Hodgkin's lymphoma medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Hodgkin's lymphoma}}
{{Hodgkin's lymphoma}}
{{CMG}}
{{CMG}}; {{AE}} {{AS}} {{M.B}}


==Overview==
==Overview==
Hodgkin lymphoma is considered as [[Cure|curable]] [[cancer]], however, treatment-related [[Toxicity|toxicities]] for this [[disease]] can be associated with significant long-term [[Complication (medicine)|complications]]. Selection of treatment protocol for Hodgkin's lymphoma depends on the type, the stage at diagnosis, age, and size of [[tumor]]. Combined [[modality]] [[therapy]] including use of [[chemotherapy]] and [[radiation therapy]] ([[Radiation therapy|RT]]) is the treatment of choice in patients with early-stage classic Hodgkin's Lymphoma.
==Medical Therapy==
Hodgkin lymphoma is considered as curable cancer, however, treatment-related toxicities for this disease can be associated with significant long-term [[Complication (medicine)|complications]]. Selection of treatment protocol for Hodgkin's lymphoma depends on the type, the stage at diagnosis, age, and size of tumor.<ref>{{Cite journal
| author = [[Andreas Engert]], [[Annette Plutschow]], [[Hans Theodor Eich]], [[Andreas Lohri]], [[Bernd Dorken]], [[Peter Borchmann]], [[Bernhard Berger]], [[Richard Greil]], [[Kay C. Willborn]], [[Martin Wilhelm]], [[Jurgen Debus]], [[Michael J. Eble]], [[Martin Sokler]], [[Antony Ho]], [[Andreas Rank]], [[Arnold Ganser]], [[Lorenz Trumper]], [[Carsten Bokemeyer]], [[Hartmut Kirchner]], [[Jorg Schubert]], [[Zdenek Kral]], [[Michael Fuchs]], [[Hans-Konrad Muller-Hermelink]], [[Rolf-Peter Muller]] & [[Volker Diehl]]
| title = Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma
| journal = [[The New England journal of medicine]]
| volume = 363
| issue = 7
| pages = 640–652
| year = 2010
| month = August
| doi = 10.1056/NEJMoa1000067
| pmid = 20818855
}}</ref><ref name="Cancer.ca">Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/treatment/?region=ab Accessed on September 10, 2015</ref>
* Disease at stage I or stage II is considered early stage. In addition, other [[clinical]] [[Features (pattern recognition)|features]], such as age, absence or presence of [[B symptoms]], number of involved sites, and size of [[lymphadenopathy]] are used by experts to stratify Hodgkin's lymphoma into favorable and unfavorable subtypes.
** The definitions of favorable disease are proposed by the European Organization for the Research and Treatment of Cancer (EORTC) are following:<ref>{{Cite journal
| author = [[J. M. Cosset]], [[M. Henry-Amar]], [[J. H. Meerwaldt]], [[P. Carde]], [[E. M. Noordijk]], [[J. Thomas]], [[J. M. Burgers]], [[R. Somers]], [[M. Hayat]] & [[M. Tubiana]]
| title = The EORTC trials for limited stage Hodgkin's disease. The EORTC Lymphoma Cooperative Group
| journal = [[European journal of cancer (Oxford, England : 1990)]]
| volume = 28A
| issue = 11
| pages = 1847–1850
| year = 1992
| month =
| pmid = 1389523
}}</ref>
*** Age under 50 years
*** No large [[Mediastinum|mediastinal]] [[Lymphadenopathy|adenopathy]]
*** [[Erythrocyte sedimentation rate|ESR]] of less than 50 mm/h and no [[B symptoms]] (or an ESR of less than 30 mm/h with B symptoms)
*** Disease limited to three or fewer regions of involvement
**The criteria are used by the German Hodgkin Study Group (GHSG) for definitions of favorable disease include:<ref>{{Cite journal
| author = [[Andreas Engert]], [[Annette Plutschow]], [[Hans Theodor Eich]], [[Andreas Lohri]], [[Bernd Dorken]], [[Peter Borchmann]], [[Bernhard Berger]], [[Richard Greil]], [[Kay C. Willborn]], [[Martin Wilhelm]], [[Jurgen Debus]], [[Michael J. Eble]], [[Martin Sokler]], [[Antony Ho]], [[Andreas Rank]], [[Arnold Ganser]], [[Lorenz Trumper]], [[Carsten Bokemeyer]], [[Hartmut Kirchner]], [[Jorg Schubert]], [[Zdenek Kral]], [[Michael Fuchs]], [[Hans-Konrad Muller-Hermelink]], [[Rolf-Peter Muller]] & [[Volker Diehl]]
| title = Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma
| journal = [[The New England journal of medicine]]
| volume = 363
| issue = 7
| pages = 640–652
| year = 2010
| month = August
| doi = 10.1056/NEJMoa1000067
| pmid = 20818855
}}</ref>
*** No more than two sites of involvement
*** No extranodal extension
*** No [[mediastinal mass]] measuring one-third the maximum thoracic diameter or greater
*** [[Erythrocyte sedimentation rate|ESR]] less than 50 mm/h (less than 30 mm/h if [[B symptoms]] present)
*  Patients without these criteria are considered to have unfavorable stratification.
* Combined modality therapy including use of [[chemotherapy]] and [[radiation therapy]] (RT) is the treatment of choice in patients with early-stage classic Hodgkin's Lymphoma.
'''The National Comprehensive Cancer Network (NCCN) guideline for treatment of  Hodgkin’s Lymphoma:'''
'''Favorable stage I to II classic Hodgkin’s Lymphoma'''
* Preferred regimen:[[ABVD regimen|ABVD]] ([[Doxorubicin hydrochloride|doxorubicin]] [Adriamycin]/ [[bleomycin]]/ [[vinblastine]]/ [[dacarbazine]]) regimen in two or four cycles for patients :
* Doxorubicin 25 mg/m<sup>2</sup> IV + Bleomycin 10 units/m<sup>2</sup> IV + Vinblastine 6 mg/m<sup>2</sup> IV + Dacarbazine 375 mg/m<sup>2</sup> IV on days 1 and 15. Two cycles for patients with fewer than two involved sites, and four cycles for other patients.
* Alternative regimen: [[Stanford V regimen]] ([[Doxorubicin hydrochloride|doxorubicin]], [[vinblastine]], [[mechlorethamine]] [or [[cyclophosphamide]]], [[etoposide]], [[Vincristine sulfate|vincristine]], [[bleomycin]], and [[prednisone]]). or alternatively patients undergo an 8-week<ref>{{Cite journal
| author = [[Richard T. Hoppe]], [[Ranjana H. Advani]], [[Weiyun Z. Ai]], [[Richard F. Ambinder]], [[Patricia Aoun]], [[Philippe Armand]], [[Celeste M. Bello]], [[Cecil M. Benitez]], [[Philip J. Bierman]], [[Robert Chen]], [[Bouthaina Dabaja]], [[Robert Dean]], [[Andres Forero]], [[Leo I. Gordon]], [[Francisco J. Hernandez-Ilizaliturri]], [[Ephraim P. Hochberg]], [[Jiayi Huang]], [[Patrick B. Johnston]], [[Mark S. Kaminski]], [[Vaishalee P. Kenkre]], [[Nadia Khan]], [[Kami Maddocks]], [[David G. Maloney]], [[Monika Metzger]], [[Joseph O. Moore]], [[David Morgan]], [[Craig H. Moskowitz]], [[Carolyn Mulroney]], [[Rachel Rabinovitch]], [[Stuart Seropian]], [[Randa Tao]], [[Jane N. Winter]], [[Joachim Yahalom]], [[Jennifer L. Burns]] & [[Ndiya Ogba]]
