Lymphoma Flashcards
what is lymphoma
cancer of the lymphatics presenting as solid tumour of lymphoid cells
what are the two types of lymphoma
hodgkins 20%
non-hodgkins 80%
how does lymphoma present
- depends on site/extent of disease
- asymptomatic lump
- B symptoms
>10% weight loss
drenching night sweats
unexplained fevers > 38deg
investigations related to staging
- routine
- Blood FBC, ESR (erythrocyte reproduction rate), U&E, LFT (liver function tests), LDH (lactate dehydrogenase), alkaline phosphatase
- CT neck, chest, abdomen and pelvis
- tissue biopsy with expert review
- immohistochemistry/ cytogenetics etc
- occasional
- PET/CT scan
- bone marrow aspirate & Trephine biopsy if B symptoms, stage III/IV or aggressive histology
- lumbar puncture if symptoms or disease close to CNS
investigations related to treatment
- semen analysis & cryopreservation
- ovarian tissue or oocyte cryopreservation
- HIV test if risk factors or unusual disease presentation
- evaluation of lung and cardiac function
staging (Ann Arbor)
- I one lymph node region
- II two or more lymph node regions on same side of the diaphragm
- III lymph node regions on both sides of diaphragm
- IV diffuse or disseminated involvement of >= 1 extralymphatic organs, including any involvement of liver, bone marrow or lungs
- add E for extra-lymphatic involvement
- add A or B for absence/presence of B symptoms
prognostic factors
- stage
- presence of symptoms (B symptoms)
- age
- LDH level
- extent of extra-nodal involvement
epidemiology of Hodgkins Lymphoma
- uncommon
- most common age 20s-30s
- second peak in 60s-80s
- > 75% of newly diagnosed HD are curable with chemo +/ or RT
aetiology of Hodgkins Lymphoma
- essentially unknown
- age two peaks 20-30 and 60-80
- Epstein-Barr Virus possible association
- immunosuppression may increase risk
pathology of Hodgkins Lymphoma
- Reed-Sternberg cells in a reactive background including normal T cells and eosinophils
- NEGATIVE
CD45
CD3
CD20
CD15 - POSITIVE
CD30
sub-types of Hodgkins Lymphoma
- classic Hodgkin’s disease includes
- nodular sclerosing
- mixed cellularity
- lymphocyte-rich classical
- lymphocyte-depleted subtypes
- non-classic
- lymphocyte-predominant Hodgkin’s disease (LPHD)
overview of treatment for Hodgkins Lymphoma
- no role for surgery
- classical hodgkins
- Stage I/IIA chemo + RT ( with some exceptions)
- Stage IIB/III/IV chemo alone + occasional RT to bulky/unresponsive sites
- nodular lymphocyte predominant HD
- stage I/II Rt alone usually
- Stage III/IV
RT volumes and definitions
Involved field
includes involved or enlarged node(s) and nodes within same region
RT volumes and definitions
Involved site
includes pre- and post-chemo tumour volumes & margin of healthy tissue
RT volumes and definitions
Involved node
includes pre- and post-chemo nodal volumes and margin of 5-10mm of healthy tissue
early stage classical HD (IA/IIA)
2-4 cycles of ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) followed 4 later by involved field RT (IFRT) (20-30Gy/10-15#/3 weeks)
2 x ABVD and 20Gy/10# in very favourable stage I-IIA HD
very favourable HD
- stage I-II
- <=3nodal regions involved
- no extra-nodal disease
- ESR<50 (or <30 if B symptoms present)
- not bulky (>=10cm)
side effects of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)
- adriamycin: nausea, vomiting, hair loss, myelosuppression, cardiomyopathy
- bleomycin: fevers or chills, bleomycin pneumonitis, skin changes
- vinblastine: neutropenia, pain in jaw, constipation
- dacarbazine: nausea, vomiting, pain at injection site
1% risk of acute leaukaemia
Classical HD (IIB-IV)
- 6-8 cycles ABVD chemotherapy or more intensive regimens
- role of RT controversial. usually only use RT if there was bulky mass or it was around the spine
- response to chemo generally poor. generally high dose chemo
Summary of RT in HD
- stage I-II
ISRT following 2-4 cycles of ABVD - stage III and IV
?consolidation RT following chemo to initial bulky sites
?consolidation RT to sites of residual disease in those who don’t achieve complete response - relapsed or refractory Hodgkin lymphoma
unresponsive to chemo - regional RT
Epidemiology of NHL
- very heterogenous group of malignancies
- more common than HD
- incidence rising (people living longer and early lives are a lot more sterile/hygienic than they used to be)
- generally affects middle aged - elderly
- less predictable pattern of behaviour
Classification of NHL
- complex - IHC, cytogenetics, behaviour (LG vs HG), cell type
- majority are tumours of B cells
- rarer sub-types: T cells, Non-killer (NK) cell, myeloproliferative
presentation of NHL
depends on subtype, stage and site
may present as losing weight, lumps in unusual places, people being unusually tired
management of NHL
- no role for surgery
?curative for early stage low grade NHL on the skin (very uncommon) - dominated by chemotherapy
- RT utilised for some subtypes
RT in NHL
subtypes where RT may form part of curative treatment ( alone or in combination )
- follicular lymphoma
- marginal zone (MALT)
- diffuse large B cell lymphoma (DLBCL)
- cutaneous lymphomas
RT may be used in palliation for any subtype
Follicular NHL
- around 20% of all NHL (developed world)
