Childhood Non-Hodgkin Lymphoma Treatment (PDQ®) 3/8 –Health Professional Version - National Cancer Institute

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version - National Cancer Institute

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version

Stage Information for Childhood NHL

In This Section

• Role of Radiographic Imaging in Childhood NHL
• St. Jude Children's Research Hospital (Murphy) Staging
  • Stage I childhood NHL
  • Stage II childhood NHL
  • Stage III childhood NHL
  • Stage IV childhood NHL

The Ann Arbor staging system is used for all lymphomas in adults and for Hodgkin lymphoma in pediatrics. However, the Ann Arbor staging system has less prognostic value in pediatric non-Hodgkin lymphoma (NHL), primarily because of the high incidence of extranodal disease. Therefore, the most widely used staging schema for childhood NHL is that of the St. Jude Children’s Research Hospital (Murphy Staging).[1] A new staging system defines bone marrow and central nervous system (CNS) involvement using modern techniques to document the presence of malignant cells. However, the basic definitions of bone marrow and CNS disease are essentially the same. The clinical utility of this staging system is under investigation.[2]

Role of Radiographic Imaging in Childhood NHL

Radiographic imaging is essential in the staging of patients with NHL. Ultrasonography may be the preferred method for assessment of an abdominal mass, but computed tomography (CT) scan and magnetic resonance imaging (MRI) have been used for staging. Radionuclide bone scans may be considered for patients in whom bone involvement is suspected.

The role of functional imaging in pediatric NHL is controversial. Gallium scans have been replaced by fluorine F 18-fludeoxyglucose positron emission tomography (PET) scanning, which is now routinely performed at many centers.[3] A review of the revised International Workshop Criteria comparing CT imaging alone or CT together with PET imaging demonstrated that the combination of CT and PET imaging was more accurate than CT imaging alone.[4,5]

While the International Harmonization Project for PET (now called the International Working Group) response criteria have been attempted in adults, the prognostic value of PET scanning for staging pediatric NHL remains under investigation.[3,6,7] Data support that PET identifies more abnormalities than does CT scanning,[8] but it is unclear whether this should be used to upstage pediatric patients and change therapy. The International Working Group has updated their response criteria for malignant lymphoma to include PET, immunohistochemistry, and flow cytometry data.[5,9]

St. Jude Children's Research Hospital (Murphy) Staging

Stage I childhood NHL

In stage I childhood NHL, a single tumor or nodal area is involved, excluding the abdomen and mediastinum.

Stage II childhood NHL

In stage II childhood NHL, disease extent is limited to a single tumor with regional node involvement, two or more tumors or nodal areas involved on one side of the diaphragm, or a primary gastrointestinal tract tumor (completely resected) with or without regional node involvement.

Stage III childhood NHL

In stage III childhood NHL, tumors or involved lymph node areas occur on both sides of the diaphragm. Stage III NHL also includes any primary intrathoracic (mediastinal, pleural, or thymic) disease, extensive primary intra-abdominal disease, or any paraspinal or epidural tumors.

Stage IV childhood NHL

In stage IV childhood NHL, tumors involve the bone marrow and/or CNS, regardless of other sites of involvement.

Bone marrow involvement has been defined as 5% or more malignant cells in an otherwise normal bone marrow, with normal peripheral blood counts and smears. Patients with lymphoblastic lymphoma who have more than 25% malignant cells in the bone marrow are usually considered to have leukemia and may be appropriately treated on leukemia clinical trials.

CNS disease in lymphoblastic lymphoma is defined by criteria similar to that used for acute lymphocytic leukemia (i.e., white blood cell count of at least 5/μL and malignant cells in the cerebrospinal fluid [CSF]). For other types of NHL, the definition of CNS disease is any malignant cell present in the CSF regardless of cell count. The Berlin-Frankfurt-Münster group analyzed the prevalence of CNS involvement in NHL in more than 2,500 patients. Overall, CNS involvement was diagnosed in 6% of patients. CNS involvement (percentage of patients) according to NHL subtype was as follows:[10]

• Burkitt lymphoma/leukemia: 8.8%
• Precursor B-cell lymphoblastic lymphoma: 5.4%
• T-cell lymphoblastic lymphoma: 3.7%
• Anaplastic large cell lymphoma: 3.3%
• Diffuse large B-cell lymphoma: 2.6%
• Primary mediastinal large B-cell lymphoma: 0%

