Lymphoma Flashcards
Lymphoma: GHSG unfavorable factors
≥3 nodal sites
bulky ≥1/3 chest
extranodal involvement
ESR ≥30 with B and ≥50 without B
Lymphoma: NCCN unfavorable factors
≥4 nodal sites
bulky disease >10 cm or mediastinal mass ratio >1/3
ANY B symptoms
Not counted: extranodal disease
Lymphoma: sim for head/neck, chest, abdomen, pelvis
H&N: do dental eval first. Use bite block to divert tongue away from field if possible. Mask.
Chest: 4DCT, vac loc. Breath hold increasing in use to spare heart and lung
Abdomen: 4DCT. Empty stomach and treat at same time each day. If using oral contrast also sim without contrast. Daily CBCT.
Pelvis: If young age, do pregnancy testing and fertility testing. Consider sperm banking, egg banking, ovarian transposition, testicular clamshell
ABVD: components and dose
Doxorubicin 25 mg/m2, d1 and 15
Bleomycin 10 U/m2, d1 and 15
Vinblastine 6 mg/m2, d1 and 15
Dacarbazine375 mg/m2, d1 and 15
Q4w
R-CHOP: components and dose
Rituximab 375 mg/m2, d1
Cyclophophamide 750 mg/m2, d1
Doxorubicin 50 mg/m2, d1
Vincristine 1.4 mg/m2 (max 2 mg), d1
Prednisone 100 mg po qd d1-5
Q3w x 6-8 cycles
BEACOPP: components
Bleomycin
Etoposide
Doxorubicin
Cyclophosphamide
Vincristine
Procarbazine
Prednisone
Q3w
Lugano staging tips for HL and DLBCL
- PET is adequate to assess bone marrow involvement and can be highly suggestive for extralymphatic involvement
- Routine bone marrow biopsy no longer indicated for HL and DLBCL.
- Consider bone marrow biopsy in HL if cytopopenias present and consider in DLBCL if suspecting a different histology
- BM biopsy still required in follicular, MZL, burkitt’s
- Use A and B status only for Hodgkin, not NHL
- For bulky, add the word “bulky” to the stage, not letter X
- Bulky disease in HL is >10 cm or >1/3 the transthoracic diameter. CT is appropriate (CXR not required)
- For extranodal, use letter E modifier. Extranodal is only applicable for Stage I-II per Lugano. No such thing as Stage IIIE or IVE. Just Stage III and IV.
- Splenomegaly is defined as size >13 cm. PET avidity is not relevant when determining splenomegaly
- Hepatomegaly is focal or disseminated PET avidity
- Bulky in NHL is definted as ≥7.5 cm per NCCN and DSHNHL RICOVER (not defined in Lugano)
Lymphoma: follow up
Year 1-2 q 3 mo, Year 3-5 q 6mo: H&P, CBC/plt/ESR
imaging at 6, 12, and 24 mos
Annual flu shot, TSH, CXR, counseling on fertility, psychosocial, reproduction, cardiovascular, breast self exam, skin cancer risk
After 5 years - annual BP check, echo/stress test/carotid US screening q10 yrs, mammogram at 8 yr or age 40 (MRI if age 10-30 at treatment), CBC/chem/TSH/lipids, CXR
Lymphoma nodal sites
HL: workup
H&P, B symptoms of fever, weight loss >10%, drenching nightsweats, performane status, ETOH induced pain/pruritis, complete LN exam, Waldeyer’s ring, palpation of abd/spleen/liver
Excisional biopsy of node. IHC. May require FISH and cytogenetics
Labs: CBC w/ diff, LFTs, CMP, ESR, LDH, beta-HCG, HIV test, Hepatitis B
Studies: CXR, CT C/A/P, PET. Now only do BM bx if PET negative and cytopenias present (Lugano)
(Note that LN regions are different per system used- many focus on GHSG regions since tx guided by these trials.)
Pre chemo assessment: Echo/MUGA, PFTs
Extra workup: dental eval if treating neck, fertility sparing: Gyn consult, oophoropexy, or sperm banking
If excisional bx not feasible, can do core needle bx with immunohistochem, flow cytometry, FISH
Early stage favorable HL: treatment paradigm
ABVD x 2 cycles then obtain post-chemo PET.
