Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma

Monika L. Metzger, Howard J. Weinstein, Melissa M. Hudson, Amy L. Billett, Eric C. Larsen, Alison Friedmann, Scott Howard, Sarah S. Donaldson, Matthew J. Krasin, Larry E. Kun, Karen J. Marcus, Torunn I. Yock, Nancy Tarbell, Catherine A. Billups, Jianrong Wu, Michael P. Link

Research output: Contribution to journalArticle

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Abstract

Context: More than90%of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects. Objective: To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone(VAMP)in patients with favorable-risk Hodgkinlymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients: Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012. Interventions: The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy. Main Outcome Measures: Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Results: Two-year event-free survival was 90.8% (95% CI, 84.7% - 96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P=.61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed. Conclusions: Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival. Trial Registration: Clinicaltrials.gov Identifier: NCT00145600.

Original languageEnglish (US)
Pages (from-to)2609-2616
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume307
Issue number24
DOIs
StatePublished - Jun 20 2012

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Hodgkin Disease
Radiotherapy
Drug Therapy
Survival
Disease-Free Survival
Febrile Neutropenia
Poisons
Doxorubicin
Outcome Assessment (Health Care)
Osteonecrosis
Second Primary Neoplasms
Vinblastine
Metabolic Bone Diseases
Left Ventricular Dysfunction
Prednisone
Hypothyroidism
Neutropenia
Methotrexate
Nausea
Vomiting

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. / Metzger, Monika L.; Weinstein, Howard J.; Hudson, Melissa M.; Billett, Amy L.; Larsen, Eric C.; Friedmann, Alison; Howard, Scott; Donaldson, Sarah S.; Krasin, Matthew J.; Kun, Larry E.; Marcus, Karen J.; Yock, Torunn I.; Tarbell, Nancy; Billups, Catherine A.; Wu, Jianrong; Link, Michael P.

In: JAMA - Journal of the American Medical Association, Vol. 307, No. 24, 20.06.2012, p. 2609-2616.

Research output: Contribution to journalArticle

Metzger, ML, Weinstein, HJ, Hudson, MM, Billett, AL, Larsen, EC, Friedmann, A, Howard, S, Donaldson, SS, Krasin, MJ, Kun, LE, Marcus, KJ, Yock, TI, Tarbell, N, Billups, CA, Wu, J & Link, MP 2012, 'Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma', JAMA - Journal of the American Medical Association, vol. 307, no. 24, pp. 2609-2616. https://doi.org/10.1001/jama.2012.5847
Metzger, Monika L. ; Weinstein, Howard J. ; Hudson, Melissa M. ; Billett, Amy L. ; Larsen, Eric C. ; Friedmann, Alison ; Howard, Scott ; Donaldson, Sarah S. ; Krasin, Matthew J. ; Kun, Larry E. ; Marcus, Karen J. ; Yock, Torunn I. ; Tarbell, Nancy ; Billups, Catherine A. ; Wu, Jianrong ; Link, Michael P. / Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 307, No. 24. pp. 2609-2616.
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abstract = "Context: More than90{\%}of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects. Objective: To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone(VAMP)in patients with favorable-risk Hodgkinlymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients: Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012. Interventions: The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy. Main Outcome Measures: Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90{\%} was desired, and 80{\%} was considered to be unacceptably low. Results: Two-year event-free survival was 90.8{\%} (95{\%} CI, 84.7{\%} - 96.9{\%}). For patients who did not require radiotherapy, it was 89.4{\%} (95{\%} CI, 80.8{\%}-98.0{\%}) compared with 92.5{\%} (95{\%} CI, 84.5{\%}-100{\%}) for those who did (P=.61). Most common acute adverse effects were neuropathic pain (2{\%} of patients), nausea or vomiting (3{\%} of patients), neutropenia (32{\%} of cycles), and febrile neutropenia (2{\%} of patients). Nine patients (10{\%}) were hospitalized 11 times (3{\%} of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10{\%}), osteonecrosis and moderate osteopenia in 2 patients each (2{\%}), subclinical pulmonary dysfunction in 12 patients (14{\%}), and asymptomatic left ventricular dysfunction in 4 patients (5{\%}). No second malignant neoplasms were observed. Conclusions: Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival. Trial Registration: Clinicaltrials.gov Identifier: NCT00145600.",
author = "Metzger, {Monika L.} and Weinstein, {Howard J.} and Hudson, {Melissa M.} and Billett, {Amy L.} and Larsen, {Eric C.} and Alison Friedmann and Scott Howard and Donaldson, {Sarah S.} and Krasin, {Matthew J.} and Kun, {Larry E.} and Marcus, {Karen J.} and Yock, {Torunn I.} and Nancy Tarbell and Billups, {Catherine A.} and Jianrong Wu and Link, {Michael P.}",
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TY - JOUR

T1 - Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma

AU - Metzger, Monika L.

AU - Weinstein, Howard J.

AU - Hudson, Melissa M.

AU - Billett, Amy L.

AU - Larsen, Eric C.

AU - Friedmann, Alison

AU - Howard, Scott

AU - Donaldson, Sarah S.

AU - Krasin, Matthew J.

AU - Kun, Larry E.

AU - Marcus, Karen J.

AU - Yock, Torunn I.

AU - Tarbell, Nancy

AU - Billups, Catherine A.

AU - Wu, Jianrong

AU - Link, Michael P.

PY - 2012/6/20

Y1 - 2012/6/20

N2 - Context: More than90%of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects. Objective: To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone(VAMP)in patients with favorable-risk Hodgkinlymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients: Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012. Interventions: The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy. Main Outcome Measures: Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Results: Two-year event-free survival was 90.8% (95% CI, 84.7% - 96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P=.61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed. Conclusions: Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival. Trial Registration: Clinicaltrials.gov Identifier: NCT00145600.

AB - Context: More than90%of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects. Objective: To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone(VAMP)in patients with favorable-risk Hodgkinlymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients: Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012. Interventions: The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy. Main Outcome Measures: Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Results: Two-year event-free survival was 90.8% (95% CI, 84.7% - 96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P=.61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed. Conclusions: Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival. Trial Registration: Clinicaltrials.gov Identifier: NCT00145600.

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