Lymphoma Flashcards
1
Q
ABVD chemo
A
- Adriamycin 25 (Doxorubicin) – heart failure
- Bleomycin 10 – lung fibrosis
- Vinblastine 6 – neuropathy, hair loss
- Dacarbazine 375 – sterility, n/v, immune suppres
- one cycle is 4 wks, doses q 2 wks
2
Q
BEACOPP
A
BEACOPP Bleomycin Etoposide Adriamycin (Doxorubicin) Cyclophosphamide Oncovin (Vincristine) Procarbazine Prednisone
Brentuximab: anti-CD30 antibody
3
Q
Reed Sternberg Cell
A
HL:
Reed Sternberg cell – binucleate
CD15+, CD30+
CD20/45-
4
Q
HL WHO classification
A
WHO classification:
1) NLPHD – CD45+, CD20+
2) Classic – CD 15+, CD30+
nodular sclerosing
mixed cellularity
lymphocyte rich - good lymphocyte depleted – rare, bad, elderly, HIV
5
Q
Deauville PET Criteria:
A
Deauville PET Criteria:
1 – no uptake > background
2 - uptake < mediastinum
1 or 2 NEGATIVE
3 – uptake < liver
3 NEG OR POS
4- uptake mod inc compared to liver
5 – uptake markedly inc compared to liver
4 or 5 POSITIVE
X – new areas of uptake not related to lymphoma
6
Q
HL H/P
A
H&P:
- B sx: fevers >38C or 100.5, drenching nightsweats, wgt loss 10%/6mo
- performance status
- pruritus
PE – nodal stations, spleen, liver, Waldeyers ring
7
Q
HL Workup
A
Labs: CBC, CMP, LFTs, ESR, LDH, albumin, pregnancy test, HIV
Imaging: CT n/c/a/p and PET/CT
Splenomegally if >13 cm (on CT)
Bx: excisional preferred (core ok, not FNA) with IHC eval
BM bx: if unexplained cytopenias and PET negative
8
Q
HL other things to do before treatment
A
Other:
- fertility eval/banking (2 Gy permanent, 0.5 Gy transient for sperm, 8-10 Gy perm for oocytes)
- dental eval if H&N
- PFTs pre/pos
- MUGA before ABVD
- vaccines if splenic RT
9
Q
Ann Arbor system:
A
Ann Arbor system:
I: 1 region or extra-lymphatic site
(cervical + SCV = 1 site)
II: 2 or more regions on same side of diaphragm
B = B symptoms only in HL (HL is either A or B, NHL only uses Bulky and E)
E = extralymphatic ie IIIE
Bulky for NHL:
>10 cm or
>1/3 intra-
thoracic
diameter at
T5/T6
10
Q
HL Management Stage I/II Favorable
A
Stage I/II Favorable: ABVD x 2 ->PET-CT > for D1-3, ISRT 20 Gy to all initially involved sites (Pre-chemo anatomically modified)
If D4 after 2 c, consider ABVD x 2 c (4 total), then 30 Gy
If D5, go to biopsy > if neg, RT. If pos, refractory pathway
11
Q
HL Unfavorable criteria
A
Unfavorable: 3 BEEs 3+ nodal sites Bulky disease ESR (>50 w/ A, >30 w/ B Sx) Extranodal disease
12
Q
HL Management Stage I/II Unfavorable
A
Stage I/II Unfavorable: ABVD x 2 c > PET/CT > for D1-3 > ABVD x 2 c (4 total) + ISRT 30 Gy (36 Gy in PR)
if D4, escBEACOPP x 2 > PET/CT > ISRT 30 Gy (36 Gy in PR)
13
Q
HL Management Stage III – IV
A
Advanced stage III/IV
ABVD x 2 -> PET/CT, if D1-3, AVD x 4 (6 cycles total)
-can escalate to BEACOPP if poor response
– RT to originally bulky (30 Gy) or PET+ residual sites (36 Gy) – otherwise no RT
(also no RT needed if CR to BEACOPP)
14
Q
GHSG criteria
A
GHSG criteria of 1-2 areas*, no extranodal lesions, MMR<0.33, ESR < 50 no B sx, ESR < 30 w B sx
15
Q
HL Stage II-Iv OS if CR/PR to chemo
A
CR to chemo:
5 yr OS = 89%
5 yr RFS = 85%
PR to chemo: OS 87%, EFS 80%
16
Q
HL simulation
A
Supine, hyper-extend neck, PET/CT simulation with contrast, fuse pre-chemo PET/CT. Oral contrast for abd/pelvis. Custom immobilization.