Deauville ≤3 give 20 Gy/ 10 fx
Deauville 4 give two more cycles and reassess
Deauville 5, biopsy first, and if positive see refractory pathway
Early stage favorable HL: 10yr OS and PFS on HD10
10yr OS 94%
10yr PFS 87%
Early stage unfavorable HL: treatment paradigm
chemo, then post-chemo PET. If Deauville 1-3, treat with RT. If Deauville 4, consider another 2 cycles of chemo
Varous regimens:
30Gy/15fxs after ABVD x4 per HD11
20Gy/10fxs after escBEACOPP x 4 per HD11
30Gy/15fxs after escBEACOPPx2 + ABVDx2 per HD14 (best results)
36Gy/18fxs for bulky
Early stage unfavorable HL: 5yr OS and PFS on HD11
5yr OS 94%
5yr PFS 87%
stage III/IV HL: indications for radiation
partial response, bulky disease, or bone involvement
typically 30Gy/15fxs, maybe higher if bone involvement
stage III/IV HL: poor prognostic factors
MASHAWL
male
age>45
stage IV
Hgb<10.5
albumin<4
WBC>15
lymphocyte<0.6
DLBCL: workup
Same workup as Hodgkins, except:
Don’t need ESR. Add uric acid.
Obtain Hepatitis B labs (for rituximab)
Karyotype or FISH for double hit (bcl2, bcl6, myc)
Bone marrow is also optional in DLBCL (Lugano criteria). Consider if PET is negative but may be looking for other subtype in marrow (still need bone marrow for follicular, MZL, and burkitt)
LP in DLBCL for testicular, paranasal sinus, epidural, or HIV assoc lymphoma, or if more than 2 extranodal sites and elevated LDH (NCCN)
IPI score
age>60
PS>1
LDH>1.5x nl
extranodal dx in more than one site
stage III/IV
IPI score: 5yr OS by score (rituximab era)
5yr OS:
score 0: 95%
score 1-2: 80%
score 3-5: 55%
Early stage DLBCL: radiation doses
36Gy for bulky tumor or bony disease
40Gy for partial response on PET
Early stage DLBCL: treatment paradigm
R-CHOP x 3-6 cycles. Some give 6 if IPI score ≥2 or bulky.
3 cycles with RT if Deaville 1-3
characteristics of primary mediastinal B-cell lymphoma
An NHL. Distinct from DLBCL by CD markers, often CD20+. CD15- and CD30 weakly + or -. BCL6 positive.
Path: fibrosis, necrosis, and thymic cells. No nodularity (nodularity is seen in classical HL and NLPHL). Sheets or irregular clusters of large cells, may resemble R-S cells.
Arises in thymus (extranodal), common in women, usually stage I-II. Arises in anterior MS, sometimes also with cervical and SCV nodes. More common in females 2:1, usually age 30s
primary mediastinal B-cell lymphoma: treatment paradigm and outcome
(DA) R-EPOCH x6 is often used (NIH), then assess response with PET.
Consider RT 30-36 Gy for Deauville 4-5
Consider RT to 36 Gy for bulky
5yr OS 95%
(DA) R-EPOCH: components
Dose Adjusted based on ANC and platelet counts
rituximab
etoposide
prednisone
vincristine
cyclophosphamide
doxorubicin
lymphocyte predominant HL: characteristics
A HL. Markers similar to PMBCL except CD30. CD20+, CD15-, CD30-(very rarely CD30+).
Path: popcorn cells (large cells with multilobulated or round nuclei) and nodularity and replacement of nodal architecture.
80% present as early stage. Usually peripheral adenopathy with central sparing. Often extranodal. Some will relapse but relapse survival still better than HL.
lymphocyte predominant HL: treatment paradigm for IA/IIA nonbulky
30 Gy if <5 cm, 36 Gy if >5 cm
treatment is RABVD or RCHOP +/- xrt for IB/IIB or bulky disease
cutaneous B-cell lymphoma: workup
(marginal zone or follicular)
Standard H&P with attention to full skin exam.