References

1. Murphy SB, Fairclough DL, Hutchison RE, et al.: Non-Hodgkin's lymphomas of childhood: an analysis of the histology, staging, and response to treatment of 338 cases at a single institution. J Clin Oncol 7 (2): 186-93, 1989. [PUBMED Abstract]
2. Rosolen A, Perkins SL, Pinkerton CR, et al.: Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol 33 (18): 2112-8, 2015. [PUBMED Abstract]
3. Juweid ME, Stroobants S, Hoekstra OS, et al.: Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 25 (5): 571-8, 2007. [PUBMED Abstract]
4. Brepoels L, Stroobants S, De Wever W, et al.: Hodgkin lymphoma: Response assessment by revised International Workshop Criteria. Leuk Lymphoma 48 (8): 1539-47, 2007. [PUBMED Abstract]
5. Cheson BD, Pfistner B, Juweid ME, et al.: Revised response criteria for malignant lymphoma. J Clin Oncol 25 (5): 579-86, 2007. [PUBMED Abstract]
6. Cheson BD: The International Harmonization Project for response criteria in lymphoma clinical trials. Hematol Oncol Clin North Am 21 (5): 841-54, 2007. [PUBMED Abstract]
7. Bakhshi S, Radhakrishnan V, Sharma P, et al.: Pediatric nonlymphoblastic non-Hodgkin lymphoma: baseline, interim, and posttreatment PET/CT versus contrast-enhanced CT for evaluation--a prospective study. Radiology 262 (3): 956-68, 2012. [PUBMED Abstract]
8. Cheng G, Servaes S, Zhuang H: Value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan versus diagnostic contrast computed tomography in initial staging of pediatric patients with lymphoma. Leuk Lymphoma 54 (4): 737-42, 2013. [PUBMED Abstract]
9. Cheson BD, Fisher RI, Barrington SF, et al.: Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32 (27): 3059-68, 2014. [PUBMED Abstract]
10. Salzburg J, Burkhardt B, Zimmermann M, et al.: Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin-Frankfurt-Munster Group Report. J Clin Oncol 25 (25): 3915-22, 2007. [PUBMED Abstract]

Treatment Option Overview for Childhood NHL

In This Section

• Medical Emergencies
  • Mediastinal masses
  • Tumor lysis syndrome
• Tumor Surveillance
• Special Considerations for the Treatment of Children With Cancer

Many of the improvements in childhood cancer survival have been made by employing combinations of known and/or new agents aimed at improving the best available, accepted therapy. Clinical trials in pediatrics are designed to compare potentially better therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms or by evaluating a single new treatment and comparing the results with those previously obtained with standard therapy.

All children with non-Hodgkin lymphoma (NHL) should be considered for entry into a clinical trial. Treatment planning by a multidisciplinary team of cancer specialists with experience treating tumors of childhood is strongly recommended to determine, coordinate, and implement treatment to achieve optimal survival. Children with NHL should be referred for treatment by a multidisciplinary team of pediatric oncologists at an institution with experience in treating pediatric cancers. Information about ongoing National Cancer Institute (NCI)–supported clinical trials is available from the NCI website.

NHL in children is generally considered to be widely disseminated at diagnosis, even when the tumor is apparently localized; as a result, combination chemotherapy is recommended for most patients.[1] Exceptions to this treatment strategy include the following:

• Peripheral T-cell lymphoma that is limited to the skin, including anaplastic large cell lymphoma.
• Indolent mature B-cell lymphomas.
• Pediatric-type follicular lymphoma.
• Posttransplant lymphoproliferative disease (when immunosuppression can be safely decreased).

In contrast to the treatment of adults with NHL, the use of radiation therapy is limited in children with NHL. Study results include the following:

• Early studies demonstrated that the routine use of radiation had no benefit for patients with low-stage (I or II) NHL.[2]
• It has been demonstrated that prophylactic central nervous system (CNS) radiation can be omitted in patients with pediatric NHL.[3-6]
• For patients with anaplastic large cell lymphoma and B-cell NHL who present with CNS disease, radiation can also be eliminated.[5,6]

Radiation therapy may have a role in treating patients who have not had a complete response to chemotherapy. Data to support limiting the use of radiation therapy in the treatment of pediatric NHL come from the Childhood Cancer Survivor Study.[7] This analysis demonstrated that radiation was a significant risk factor for subsequent neoplasms and death in long-term survivors.