| title = NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018
| journal = [[Journal of the National Comprehensive Cancer Network : JNCCN]]
| volume = 16
| issue = 3
| pages = 245–254
| year = 2018
| month = March
| doi = 10.6004/jnccn.2018.0013
| pmid = 29523663
}}</ref>
Two cycles of [[ABVD]] followed by 20 Gy [[radiation therapy]] is suggested for patients with favorable stage I to II HL, as defined by The European Society for Medical Oncology (ESMO) guidelines, or doing [[Positron emission tomography|PET]]-[[Computed tomography|CT scanning]] after two cycles of ABVD. If PET-CT result is positive, then patients receive two cycles of BEACOPPesc ([[bleomycin]]/ [[etoposide]]/ [[Doxorubicin hydrochloride|doxorubicin]]/ [[cyclophosphamide]]/ [[Vincristine sulfate|vincristine]]/ [[procarbazine]]/ [[prednisone]] in escalated dose) followed by 30 Gy RT. PET-CT negative patients need one cycle of BEACOPPesc followed by 20 Gy [[Radiation therapy|radiotherapy]] (RT).<ref>{{Cite journal
| author = [[D. A. Eichenauer]], [[B. M. P. Aleman]], [[M. Andre]], [[M. Federico]], [[M. Hutchings]], [[T. Illidge]], [[A. Engert]] & [[M. Ladetto]]
| title = Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
| journal = [[Annals of oncology : official journal of the European Society for Medical Oncology]]
| volume = 29
| issue = Supplement_4
| pages = iv19–iv29
| year = 2018
| month = October
| doi = 10.1093/annonc/mdy080
| pmid = 29796651
}}</ref>
For treatment of non-bulky classic Hodgkin's Lymphoma at unfavorable stage I-II, the National Comprehensive Cancer Network (NCCN) guidelines recommend :<ref>{{Cite journal
| author = [[Andreas Engert]], [[Annette Plutschow]], [[Hans Theodor Eich]], [[Andreas Lohri]], [[Bernd Dorken]], [[Peter Borchmann]], [[Bernhard Berger]], [[Richard Greil]], [[Kay C. Willborn]], [[Martin Wilhelm]], [[Jurgen Debus]], [[Michael J. Eble]], [[Martin Sokler]], [[Antony Ho]], [[Andreas Rank]], [[Arnold Ganser]], [[Lorenz Trumper]], [[Carsten Bokemeyer]], [[Hartmut Kirchner]], [[Jorg Schubert]], [[Zdenek Kral]], [[Michael Fuchs]], [[Hans-Konrad Muller-Hermelink]], [[Rolf-Peter Muller]] & [[Volker Diehl]]
| title = Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma
| journal = [[The New England journal of medicine]]
| volume = 363
| issue = 7
| pages = 640–652
| year = 2010
| month = August
| doi = 10.1056/NEJMoa1000067
| pmid = 20818855
}}</ref>
* Two cycles of [[ABVD regimen]] and additional ABVD cycles or ABVD with [[radiation therapy]] (RT), or
* Three cycles of [[Stanford V regimen]] for  (12 weeks) and [[radiation therapy]] (RT), or
* BEACOPP ( [[bleomycin]], [[etoposide]], [[Doxorubicin hydrochloride|doxorubicin]], [[cyclophosphamide]], [[Vincristine sulfate|vincristine]], [[procarbazine]], [[prednisone]]) regimen for two cycles with [[radiation therapy]] (RT)
For treatment of bulky classic Hodgkin's Lymphoma at unfavorable stage I-II, the National Comprehensive Cancer Network (NCCN) guidelines recommend:<ref>{{Cite journal
| author = [[Andreas Engert]], [[Annette Plutschow]], [[Hans Theodor Eich]], [[Andreas Lohri]], [[Bernd Dorken]], [[Peter Borchmann]], [[Bernhard Berger]], [[Richard Greil]], [[Kay C. Willborn]], [[Martin Wilhelm]], [[Jurgen Debus]], [[Michael J. Eble]], [[Martin Sokler]], [[Antony Ho]], [[Andreas Rank]], [[Arnold Ganser]], [[Lorenz Trumper]], [[Carsten Bokemeyer]], [[Hartmut Kirchner]], [[Jorg Schubert]], [[Zdenek Kral]], [[Michael Fuchs]], [[Hans-Konrad Muller-Hermelink]], [[Rolf-Peter Muller]] & [[Volker Diehl]]
| title = Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma
| journal = [[The New England journal of medicine]]
| volume = 363
| issue = 7
| pages = 640–652
| year = 2010
| month = August
| doi = 10.1056/NEJMoa1000067
| pmid = 20818855
}}</ref>
* [[ABVD]] for four cycles and radiation therapy or
* [[Stanford V regimen]] for three cycles (12 weeks) or
* BEACOPP regimen for two cycles and ABVD for two cycles with radiation therapy
The National Comprehensive Cancer Network (NCCN) guidelines recommend [[ABVD]] for six cycles or three cycles (12 weeks) of [[Stanford V regimen]] or [[BEACOPP regimen]] for six cycles for treatment of non-bulky advanced-stage disease (at stage III-IV). For treatment of bulky advanced disease addition of radiation therapy is recommended.
For refractory or relapsed disease both the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) guidelines recommend high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).<ref>{{Cite journal
| author = [[Andreas Engert]], [[Annette Plutschow]], [[Hans Theodor Eich]], [[Andreas Lohri]], [[Bernd Dorken]], [[Peter Borchmann]], [[Bernhard Berger]], [[Richard Greil]], [[Kay C. Willborn]], [[Martin Wilhelm]], [[Jurgen Debus]], [[Michael J. Eble]], [[Martin Sokler]], [[Antony Ho]], [[Andreas Rank]], [[Arnold Ganser]], [[Lorenz Trumper]], [[Carsten Bokemeyer]], [[Hartmut Kirchner]], [[Jorg Schubert]], [[Zdenek Kral]], [[Michael Fuchs]], [[Hans-Konrad Muller-Hermelink]], [[Rolf-Peter Muller]] & [[Volker Diehl]]
| title = Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma
| journal = [[The New England journal of medicine]]
| volume = 363
| issue = 7
| pages = 640–652
| year = 2010
| month = August
| doi = 10.1056/NEJMoa1000067
| pmid = 20818855
}}</ref><ref>{{Cite journal
| author = [[D. A. Eichenauer]], [[B. M. P. Aleman]], [[M. Andre]], [[M. Federico]], [[M. Hutchings]], [[T. Illidge]], [[A. Engert]] & [[M. Ladetto]]
| title = Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
| journal = [[Annals of oncology : official journal of the European Society for Medical Oncology]]
| volume = 29
| issue = Supplement_4
| pages = iv19–iv29
| year = 2018
| month = October
| doi = 10.1093/annonc/mdy080
| pmid = 29796651
}}</ref>
The table below summarizes the treatment for each stage of  Hodgkin's lymphoma according to the National Comprehensive Cancer Network (NCCN) guidelines:
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+ '''Medical therapy for Hodgkin's lymphoma according to the National Comprehensive Cancer Network (NCCN) guidelines'''
! style="background: #4479BA; color:#FFF;" | Stage
! style="background: #4479BA; color:#FFF;" | Chemotherapy
! style="background: #4479BA; color:#FFF;" | Radiotherapy
