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Cancer Medicine Sep 2020We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and... (Comparative Study)
Comparative Study Review
PURPOSE
We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials.
PATIENTS AND METHODS
Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT).
RESULTS
About 1227 patients were included. The 7-year OS was 84.3% (95% CI 80.8-87.2) for ABVD vs 87.7% (95% CI 84.5-90.2) for BEACOPP. Two follow-up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HR = 1.59; 95% CI 1.09-2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7-year PFS was 71.1% (95% CI 67.1-74.6) for ABVD vs 81.1% (95% CI 77.5-84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP.
CONCLUSIONS
This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials, Phase III as Topic; Cyclophosphamide; Dacarbazine; Disease Progression; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasms, Second Primary; Prednisone; Procarbazine; Progression-Free Survival; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stem Cell Transplantation; Time Factors; Transplantation, Autologous; Vinblastine; Vincristine; Young Adult
PubMed: 32710498
DOI: 10.1002/cam4.3298 -
Acta Bio-medica : Atenei Parmensis May 2020A first-line chemotherapy program based on the ABVD regimen is currently considered the golden standard by most hematologists, being able to achieve a cure without any...
A first-line chemotherapy program based on the ABVD regimen is currently considered the golden standard by most hematologists, being able to achieve a cure without any need of subsequent therapies in >70% of patients with advanced-stage Hodgkin's lymphoma (HL). To increase this percentage, efforts in recent decades focused on the development of new therapeutic strategies. A first major effort was the introduction of the BEACOPP chemotherapy regimen, which is able to increase the response rate and to reduce the need of salvage therapies. However, this result did not demonstrate an advantage in terms of overall survival compared to ABVD, mainly due to an excess of non lymphoma-related events in the follow-up phase. Here we describe three clinical cases of young HL patients who had relapsed/refractory disease after the induction chemotherapy. These three clinical cases provide practical and real world evidence in favor of the use of BV in monotherapy as consolidation treatment after autologous stem cells transplantation in patients with relapsed/refractory HL.
Topics: Adult; Consolidation Chemotherapy; Female; Hodgkin Disease; Humans; Neoplasm Recurrence, Local; Stem Cell Transplantation; Transplantation, Autologous; Young Adult
PubMed: 32525131
DOI: 10.23750/abm.v91iS-5.9914 -
Medicine May 2020Ustekinumab is a biological agent that inhibits interleukin 12 and 23 and has been approved for the treatment of moderate and severe plaque psoriasis. There have been...
RATIONALE
Ustekinumab is a biological agent that inhibits interleukin 12 and 23 and has been approved for the treatment of moderate and severe plaque psoriasis. There have been case reports that raise concerns about its oncogenic potential. We are the first authors to report a case of Hodgkin lymphoma in a psoriatic patient receiving ustekinumab.
PATIENT CONCERNS
A 22-year-old asymptomatic female patient presented to our department to investigate an enlarged cervical lymph node. Her past history was unremarkable, except for psoriasis since age 13. Two months before presentation the decision to administer Ustekinumab was taken and the patient had already received 3 doses.
DIAGNOSES
During workup a Stage IV Hodgkin lymphoma was discovered.
INTERVENTIONS
Ustekinumab administration was discontinued. The patient received treatment with the ABVD regimen.
OUTCOMES
The patient's disease was refractory to the above-mentioned treatment. Therefore, a more aggressive regimen (BEACOPP escalated) was administered.
