. Male sex additionally increased the risk of symptomatic ON. The prognostic value of the corresponding logistic regression model was rather high (AUC = 0.78). Other tested potential risk factors including obesity, IPS and radiotherapy did not further increase the risk of ON. Further development of current treatment protocols should aim to reduce the cumulative corticosteroid dose.