! style="background: #4479BA; color:#FFF;" | Stem cell transplant
|-
| colspan="4" style="padding: 5px 5px; background: #DCDCDC;" | '''Stage I-II'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I-II with '''favorable prognosis'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[ABVD]] regimen: [[Adriamycin]] ([[Doxorubicin hydrochloride|Doxorubicin]]), [[Bleomycin|Bleomycin,]] [[Vinblastine]], [[Dacarbazine]] four cycles OR
* [[Stanford V regimen]]: [[Doxorubicin hydrochloride|Doxorubicin]], [[Vinblastine]], [[Mechlorethamine]] [or [[cyclophosphamide]]], [[Etoposide]], [[Vincristine sulfate|Vincristine]], [[Bleomycin]], and [[prednisone]] for 8-week
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; text-align: center; background: #F5F5F5;" | ---------
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I-II with '''unfavorable prognosis'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[ABVD]]: [[Adriamycin]] {{and}} [[Bleomycin]] {{and}} [[Vinblastine]] {{and}} [[Dacarbazine]] two cycles OR
* [[Stanford V regimen]] Three cycles of for  12 -weeks OR
* [[BEACOPP regimen|BEACOPP]] ( [[bleomycin]], [[etoposide]], [[Doxorubicin hydrochloride|doxorubicin]], [[cyclophosphamide]], [[Vincristine sulfate|vincristine]], [[procarbazine]], [[prednisone]]) regimen for two cycles
| style="padding: 5px 5px; background: #F5F5F5;" | 20 Gy  Radiation Therapy
| style="padding: 5px 5px; text-align: center; background: #F5F5F5;" | ---------
|-
| colspan="4" style="padding: 5px 5px; background: #DCDCDC;" | '''Stage III & IV'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Non-bulky advanced-stage disease (at stage III-IV)
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[ABVD]]: [[Adriamycin]] {{and}} [[Bleomycin]] {{and}} [[Vinblastine]] {{and}} [[Dacarbazine]]  two cycles OR
* [[Stanford V regimen]] Three cycles of for  12 -weeks OR
* [[BEACOPP regimen|BEACOPP]] ( [[bleomycin]], [[etoposide]], [[Doxorubicin hydrochloride|doxorubicin]], [[cyclophosphamide]], [[Vincristine sulfate|vincristine]], [[procarbazine]], [[prednisone]]) regimen for two cycles
* [[Brentuximab vedotin]] plus AVD (BV-AVD) every 2 weeks for a maximum of 12 doses
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; text-align: center; background: #F5F5F5;" | ---------
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* ([[MOPP regimen|MOPP]]) [[Mechlorethamine]] {{and}} [[Oncovin]] {{and}} [[Prednisone]] {{and}} [[Procarbazine]]  <BR>
* ([[ABVD]]) [[Adriamycin]] {{and}} [[Bleomycin]] {{and}} [[Vinblastine]] {{and}} [[Dacarbazine]] <BR>
* ([[Stanford V]]) [[Adriamycin]] {{and}}  [[Bleomycin]] {{and}} [[Vinblastine]] {{and}} [[Vincristine]] {{and}} [[Mechlorethamine]] {{and}} [[Etoposide]] {{and}} [[Prednisone]] <BR>
* ([[BEACOPP]]) [[Bleomycin]] {{and}} [[Etoposide]] {{and}} [[Adriamycin]] {{and}} [[Cyclophosphamide]] {{and}} [[Oncovin]] {{and}} [[Procarbazine]] {{and}} [[Prednisone]]
| style="padding: 5px 5px; text-align: center; background: #F5F5F5;" | ---------
| style="padding: 5px 5px; text-align: center; background: #F5F5F5;" | ---------
|-
| colspan="4" style="padding: 5px 5px; background: #DCDCDC;" | '''Recurrent disease'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Recurrence
| style="padding: 5px 5px; background: #F5F5F5;" |
* ([[MOPP regimen|MOPP]]) [[Mechlorethamine]] {{and}} [[Oncovin]] {{and}} [[Prednisone]] {{and}} [[Procarbazine]]  <BR>
* ([[ABVD]]) [[Adriamycin]] {{and}} [[Bleomycin]] {{and}} [[Vinblastine]] {{and}} [[Dacarbazine]]  <BR>
* ([[Stanford V]]) [[Adriamycin]] {{and}}  [[Bleomycin]] {{and}} [[Vinblastine]] {{and}} [[Vincristine]] {{and}} [[Mechlorethamine]] {{and}} [[Etoposide]] {{and}} [[Prednisone]]  <BR>
* ([[BEACOPP]]) [[Bleomycin]] {{and}} [[Etoposide]] {{and}} [[Adriamycin]] {{and}} [[Cyclophosphamide]] {{and}} [[Oncovin]] {{and}} [[Procarbazine]] {{and}} [[Prednisone]] <BR>
* (GDP) [[Gemcitabine]] {{and}} [[Dexamethasone]] {{and}} [[Cisplatin]] <BR>
* (CBV) [[Cyclophosphamide]] {{and}} [[Carmustine]] {{and}} [[Etoposide]]  <BR>
* (BEAM) [[Carmustine]] {{and}} [[Etoposide]] {{and}} [[Cytarabine]] {{and}} [[Melphalan]]
* [[Pembrolizumab]] every 3 weeks (if relapse occurred with 3 or more lines of therapy)
| style="padding: 5px 5px; background: #F5F5F5;" | External beam radiation therapy may be offered
| style="padding: 5px 5px; background: #F5F5F5;" | Stem cell transplant may be offered
|}
The algorithms below summarize the treatment for each stage of  Hodgkin's lymphoma according to the European Society for Medical Oncology (ESMO) guidelines:
{{familytree/start |summary=Sample 1}}
{{familytree | | | | | | | | A01 |A01=Favorable prognosis
stage I-II}}
{{familytree | | | | |,|-|-|-|^|-|-|-|-|.| | | }}
{{familytree | | | B01 | | | | | | | | B02 | | |B01=ABVD x 2 Cycles|B02=ABVD x 2 Cycles}}
{{familytree | | | |!| | | | | | | | | |!| }}
{{familytree | | | C01 | | | | | | | | |!| |C01=20 Gy RT}}
{{familytree | | | | | | | | | | | | | D03 |D03=PET-CT scan}}
{{familytree | | | | | | | | | | | |,|-|^|.| }}
{{familytree | | | | | | | | | | E02 | | | E03 |E01=E01|E02=PET-positive|E03=PET-negative}}
{{familytree | | | | | | | | | | |!| | | | |!| }}
{{familytree | | | | | | | | | | F01 | | | F02 |F01=BEACOPPesc x 2 Cycles|F02=ABVD x 1 Cycle}}
{{familytree | | | | | | | | | | |!| | | | |!| | |}}
{{familytree | | | | | | | | | | G01 | | | G02 | |G01=30 Gy RT|G02=20 Gy RT}}
{{familytree/end}}
{{familytree/start |summary=Sample 1}}
{{familytree | | | | | | | | A01 |A01=Unfavorable prognosis
stage I-II}}
{{familytree | | | | |,|-|-|-|^|-|-|-|-|.| | | }}
{{familytree | | | B01 | | | | | | | | B02 | | |B01=ABVD x 4 Cycles OR BEACOPPesc x 2 Cycles + ABVD x 2 Cycles|B02=ABVD x 2 Cycles}}
{{familytree | | | |!| | | | | | | | | |!| }}
{{familytree | | | C01 | | | | | | | | |!| |C01=30 Gy RT}}
{{familytree | | | | | | | | | | | | | D03 |D03=PET-CT scan}}
{{familytree | | | | | | | | | | | |,|-|^|.| }}
{{familytree | | | | | | | | | | E02 | | | E03 |E01=E01|E02=PET-positive|E03=PET-negative}}
{{familytree | | | | | | | | | | |!| | | | |!| }}
{{familytree | | | | | | | | | | F01 | | | F02 |F01=BEACOPPesc x 2 Cycles|F02=ABVD x 2 Cycles}}
{{familytree | | | | | | | | | | |!| | | | |!| | |}}
{{familytree | | | | | | | | | | G01 | | | G02 | |G01=30 Gy RT|G02=30 Gy RT}}
{{familytree/end}}


