Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial.
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SUBMITTER: Mauz-Korholz C
PROVIDER: S-EPMC8716340 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC11291946 | biostudies-literature
Project description:Approximately 90% of limited-stage Hodgkin lymphoma (HL) patients are projected to be cured with standard therapy, but many do not live their expected life span because of late treatment-related complications. New treatment paradigms are needed to reduce the use of radiation therapy (RT) as well as conventional chemotherapy drugs while improving upon current standard-of-care survival outcomes. In this phase 2 multicenter study, patients with non-bulky limited-stage HL received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by brentuximab vedotin (BV) consolidation. Forty-one patients were enrolled, and patient characteristics included median age of 29 years (range, 19 to 67 years), 58% were female, 45% had unfavorable disease, and 98% had stage II disease. Based on positron emission tomography (PET)-based risk stratification, patients received 2 to 6 cycles of ABVD followed by 6 cycles of BV. After ABVD followed by BV, 95% of evaluable patients (37 out of 39; 95% confidence interval [CI], 83%-99%) achieved PET-negative status. In the intent-to-treat patient population, the estimated 3-year progression-free survival (PFS) rate was 92%, and the overall survival (OS) rate was 97%, with a median follow-up of 47 months. All 37 patients who achieved negative PET status after BV consolidation effectively avoided RT and remain in remission with estimated 3-year PFS and OS rates of 100%. In conclusion, BV demonstrates encouraging clinical activity when it follows ABVD therapy in limited-stage HL. Early incorporation of BV may reduce the use of RT as well as conventional chemotherapy drugs while achieving favorable survival outcomes in risk-stratified patients with non-bulky limited-stage HL. This trial was registered at www.clinicaltrials.gov as #NCT01578967.
| S-EPMC7284091 | biostudies-literature
Project description:Despite a number of randomized trials, there is clinical equipoise whether de-escalation with the omission of radiotherapy (RT) in positron emission tomography (PET) responders is safe in early-stage Hodgkin lymphoma (HL). A comprehensive Medline and conference abstracts search was performed to identify prospective studies with the following criteria: early-stage (stage I/II) HL treated with anthracycline-based chemotherapy with PET-directed randomization to ± consolidation RT. Four studies were meta-analyzed with a total of 2267 patients (RT: n = 1136, no RT: n = 1131). Pooled analysis showed a significant progression-free survival (PFS) benefit with RT (HR = 2.08, 95% CI 1.27- 3.43 p = .004, RE). There was no statistically significant overall survival (OS) benefit with RT for all patients (HR = 0.92, 95% CI 0.37-2.30, p = 0.85), nor in favorable (HR = 0.90, p = .89) or unfavorable risk (HR = 1.01, p = .99). In early-stage PET-negative HL, consolidative RT consistently improves PFS across risk stratifications over PET-directed omission of RT, with no significant impact on OS.
| S-EPMC7422924 | biostudies-literature
Project description:Patients with advanced aggressive B-cell non-Hodgkin lymphomas (NHL) are usually treated with rituximab in combination with chemotherapy. However, disease relapse rates are high. Radiotherapy (RT) has been shown to be efficacious in treating early-stage NHL but its role in advanced stage diseases is unclear. We performed a systematic review of randomized controlled trials (RCTs) comparing chemotherapy with RT to chemotherapy alone in patients with newly diagnosed advanced aggressive NHL. We searched online databases and pooled similar outcome estimates. For time-to-event outcomes, we estimated hazard ratios (HR) for overall survival (OS) and event-free survival (EFS) using the fixed-effect model. Two RCTs involving 254 patients met inclusion criteria. The trials were single-centre RCTs with follow-up period of five and ten years. Both trials were conducted in the pre-rituximab era. Patients treated with consolidation RT had better OS (HR for mortality 0.61; 95 % CI 0.38 to 0.97) and EFS (HR for mortality 0.67; 95 % CI 0.46 to 0.98) compared to those who received no RT. There was an apparent benefit of RT on local control (OR 0.09; 95 % CI 0.04 to 0.20); although this was estimated as a dichotomous rather than time-to-event outcome. Limited evidence shows benefits of consolidation RT in advanced aggressive NHL. However, we were not able to estimate the effect size with confidence due to small number of trials and sample size. We cannot recommend routine consolidation RT in advanced aggressive NHL. More RCTs with the inclusion of rituximab and PET-CT monitoring are needed.
| S-EPMC5735338 | biostudies-literature
Project description: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.
| S-EPMC7000476 | biostudies-literature
Project description:Activated brown fat (aBAT) is known to affect the evaluation of 18F-FDG PET scans, especially in young patients. The aim of this study was to determine factors influencing the occurrence of aBAT, and to investigate the effectiveness of the two preventive measures, warming and beta-blocker (propranolol) administration. Five-hundred-twenty-eight 18F-FDG-PET scans of 241 EuroNet-PHL-C2 trial patients from 41 nuclear medicine departments in Germany and Czech Republic were screened for aBAT. The occurrence of aBAT was analyzed with patient characteristics (age, sex, body mass index, predisposition to aBAT), weather data at the day of 18F-FDG PET scanning as well as the preventive measures taken. Potentially important factors from univariate analyses were included into a logistic regression model. Warming as a preventive measure was used in 243 18F-FDG-PET scans, propranolol was administered in 36, warming and propranolol were combined in 84, and no preventive measures were taken in 165 scans. Whereas age, sex and body mass index had no clear impact, there was an individual predisposition to aBAT. Logistic regression model revealed that the frequency of aBAT mainly depends on the outside temperature (p = 0.005) and can be effectively reduced by warming (p = 0.004), the administration of unselective beta-blocker or the combination of both. Warming is a simple, cheap and non-invasive method to reduce the frequency of aBAT. However, the effect of warming decreases with increasing outside temperatures. Administration of propranolol seems to be equally effective and provides advantages whenever the positive effect of warming is compromised. The combination of both preventive measures could have an additive effect.