LESSONS
Growing postmarketing surveillance data and case reports indicate that further research is warranted in order to elucidate a potential association between Ustekinumab and malignancy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dermatologic Agents; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Prednisone; Procarbazine; Psoriasis; Ustekinumab; Vincristine; Young Adult
PubMed: 32481271
DOI: 10.1097/MD.0000000000020048 -
American Journal of Hematology Sep 2020The optimal first-line treatment for advanced-stage Hodgkin's lymphoma (HL) is still a matter of debate. While ABVD is less toxic and as effective as other, more... (Clinical Trial)
Clinical Trial Comparative Study
The optimal first-line treatment for advanced-stage Hodgkin's lymphoma (HL) is still a matter of debate. While ABVD is less toxic and as effective as other, more intensive chemotherapy regimens, escalated BEACOPP (BEACOPPesc) is superior to ABVD for initial disease control and prolonged time-to-relapse. However, this advantage is associated with higher rate of early and late toxicities. As most of these data have been accumulated from clinical trials, a retrospective analysis was conducted in a large database of patients treated outside clinical trials to investigate the advantages and disadvantages of these regimes in a real-world setting. From October 2009 to October 2018, 397 advanced-stage HL patients treated with either ABVD or BEACOPPesc were retrospectively assessed in 7 European cancer centers (2 Austrian and 5 Italian centers). Complete metabolic remission (CMR) by PET was achieved in 76% and 85% of patients in the ABVD and BEACOPPesc groups, respectively (p = .01). Severe adverse events occurred more frequently with BEACOPPesc than ABVD. At a median follow-up of 8 years, 9% of the patients who achieved CMR after BEACOPPesc relapsed compared to 16.6% in the ABVD group (p = .043). No statistical difference in progression free survival (PFS) was observed between the two cohorts overall (p = .11), but there was a trend towards a superior PFS in high-risk patients treated with BEACOPPesc (p = .074). Nevertheless, overall survival was similar between the two groups (p = .94). In conclusion, we confirm that ABVD is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control, the long-term outcome remains similar between the two regimens.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Austria; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Italy; Male; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Survival Rate; Vinblastine; Vincristine
PubMed: 32419224
DOI: 10.1002/ajh.25871 -
Haematologica Jun 2021A subset of patients with advanced-stage classical Hodgkin Lymphoma (cHL) relapse or progress following standard treatment. Given their dismal prognosis, identifying...
Whole-slide image analysis of the tumor microenvironment identifies low B-cell content as a predictor of adverse outcome in patients with advanced-stage classical Hodgkin lymphoma treated with BEACOPP.
A subset of patients with advanced-stage classical Hodgkin Lymphoma (cHL) relapse or progress following standard treatment. Given their dismal prognosis, identifying this group of patients upfront represents an important medical need. While prior research has identified characteristics of the tumor microenvironment, which are associated with cHL outcomes, biomarkers that are developed and validated in this high-risk group are still missing. Here, we applied whole-slide image analysis (WSI), a quantitative, large-scale assessment of tumor composition that utilizes conventional histopathology slides. We conducted WSI on a study cohort with pre-treatment biopsies of 340 advanced-stage cHL patients enrolled in the HD12 and HD15 trials of the German Hodgkin Study Group (GHSG), and tested our results in in a validation cohort of 147 advanced-stage cHL patients within the GHSG HD18 trial. All patients were treated with BEACOPP-based regimens. By quantifying T cells, B cells, Hodgkin-Reed-Sternberg-cells and macrophages with WSI, 80% of all cells in the tumor tissue were identified. Crucially, low B cell count was associated with significantly reduced progression-free survival (PFS) and overall survival (OS), while T cell-, macrophage- and Hodgkin-Reed-Sternberg-cell content was not associated with the risk of progression or relapse in the study cohort. We further validated low B cell content as a prognostic factor of PFS and OS in the validation cohort and demonstrate good inter-observer agreement of WSI. WSI may represent a key tool for risk stratification of advanced-stage cHL that can easily be added to the standard diagnostic histopathology work-up.
Topics: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Hodgkin Disease; Humans; Neoplasm Recurrence, Local; Tumor Microenvironment
PubMed: 32381573
DOI: 10.3324/haematol.2019.243287 -
British Journal of Haematology Jul 2020
Topics: Adult; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Betacoronavirus; Bleomycin; COVID-19; Coronavirus Infections; Cyclophosphamide; Cytarabine; Dacarbazine; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Hydroxychloroquine; Idarubicin; Mediastinal Neoplasms; Pandemics; Pneumonia, Viral; Positron-Emission Tomography; Prednisone; Procarbazine; SARS-CoV-2; Treatment Outcome; Vinblastine; Vincristine
PubMed: 32379903
DOI: 10.1111/bjh.16798 -
The Cochrane Database of Systematic... Jan 2020Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of individuals. Positron emission tomography (PET) is an imaging tool used to monitor a tumour's metabolic activity, stage and progression. Interim PET during chemotherapy has been posited as a prognostic factor in individuals with HL to distinguish between those with a poor prognosis and those with a better prognosis. This distinction is important to inform decision-making on the clinical pathway of individuals with HL.
OBJECTIVES
To determine whether in previously untreated adults with HL receiving first-line therapy, interim PET scan results can distinguish between those with a poor prognosis and those with a better prognosis, and thereby predict survival outcomes in each group.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL and conference proceedings up until April 2019. We also searched one trial registry (ClinicalTrials.gov).