Patients with early stage disease (IA or IIA) are effectively treated with [[radiation]] therapy or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone.  Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.


==Medical Therapy==


===Chemotherapy===
{{familytree/start |summary=Sample 1}}
Currently, the ''[[ABVD]]'' [[chemotherapy]] regimen is the gold standard for treatment of Hodgkin's disease. The abbreviation stands for the four drugs [[Adriamycin]], [[bleomycin]], [[vinblastine]], and [[dacarbazine]]. Developed in Italy in the 1970s, the ABVD treatment typically takes between six and eight months, although longer treatments may be required. Another form of treatment is the newer [[Stanford V]] regimen, which is typically only half as long as the ABVD but which involves a more intensive chemotherapy schedule and incorporates radiation therapy. However, in a randomized controlled study, Stanford V was inferior.<ref name="pmid16172458">{{cite journal |author=Gobbi PG, Levis A, Chisesi T, ''et al'' |title=ABVD versus modified stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi |journal=J. Clin. Oncol. |volume=23 |issue=36 |pages=9198-207 |year=2005 |pmid=16172458 |doi=10.1200/JCO.2005.02.907}}</ref>
{{familytree | | | | | | | | | A01 |A01=Advanced Stages HL}}
{{familytree | | | | |,|-|-|-|-|^|-|-|-|-|-|-|-|.| | }}
{{familytree | | | B01 | | | | B02 | | | | | | B03 | | |B01=ABVD x 6 OR BEACOPPesc x 6|B02=BEACOPPesc x 2 Cycles|B03=ABVD x 2 }}
{{familytree | | | |!| | | | | |!| | | | | | | |!| }}
{{familytree | | | C01 | | | | C02 | | | | | | C03 |C01=RT to residual lymphoma > 2.5cm|C02=PET-CT scan|C03=PET-CT scan}}
{{familytree | | | | | | | |,|-|^|-|.| | | |,|-|^|-|.| | | | | }}
{{familytree | | | | | | | D01| |D02| | D03| |D04 |D01=PET-positive|D02=PET-negative |D03=PET-positive|D04=PET-negative }}
{{familytree | | | | | | | |!| | | |!| | | |!| | | |!| | | | | }}
{{familytree | | | | | | | E01 | | E02 | | E03 | | E04 | | | | E01=BEACOPPesc x 4 Cycles|E02=BEACOPPesc x 2 Cycles|E03=ABVD x 4 Cycles OR BEACOPPesc x 4 Cycles|E04=AVD x 4 Cycles}}
{{familytree | | | | | | | |`|-|v|-|'| | | |`|-|v|-|'| | | | | }}
{{familytree | | | | | | | | | F01 | | | | | | F02 | | | | | |F01=PET-CT|F02=PET-CT}}
{{familytree | | | | | | | |,|-|^|-|.| | | |,|-|^|-|.| | | | | }}
{{familytree | | | | | | | G01 | | G02 | | G03 | | G04 | | | |G01=PET-positive|G02=PET-negative |G03=PET-positive|G04=PET-negative }}
{{familytree | | | | | | | |!| | | |!| | | |!| | | |!| | | | | }}
{{familytree | | | | | | | H01 | | H02 | | H03 | | H04 | | | |H01=RT to residual lymphoma>2.5 cm|H02=Follow up |H03=RT to residual lymphoma>2.5 cm|H04=Follow up  }}
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | }}
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | }}
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | }}
{{familytree/end}}