4D and Breathold often useful
17
Q
HL volumes
A
CTV–pre-chemo volume excluding uninvolved normals like lung, kidneys, muscles + 1.5 margin (pre-chemo GTV_CT and GTV_PET less normal structures previously uninvolved)
4DCT and ITV – if treating mediastinum
If RT alone, use 3-5 cm margins
PTV = CTV + 1 cm (for HN, 3-5 mm)
If < CR (dose 30 Gy + boost to 36 Gy):
CTV initial = pre-CTX tumor volume + 1.5 cm cropped
GTVboost = post-CTX GTV
PTVboost = GTV (or ITV) boost + 5 mm
REMEMBER IF TREATING BOTH SIDES OF DIAPHRAGM, NEED TO STAGE TX WITH 2 WEEK BREAK IN BETWEEN
18
Q
HL constraints
A
ALARA!
LE/Groin
Femoral Head <25
To Prevent SCFE (slipped capital femoral epiphysis)
Neck
Thyroid V25 <63.5%
Chest:
Breast Mean < 4 Gy
Heart mean <15 Gy and ALARA (<5 Gy ideal)
Lungs mean < 15 Gy
Hotspot < 110%
19
Q
HL DFS/OS
A
DFS/OS
Early favorable – 90/95
Early unfavorable – 80/85
Advanced – 65/75
20
Q
HL subacute Side effects
A
SubAcute: Lhermites – 15% Pericarditis Pneumonitis Treat with slow prednisone taper over 2-3 mo, 1mg/kg
21
Q
HL Late Side effects
A
Late:
- CAD
- Hypothyroid – annual TSH, neck RT
- Gastric Ulcer
- Pulmonary Toxicity
- Decreased Immunity (spleen)
- Infertility
- 2nd Malignancy
- leukemia (AML) RR 22x
- solid: breast, thyroid, lung (RR 2)
- 0.5%/year
22
Q
HL followup
A
Follow-up:
- H&P, CBC, ESR q3mo (year 1-2), q6mo (year 2-3), annually after
- CT c/a/p at 6, 12, 24 mo
- do NOT routinely do PET
- TSH annual
- baseilne echo, stress test at 10 yrs
- cartoid ultrasound if neck tx
- Mammogram at 8yrs or age 40 (MRI if XRT b/t 10-30 yrs)
- Survivorship clinic
23
Q
NHL translocations •Burkitt’s •Mantle •MALT •Follicular
A
Translocations •Burkitt’s 8:14 •Mantle 11:14 •MALT 11:18 •Follicular 14:18
24
Q
NLPHL
A
NLPHL: CD15/30-, CD 20+: 30-36 Gy no chemo
CD 20+!!
No RS cells
Most w early stage disease
I-IIA: ISRT alone 30 Gy (no chemo!)
-10 yr OS > 90%
-10 yr RFS = 75
If doing RT alone, want to use larger margins (4-5 cm)!
B symptoms or bulky (IB-IIB): ABVD + Rituximab + ISRT-> Rituximab because of CD20+
Adv: ABVD + Rituximab + palliative RT
25
RCHOP
R-CHOP
Rituxan: monocolonal antibody to CD 20; 325 mg/m2
```
CHOP q3 wks
Cyclophos 750mm2
Adriamycin 50mm2
Vincristine 1.4 mg/m2
Prednisone 100 mg day 1 – 5
```
26
Hyper CVAD
HyperCVAD:
Two alternating courses:
Course 1: cyclo, vincristine, doxo, dexamethasone
Course 2: MTX, cytarabine
27
NHL low grade
```
Low Grade:
•Follicular, Grade 1-2 (note 3%/yr risk of DLBCL transformation)
•MALT
•CLL/SLL
•Mycosis Fungoides
```
28
High Grade NHL types:
```
High Grade:
•DLBCL
•Follicular 3
•Mantle
•Burkitts
```
29
DLBCL -- IPI
```
DLBCL -- IPI (NEJM 1993): APLES
Age > 60
PS ECOG ≥2
LDH inc (>250 u/L)
Extranodal site 2 or more
Stage III, IV
```
```
IPI with R-CHEMO
5y OS
0-1 85%
2-3 60
4-5 35
```
30
FL -- FLIPI:
```
FL -- FLIPI:
HASSL
Hgb <12
Age > 60
Stage III, IV
Sites: # nodal >4
LDH increased
```
```
0-1 = low; OS5 ~90%
2 = int; OS5 80%
3+ = high; OS5 50%
```
-10% to 15% undergo “Richter’s transformation” from SLL/CLL to DLBCL. MS 5-8 month
31
NHL H/P
History: attention to duration, onset, B symptoms
RFs immunosuppression, HIV status. PS. Waxing and waning nodes suggest indolent/low grade.
