Radiation Oncology/NHL/Overview

Classification Historically several systems, both in USA and Europe WHO classification is used today WHO classification B-cell neoplasms Precursor B-cell neoplasms Precursor B-lymphoblastic leukemia/lymphoma (precursor B-cell acute lymphoblastic leukemia) Mature (peripheral) B-cell neoplasms B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic lymphoma Splenic marginal zone B-cell lymphoma Hairy cell leukemia Plasma cell myeloma/plasmacytoma Extranodal marginal zone B-cell lymphoma of MALT type Nodal marginal zone B-cell lymphoma Follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma Burkitt lymphoma / Burkitt cell leukemia T-cell and NK-cell neoplasms Precursor T-cell neoplasm Precursor T-lymphoblastic lymphoma/leukemia (precursor T-cell acute lymphoblastic leukemia) Mature (peripheral) T/NK-cell neoplasms T-cell prolymphocytic leukemia T-cell granular lymphocytic leukemia Aggressive NK-cell leukemia Adult T-cell lymphoma/leukemia (HTLV1+) Extranodal NK/T-cell lymphoma, nasal type Enteropathy-type T-cell lymphoma Hepatosplenic gamma-delta T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides / Sezary syndrome Anaplastic large cell lymphoma, T/null cell, primary cutaneous type Anaplastic large cell lymphoma, T/null cell, primary systemic type Peripheral T-cell lymphoma, not otherwise characterized Angioimmunoblastic T-cell lymphoma WHO by aggressiveness Grade HistologiesIndolent B-cell: Follicular (Grade I/II), SLL/CLL, lymphoplasmatic lymphoma, plasma cell/myeloma, hairy cell leukemia, marginal zone B-cell, mantle cell, T-cell: T-cell large granular lymphocyte leukemia, mycosis fungoides, T-cell prolymphocytic leukemia, NK cell Aggressive B-cell: Follicular (Grade III), DLBCL, mantle cell, T-cell: peripheral T-cell lymphoma, anaplastic large cell lymphoma Highly aggressive B-cell: Burkitt's lymphoma, precursor B lymphoblastic leukemia/lymphoma, T-cell: adult T-cell lymphoma/leukemia, precursor T lymphoblastic leukemia/lymphoma Translocations Lymphoma cells generally do not exhibit significant microsatellite instability (unlike many solid tumors) Chromosomal translocations are a hallmark of lymphomatous disorders t(8;14) - Burkitt's lymphoma (c-myc) t(11;14) - mantle cell lymphoma (bcl-1) t(11;18) - MALT lymphoma t(14;18) - follicular lymphoma (bcl-2) mnemonic: The common ones (on exams anyway) have 14 in common. The 11 sits on top of 14 (they're in sequence) like something sitting on a mantle. The 8 in Burkitt's resembles the bilaterally swollen neck lymph nodes like you typically see in a picture of a child with Burkitt's. The 8 (18) of follicular resembles two little follicles stuck together to form the 8. The oddball one is MALT which doesn't have the 14. Epidemiology USA - 59,000 cases/yr (in 2006) ILSG, 1997 9166827 -- "A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project." ([No authors listed], Blood. 1997 Jun 1;89(11):3909-18.) Multinational. 1403 cases at 9 sites around the world classified by 5 pathologists Adult Type Proportion Diffuse large B-cell 31% Follicular 22% Marginal zone B-cell (MALT) 8% Peripheral T-cell 7% CLL 7% Mantle cell 6% Mediastinal large B-cell 2% Anaplastic large T-cell 2% Burkitt-like B-cell 2% Marginal zone B-cell (nodal) 2% Precursor T-lymphoblastic 2% Lymphoplasmacytoid 1% Marginal zone B-cell (splenic) <1% Mycosis fungoides <1% Burkitt's <1% All others <1% Pediatric (based on Cancer, DeVita, 7th edition, 2005) Pediatric Type Proportion Burkitt's lymphoma 40-50% Precursor T-lymphoblastic 25% Diffuse large B-cell 15% Anaplastic large cell 10% Precursor B-lymphoblastic 5% Staging Uses the Ann Arbor classification, which was developed for Hodgkin's lymphoma. Since disease spread in non-Hodgkin's lymphoma differs from that in Hodgkin's lymphoma, in which spread occurs to adjacent nodal groups in a stepwise fashion, the Ann Arbor classification which relies on nodal staging is not as predictive for NHL. International Prognostic Index Risk factors: LDH greater than normal Age > 60 Performance status ECOG 2 or worse Extranodal sites of disease (more than 1) Stage III or IV Mnemonic: LAKES (LDH,age,Karnofsky,Extranodal,Stage) Risk groups: Low - 0 or 1 risk factors Low intermediate - 2 High intermediate - 3 High - 4 or 5 Prognosis: Low risk: 87% CR and 73% OS at 5 years High risk: 44% CR and 26% OS Based on pts with aggressive lymphomas treated with doxorubicin-based combination chemotherapy. It is also useful in indolent lymphomas and T-cell lymphomas. These factors independently predict complete response to therapy, relapse-free survival, and overall survival. From 8141877 Full text — "A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project." N Engl J Med. 1993 Sep 30;329(14):987-94. Modifications Age-Adjusted International Prognostic Index: Developed for pts younger than 60. Uses tumor stage, performance status, and LDH (but not extranodal sites or age). Assigned score of 0 to 3 based on number of risk factors and assigned same labels (low, low int, high int, or high). Reference: 8141877 Full text - "A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project." N Engl J Med. 1993 Sep 30;329(14):987-94. 