scholarly journals Frontline Therapy for Classical Hodgkin Lymphoma by Stage and Prognostic Factors

2017 ◽  
Vol 11 ◽  
pp. 117955491773107 ◽  
Author(s):  
Pamela B Allen ◽  
Leo I Gordon

Hodgkin lymphoma is a highly curable malignancy in early and advanced stages. Most patients are diagnosed in their teens or twenties and are expected to live decades beyond their treatment. Therefore, the toxicity of treatment must be balanced with the goal of cure. Thus, treatment has been refined through prognostic models and positron emission tomography-computed tomography (PET-CT)-directed therapy. Stratification by prognostic models defines groups of patients with favorable characteristics who may be treated with less intensive therapy upfront, including fewer cycles of chemotherapy, lower doses of radiation, or omission of radiation altogether. Alternatively, high-risk patients may be assigned to a more aggressive initial approach. The modern use of interim PET-CT allows further tailoring of treatment by response.

2018 ◽  
pp. 1-7
Author(s):  
Sidharth Totadri ◽  
Venkatraman Radhakrishnan ◽  
Trivadi S. Ganesan ◽  
Prasanth Ganesan ◽  
Krishnarathnam Kannan ◽  
...  

Purpose Treating pediatric Hodgkin lymphoma (HL) involves a delicate balance between cure and reducing late toxicity. Fluorodeoxyglucose positron emission tomography (PET) combined with computed tomography (CT) identifies patients with early response to chemotherapy, for whom radiotherapy may be avoided. The role of PET-CT in upfront risk stratification and response–adapted treatment is evaluated in this study. Methods Patients with HL, who were younger than 18 years, were included. PET-CT was performed at baseline and after two cycles of chemotherapy. Patients were stratified into three risk groups: group 1 (stage I or II with no unfavorable features); group 2 (stage I or II with bulky disease/B symptoms); and group 3 (stage III/IV). A doxorubicin, bleomycin, vinblastine, dacarbazine–based regimen was used in early disease. A cyclophosphamide, vincristine, prednisolone, procarbazine, doxorubicin, bleomycin, vinblastine–based regimen was used in advanced disease. Results Forty-nine patients were included. Fifteen (31%), seven (14%), and 27 (55%) patients were included in groups 1, 2, and 3, respectively. Among 36 patients who underwent staging by PET-CT at diagnosis, seven (19%) patients were upstaged and one (3%) patient was downstaged by PET compared with CT. On the basis of negative interim PET responses, 39 (80%) patients were treated without radiotherapy. The 3-year event-free survival for the entire cohort was 91% (± 5.2%) and overall survival was 100%. Conclusion PET-CT is an excellent stand-alone staging modality in HL. The omission of radiotherapy can be considered in patients who achieve metabolic remission on interim PET.


2013 ◽  
Vol 31 (23) ◽  
pp. 2861-2869 ◽  
Author(s):  
Lin-Quan Tang ◽  
Qiu-Yan Chen ◽  
Wei Fan ◽  
Huai Liu ◽  
Lu Zhang ◽  
...  

Purpose To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [18F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. Patients and Methods Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared. Results Eighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low–risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈$47,458), ¥96,907 (≈$14,188), and ¥34,182 (≈$5,005), respectively. Conclusion PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.


Author(s):  
René-Olivier Casasnovas ◽  
Reda Bouabdallah ◽  
Pauline Brice ◽  
Julien Lazarovici ◽  
Hervé Ghesquieres ◽  
...  

PURPOSE The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747 ) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2– and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2–/PET4–, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4– and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4– patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2–/PET4– patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.


Author(s):  
Ryan C. Lynch ◽  
Ranjana H. Advani

Although patients with advanced-stage classic Hodgkin lymphoma have excellent outcomes with contemporary therapy, the outcomes of patients with refractory disease is suboptimal. Identification of these high-risk patients at diagnosis is challenging as the differences in outcomes using clinical criteria are less marked using current modern therapy. Data suggest that an interim PET-CT may be a powerful tool in risk-stratifying patients. Retrospective studies show that a negative interim PET-CT after two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is predictive of favorable outcome independent of IPS score. Currently, there are several ongoing trials that aim to determine whether early-response assessment can be used to select patients who might benefit from modifications of subsequent therapy, either by intensifying or abbreviating regimens and/or omitting radiotherapy with promising early results. Longer follow-up is required to assess whether this strategy impacts overall survival (OS). Herein, we review the results of recent trials using interim PET-CT-based adaptive design in the treatment of advanced HL.