Physical: compehensive nodal exam, including all LN sites, waldeyer’s ring, organomegaly, NPL prn
32
NHL workup
Labs:
CBC, CMP, LFT, ESR, alk phos, LDH, albumin, B2 micro
Hep B (surface Ag and core Ab), C, HIV
Pregnancy test
Imaging: contrasted PET-CT
Biopsy:
Excisional bx or core bx to architecture and full histology and immunophenotyping.
Bone marrow – for follicular stage I-II
```
CSF if:
(•Paranasal sinus)
(•Epidural)
(•Bone marrow with large cell lymphoma)
•Testicular
•HIV lymphoma
•Double hit lymphoma
•4-6 of APLS (IPI), any extranodal, (ad)renal involvement
```
Other:
Karyotype or FISH for DLBCL: MYC, BCL2, BCL6
Peripheral blood for:
CLL: monoclonal B-cells > 5 x 109 per liter
SLL: LAD or splenomeg w peripheral B-cells < 5 x 109 per liter
Fertility counseling!
33
Low grade NHL man Stage I-II
Stage I-II (MS 10-15 yrs, DFS10 50%, OS10 70%)
Stage I/continguous stage II: ISRT alone, 24 Gy (30 gy in bulky)
Stage II/bulky: chemo (R-CHOP, RCVP)->ISRT 30 Gy
34
Low grade NHL man Stage III-IV
¬¬¬Stage III-IV (MS 8-9 yrs)
- Obs if asymptomatic
- If symptomatic, bulky dz, cytopenias, or steady progression:
- Chemo (RCHOP or BR, bendamustine-rituxan), or
- Palliative RT (boom-boom 2x2 or 24/12)
- not curable
Relapsed: RadioImmunotherapy
- Must biopsy relapsed follicular
35
DLBCL man Stage I-II
Stage I-II
Non-bulky: R-CHOP x 3 -> PET -> RT or R-CHOP x 6 (+/- RT)
Bulky (>7.5 cm): R-CHOP x 6 +/- RT
(“High risk:” IPI>1, bulky, double/triple hit, double expression, non-germinal center type)
(30 Gy CR, 36 Gy PR, 45 Gy if bulky)
-if PR, repeat PET/CT after RT. If positive, bx. If positive for tumor, tx as refractory
36
DLBCL man Stage III-IV
Stage III-IV
- RCHOP x 6 alone
- PET/CT after 2-4 cycles:
- if responding continue to 6 cycles
- if no response or progressive, biopsy then tx as per relapsed/refractory
- RT for limited stage III, bulky disease (30 Gy), persistent, PET positive disease (36 Gy)
Relapsed/refractory (similar to HL)
1) 2nd line chemo
2) high dose chemo (R-ICE) with stem cell transplant
3) ISRT for bulky sites/consolidation (40-55 Gy)
** if using RT without chemo, go to higher doses 45 Gy
CSF treatment: 4-8 cycles IT MTX for testicular, paranasal sinus, epidural, BM involvement
37
MALT
| mucosa associated lymphoid tissue trans
-Endoscopic bx and H. pylori testing; look for t(11:18)
| t(11:18) = poor Abx reponse
38
Gastric MALT man
Gastric –
- H. pylori positive: antibiotics repeat endoscopy q3 mo, if still+ after 9-12 months, then RT
- H. pylori positive and t(11:18): antibiotics, endoscopy at 3 mo, if positive, then RT
- H. pylori negative: RT (30/1.5)
- 3 drug regimen x 2 wks
- PPI, amox/metronidazole, clarithromycin
- LC 95% with 30/1.5 Gy
- for stage III-IV, tx for sx, bulky dz, steady progression
39
Gastric technique
Gastric: 30/1.5 IFRT to entire stomach
- Arms up, vac lock
- Fasting CT (4 hr) with oral contrast, 4D CT
- AP-PA vs 4 fields vs VMAT to empty stomach + gastroduodenal junction + 2 cm (includes perigastric nodes)
- Give PPI during RT, consider Zofran
- Daily CBCT
Gastric follow-up:
Endoscopy at 3 months, then every 3-6 months until resolution, then annually
