Results of the AHOD0431 trial of response adapted therapy and a salvage strategy for limited stage, classical Hodgkin lymphoma: A report from the Children's Oncology Group

Keller, Frank G.; Castellino, Sharon M.; Chen, Lu; Pei, Qinglin; Voss, Stephan D.; McCarten, Kathleen; Senn, Stacy L.; Buxton, Allen; Bush, Rizvan; Constine, Louis S.; Schwartz, Cindy L.

doi:10.1002/cncr.31519

Cited by 45 publications

(46 citation statements)

References 16 publications

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“…For the low-risk group, prospective studies have reported an excellent survival with low-dose IFRT [ 9 , 10 , 19 ]. There is controversy about the necessity of RT for patients with a good response after initial chemotherapy, with concerns about balancing disease control with the risk of long-term toxicities.…”

Section: Discussionmentioning

confidence: 99%

“…However, patients in our study received heterogeneous treatment because of the long duration of the case collection period and the development of the riskbased chemotherapy regimen. For the low-risk group, prospective studies have reported an excellent survival with low-dose IFRT [9,10,19]. There is controversy about the necessity of RT for patients with a good response after initial chemotherapy, with concerns about balancing disease control with the risk of long-term toxicities.…”

Section: Variablementioning

confidence: 99%

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Survival and long-term toxicities of pediatric Hodgkin lymphoma after combined modality treatment: a single institute experience

Song

Park

et al. 2020

Radiat Oncol J

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Pediatric Hodgkin lymphoma (pHL) is a rare disease in Korea with a crude incidence of 1.3 per million among ages 0 to 14 years [1]. In the United States, pHL accounts for nearly 5%-10% of pediatric malignancies, with approximately 1,700 newly diagnosed cases among children under 20 years old [2]. Studies conducted in western countries report that pHL is a highly curable disease with 5-year event-free survival (EFS) and overall survival (OS) exceeding Purpose: To analyze the clinical outcomes and long-term toxicity of pediatric patients with Hodgkin lymphoma after combined-modality treatment (CMT) with involved-field or involved-nodal radiotherapy (RT). Materials and Methods: We retrospectively reviewed the records of 27 pediatric Hodgkin lymphoma patients who received CMT at a single institution between January 1990 and July 2017. Patients with stage I-III received a heterogeneous chemotherapy regimen depending on their risk group followed by 19.8-36 Gy RT, with the dose based on their response to the chemotherapy before RT. An optional 9-20 Gy boost was delivered to residual sites. The risk group was determined based on the initial stage, the presence of bulky disease, and any B symptoms. We evaluated overall survival, event-free survival, and long-term toxicities. Results: A total of 27 patients completed the CMT. At a median follow-up of 125 months (range, 9 to 337 months), the estimated 5-year event-free survival and overall survival were 88.9% and 96.3%, respectively. Late symptomatic cardiopulmonary toxicity was not observed, and only one patient was positive on a subclinical obstructive pulmonary function test. The incidence of hypothyroidism was 58.3% among 12 patients with an available thyroid function test. There was one papillary thyroid cancer diagnosed 7.2 years after treatment. Conclusion: CMT for pediatric Hodgkin lymphoma with involved-field and involved-nodal RT achieved an excellent survival with only modest long-term toxicity. Smaller-field RT seemed to decrease long-term toxicities and had good local control.

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Section: Discussionmentioning

confidence: 99%

Section: Variablementioning

confidence: 99%

Survival and long-term toxicities of pediatric Hodgkin lymphoma after combined modality treatment: a single institute experience

Song

Park

et al. 2020

Radiat Oncol J

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“…A comprehensive review in 2015 summarized contemporary paediatric treatment approaches for de novo HL (Kelly, ). Five‐year DFS in paediatric HL ranged from 79·8% to 97% for low risk HL (Landman‐Parker et al , ; Mauz‐Korholz et al , ; Metzger et al , ; Tebbi et al , ; Wolden et al , ; Keller et al , ) to 77 to 90 % for high risk disease (Schwartz et al , ; Mauz‐Korholz et al , ; Kelly et al , ; Wolden et al , ; Friedman et al , ; Kelly et al , ) in completed trials. With the goal of lowering cumulative doses of anthracyclines to a doxorubicin equivalent dose of ≤250 mg/m 2 and alkylating agents to <7 g/m 2 (cyclophosphamide equivalent dose) (Green et al , ), contemporary paediatric chemotherapy regimens have diverged from the conventional adult approaches of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, prednisone, procarbazine) by using combination chemotherapy with non‐cross‐resistant agents [adriamycin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE‐PC) or vincristine, etoposide, prednisone, adriamycin/ cyclophosphamide vincristine, prednisone, dacarbazine (OEPA/COPDac)] (Mauz‐Korholz et al , ; Friedman et al , ).…”