Another form of treatment, mainly in Europe for stages > II is [[BEACOPP]]. The cure rate with the BEACOPP esc. regimen is approximately 10-15% higher than with standard ABVD in advanced stages. Although this was shown in a landmark paper in The New England Journal of Medicine (Diehl et al.), the US physicians still favor ABVD. Probably because some physicians think that BEACOPP induces more secondary leukemia. However, this seems negligible compared to the higher cure rates. Also, BEACOPP is more expensive because of the G-CSF-support that is required. Currently, the German Hodgkin Study group tests 8x BEACOPP esc vs. 6x BEACOPP esc vs. 8x BEACOPP-14 baseline (HD15-trial).


With appropriate treatment, over 93% of Hodgkin's lymphoma cases are curable.


The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute [[leukemia]]s, lymphomas, and solid tumors within the radiation therapy field. Most patients with early stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemo-therapy with no radiation.
===Medical therapy during pregnancy<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq</ref>===
====First trimester of pregnancy====
* < 32 weeks
:* Watchful waiting when the cancer is above the diaphragm and is slow-growing
* > 32 weeks
:* Delivery may be induced, systemic chemotherapy using one or more drugs
:* Radiation therapy above the diaphragm  (A lead shield is used to protect the fetus from the radiation as much as possible)
====Second half of pregnancy====
* < 32 weeks
:* Watchful waiting, most women can delay treatment until after the baby is born
* > 32 weeks
:* Systemic chemotherapy using one or more drugs
:* Steroid therapy
:* Radiation therapy to relieve breathing problems caused by a large tumor in the chest
===Chemotherapy===
*Chemotherapy may be used:<ref name="Cancer.ca">Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/treatment/?region=ab Accessed on September 10, 2015</ref>
:* As the primary treatment, with or without radiation therapy, to destroy cancer cells
:* To treat relapsed Hodgkin's lymphoma (that comes back after treatment) or refractory Hodgkin's lymphoma (that is resistant to the initial treatment)
:* To control the symptoms of advanced  (palliative chemotherapy)
===Radiation therapy===
* Radiation may be used for Hodgkin's lymphoma (HL):<ref name="Cancer.ca">Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/treatment/?region=ab Accessed on September 10, 2015</ref><ref>{{Cite journal
| author = [[J. M. Andrieu]], [[C. Bayle-Weisgerber]], [[M. Boiron]], [[J. F. Briere]], [[P. Clot]], [[M. Dana]], [[C. Jacquillat]], [[M. Katz]] & [[F. Teillet]]
| title = The chemotherapy--radiotherapy sequence in the management of Hodgkin's disease. Results of a clinical trial
| journal = [[European journal of cancer]]
| volume = 15
| issue = 2
| pages = 153–161
| year = 1979
| month = February
| pmid = 374084
}}</ref>
:* As the primary treatment with chemotherapy to reduce the risk of recurrence
:* For stage I & II Hodgkin's lymphoma, given after chemotherapy to the areas where the Hodgkin's lymphoma was initially found or before chemotherapy to shrink a large tumor. Radiation therapy may be given alone:
:::* If the person cannot tolerate chemotherapy because of other health issues
:::* If the Hodgkin's lymphoma is localized in a small area of lymph nodes
:::* For nodular lymphocyte predominant Hodgkin's lymphoma when no B symptoms are present
:* For stage III Hodgkin's lymphoma, given after chemotherapy if the Hodgkin's lymphoma is localized in an area of the body and can be included in the radiation field
:* For relapsed or primary refractory Hodgkin's lymphoma if the original treatment was chemotherapy only and the Hodgkin's lymphoma remains or returns in only a single area
:* To shrink bulky tumors before chemotherapy
:* Alone, in certain situations
::* For early stage favorable Hodgkin's lymphoma when the person cannot tolerate chemotherapy because of other health problems
::* When the Hodgkin's lymphoma is a small localized area and the lymph nodes are very small
::* For early stage nodular lymphocyte predominant Hodgkin's lymphoma without B symptoms
:* To control the symptoms of advanced Hodgkin's lymphoma (palliative radiation therapy)
* The dose and schedule for the radiation therapy are determined by:
:* The extent of the disease
:* Whether or not the radiation therapy is given with chemotherapy
:* Whether the treatment is intended to be curative or palliative
====External beam radiation therapy====
Hodgkin's lymphoma is often treated with external beam radiation therapy. A machine directs radiation to the tumor and some of the surrounding tissue.
====Radiation field====
* Each person’s situation is unique, and the radiation fields may be adjusted depending on the extent of the disease. Radiation treatments are given to different areas of the body when treating Hodgkin's lymphoma. The radiation field is the part of the body that receives the radiation. Some of radiation fields to treat Hodgkin's lymphoma are:
:* Involved field: only the lymph node areas with Hodgkin's lymphoma (the standard field used in combination with chemotherapy)
::* Chemotherapy is given first, followed by involved field radiation to the original site of the disease
:* Mantle field: lymph nodes in the neck, chest and axilla
:* Upper abdominal field: lymph nodes in the upper abdomen and possibly the spleen
:* Pelvic field, or Inverted (upside down) Y field: lymph nodes in the pelvis and groin
:* Extended field: the mantle field and uppermost part of the inverted Y field
::* This is seldom used anymore because nearly all people with Hodgkin's lymphoma are treated with chemotherapy
* Total nodal irradiation
:* Is the term used when radiation is given to all fields
:* Is basically a combination of the mantle and inverted Y fields
:* May be used for people with widespread, advanced stage disease
:* Is used when low-dose radiation is given to the entire body in preparation for a stem cell transplant
====Stem cell transplantation====
* Stem cell transplantation may be considered for individuals with Hodgkin's lymphoma in the following cases:<ref name="Cancer.ca">Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/treatment/?region=ab Accessed on September 10, 2015</ref>
:* When the Hodgkin's lymphoma is not responding to other treatments or standard treatment has failed to work (refractory disease)
:* If the Hodgkin's lymphoma comes back after an initial response to treatment (relapsed disease)