40
Orbital technique
```
Orbital: treat entire orbit (for low grade can consider partial orbit)
-Ant oblique or en face electrons
- consider hanging lens block
Lacrimal:
MALT – can treated just gland (24/1.8)
DLBCL – treat whole orbit (30.6 Gy)
```
Lacrimal gland: 50% < 35 Gy
41
DLBCL bone (IE)
R-CHOP x 6 -> ISRT TO 45 Gy (pre-chemo + 0.5-1 cm margin for PTV)
42
DLBCL testicle
Elderly gentleman
Get MRI Brain and LP
Orchiectomy -> RCHOP x 6 w/ high dose IT MTX -> RT 30 Gy to contralateral testicle + scrotum
Follow-up: Testosterone
43
Primary mediastinal B-cell lymphoma
Young woman CD15-, CD20/30+, compressive symptoms
PET/CT w/ contrast
Preferred: Dose adjusted EPOCH-R x 6 c (NEJM 2013) -> PET/CT, if D1-3, FNT
-> if D4-5, consider bx, ISRT 30 Gy
2.. R-CHOP x 6 + ISRT (30 Gy) for CR
44
Mantle cell
EGD/Cscope to r/o lymphomatous polyposis
Stage I/II (rare): IFRT alone (30 Gy)
Stage IIX/III/IV: (HyperCVAD alternating with HD-MTX + ARA-C) + Rituxan → HD CTX + ASCR
Poor Prognosis
45
Nasal NK T cell
Stage IE/IIE:
Concurrent RT 50 Gy + DeVIC x3c
(Dex, etoposide, ifos, carbo)
46
MGUS:
MGUS:
•serum or urine M protein without lesions
•no end-organ damage,
• < 10% plasma cells in BM
47
Plasmacytoma criteria:
Plasmacytoma criteria:
•one lesion +/- M protein
•< 10% plasma cells in BM
•No end ogan damange
48
Smoldering/Active myeloma
ie rule out MM if have Solitary plasma
Smoldering myeloma
•M protein in serum
•>10% plasma cells in BM
•No end organ damage
```
Active meyloma (CRAB)
•Smoldering + end organ
-calcium (>11.5)
-renal insufficiency (Cr>2)
-anemia (Hb<10)
-bone (lytic lesions)
```
49
Solitary plasmacytoma (10%) man
40 Gy with 0.5 - 2cm margin
| there is a range but just say 40 Gy, in 2 Gy fractions
50
Solitary plasmacytoma (10%) outcome
70% w bone SP progress to MM in 10 yrs
50% OS after tx
30% of extramed SP progress to MM in 10 yrs
70% OS
LC 90%
```
Prognostic = BLAC (lesions look black on xray)
•Beta2micro
•LDH
•Albumin
•CRP
```
51
Solitary plasmacytoma tech
Bone only:
Gross disease + 2 cm margin
Extramedullary:
Gross disease + 2 cm margin
- can include primary draining LN for H&N
52
`MM/solitary workup
Labs:
- CBC, CMP, LDH
- Ca++, albumin
- beta-2 microglobulin
- serum quantitative immunoglobulins (IgA/IgG/ IgM), SPEP, SIFE
- UPEP, UIFE, 24 hr urine for Bence-Jones protein
- M-Protein
- serum free light chain assay (FLC)
Imaging: skeletal survey
-non-contrast CT or MRI can be useful if sx but no lesion on skeletal survey
- Bx of lesion if solitary
- Unilateral BM biopsy w cytogenetics and FISH
- Bone densitometry if considering bisphosphonate
53
Chloroma (aka myeloid sarcoma, granulocytic sarcoma) man, Type of luekemia
24 Gy in 12 fractions
54
ALL man
CNS1: negative CNS
CNS 2: + blasts with <5 WBC / ul
CNS 3: + blasts with ≥ 5 WBC / ul or symptomatic CNS disease
```
Low risk:
Age 1-10
Initial WBC < 50,000
Rapid early responder, M1 (<5% blasts) on day 15
Negative MRD (<0.1%) on day 29
CNS 1
No testicular disease at diagnosis
```
T cell ALL:
Intermediate and high risk receive CNS prophylaxis
CNS 1 and 2: 12 Gy/1.5