| S-EPMC10713612 | biostudies-literature
Project description:Hodgkin lymphoma (HL) is a rare type of B-cell malignancy with bimodal age distribution targeting young adults and elderly. Prognostic models are available to identify risk of recurrence and response to treatment. Currently, positron emission tomography scanning is most useful in optimizing therapy. Outcomes are generally excellent with standard chemotherapy or combined modality therapy. Balancing efficacy and the risk of late effects in Hodgkin lymphoma is essential, including early detection of potential complications. Incorporation of novel therapies such as brentuximab vedotin and checkpoint inhibitors are being explored in the frontline setting, having already demonstrated improved survival and tolerable toxicity in advanced HL. Furthermore, the addition of these agents have the potential to transform treatment paradigms for early-stage HL and may result in improved outcomes with decreased risks of late toxicities that continue to afflict long-term survivors. However, the patient population, sequencing, and combinations with cytotoxic chemotherapy all remain still standing questions as results of current and upcoming randomized trials are awaited. In this article, we discuss the current data on the approach to initial treatment of early-stage classical HL, review toxicity profiles, and examine upcoming novel therapy trials.
| S-EPMC10905319 | biostudies-literature
Project description:BackgroundThe aim of this work is to provide the currently missing evidence that may allow an update of the Paediatric Dosage Card provided by the European Association of Nuclear Medicine (EANM) for conventional PET/CT systems.MethodsIn a total of 2082 consecutive [18F]FDG-PET scans performed within the EuroNet-PHL-C2 trial, the administered [18F]FDG activity was compared to the activity recommended by the EANM Paediatric Dosage Card. None of these scans had been rejected beforehand by the reference nuclear medicine panel of the trial because of poor image quality. For detailed quality assessment, a subset of 91 [18F]FDG-PET scans, all performed in different patients at staging, was selected according to pre-defined criteria, which (a) included only patients who had received substantially lower activities than those recommended by the EANM Paediatric Dosage Card, and (b) included as wide a range of different PET systems and imaging parameters as possible to ensure that the conclusions drawn in this work are as generally valid as possible. The image quality of the subset was evaluated visually by two independent readers using a quality scoring system as well as analytically based on a volume-of-interest analysis in 244 lesions and the healthy liver. Finally, recommendations for an update of the EANM Paediatric Dosage Card were derived based on the available data.ResultsThe activity recommended by the EANM Paediatric Dosage Card was undercut by a median of 99.4 MBq in 1960 [18F]FDG-PET scans and exceeded by a median of 15.1 MBq in 119 scans. In the subset analysis (n = 91), all image data were visually classified as clinically useful. In addition, only a very weak correlation (r = 0.06) between activity reduction and tumour-to-background ratio was found. Due to the intended heterogeneity of the dataset, the noise could not be analysed statistically sound as the high range of different imaging variables resulted in very small subsets. Finally, a suggestion for an update of the EANM Paediatric Dosage Card was developed, based on the analysis presented, resulting in a mean activity reduction by 39%.ConclusionThe results of this work allow for a conservative update of the EANM Paediatric Dosage Card for [18F]FDG-PET/CT scans performed with conventional PET/CT systems.
| S-EPMC10774179 | biostudies-literature
Project description:PurposeAdvances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies.MethodsThe Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.DiscussionThis study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.Trial registrationClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.
| S-EPMC10912576 | biostudies-literature
Project description:Several pediatric Hodgkin lymphoma (HL) consortia have demonstrated safe omission of radiotherapy (RT) in early stage HL, whereas feasibility of omitting RT in advanced HL is still under investigation. This is a single institution retrospective analysis of 27 patients with intermediate-risk or high-risk HL (age 22?y and younger), treated with a modification of the dose-intensive OEPA-COPDAC (vincristine, etoposide, prednisone, doxorubicin-cyclophosphamide, vincristine, prednisone, dacarbazine) regimen, with radiation restricted to only sites of inadequate early response (Deauville ?3 and/or ?75% tumor shrinkage). Their outcome was compared with a historical cohort (n=42) treated with Stanford V or ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), who received consolidative involved-field RT. RT was omitted in 15 of 27 (56%) of patients treated with OEPA-COPDAC, majority of whom (67%) had high-risk disease. At a median follow-up of 3.1 years, the 3-year progression-free survival was 100% in patients who received OEPA-COPDAC, versus 83.3% (95% confidence interval, 68.2%-91.7%) in the historical cohort, P=0.03. Our analysis demonstrates excellent survival with omission of RT in more than 50% of patients with pediatric advanced HL, treated with a dose-intensive chemotherapy regimen. When administered, RT was restricted to only sites of inadequate early response. Results of large prospective studies are needed to validate these findings.
| S-EPMC6026082 | biostudies-literature