==References==
==References==
{{reflist|2}}
{{reflist|2}}
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{{WikiDoc Sources}}


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Latest revision as of 22:13, 29 July 2020

Hodgkin's lymphoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2] Mohsen Basiri M.D.

Overview

Hodgkin lymphoma is considered as curable cancer, however, treatment-related toxicities for this disease can be associated with significant long-term complications. Selection of treatment protocol for Hodgkin's lymphoma depends on the type, the stage at diagnosis, age, and size of tumor. Combined modality therapy including use of chemotherapy and radiation therapy (RT) is the treatment of choice in patients with early-stage classic Hodgkin's Lymphoma.

Medical Therapy

Hodgkin lymphoma is considered as curable cancer, however, treatment-related toxicities for this disease can be associated with significant long-term complications. Selection of treatment protocol for Hodgkin's lymphoma depends on the type, the stage at diagnosis, age, and size of tumor.[1][2]

  • Disease at stage I or stage II is considered early stage. In addition, other clinical features, such as age, absence or presence of B symptoms, number of involved sites, and size of lymphadenopathy are used by experts to stratify Hodgkin's lymphoma into favorable and unfavorable subtypes.
    • The definitions of favorable disease are proposed by the European Organization for the Research and Treatment of Cancer (EORTC) are following:[3]
      • Age under 50 years
      • No large mediastinal adenopathy
      • ESR of less than 50 mm/h and no B symptoms (or an ESR of less than 30 mm/h with B symptoms)
      • Disease limited to three or fewer regions of involvement


    • The criteria are used by the German Hodgkin Study Group (GHSG) for definitions of favorable disease include:[4]
      • No more than two sites of involvement
      • No extranodal extension
      • No mediastinal mass measuring one-third the maximum thoracic diameter or greater
      • ESR less than 50 mm/h (less than 30 mm/h if B symptoms present)
  • Patients without these criteria are considered to have unfavorable stratification.
  • Combined modality therapy including use of chemotherapy and radiation therapy (RT) is the treatment of choice in patients with early-stage classic Hodgkin's Lymphoma.

The National Comprehensive Cancer Network (NCCN) guideline for treatment of Hodgkin’s Lymphoma:

Favorable stage I to II classic Hodgkin’s Lymphoma

Two cycles of ABVD followed by 20 Gy radiation therapy is suggested for patients with favorable stage I to II HL, as defined by The European Society for Medical Oncology (ESMO) guidelines, or doing PET-CT scanning after two cycles of ABVD. If PET-CT result is positive, then patients receive two cycles of BEACOPPesc (bleomycin/ etoposide/ doxorubicin/ cyclophosphamide/ vincristine/ procarbazine/ prednisone in escalated dose) followed by 30 Gy RT. PET-CT negative patients need one cycle of BEACOPPesc followed by 20 Gy radiotherapy (RT).[6]


For treatment of non-bulky classic Hodgkin's Lymphoma at unfavorable stage I-II, the National Comprehensive Cancer Network (NCCN) guidelines recommend :[7]

For treatment of bulky classic Hodgkin's Lymphoma at unfavorable stage I-II, the National Comprehensive Cancer Network (NCCN) guidelines recommend:[8]

  • ABVD for four cycles and radiation therapy or
  • Stanford V regimen for three cycles (12 weeks) or
  • BEACOPP regimen for two cycles and ABVD for two cycles with radiation therapy

The National Comprehensive Cancer Network (NCCN) guidelines recommend ABVD for six cycles or three cycles (12 weeks) of Stanford V regimen or BEACOPP regimen for six cycles for treatment of non-bulky advanced-stage disease (at stage III-IV). For treatment of bulky advanced disease addition of radiation therapy is recommended.

For refractory or relapsed disease both the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) guidelines recommend high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).[9][10]


The table below summarizes the treatment for each stage of Hodgkin's lymphoma according to the National Comprehensive Cancer Network (NCCN) guidelines:

Medical therapy for Hodgkin's lymphoma according to the National Comprehensive Cancer Network (NCCN) guidelines
Stage Chemotherapy Radiotherapy Stem cell transplant
Stage I-II
Stage I-II with favorable prognosis ---------
Stage I-II with unfavorable prognosis 20 Gy Radiation Therapy ---------
Stage III & IV
Non-bulky advanced-stage disease (at stage III-IV) ---------
--------- ---------
Recurrent disease
Recurrence External beam radiation therapy may be offered Stem cell transplant may be offered

The algorithms below summarize the treatment for each stage of Hodgkin's lymphoma according to the European Society for Medical Oncology (ESMO) guidelines:


 
 
 
 
 
 
 
Favorable prognosis stage I-II
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ABVD x 2 Cycles
 
 
 
 
 
 
 
ABVD x 2 Cycles
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
20 Gy RT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PET-CT scan
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PET-positive
 
 
PET-negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BEACOPPesc x 2 Cycles
 
 
ABVD x 1 Cycle
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
30 Gy RT
 
 
20 Gy RT
 


 
 