The treatment of NHL in childhood and adolescence has historically been based on the histologic subtype of the disease. A study by the Children’s Cancer Group demonstrated that the outcome for lymphoblastic lymphoma was superior with longer acute lymphoblastic leukemia–like therapy, while nonlymphoblastic NHL (Burkitt lymphoma/leukemia) had superior outcome with short, intensive, pulsed therapy; the large cell lymphoma outcome was similar with either approach.[8]

Outcomes for recurrent NHL in children and adolescents remain very poor, with the exception of anaplastic large cell lymphoma.[9-13] Patients or families who desire additional disease-directed therapy should consider entering trials of novel therapeutic approaches. Regardless of whether a decision is made to pursue disease-directed therapy at the time of progression, palliative care remains a central focus of management. This ensures that quality of life is maximized while attempting to reduce symptoms and stress related to the terminal illness.

Table 3 describes the treatment options for newly diagnosed and recurrent childhood NHL.

Table 3. Treatment Options for Childhood Non-Hodgkin Lymphoma (NHL)

Treatment Group			Treatment Options
CNS = central nervous system; EBV = Epstein-Barr virus; MALT = mucosa-associated lymphoid tissue; PTLD = posttransplant lymphoproliferative disease; SCT = stem cell transplantation.
Mature B-cell NHL:
	Burkitt and Burkitt-like lymphoma/leukemia	Newly diagnosed	Surgery (for stage I and II only)
			Chemotherapy with or without rituximab
		Recurrent	Chemotherapy with or without rituximab
			Allogeneic or autologous SCT
	Diffuse large B-cell lymphoma	Newly diagnosed	Surgery (for stage I and II only)
			Chemotherapy with or without rituximab
		Recurrent	Chemotherapy with or without rituximab
			Allogeneic or autologous SCT
	Primary mediastinal B-cell lymphoma		Chemotherapy and rituximab
Lymphoblastic lymphoma		Newly diagnosed	Chemotherapy
			Cranial radiation therapy for overt CNS disease only
		Recurrent	Nelarabine or nelarabine-containing chemotherapy regimens
			Chemotherapy
			Allogeneic SCT
Anaplastic large cell lymphoma		Newly diagnosed	Surgery followed by chemotherapy (for stage I)
			Chemotherapy
		Recurrent	Chemotherapy, brentuximab, and/or crizotinib
			Allogeneic or autologous SCT
Lymphoproliferative disease associated with immunodeficiency:
	Lymphoproliferative disease associated with primary immunodeficiency		Chemotherapy with or without rituximab
			Allogeneic SCT
	NHL associated with DNA repair defect syndromes		Chemotherapy
	HIV-associated NHL		Chemotherapy with or without rituximab
	PTLD		Surgery and reduction of immunosuppressive therapy, if possible
			Rituximab alone
			Standard or slightly modified chemotherapy with or without rituximab (for B-cell PTLD)
			Low-dose chemotherapy with or without rituximab (for EBV-positive B-cell PTLD)
Rare NHL:
	Pediatric-type follicular lymphoma		Surgery only
			Chemotherapy with or without rituximab
	Marginal zone lymphoma		Surgery only
			Radiation therapy
			Rituximab with or without chemotherapy
			Antibiotic therapy, for MALT lymphoma
	Primary CNS lymphoma		Chemotherapy
	Peripheral T-cell lymphoma		Chemotherapy
			Radiation therapy
			Allogeneic or autologous SCT
	Cutaneous T-cell lymphoma		No standard treatments have been established

Medical Emergencies

The most common potentially life-threatening clinical situations, seen most frequently in patients with lymphoblastic lymphoma and Burkitt or Burkitt-like lymphoma/leukemia, are the following:

• Mediastinal masses.
• Tumor lysis syndrome.

Mediastinal masses

Patients with large mediastinal masses are at risk of tracheal compression, superior vena caval compression, large pleural and pericardial effusions, and right and left ventricular outflow compression. Thus, cardiac or respiratory arrest is a significant risk, particularly if the patient is placed in a supine position for procedures such as computed tomography (CT) scans or echocardiograms.[14]

Because of the risk of complications from general anesthesia or heavy sedation, a careful physiologic and radiographic evaluation of the patient should be completed, and the least invasive procedure should be used to establish the diagnosis of lymphoma.[15,16] The following procedures may be used:

• Bone marrow aspirate and biopsy.
• Thoracentesis. If a pleural or pericardial effusion is present, a cytologic diagnosis is frequently possible using thoracentesis, with confirmation of the diagnosis and cell lineage by flow cytometry.
• Lymph node biopsy. In children who present with peripheral adenopathy, a lymph node biopsy performed under local anesthesia and with the patient in an upright position may be possible.[17]

In situations when the above procedures do not yield a diagnosis, the use of a CT-guided core-needle biopsy should be considered. This procedure can frequently be performed using light sedation and local anesthesia before more invasive procedures are undertaken. Care should be taken to keep patients out of a supine position. Most procedures, including CT and echocardiography, can be performed with the patient on his or her side or prone. Mediastinoscopy, anterior mediastinotomy, or thoracoscopy are the procedures of choice when other diagnostic modalities fail to establish the diagnosis. A formal thoracotomy is rarely, if ever, indicated for the diagnosis or treatment of childhood lymphoma.