Biopsy (punch, excisional, or incisional).
For T cell get peripheral smear for Sezary cells (necessary for staging)
CT C/A/P and/or PET. BM Bx useful for select cases
5-10% present with sezary syndrome: >1000 cells/uL usually with generalized erythroderma
total skin electron beam therapy: narrative
I would position the patient at 3 m SSD with beam spoiler 1 cm thick placed in front of the patient. I would treat 3, out of total 6, positions per day for 4 days per week, delivering 1 Gy per day, ensuring to boost areas of possible underdosage including soles, perineum, scalp, under breasts and pannus. I would place TLDs to confirm adequate dosage. The beam would be moved + and – 20 degrees.”;;Treat in 6 positions to cover total skin, 3 positions per day, 4 days per week. Boost to soles, perineum, and scalp. Also need to boost “shadow areas” under breast, pannus, etc. Can shield eyes. Can intermittently shield nail beds and tops of feet to reduce risk of edema. Put TLDs on areas at risk of underdosage such as scalp vertex, axilla, inframmary folds, perineum, intergluteal cleft, medial thighs, soles of feet, palms (patient usually is supported by handles).;;A beam spoiler 1 cm thick is placed in front of patient to increase large angle scatter and improve dose homogeneity. The beam is positioned 3 m SSD and moved +/- 20 degrees (angles reduce photon contamination to less than 1%). Goal is to achieve dose homogeneity in the coronal plane. Rx and Dmax are at skin surface, and 80% dose is at 0.7-1.0 cm depth
cutaneous B-cell lymphoma: doses
Generally only local RT for B cell; never total skin.
1.0-1.5 cm margin
Low grade: 24-40 Gy
Int grade: RCHOP x3 + RT up to 36 Gy
Palliative: 2x2 Gy gives CR in 70%
cutaneous T-cell lymphoma: doses
Localized: electrons to 20-24 Gy with at least 2 cm margin. Some treat up to 36 Gy.
Generalized: TSEBT to 10-12 Gy (1 Gy per day, 4 days per week, for 3 weeks) per guidelines. With this regimen retreatment is allowed
Palliation: 2x2 Gy repeated until good response or single dose 8 Gy. Margin 1-2 cm
(ILROG guidelines)
cutaneous B-cell lymphoma: treatment options aside from xrt
intralesional steroids, R,topicals, other systemic therapy such as is used for follicular lymphoma
cutaneous T-cell lymphoma: treatment options aside from xrt
Localized options: topical corticosteroids, nitrogen mustard, imiquinod, retinoids, phototherapy
Systemic options (localized or diffuse): retinoids, interferon, HDAC inhibitors (vorinistat), electrocorporeal photophoresis, methotrexate
total skin electron beam therapy: side effects
desquamation, hair loss, lymphedema, nail loss, loss of sweating, second malignancy
gastric MALT: workup
H&P per lymphoma.
Imaging: CT C/A/P. Upper endoscopy, EUS and biopsy.
FISH for t(11;18). Look for H pylori on path (use modified Geimsa stain). If negative, get blood Ab test, urea breath test, or stool Ab test.
Labs: CBC, LDH, CMP. Consider BHCG
Staging imaging: CT C/A/P and PET (PET is now rec on NCCN, but caution: often not FDG avid)
H. pylori+ gastric MALT: antibiotic regimens
1st line triple therapy: PPI, clarithromycin, amoxicillin. (“CAP”)
2nd line quadruple therapy: PPI, bismuth, metronidazole, tetracycline. (“P BMT”);
gastric MALT: indications for xrt
H. pylori positive after failure with antibiotics
H. pylori negative
t(11;18) positive more likely to fail antibiotics but still try
gastric MALT: follow up after antibiotics
Endoscopy with bx in 3 mos. General guide: if still H pylori+ give 2nd line abx, if lymph+ give RT:
pylori/lymph- —> no further therapy
H pylori+/lymph- —> 2nd line abx (PBMT)
H pylori-/lymph+ —> RT
lymph+/H pylori+ —> 2nd line abx PBMT if stable. If symptoms or progessive dz give RT + 2nd ABX PBMT
gastric MALT: sim
supine, wingboard, 4DCT, optional 10 cc oral contrast, empty stomach (treat in AM or NPO for 3 hours).