 
 
 
 
 
Unfavorable prognosis stage I-II
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ABVD x 4 Cycles OR BEACOPPesc x 2 Cycles + ABVD x 2 Cycles
 
 
 
 
 
 
 
ABVD x 2 Cycles
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
30 Gy RT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PET-CT scan
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PET-positive
 
 
PET-negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BEACOPPesc x 2 Cycles
 
 
ABVD x 2 Cycles
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
30 Gy RT
 
 
30 Gy RT
 


 
 
 
 
 
 
 
 
Advanced Stages HL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ABVD x 6 OR BEACOPPesc x 6
 
 
 
BEACOPPesc x 2 Cycles
 
 
 
 
 
ABVD x 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RT to residual lymphoma > 2.5cm
 
 
 
PET-CT scan
 
 
 
 
 
PET-CT scan
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PET-positive
 
PET-negative
 
PET-positive
 
PET-negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BEACOPPesc x 4 Cycles
 
BEACOPPesc x 2 Cycles
 
ABVD x 4 Cycles OR BEACOPPesc x 4 Cycles
 
AVD x 4 Cycles
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PET-CT
 
 
 
 
 
PET-CT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PET-positive
 
PET-negative
 
PET-positive
 
PET-negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RT to residual lymphoma>2.5 cm
 
Follow up
 
RT to residual lymphoma>2.5 cm
 
Follow up
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Medical therapy during pregnancy[11]

First trimester of pregnancy

  • < 32 weeks
  • Watchful waiting when the cancer is above the diaphragm and is slow-growing
  • > 32 weeks
  • Delivery may be induced, systemic chemotherapy using one or more drugs
  • Radiation therapy above the diaphragm (A lead shield is used to protect the fetus from the radiation as much as possible)

Second half of pregnancy

  • < 32 weeks
  • Watchful waiting, most women can delay treatment until after the baby is born
  • > 32 weeks
  • Systemic chemotherapy using one or more drugs
  • Steroid therapy
  • Radiation therapy to relieve breathing problems caused by a large tumor in the chest

Chemotherapy

  • Chemotherapy may be used:[2]
  • As the primary treatment, with or without radiation therapy, to destroy cancer cells
  • To treat relapsed Hodgkin's lymphoma (that comes back after treatment) or refractory Hodgkin's lymphoma (that is resistant to the initial treatment)
  • To control the symptoms of advanced (palliative chemotherapy)

Radiation therapy

  • Radiation may be used for Hodgkin's lymphoma (HL):[2][12]
  • As the primary treatment with chemotherapy to reduce the risk of recurrence
  • For stage I & II Hodgkin's lymphoma, given after chemotherapy to the areas where the Hodgkin's lymphoma was initially found or before chemotherapy to shrink a large tumor. Radiation therapy may be given alone:
  • If the person cannot tolerate chemotherapy because of other health issues
  • If the Hodgkin's lymphoma is localized in a small area of lymph nodes
  • For nodular lymphocyte predominant Hodgkin's lymphoma when no B symptoms are present
  • For stage III Hodgkin's lymphoma, given after chemotherapy if the Hodgkin's lymphoma is localized in an area of the body and can be included in the radiation field
  • For relapsed or primary refractory Hodgkin's lymphoma if the original treatment was chemotherapy only and the Hodgkin's lymphoma remains or returns in only a single area
  • To shrink bulky tumors before chemotherapy
  • Alone, in certain situations
  • For early stage favorable Hodgkin's lymphoma when the person cannot tolerate chemotherapy because of other health problems
  • When the Hodgkin's lymphoma is a small localized area and the lymph nodes are very small
  • For early stage nodular lymphocyte predominant Hodgkin's lymphoma without B symptoms
  • To control the symptoms of advanced Hodgkin's lymphoma (palliative radiation therapy)
  • The dose and schedule for the radiation therapy are determined by:
  • The extent of the disease
  • Whether or not the radiation therapy is given with chemotherapy
  • Whether the treatment is intended to be curative or palliative

External beam radiation therapy

Hodgkin's lymphoma is often treated with external beam radiation therapy. A machine directs radiation to the tumor and some of the surrounding tissue.

Radiation field

  • Each person’s situation is unique, and the radiation fields may be adjusted depending on the extent of the disease. Radiation treatments are given to different areas of the body when treating Hodgkin's lymphoma. The radiation field is the part of the body that receives the radiation. Some of radiation fields to treat Hodgkin's lymphoma are:
  • Involved field: only the lymph node areas with Hodgkin's lymphoma (the standard field used in combination with chemotherapy)
  • Chemotherapy is given first, followed by involved field radiation to the original site of the disease
  • Mantle field: lymph nodes in the neck, chest and axilla
  • Upper abdominal field: lymph nodes in the upper abdomen and possibly the spleen
  • Pelvic field, or Inverted (upside down) Y field: lymph nodes in the pelvis and groin
  • Extended field: the mantle field and uppermost part of the inverted Y field
  • This is seldom used anymore because nearly all people with Hodgkin's lymphoma are treated with chemotherapy
  • Total nodal irradiation
  • Is the term used when radiation is given to all fields
  • Is basically a combination of the mantle and inverted Y fields
  • May be used for people with widespread, advanced stage disease
  • Is used when low-dose radiation is given to the entire body in preparation for a stem cell transplant

Stem cell transplantation

  • Stem cell transplantation may be considered for individuals with Hodgkin's lymphoma in the following cases:[2]
  • When the Hodgkin's lymphoma is not responding to other treatments or standard treatment has failed to work (refractory disease)
  • If the Hodgkin's lymphoma comes back after an initial response to treatment (relapsed disease)