CNS 3: 18 Gy
B cell ALL
- low risk CNS3: 18 Gy
- int/high risk as above
55
Cut Lymph types
```
T-cell (75%)
Mycosis fungoides (70%)
(indolent)
Sezary syndrome
(aggressive)
CD 30 positive LPD
(30%, includes primary
cutaneous anaplastic
large cell)
```
B-cell (follicle, dlbcl,follicular)
56
Cut Lymph MF stage
```
MF:
T1: patch/plaque <10% BSA
T2: patch/plaque ≥ 10% BSA
T3: cutaneous tumors (≥ 1 cm)
T4: generalized erythroderma ≥ 80% BSA
```
57
Cut Lymph Workup
```
H&P
Full skin exam
Labs/CBC
Biopsy
Blood smear for Sezary cells if T cell
Pregnancy test
PET/CT for ≥ T2
BM biopsy if DLBCL/Tcell/MZBcell
Biopsy of any suspicious LN
CT CAP, PET
Skin lesion -> exc biopsy
Check peripheral smear for Sesary cells
```
MF/SS - “pantareer’s mircroabscess on path”
58
Cut Lymph outcomes
T1 with local RT:
>90% CR rate
50% overall relapse rate
```
MS:
T1 = same as general population
T2 = 10 yrs
T3-4 = 5 yrs
N+ or M+ = 1 yr
```
Overall CR rate with TSEBT >80% even for advanced T stage, but very high risk of relapse (palliation)
Patients with T2+ and CR to TSEBT may benefit from adjuvant therapy (ie PUVA, photophoresis, or mechlorethamine)
TSEBT toxicity:
Fatigue, erythema, edema, loss of nails, alopecia, hypohydrosis,
Can repeat TSEBT after 6 – 12 months if needed to 20 – 24 Gy
59
Primary cutaneous anaplastic large cell:
Primary cutaneous anaplastic large cell:
| RT alone to 40 Gy
60
Mycosis fungoides:
| T1:
Mycosis fungoides:
T1:
Skin directed therapies (UV, topical)
If unilesional, can treat with definitive RT alone to 24 Gy + 2 cm margin
61
Mycosis fungoides:
| T2-4
T2 – T4
TSEBT
Low-dose 12 Gy in 6 fractions, re-eval in 8-12 weeks, additional 12 Gy cycles as needed
62
B-cell cutaneous lymphomas:
B-cell cutaneous lymphomas:
For follicular, marginal zone: RT alone 24 Gy (definitive) or 2 Gy x 2 Gy (“palliative”- most common)
DLBCL leg type: RCHOP + ISRT to 36 Gy or ISRT to 40 Gy if RT alone
63
total skin tech
Treat the patient with a rotating platform technique
to a total dose of 12 Gy using 6MeV electrons and a beam spoiler (4 MeV)
Superior and inferior beams +/- 20 degrees from midline
Internal eye shields daily
Toe/finger nail shields after 9 Gy
Boost shadowed areas with en-face beam
Total skin (FML)
Treat 4 days per week
Stanford technique: 6 field therapy: AP/LPO/RPO on day 1 and PA/LAO/RAO on day 2, alternating
1 week break after 18 Gy
Internal eye shields daily
Toe/finger nail shields after 9 Gy
TLDs placed once prior to break to plan boost
Typical boost regions: perineum, inguinal, axilla, IMF, intergluteal, vertex, soles*
Boost 1 Gy daily starting with 2nd half of radiation
*Soles only boosted to 14 Gy
Typically 6 MEV electron with beam spoiler to make 4 MEV electron
Superior and inferior beams +/- 20 degrees from midline
80% IDL ≥ 4 mm from surface
20% IDL < 20 mm from surface
<10% heterogeneity in air
<15% of dose to eyes
64
Cutaneous outcomes based on type
Outcomes FCL> MZL > leg type
65
Follicular translocation and determinants of Grade
t(14:18)
```
# of centroblasts:
G1: <5
G2: 6-15
G3: >15
3A: centrocytes present
3B: all centroblasts
```