gastric malt: dose and fields
30Gy/20fxs
CTV: EGD to duodenal bulb, also including any positive nodes
ITV: add another 1-2 cm per extranodal guidelines
PTV: add another 1 cm
Might be able to reduce margins with daily CBCT
IMRT or 4-field
gastric MALT: outcomes
MALT 5-yr OS 95%
90% MALT are H pylori +
NK T-cell lymphoma: workup
Include evaluation of nasopharynx with flexible scope, testicular exam, skin exam, CSF analysis, EBV viral load, MRI nasopharynx
NK T-cell lymphoma: treatment paradigm
stage I: radiation alone (50Gy + boost)
stage II-IV: chemoradiation
VIPD then 45Gy
40Gy with concurrent cisplatin then VIPD x3 cycles (Korea)
VIPD: components
etoposide, ifosfamide, cisplatin, dexamethasone
SMILE: components
steroid dex, MTX, ifosphamide, pegaspargase, etoposide
NK T-cell lymphoma: xrt fields
Always include bilateral nasal cavity, bilateral anterior ethmoid, hard palate and ipsilateral maxillary sinus. Bilateral maxillary sinus tumor of bilateral or posterior nasal cavity.
Include adjacent structures or nodes only if these are involved
No elective neck radiation, even if nodes involved.
Use ISRT.
Waldeyers ring location: cover entire ring.
NK T-cell lymphoma: outcomes
3yr OS 85%
3yr LC 60%
follicular lymphoma: workup
In follicular lymphoma, excisional biopsy still recommended as in all lymphomas. If excisional bx not feasible, can do core needle bx with immunohistochem, flow cytometry, FISH.
FISH testing: if 1p36 translocation positive, disease will be localized and no staging studies are needed
Labs: Hep B, B2 microglobin plus standard
BM bx (still required in follicular with Lugano)
follicular lymphoma: treatment paradigm
stage I-II, grade 1-2: xrt alone (24Gy)
stage I-II, grade 3: treated like DLBCL (R-CHOP + xrt)
FLIPI score components
LNASH
LDH elevated
Nodal areas > 4
Age > 60
stage III-IV
Hgb < 12
FLIPI 5yr OS by score
5yr OS:
0-1 points 90%
2 points 80%
3-5 points 50%
FLIPI-2 score components
BBLAH
B2 microglobin elevated
bone marrow positive
ymph node > 6cm
age > 60
Hgb < 12
Testicular DLBCL: workup
Standard workup and PET plus:
LP and CSF
MRI brain
skin exam
(bilateral involvement is still stage I)
Testicular DLBCL: treatment paradigm
orchiectomy -> 6 cycles RCHOP + 4 cycles intrathecal MTX -> RT to contralateral testicle, scrotum
25-30 Gy in 1.5-2 Gy per fx, use electrons. Include nodes only if involved
Testicular DLBCL: 5yr OS
5yr OS 85%
Ocular lymphoma: workup
For MALT: upper and lower endoscopy
CT C/A/P
Consider PET
Orbital DLBCL: treatment paradigm
30 Gy for CR if after chemo.
For residual disease consider 40-45 Gy.
Include entire orbit. May boost to gross disease
intraocular DLBCL: treatment paradigm
vitreous biosy
36Gy to globe and optic nerve extending to chiasm
MZL/MALT: general approach
PET. BM bx is required per Lugano.