References

  1. ↑ Andreas Engert, Annette Plutschow, Hans Theodor Eich, Andreas Lohri, Bernd Dorken, Peter Borchmann, Bernhard Berger, Richard Greil, Kay C. Willborn, Martin Wilhelm, Jurgen Debus, Michael J. Eble, Martin Sokler, Antony Ho, Andreas Rank, Arnold Ganser, Lorenz Trumper, Carsten Bokemeyer, Hartmut Kirchner, Jorg Schubert, Zdenek Kral, Michael Fuchs, Hans-Konrad Muller-Hermelink, Rolf-Peter Muller & Volker Diehl (2010). "Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma". The New England journal of medicine. 363 (7): 640–652. doi:10.1056/NEJMoa1000067. PMID 20818855. Unknown parameter |month= ignored (help)
  2. ↑ 2.0 2.1 2.2 2.3 Hodgkin-lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/hodgkin-lymphoma/treatment/?region=ab Accessed on September 10, 2015
  3. ↑ J. M. Cosset, M. Henry-Amar, J. H. Meerwaldt, P. Carde, E. M. Noordijk, J. Thomas, J. M. Burgers, R. Somers, M. Hayat & M. Tubiana (1992). "The EORTC trials for limited stage Hodgkin's disease. The EORTC Lymphoma Cooperative Group". European journal of cancer (Oxford, England : 1990). 28A (11): 1847–1850. PMID 1389523.
  4. ↑ Andreas Engert, Annette Plutschow, Hans Theodor Eich, Andreas Lohri, Bernd Dorken, Peter Borchmann, Bernhard Berger, Richard Greil, Kay C. Willborn, Martin Wilhelm, Jurgen Debus, Michael J. Eble, Martin Sokler, Antony Ho, Andreas Rank, Arnold Ganser, Lorenz Trumper, Carsten Bokemeyer, Hartmut Kirchner, Jorg Schubert, Zdenek Kral, Michael Fuchs, Hans-Konrad Muller-Hermelink, Rolf-Peter Muller & Volker Diehl (2010). "Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma". The New England journal of medicine. 363 (7): 640–652. doi:10.1056/NEJMoa1000067. PMID 20818855. Unknown parameter |month= ignored (help)
  5. ↑ Richard T. Hoppe, Ranjana H. Advani, Weiyun Z. Ai, Richard F. Ambinder, Patricia Aoun, Philippe Armand, Celeste M. Bello, Cecil M. Benitez, Philip J. Bierman, Robert Chen, Bouthaina Dabaja, Robert Dean, Andres Forero, Leo I. Gordon, Francisco J. Hernandez-Ilizaliturri, Ephraim P. Hochberg, Jiayi Huang, Patrick B. Johnston, Mark S. Kaminski, Vaishalee P. Kenkre, Nadia Khan, Kami Maddocks, David G. Maloney, Monika Metzger, Joseph O. Moore, David Morgan, Craig H. Moskowitz, Carolyn Mulroney, Rachel Rabinovitch, Stuart Seropian, Randa Tao, Jane N. Winter, Joachim Yahalom, Jennifer L. Burns & Ndiya Ogba (2018). "NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018". Journal of the National Comprehensive Cancer Network : JNCCN. 16 (3): 245–254. doi:10.6004/jnccn.2018.0013. PMID 29523663. Unknown parameter |month= ignored (help)
  6. ↑ D. A. Eichenauer, B. M. P. Aleman, M. Andre, M. Federico, M. Hutchings, T. Illidge, A. Engert & M. Ladetto (2018). "Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Annals of oncology : official journal of the European Society for Medical Oncology. 29 (Supplement_4): iv19–iv29. doi:10.1093/annonc/mdy080. PMID 29796651. Unknown parameter |month= ignored (help)
  7. ↑ Andreas Engert, Annette Plutschow, Hans Theodor Eich, Andreas Lohri, Bernd Dorken, Peter Borchmann, Bernhard Berger, Richard Greil, Kay C. Willborn, Martin Wilhelm, Jurgen Debus, Michael J. Eble, Martin Sokler, Antony Ho, Andreas Rank, Arnold Ganser, Lorenz Trumper, Carsten Bokemeyer, Hartmut Kirchner, Jorg Schubert, Zdenek Kral, Michael Fuchs, Hans-Konrad Muller-Hermelink, Rolf-Peter Muller & Volker Diehl (2010). "Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma". The New England journal of medicine. 363 (7): 640–652. doi:10.1056/NEJMoa1000067. PMID 20818855. Unknown parameter |month= ignored (help)
  8. ↑ Andreas Engert, Annette Plutschow, Hans Theodor Eich, Andreas Lohri, Bernd Dorken, Peter Borchmann, Bernhard Berger, Richard Greil, Kay C. Willborn, Martin Wilhelm, Jurgen Debus, Michael J. Eble, Martin Sokler, Antony Ho, Andreas Rank, Arnold Ganser, Lorenz Trumper, Carsten Bokemeyer, Hartmut Kirchner, Jorg Schubert, Zdenek Kral, Michael Fuchs, Hans-Konrad Muller-Hermelink, Rolf-Peter Muller & Volker Diehl (2010). "Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma". The New England journal of medicine. 363 (7): 640–652. doi:10.1056/NEJMoa1000067. PMID 20818855. Unknown parameter |month= ignored (help)
  9. ↑ Andreas Engert, Annette Plutschow, Hans Theodor Eich, Andreas Lohri, Bernd Dorken, Peter Borchmann, Bernhard Berger, Richard Greil, Kay C. Willborn, Martin Wilhelm, Jurgen Debus, Michael J. Eble, Martin Sokler, Antony Ho, Andreas Rank, Arnold Ganser, Lorenz Trumper, Carsten Bokemeyer, Hartmut Kirchner, Jorg Schubert, Zdenek Kral, Michael Fuchs, Hans-Konrad Muller-Hermelink, Rolf-Peter Muller & Volker Diehl (2010). "Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma". The New England journal of medicine. 363 (7): 640–652. doi:10.1056/NEJMoa1000067. PMID 20818855. Unknown parameter |month= ignored (help)
  10. ↑ D. A. Eichenauer, B. M. P. Aleman, M. Andre, M. Federico, M. Hutchings, T. Illidge, A. Engert & M. Ladetto (2018). "Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Annals of oncology : official journal of the European Society for Medical Oncology. 29 (Supplement_4): iv19–iv29. doi:10.1093/annonc/mdy080. PMID 29796651. Unknown parameter |month= ignored (help)
  11. ↑ National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq
  12. ↑ J. M. Andrieu, C. Bayle-Weisgerber, M. Boiron, J. F. Briere, P. Clot, M. Dana, C. Jacquillat, M. Katz & F. Teillet (1979). "The chemotherapy--radiotherapy sequence in the management of Hodgkin's disease. Results of a clinical trial". European journal of cancer. 15 (2): 153–161. PMID 374084. Unknown parameter |month= ignored (help)


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