SELECTION CRITERIA
We included retrospective and prospective studies evaluating interim PET scans in a minimum of 10 individuals with HL (all stages) undergoing first-line therapy. Interim PET was defined as conducted during therapy (after one, two, three or four treatment cycles). The minimum follow-up period was at least 12 months. We excluded studies if the trial design allowed treatment modification based on the interim PET scan results.
DATA COLLECTION AND ANALYSIS
We developed a data extraction form according to the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Two teams of two review authors independently screened the studies, extracted data on overall survival (OS), progression-free survival (PFS) and PET-associated adverse events (AEs), assessed risk of bias (per outcome) according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). We contacted investigators to obtain missing information and data.
MAIN RESULTS
Our literature search yielded 11,277 results. In total, we included 23 studies (99 references) with 7335 newly-diagnosed individuals with classic HL (all stages). Participants in 16 studies underwent (interim) PET combined with computed tomography (PET-CT), compared to PET only in the remaining seven studies. The standard chemotherapy regimen included ABVD (16) studies, compared to BEACOPP or other regimens (seven studies). Most studies (N = 21) conducted interim PET scans after two cycles (PET2) of chemotherapy, although PET1, PET3 and PET4 were also reported in some studies. In the meta-analyses, we used PET2 data if available as we wanted to ensure homogeneity between studies. In most studies interim PET scan results were evaluated according to the Deauville 5-point scale (N = 12). Eight studies were not included in meta-analyses due to missing information and/or data; results were reported narratively. For the remaining studies, we pooled the unadjusted hazard ratio (HR). The timing of the outcome measurement was after two or three years (the median follow-up time ranged from 22 to 65 months) in the pooled studies. Eight studies explored the independent prognostic ability of interim PET by adjusting for other established prognostic factors (e.g. disease stage, B symptoms). We did not pool the results because the multivariable analyses adjusted for a different set of factors in each study. Overall survival Twelve (out of 23) studies reported OS. Six of these were assessed as low risk of bias in all of the first four domains of QUIPS (study participation, study attrition, prognostic factor measurement and outcome measurement). The other six studies were assessed as unclear, moderate or high risk of bias in at least one of these four domains. Four studies were assessed as low risk, and eight studies as high risk of bias for the domain other prognostic factors (covariates). Nine studies were assessed as low risk, and three studies as high risk of bias for the domain 'statistical analysis and reporting'. We pooled nine studies with 1802 participants. Participants with HL who have a negative interim PET scan result probably have a large advantage in OS compared to those with a positive interim PET scan result (unadjusted HR 5.09, 95% confidence interval (CI) 2.64 to 9.81, I² = 44%, moderate-certainty evidence). In absolute values, this means that 900 out of 1000 participants with a negative interim PET scan result will probably survive longer than three years compared to 585 (95% CI 356 to 757) out of 1000 participants with a positive result. Adjusted results from two studies also indicate an independent prognostic value of interim PET scan results (moderate-certainty evidence). Progression-free survival Twenty-one studies reported PFS. Eleven out of 21 were assessed as low risk of bias in the first four domains. The remaining were assessed as unclear, moderate or high risk of bias in at least one of the four domains. Eleven studies were assessed as low risk, and ten studies as high risk of bias for the domain other prognostic factors (covariates). Eight studies were assessed as high risk, thirteen as low risk of bias for statistical analysis and reporting. We pooled 14 studies with 2079 participants. Participants who have a negative interim PET scan result may have an advantage in PFS compared to those with a positive interim PET scan result, but the evidence is very uncertain (unadjusted HR 4.90, 95% CI 3.47 to 6.90, I² = 45%, very low-certainty evidence). This means that 850 out of 1000 participants with a negative interim PET scan result may be progression-free longer than three years compared to 451 (95% CI 326 to 569) out of 1000 participants with a positive result. Adjusted results (not pooled) from eight studies also indicate that there may be an independent prognostic value of interim PET scan results (low-certainty evidence). PET-associated adverse events No study measured PET-associated AEs.