Occasionally, it will not be possible to perform a diagnostic operative procedure because of the risk of complications from general anesthesia or heavy sedation. In these situations, preoperative treatment with steroids or, less commonly, localized radiation therapy should be considered. Because preoperative treatment may affect the ability to obtain an accurate tissue diagnosis, a diagnostic biopsy should be obtained as soon as the risk of complications from general anesthesia or heavy sedation is reduced.

Tumor lysis syndrome

Tumor lysis syndrome results from rapid breakdown of malignant cells, causing a number of metabolic abnormalities, most notably hyperuricemia, hyperkalemia, and hyperphosphatemia. Patients may present with tumor lysis syndrome before the start of therapy.

Hyperhydration and allopurinol or rasburicase (urate oxidase) are essential components of therapy in all patients, except those with the most limited disease.[18-23] In patients with G6PD deficiency, rasburicase may cause hemolysis or methemoglobinuria and should be avoided. An initial prephase consisting of low-dose cyclophosphamide and vincristine does not obviate the need for allopurinol or rasburicase and hydration.

Hyperuricemia and tumor lysis syndrome, particularly when associated with ureteral obstruction, frequently result in life-threatening complications.

Tumor Surveillance

Although the use of positron emission tomography (PET) to assess rapidity of response to therapy appears to have prognostic value in Hodgkin lymphoma and some types of NHL observed in adult patients, it remains under investigation in pediatric NHL. To date, there are insufficient data for pediatric NHL to support a finding that early response to therapy assessed by PET has prognostic value.

Diagnosing relapsed disease solely on the basis of imaging requires caution because false-positive results are common.[24-26] Data also demonstrate that PET scanning can produce false-negative results.[27] A study of young adults with primary mediastinal B-cell lymphoma demonstrated that 9 of 12 patients who had residual mediastinal masses at the end of therapy had positive PET scans. Seven of these nine patients had the masses resected, but no viable tumor was found.[28] Before changes in therapy are undertaken on the basis of residual masses noted by imaging, even if the PET scan is positive, a biopsy to prove residual disease is warranted.[29]

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[30] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive the treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

• Primary care physicians.
• Pediatric surgical surgeons.
• Radiation oncologists.
• Pediatric medical oncologists/hematologists.
• Rehabilitation specialists.
• Pediatric nurse specialists.
• Social workers.
• Child life professionals.
• Psychologists.

(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

Guidelines for pediatric cancer centers and their role in the treatment of children with cancer have been outlined by the American Academy of Pediatrics.[31] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare therapy that is accepted as the best currently available therapy (standard therapy) with potentially better therapy. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing NCI-supported clinical trials is available from the NCI website.