- around 20-30% present with stage I-II
- chemo-/radiosensitive but relapse common
- median survival 7-10 years
- usually CD20+
- treatment varies from observation to HD chemo and stem cell transplant
- may undergo HG transformation
Follicular NHL: Stage I-II
- around 30% present with stage I-II
- IFRT 24Gy/12#
- ongoing trials - smaller doses to smaller volumes ?addition chemo
- 10 year DFS 40-60%
median survival 14-15 years
Follicular NHL: stage III-IV
- 70% present with stage III-IV
- options:
observation
single or multi-agent chemo
+/- rituximab
HD chemo (in select few)
RT (4Gy/2#) to symptomatic sites
Mucosa Associated Lymphoid Tissue (MALT) Lymphoma
- 7-9% of lymphomas
- usually affects stomach
- other sites: orbit, skin, salivary glands, thyroid
- rarely: bladder, cervix, breast, lung
- 60-70% present with stage I-II
- local RT (24Gy/12#) or in H. pylori +ve gastric MALT -> antibiotics
MALT stage III-IV
- slowly progressive
- incurable
- may transform into high grade NHL
- treated when symptomatic with chemo +/- RT (4Gy/2#)
Diffuse Large B Cell NHL (DLBCL)
stage I-II
- evidence base: numerous trials/ mixed inclusion criteria/ different treatment schedules
- RT alone: survival around 50%
- Chemo + RT: survival around 70-80%
- Chemo alone: survival ?as good as CRT
treatment is very individualised
stage I-II DLBCL
- 3 cycles R-CHOP chemo (rituximab, cyclophosphamide, hydroxyurea, vincristine, prednisiolone) followed by IFRT (30Gy/15#)
- ?4-6 cycles if poor prognosis features - bulk, B symptoms, LHD, etc.
- generally avoid RT in sites where toxicity significant e.g. H&N
primary central nervous system NHL
- usually B cell NHL
- uncommon
- often multifocal or diffuse
- young patients: chemo +/- RT (45Gy/25#). median survival up to 5 years (excluding HIV+)
- older patients: RT alone (40-50Gy). median survival up to 18 months
cutaneous NHL
mixed group comprising
- B cell NHL around 25% (follicular, MALT, DLBCL)
- T cell NHL of large cells around 10%
- indolent T cell NHL around 65%
- often treated with RT (30Gy/15#) when localised
- most have good prognosis
RT planning in lymphomas (non-cutaneous)
- optimally CT- simulated
- supine
- arm position depends on target volume
- international guidelines for CTV delineation
- OAR delineated - conscious of longterm survival and late toxicity
- usually AP/PA fields
- DIBH/IMRT?
(often in H&N shell)
acute RT toxicity
depends on site irradiated
general - fatigue, skin erythema, anaemia, leucopenia, thrombocytopenia
- H&N: dry mouth, mucositis, hoarseness, alopecia
- thorax: dysphagia, dyspnoea, cough, etc.
- abdo/pelvis: nausea/diarrhoea
late toxicity - mediastinum
- lung
pulmonary fibrosis
minimised by:
-> careful treatment planning
-> allowing an interval of 4 weeks between chemo and RT
many chemo drugs may potentiate the effects of RT on lung tissue e.g. bleomycin, cyclophosphamide and doxorubicin - heart
-> coronary artery disease, valvular disease, conduction defects
-> following (now outdated) treatment risk of developing symptomatic coronary artery disease is 6-10% at 10 years and 10-20% at 20 years
-> actuarial risk of death from cardiac ischaemia appear to be 2-6% at 10 years and 10-12% at 15-20 years
-> minimised by: - careful treatment planning
- maximum cardiac shielding (subcarinal area and left ventricle)
- avoidance of dose per # over 2Gy
potential cardiotoxic effects of doxorubicin may also be additive to the long term damaging effects of radiation to the heart - thyroid (if included in field)
-> hypothyroidism
-> thyroid nodules
-> thyroid cancer
late RT toxicity - pelvis
- genital organs
-> large fields - direct and scattered radiation
-> 20-24Gy - ovarian ablation -> menopause and sterility
-> spare one ovary if possible with ultrasound or CT guidance to locate the ovary
-> when bilateral pelvic irradiation is inevitable -> surgical oophoropexy with transposition of one ovary to lateral abdomen should be considered
-> however vascular supply can be damaged -> infertility - testis
-> very radisensitive
-> 15cGy -> transient oligospermia
-> 4-6Gy -> permanent azospermia
-> infertility always follows scrotal irradiation
-> testosterone production can be preserved after doses of 30-35Gy
-> scattered dose should be considered in fields close to scrotum
late toxicity - second malignancies
- increased risk of 2nd malignancies in HL survivors
- 55-65 excess malignancies per 10,000 years of follow up among patients treated for HL
- 20 year cumulative incidence of malignancy of around 15-20%
- excess risk of a 2nd solid tumour
-> breast - more common in those treated in adolescence
-> lung - worse in smokers
-> oesophagus
-> thyroid
late effects of RT - breast cancer
following mediastinal RT (ie including some breast tissue)
- as children/adolescents: risk of breast cancer 1 in 3-5 over next 25 years
- 20-30: risk of breast cancer 1 in 4-7 over next 25 years
- >30s: risk of breast cancer not dissimilar to background risk (1 in 11)
consider avoiding RT in lymphoma
significant risk of late side effects
- young women (<30years) where treatment would involve breast irradiation
- smokers
- risk of permanent xerostomia
- pre-existing lung/cardiac disease