AUTHORS' CONCLUSIONS
This review provides moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict progression-free survival in treated individuals with HL. This evidence is primarily based on unadjusted data. More studies are needed to test the adjusted prognostic ability of interim PET against established prognostic factors.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Decision Making; Disease Progression; Disease-Free Survival; Hodgkin Disease; Humans; Positron Emission Tomography Computed Tomography; Prognosis; Young Adult
PubMed: 31930780
DOI: 10.1002/14651858.CD012643.pub3 -
American Family Physician Jan 2020Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma.... (Review)
Review
Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma. Approximately 82,000 new U.S. patients are diagnosed with lymphoma annually. Any tobacco use and obesity are major modifiable risk factors, with genetic, infectious, and inflammatory etiologies also contributing. Lymphoma typically presents as painless adenopathy, with systemic symptoms of fever, unexplained weight loss, and night sweats occurring in more advanced stages of the disease. An open lymph node biopsy is preferred for diagnosis. The Lugano classification system incorporates symptoms and the extent of the disease as shown on positron emission tomography/computed tomography to stage lymphoma, which is then used to determine treatment. Chemotherapy treatment plans differ between the main subtypes of lymphoma. Non-Hodgkin lymphoma is treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (R-CHOP), bendamustine, and lenalidomide. Hodgkin lymphoma is treated with combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), Stanford V (a chemotherapy regimen consisting of mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone), or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with radiotherapy. Subsequent chemotherapy toxicities include neuropathy, cardiotoxicity, and secondary cancers such as lung and breast, and should be considered in the shared decision-making process to select a treatment regimen. Once remission is achieved, patients need routine surveillance to monitor for complications and relapse, in addition to age-appropriate screenings recommended by the U.S. Preventive Services Task Force. Patients should receive a 13-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide vaccine at least eight weeks later with additional age-appropriate vaccinations because lymphoma is an immunosuppressive condition. Household contacts should also be current with their immunizations.
Topics: Adult; Aged; Antineoplastic Agents; Biopsy; Evidence-Based Medicine; Female; Humans; Lymphoma; Male; Middle Aged; Neoplasm Staging; Risk Factors; United States
PubMed: 31894937
DOI: No ID Found -
International Journal of Radiation... Jan 2020
What to Do With Deauville 3 Interim Positron Emission Tomography/Computed Tomography Response in a Young Woman With Classic Unfavorable Hodgkin's Lymphoma: To Irradiate or Not to Irradiate?
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Lymph Nodes; Mediastinal Neoplasms; Positron Emission Tomography Computed Tomography; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 31836075
DOI: 10.1016/j.ijrobp.2018.02.162 -
Journal of Global Oncology Nov 2019Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with...
PURPOSE
Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with Hodgkin lymphoma (HL) relative to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. However, the associated higher cost and toxicity discourage clinicians from prescribing it. Identifying high-risk patients and administering escalated BEACOPP remains an effective strategy. We assessed the significance of interim positron emission tomography (iPET) scan after 2 cycles (iPET2) in identifying this high-risk subset.
PATIENTS AND METHODS
This cohort study used secondary data from 12 tertiary care centers in South India gathered over 10 years (2008-2018). OS, event-free survival (EFS), determinants of EFS, and complete response (CR) in iPET2 were assessed.
RESULTS
The study included 409 patients with HL (mean age, 34.5 years; male/female ratio, 1.4:1). The median duration of follow-up was 2.8 years. Of 409 patients, 63% underwent PET-based staging and 37% underwent computerized tomography (CT) staging. Stage IV (28.9%) and bone involvement (9.2%) were seen more often with PET than with CT staging (9.2% and 2%, respectively). Among 171 patients with iPET2 results, 24% did not achieve CR, and no factors were significantly associated. The 5-year EFS and OS rates of the entire cohort were 78% and 97%, respectively. The 5-year EFS and OS rates of patients with CR on iPET2 were 90% and 99%, respectively, whereas these were 65% and 100%, respectively, for patients not achieving CR. On univariable analysis, sex, stage, and iPET2 response significantly predicted inferior EFS. On multivariate analysis, only iPET2 response significantly predicted EFS ( < .000).
CONCLUSION
Our study supports the use of PET for staging and iPET2 for response assessment. Nonachievement of CR on iPET2 indicates unfavorable outcome, and such patients may benefit from more intensive treatment.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Child, Preschool; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; India; Infant; Infant, Newborn; Male; Middle Aged; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Survival Analysis; Treatment Outcome; Vinblastine; Young Adult
PubMed: 31834832
DOI: 10.1200/JGO.19.00179