2012 ◽  
Vol 30 (36) ◽  
pp. 4508-4514 ◽  
Author(s):  
Tarec Christoffer El-Galaly ◽  
Francesco d'Amore ◽  
Karen Juul Mylam ◽  
Peter de Nully Brown ◽  
Martin Bøgsted ◽  
...  

Purpose To investigate whether bone marrow biopsy (BMB) adds useful information to [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) staging in patients with Hodgkin lymphoma (HL). Patients and Methods Newly diagnosed patients with HL undergoing a pretherapeutic staging that encompasses both PET/CT and BMB were included in this retrospective study. The pattern of skeletal FDG uptake was categorized as uni-, bi-, or multifocal (≥ three lesions). Clinical stage, risk assessment, and treatment plan were determined with and without the contribution of BMB results according to the Ann Arbor classification and the guidelines from the German Hodgkin Study Group. Results A total of 454 patients with HL were included of whom 82 (18%) had focal skeletal PET/CT lesions and 27 (6%) had positive BMB. No patients with positive BMB were assessed as having stage I to II disease by PET/CT staging. BMB upstaged five patients, assessed as being stage III before BMB; none of the 454 patients would have been allocated to another treatment on the basis of BMB results. Focal skeletal PET/CT lesions identified positive and negative BMBs with a sensitivity and specificity of 85% and 86%, respectively. The positive and negative predictive values of focal skeletal PET/CT lesions for BMB results were 28% and 99%, respectively. Conclusion A consistent finding of this study was the absence of positive BMBs in PET/CT-assessed stage I to II disease. The omission of staging BMB would not have changed the risk assessment or treatment strategy in this cohort of 454 newly diagnosed patients with HL.


Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 322-327 ◽  
Author(s):  
Martin Hutchings

Abstract Positron emission tomography/computed tomography (PET/CT) has emerged as the most accurate tool for staging, treatment monitoring, and response evaluation in Hodgkin lymphoma (HL). Accurate staging and restaging are very important for the optimal management of HL, but we are only beginning to understand how to use PET/CT to improve treatment outcome. More precise determination of disease extent may result in more precise pretreatment risk stratification, and is also essential for the minimal and highly individualized radiotherapy volumes of the present era. Several trials are currently investigating the use of PET/CT for early response-adapted therapy, with therapeutic stratification based on interim PET/CT results. Posttreatment PET/CT is a cornerstone of the revised response criteria and enables the selection of advanced-stage patients without the need for consolidation radiotherapy. Once remission is achieved after first-line therapy, PET/CT seems to have little or no role in the routine surveillance of HL patients. PET/CT looks promising for the selection of therapy in relapsed and refractory disease, but its role in this setting is still unclear.


2021 ◽  
Vol 10 (24) ◽  
pp. 5979
Author(s):  
Janet Denise Reed ◽  
Andries Masenge ◽  
Ane Buchner ◽  
Fareed Omar ◽  
David Reynders ◽  
...  

Lymphoma is the third most common paediatric cancer. Early detection of high-risk patients is necessary to anticipate those who require intensive therapy and follow-up. Current literature shows that residual tumor avidity on PET (Positron Emission Tomography) following chemotherapy corresponds with decreased survival. However, the value of metabolic parameters has not been adequately investigated. In this retrospective study, we aimed to evaluate the prognostic value of metabolic and other parameters in paediatric and adolescent Hodgkin lymphoma. We recorded tMTV (total Metabolic Tumor Volume), TLG (Total Lesion Glycolysis), and SUVmax (maximum Standard Uptake Value) on baseline PET, as well the presence of bone marrow or visceral involvement. HIV (human immunodeficiency virus) status and baseline biochemistry from clinical records were noted. All patients received stage-specific standard of care therapy. Response assessment on end-of-treatment PET was evaluated according to the Deauville criteria. We found that bone marrow involvement (p = 0.028), effusion (p < 0.001), and treatment response (p < 0.001) on baseline PET, as well as HIV status (p = 0.036) and baseline haemoglobin (p = 0.039), were significantly related to progression-free survival (PFS), whereas only effusion (p = 0.017) and treatment response (p = 0.050) were predictive of overall survival (OS). Only baseline tMTV predicted treatment response (p = 0.017). This confirms the value of F-18 FDG PET/CT (Fluoro-deoxy-glucose Positron Emission Tomography/Computed Tomography) in prognostication in paediatric and adolescent Hodgkin lymphoma; however, further studies are required to define the significance of metabolic parameters.


Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 200-206 ◽  
Author(s):  
Michael A. Spinner ◽  
Ranjana H. Advani

Abstract More than 80% of patients with advanced-stage Hodgkin lymphoma are now cured with contemporary treatment approaches. The ongoing challenge is how to further improve outcomes by identifying both high-risk patients who may benefit from more intensive frontline therapy to reduce the risk of relapse as well as lower-risk patients who may do just as well with less intensive therapy. Numerous trials have used an interim positron emission tomography (PET) response-adapted approach to evaluate early escalation or deescalation of therapy for patients with a positive or negative interim PET scan, respectively. Recent trials have incorporated novel agents, including brentuximab vedotin (BV) and the immune checkpoint inhibitors, in the frontline setting. Based on results of the ECHELON-1 trial, the Food and Drug Administration approved BV in combination with adriamycin, vinblastine, and dacarbazine chemotherapy for stage III to IV Hodgkin lymphoma. Improved methods to assess higher risk at diagnosis using quantitative PET metrics, such as metabolic tumor volume and total lesion glycolysis, and incorporation of emerging biomarkers may further refine patient selection for more intensive upfront therapy. The ultimate goal is to achieve the highest level of efficacy for an individual patient while minimizing the short- and long-term toxicities.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1552-1552 ◽  
Author(s):  
Eldad Dann ◽  
Rachel Bar-Shalom ◽  
Ada Tamir ◽  
Menachem Ben-Shachar ◽  
Irit Avivi ◽  
...  

Abstract Abstract 1552 Poster Board I-575 This prospective study (124 patients) evaluated the outcome of patients with Hodgkin lymphoma (HL) whose therapy was tailored based on results of scans performed after 2 cycles of chemotherapy, thus reducing the dose for early responders and maximizing the dose for those with subptimal early response or progression. The study was initiated in 1999 for patients with HL aged 18-60 years. Eligibility criteria were: unfavorable HL stages I, II and stage III or IV. Disease was defined according to the International Prognostic Score (IPS). Standard risk patients were treated with 2 cycles of standard BEACOPP (SB) and those with IPS of 3 3 got 2 cycles of escalated BEACOPP (EB): Ga67(on 57 patients prior to 2001) or hybrid PET/CT scan (on all 67 since 2001) were performed at diagnosis and after the 1st or 2nd cycle for all 124 patients. If early interim scan remained positive, additional 4 cycles of EB were used; otherwise, SB was given. Data for 108 patients were previously reported (Blood, 2007); albeit with a median follow-up of only 4 years. Herein is an updated 6- year median follow-up for all previously reported patients who had Ga67 or PET/CT as well as 16 additional patients who underwent interim PET/CT. Furthermore, importantly, the fertility of all young female patients is herein reported. For all 124 patients on study, the 7-year event-free survival (EFS) for patients with IPS 0-2 is 89% and for those with IPS of 3 3 87%. Seven year overall survival (OS) is 90%. Sixty seven patients (39 males and 28 females aged 18-55 [median 33]) were treated after 2001 when hybrid FDG-PET/CT became available. Forty one patients had IPS of 0-2 and 26 ≥3. Complete remission (CR) rate was 96%, 5-y FFS and OS were 92% and 97%, respectively at a median follow-up of 56 months (8-90). 5-y EFS and OS were similar for standard and high risk patients. HL progressed in 2/12 patients with interim positive PET/CT versus 3/55 with negative PET (p<0.02) (Table 1). Ninety four percent of patients with negative interim PET/CT had no disease progression during the follow-up, while 17% of patients with interim positive PET/CT progressed. One patient died from breast cancer. Thirty-eight females < 40 years old who had been treated with tailored BEACOPP since 1998 were assessed for fertility status. This is described in Table 2. Twenty six were co-treated with the GnRH agonist triptorelin, concomitantly with chemotherapy. Nineteen conceived during follow-up. Thirteen delivered 17 healthy babies, 6 terminated their pregnancy. Conclusion PET/CT is useful for making an early interim decision about chemotherapy dose on an individual basis, thus reducing unnecessary toxicity and escalating therapy where appropriate based on poor interim prognostic features. The results of 6 cycles of risk-adapted BEACOPP compare favorably with the reported data following 8 cycles of EB. Use of tailored therapy enables reduction of cumulative chemotherapy and preservation of fertility in the majority of young female patients. Disclosures Rowe: Teva Pharmaceuticals: Consultancy; EpiCept Corporation: Consultancy.


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