An Indolent lymphoma per ILROG extranodal guidelines
RT alone to 24 Gy (20-30 Gy)
Per NCCN surgery alone is allowed for parotid, breast, lung, thyroid
mantle cell lymphoma: workup
Standard workup
Examine H&N area including waldeyer ring, size of liver and spleen
EGD to look for MALT is optional
PET
BM bx in all
Extremely rare to see localized disease
mantle cell lymphoma: treatment paradigm for stage I-III
induction hyper-CVAD
30Gy ISRT
solitary plasmacytoma: workup
CT and MRI of affected area. Consider MRI spine
H&P, CBC, CMP (Calcium, albumin), LDH, beta-2 microglobulin, SPEP, UPEP, serum and urine immunofixation, skeletal survey, bone marrow bx with IHC + flow, cytogenetics, FISH analysis, serum free light chain, 24 hr urine protein
For multiple myeloma need all of:
- BM plasma cells >10% OR plasmacytoma
- serum or urine monoclonal protein
- CRAB: one of calcium, renal insufficiency, anemia, osteolytic bone lesions
Multiple skeletal lesions also diagnoses MM
solitary plasmacytoma: dose and field
40-50Gy
Osseous: involved lesion plus margin
Extraosseous: involved lesion, and consider adding regional lymph nodes
Conservative: Give 2-3 cm to block edge. If vertebral body, treat that entire vertebra, 1 level only
Other strategy: Treat whole bone. Treat one vertebral body above and below
solitary plasmacytoma: likelihood of transformation to multiple myeloma
osseous: 60%
extraosseous: 40%
TBI narrative
I would position the patient at 4 m SSD standing, treating AP/PA. I would have measured the patient to create compensators and I would place a beam spoiler in front of the patient for appropriate dose distribution. Lead would be used to protect the lungs. (ablative) I would deliver 1.5 Gy BID for four days total to total 12 Gy, 5-10 cGy/min for ablation, with fludarabine and cyclophosphamide chemotherapy and nausea prophylaxis. I would keep the lung dose <10 Gy.
TBI treatment fields
Treat AP/PA
- Treat at 400 cm SSD
- I would first measure the patient to create compensators for appropriate dose distribution. I would give zofran for nausea prophylaxis
- Patient standing
- Treat at extended SSD with beam spoiler
- Treat with 12 Gy, BID dosing, 5-10 cGy/min, lung dose <10 Gy for ablative with fludarabine/cyclophosphamide
relapsed/refractory HL: criteria for transplant
General indications:
Localized relapse
Bulky disease
Persistent FDG uptake after ICE or ASCT
Critical for LC (nerve compression, SVC compression, airway compression, lymphedema, hydronephrosis)
Desseminated disease may be all treated with RT of toxicity profile is reasonable
relapsed/refractory HL: treatment paradigm
(ILROG guidelines)
ISRT is appropriate with autologous SCT and can be given before or after SCT.
CR after salvage chemo (often ICE):
CR Deauville 1-3: consider 30 Gy, or 36 Gy for Deauvile 3
CR on PET (D score 1-3) but >2.5 cm on CT: 36 Gy
Previously irradiated: ≥18 Gy as dosimetry allows
Prior to ASCT or 4-12 weeks after
PR (Deauville 4) after salvage chemo:
PR sites to 36-40 Gy and CR sites to 30-36 Gy
May treat only PR sites if volume is large
TLI: 18 Gy in 1.8 Gy BID over 1-2 weeks to refractory disease followed by 18 Gy in same fx to TLI
Give RT prior to ASCT with goal of minimal residual disease
May also consider further chemo
Deauville 5 after salvage chemo:
If limited refractory, consider RT as above
RT not rec for disseminated disease
RT before ASCT is favored
consider 40-45 Gy
relapsed/refractory DLBCL: treatment paradigm
(ILROG guidelines)
CR (Deauville 1-3) to salvage chemo:
30-36 Gy / 1.5-2.0 Gy per fx pre- or post-transplant
30 Gy / 1.5 Gy BID is an option for urgency pre-transplant
Post-transplant is done within 4-12 wks after
Pre-transplant is done ASAP, within 4 weeks after chemo
Volume: ISRT. Can consider including adjacent nodes that responded to first line chemo
PR (Deauville 4-5) residual focus after salvage chemo:
36 Gy / 1.8-2 Gy per fx with boost to 40-45 Gy / 1.8-2.2 Gy per fx to PR site
Volume and timing as above
Deauville scoring
- No uptake
- Uptake ≤mediastinum
- Uptake >mediastinum but ≤liver
- Uptake moderately >liver
- Uptake markedly >>liver
Score of 4 and 5 are always positive. In some situations, 3 is considered positive.