Section: Primary Prevention To Close the Survivorship Gapmentioning

confidence: 99%

“…These studies demonstrate anti‐lymphoma efficacy with lower cumulative doses of alkylating agents and anthracyclines (Table ) than are customary with adult treatment regimens (Kelly, ). Furthermore, risk‐based response adapted approaches, facilitated by interim imaging in recent paediatric trials have decreased RT delivery (Friedman et al , ; Keller et al , ; Kelly et al , ).…”

Section: Primary Prevention To Close the Survivorship Gapmentioning

confidence: 99%

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

2019

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Summary The treatment of Hodgkin lymphoma (HL) is one of early success. However, disease‐free survival (DFS) does not reflect latent organ injury and its impact on health status and well‐being beyond 5 years. In fact, we are at a crossroads, in terms of needing individualized approaches to maintain DFS, while minimizing late effects and preserving health‐related quality of life (HRQoL). Premature morbidity and mortality translate to a high societal cost associated with the potential number of productive life years ahead in this population who are young at diagnosis. The discordance between short‐term lymphoma‐free survival and long‐term health and HRQoL creates a “survivorship gap” which can be characterized for individuals and for subgroups of patients. The current review delineates contributors to compromised outcomes and health status in child and adolescent (paediatric) HL and frames the survivorship gap in terms of primary and secondary prevention. Primary prevention aims to titrate therapy. Secondary prevention entails strategies to intervene against late effects. Bridging the survivorship gap will be attained with enhanced knowledge of and attention to biology of the tumour and microenvironment, host genetic factors, HRQoL and sub‐populations with disparate outcomes.

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“…6,7 For example, current treatment strategies for Hodgkin's lymphoma employ radiation sparingly to minimize the long-term risks of second malignancies and cardiac toxicity even if this increases the risk of recurrence. 6,8,9 Authors of recent and ongoing studies are investigating the impact of reduction of therapy on the incidence of late effects and risk of relapse in other pediatric cancers.…”

mentioning

confidence: 99%

Parental Considerations Regarding Cure and Late Effects for Children With Cancer

Greenzang

Al‐Sayegh

Ma³

et al. 2020

Pediatrics

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BACKGROUND: More than 80% of children with cancer become long-term survivors, yet most survivors experience late effects of treatment. Little is known about how parents and physicians consider late-effects risks against a potential survival benefit when making treatment decisions. METHODS: We used a discrete choice experiment to assess the importance of late effects on treatment decision-making and acceptable trade-offs between late-effects risks and survival benefit. We surveyed 95 parents of children with cancer and 41 physicians at Dana-Farber/ Boston Children's Cancer and Blood Disorders Center to assess preferences for 5 late effects of treatment: neurocognitive impairment, infertility, cardiac toxicity, second malignancies, and impaired growth and development. RESULTS: Each late effect had a statistically significant association with treatment choice, as did survival benefit (P , .001). Avoidance of severe cognitive impairment was the most important treatment consideration to parents and physicians. Parents also valued cure and decreased risk of second malignancies; physician decision-making was driven by avoidance of second malignancies and infertility. Both parents and physicians accepted a high risk of infertility (parents, a 137% increased risk; physicians, an 80% increased risk) in exchange for a 10% greater chance of cure. CONCLUSIONS: Avoidance of severe neurocognitive impairment was the predominant driver of parent and physician treatment preferences, even over an increased chance of cure. This highlights the importance of exploring parental late-effects priorities when discussing treatment options. WHAT'S KNOWN ON THIS SUBJECT: Decision-making for pediatric cancer treatment involves numerous considerations, including optimizing cure and minimizing acute and late toxicities of treatment. Questions remain about how parents and physicians weigh late-effects risks and make trade-offs between cure and potential toxicities. WHAT THIS STUDY ADDS: Parents and physicians prioritize avoidance of certain late effects, specifically severe neurocognitive impairment, over an increased chance of cure. Both parents and physicians are willing to accept a high risk of infertility in exchange for an increased chance of cure.

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Results of the AHOD0431 trial of response adapted therapy and a salvage strategy for limited stage, classical Hodgkin lymphoma: A report from the Children's Oncology Group

Cited by 45 publications

References 16 publications

Survival and long-term toxicities of pediatric Hodgkin lymphoma after combined modality treatment: a single institute experience

Survival and long-term toxicities of pediatric Hodgkin lymphoma after combined modality treatment: a single institute experience

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

Parental Considerations Regarding Cure and Late Effects for Children With Cancer

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