References

1. Sandlund JT, Downing JR, Crist WM: Non-Hodgkin's lymphoma in childhood. N Engl J Med 334 (19): 1238-48, 1996. [PUBMED Abstract]
2. Link MP, Shuster JJ, Donaldson SS, et al.: Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med 337 (18): 1259-66, 1997. [PUBMED Abstract]
3. Burkhardt B, Woessmann W, Zimmermann M, et al.: Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. J Clin Oncol 24 (3): 491-9, 2006. [PUBMED Abstract]
4. Sandlund JT, Pui CH, Zhou Y, et al.: Effective treatment of advanced-stage childhood lymphoblastic lymphoma without prophylactic cranial irradiation: results of St Jude NHL13 study. Leukemia 23 (6): 1127-30, 2009. [PUBMED Abstract]
5. Seidemann K, Tiemann M, Schrappe M, et al.: Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 97 (12): 3699-706, 2001. [PUBMED Abstract]
6. Cairo MS, Gerrard M, Sposto R, et al.: Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood 109 (7): 2736-43, 2007. [PUBMED Abstract]
7. Bluhm EC, Ronckers C, Hayashi RJ, et al.: Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 111 (8): 4014-21, 2008. [PUBMED Abstract]
8. Anderson JR, Jenkin RD, Wilson JF, et al.: Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group. J Clin Oncol 11 (6): 1024-32, 1993. [PUBMED Abstract]
9. Brugières L, Pacquement H, Le Deley MC, et al.: Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma: a report from the French Society of Pediatric Oncology. J Clin Oncol 27 (30): 5056-61, 2009. [PUBMED Abstract]
10. Mori T, Takimoto T, Katano N, et al.: Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan. Br J Haematol 132 (5): 594-7, 2006. [PUBMED Abstract]
11. Woessmann W, Zimmermann M, Lenhard M, et al.: Relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster (BFM)-type first-line therapy: a BFM-group study. J Clin Oncol 29 (22): 3065-71, 2011. [PUBMED Abstract]
12. Mossé YP, Lim MS, Voss SD, et al.: Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol 14 (6): 472-80, 2013. [PUBMED Abstract]
13. Pro B, Advani R, Brice P, et al.: Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol 30 (18): 2190-6, 2012. [PUBMED Abstract]
14. Azizkhan RG, Dudgeon DL, Buck JR, et al.: Life-threatening airway obstruction as a complication to the management of mediastinal masses in children. J Pediatr Surg 20 (6): 816-22, 1985. [PUBMED Abstract]
15. King DR, Patrick LE, Ginn-Pease ME, et al.: Pulmonary function is compromised in children with mediastinal lymphoma. J Pediatr Surg 32 (2): 294-9; discussion 299-300, 1997. [PUBMED Abstract]
16. Shamberger RC, Holzman RS, Griscom NT, et al.: Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses. Surgery 118 (3): 468-71, 1995. [PUBMED Abstract]
17. Prakash UB, Abel MD, Hubmayr RD: Mediastinal mass and tracheal obstruction during general anesthesia. Mayo Clin Proc 63 (10): 1004-11, 1988. [PUBMED Abstract]
18. Pui CH, Mahmoud HH, Wiley JM, et al.: Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma. J Clin Oncol 19 (3): 697-704, 2001. [PUBMED Abstract]
19. Goldman SC, Holcenberg JS, Finklestein JZ, et al.: A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood 97 (10): 2998-3003, 2001. [PUBMED Abstract]
20. Cairo MS, Bishop M: Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol 127 (1): 3-11, 2004. [PUBMED Abstract]
21. Cairo MS, Coiffier B, Reiter A, et al.: Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol 149 (4): 578-86, 2010. [PUBMED Abstract]
22. Galardy PJ, Hochberg J, Perkins SL, et al.: Rasburicase in the prevention of laboratory/clinical tumour lysis syndrome in children with advanced mature B-NHL: a Children's Oncology Group Report. Br J Haematol 163 (3): 365-72, 2013. [PUBMED Abstract]
23. Coiffier B, Altman A, Pui CH, et al.: Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 26 (16): 2767-78, 2008. [PUBMED Abstract]
24. Rhodes MM, Delbeke D, Whitlock JA, et al.: Utility of FDG-PET/CT in follow-up of children treated for Hodgkin and non-Hodgkin lymphoma. J Pediatr Hematol Oncol 28 (5): 300-6, 2006. [PUBMED Abstract]
25. Nakatani K, Nakamoto Y, Watanabe K, et al.: Roles and limitations of FDG PET in pediatric non-Hodgkin lymphoma. Clin Nucl Med 37 (7): 656-62, 2012. [PUBMED Abstract]
26. Ulaner GA, Lilienstein J, Gönen M, et al.: False-Positive [18F]fluorodeoxyglucose-avid lymph nodes on positron emission tomography-computed tomography after allogeneic but not autologous stem-cell transplantation in patients with lymphoma. J Clin Oncol 32 (1): 51-6, 2014. [PUBMED Abstract]
27. Picardi M, De Renzo A, Pane F, et al.: Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans. Leuk Lymphoma 48 (9): 1721-7, 2007. [PUBMED Abstract]
28. Dunleavy K, Pittaluga S, Maeda LS, et al.: Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med 368 (15): 1408-16, 2013. [PUBMED Abstract]
29. Bhojwani D, McCarville MB, Choi JK, et al.: The role of FDG-PET/CT in the evaluation of residual disease in paediatric non-Hodgkin lymphoma. Br J Haematol 168 (6): 845-53, 2015. [PUBMED Abstract]
30. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
31. Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004. [PUBMED Abstract]