1982-1987. 3273 pts. Allowed diffuse mixed, diffuse large-cell, or large-cell immunoblastic histologies from the Working Formulation (overlaps with intermediate and high grade but doesn't include all subtypes). Also allowed Kiel and Rappaport. Pts were treated on Phase II-III study. All received combination chemo consisting of doxorubicin. Evaluated potential prognostic factors: sex, age, tumor stage, performance status, B symptoms, sites of involvement, number of extranodal sites, size of tumor, LDH, albumin, and beta-2-microglobulin. Complete information obtained in 1872 pts. Miller's Stage-Modified IPI: (LDH, Age > 60, Performance Status, Stage II). Doesn't include extranodal. Used for Stage I-II pts. Low 0-1, Intermediate 2, High 3-4 5-yr PFS: Low 77%, Int 60%, High 34% 5-yr OS: Low 82%, Int 71%, High 48% 9647875 (1998) NCCN IPI: Rituximab era 24264230 (2014) -- "An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era." (Zhou Z,Blood. 2014 Feb 6;123(6):837-42.) Survival Estimates from AJCC staging manual, 6th edition: Follicular lymphoma: 2-year OS 85%, 5-year 70%. FFS (failure free survival) 2-year 65%, 5-year 45%. Diffuse large B-cell lymphoma: 2-year OS 60%, 5-year 50%. FFS 2-year 50%, 5-year 45%. Mantle cell lymphoma: 2-year OS 60%, 5-year 25%. FFS 2-year 30%, 5-year 10%. Small lymphocytic lymphoma: 2-year OS 70%, 5-year 50%. FFS 2-year 50%, 5-year 30%. Response Assessment Lugano Classification 2014 25113753 -- "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification." (Cheson DB, J Clin Oncol. 2014 Sep 20;32(27):3059-68.) International Harmonization Project on Lymphoma 2007 17242396 -- "Revised response criteria for malignant lymphoma." (Cheson BD, J Clin Oncol. 2007 Feb 10;25(5):579-86.) Response Definition Nodal Masses Spleen/Liver Bone Marrow CR Disappearance of all disease 1) If FDG avid prior, FDG cold but can be any size on CT post 2) If FDG variable/cold prior, FDG cold and normal size on CT post 1) Not palpable 2) No nodules on CT Repeat BMBx negative PR Regression of measurable disease and no new sites >= 50% in SPD in up to 6 largest masses >=50% in SPD of nodules If positive prior, irrelevant SD Not CR/PR or PD No new sites N/A N/A PD 1) Any new lesion 2) Increase >=50% in SPD 1) New lesion >1.5cm 2) >=50% increase in SPD >50% increase in SPD New/recurrent involvement SPD = sum of the product of the diameters 2007 17242397 -- "Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma." (Juweid ME, J Clin Oncol. 2007 Feb 10;25(5):571-8.) PET after Chemotherapy/chemoimmunotherapy: at least 3 weeks, preferably 6-8 weeks PET after Radiotherapy/Chemoradiotherapy: 8-12 weeks External links Heme-Path at UMDNJ - fairly basic overview of different types of lymphomas. Great histology slides. Molecular diagnosis See also: List of chromosomal translocations Burkitt lymphoma - t(8;14) / c-myc translocation, Ki-67 > 90%, CD10+ and/or BCL-6+, CD19+ or CD20+ Usually BCL-2 and t(14;18) negative. Follicular lymphoma - t(14;18), most common translocation in lmphoma / bcl-2 translocation. Is CD10+ Mnemonic: "F is for follicular and fourteen" Mantle cell lymphoma - t(11;14), bcl-1, CD15-, cyclin D1 MALT lymphoma - t(11;18) Diffuse large B-cell lymphoma - bcl-6 (is favorable) Anaplastic lymphoma - CD30+, Ki-1 Radiation technique See also: Radiation_Oncology/Hodgkin#Radiation_fields Involved field CALGB guidelines (done for Hodgkin's disease) - 12078908 Full text (2002) — "The involved field is back: issues in delineating the radiation field in Hodgkin's disease." Yahalom J et al. Ann Oncol. 2002;13 Suppl 1:79-83. Boundaries of the involved fields. Whole-Abdomen Washington University, 1994 (1978-1990) 8029434 -- "Non-Hodgkin lymphoma: whole-abdomen irradiation as an adjuvant to chemotherapy." (Valicenti RK, Radiology. 1994 Aug;192(2):571-6.) Retrospective. 39 patients with abdominal NHL treated with modified whole-abdomen RT. 34 adjunct to chemo, 5 primary Toxicity: treatment terminated in 4 patients, interrupted in 19. Four Grade 3-4 late toxicities Conclusion: Whole-abdomen RT is safe adjunct in high risk for intraabdominal failure Reviews 1985: 2579725 Full text -- "The role of radiation therapy in the management of the non-Hodgkin's lymphomas." (Hoppe RT, Cancer. 1985 May 1;55(9 Suppl):2176-83.)