Hematologic Flashcards
1
Q
History questions for lymphoma
A
- Duration and rate of growth of palpable masses
- Tenderness of nodes
- B symptoms
- Fatigue
- Pruritis
- Performance status
- Exposure to EBV
- Smoking history
- Cardiac and pulmonary history given necessity of chemo
2
Q
Lymphoma usually painless or painful adenopathy
A
painless
3
Q
Physical exam for lymphoma
A
Detailed nodal exam
Check for hepatosplenomegaly
If concern for upperaerodigestive involvement –> nasopharyngoscopy of Waldeyer ring
4
Q
How many patients present with splenomegaly
A
30%
5
Q
What are the B symptoms
A
- Fever >38
- Weight loss >10% over prior 6 months
- Drenching nightsweats
6
Q
Discuss lymph node regions and areas
A
17 different Ann Arbor nodal regions
Each of the cooperative groups has different definitions of nodal areas
7
Q
How does GHSG classify neck?
A
R cervical, occipital, pre-auricular, supraclav, infraclav and subpectoral
8
Q
What is difference for Ann Arbor staging of neck
A
Cervical, Supraclav, Occipital, PreAuricular
Infraclav, Subpectoral (separate)
9
Q
How does GHSG classify chest
A
Mediastinum + Bilateral hila
10
Q
Where do 80-90% of cHL start?
A
SCV and cervical nodes
11
Q
How to biopsy if suspicion for lymphoma?
A
excisional biopsy preferred
core ok if necessary
12
Q
For DLBCL, what should the path be sent for?
A
If clinical suspicion of high grade lymphoma send
myc, BCL2 and BCL6 translocation
13
Q
Which labs should be ordered for suspected lymphoma patient?
A
- CBC
- CMP
- HIV
- Hep serologies
- LDH
- EBV titer
- ESR
- PREGNANCY TEST
14
Q
What other tests should a lymphoma patient be sent for?
A
ECHO
PFTs (if considering bleo)
Fertility
Vaccines if splenic RT
15
Q
What imaging is needed
A
PET
Consider CT CAP with contrast
Consider MRI given location
16
Q
Which DLBCL patients need CNS staging?
A
HIV-associated
Testicular or paranasal sinus DLBCL
>2 EN sites with elevated LDH
17
Q
What is Deauville 1
A
Background avidity
18
Q
What is Deauville 2
A
Avidity above background below mediastinal blood pool
19
Q
What is Deauville 3
A
Avidity between mediastinum and liver
20
Q
What is Deauville 4
A
Uptake above liver, no new sites
21
Q
What is Deauville 5
A
Update markedly above liver or new site of disease
22
Q
What Deauville levels should be considered positive for therapeutic de-escalation?
A
3, 4, 5
23
Q
What is the Lugano staging?
A
Limited = Stage I and II
Advanced = Stage III and IV
24
Q
What is stage I?
A
One node or one group of adjacent nodes
One lymphoid tissue structure (spleen, Waldeyer, thymus)
25
What is stage IE?
single extra-nodal lesion, without nodal involvement
26
Stage II
Two or more nodal areas and/or lymphoid structures on same side of the diaphragm
27
Stage IIE
One or two node/nodal groups on same side with limited CONTIGUOUS extranodal involvement
28
What is stage III
nodes above and below diaphragm
nodes above diaphragm w spleen involvement
29
What is stage IV
Non contiguous extralymphatic tissues
30
What is bulky disease for cHL
Classically 1/3 intrathoracic diameter between T5 and T6
But ranges 7-10 cm per study
31
What is bulky for DLBCL?
7.5 cm (UNFOLDER definition)
32
What is bulky for FL?
6 cm
33
How to do ISRT
* Fuse pre-chemo PET and CT to simulation CT
* Contour several areas to form GTVpre
* CT abnormality on pre-chemo CT
* CT abnormality of pre-chemo PET/CT
* PET abnormality on pre-chemo PET
* Contour GTV on post chemo sim scan
* Fuse these images
* Form a CTV respecting anatomic boundaries (bone, muscle, lung) and generally do 1-2 cm craniocaudal expansion depending on site
* More uncertainty in setip, the larger the expansion
* Join CTVs if \<5 cm apart
* Account for motion with ITVs
* PTV margin of 0.5-1.0 cm depending on site
34
If two CTVs are \> X distance apart, they can remain separate
5 cm
35
Which patients should be referred for protons
Mediastinal disease in young women to reduce breast dose
Heavily pre-treated patients with RT-related risk for heart and lung toxicity
36
Benefits of arms up for treating neck/mediastinum
Pulls axillary nodes away from chest wall and gives more lung shielding
37
Benefits of arms akimbo for treating neck/mediastinum
Better humeral head shielding and reduces SCV skin folds
38
Risk of L'hermitte's for cHL
15-20%
39
Risk of pneumonitis for cHL treatment
15% (due to bleo)
40
Risk of pericarditis from cHL treatment
\<5%
41
Risk of thyroid dysfunction from mediastinal treatment
30-50%
42
Late toxicity risks for cHL treatment
* Hypothyroidism
* Infertility
* Secondary malignancies (thyroid, lung, breast)
* CAD
43
Which women should get breast screening?
Women who got thoracic RT between 10-30
44
How should women with prior thoracic RT be screened for breast ca
Counsel for breast self-exam
Annual mammo
Breast MRI
45
When should breast screening start for these women?
8-10 years after completion of RT or age 40, whichever is sooner
46
How often should TSH be checked if neck RT?
annual
47
What is immunohistochemistry phenotype of cHL
CD15+
CD30+
48
What subtype of cHL is most common?
Nodular sclerosing
70%
Often mediastinum
49
Characteristics of mixed cellularity cHL
20%
Young kids, EBV+
Advanced stage
50
Lymphocyte rich subtype
10%
Best prognosis
Confused with NLPHL
51
Lymphocyte depleted subtype
rarest but worst prognosis
Older patients
B sx
HIV+
52
What are the German Hodgkin Study group risk factors
* 3 or more nodal areas
* Extranodal disease
* ESR \> 50 if A, \>30 if B
* Bulky mediastinal mass
53
What age is considered higher risk for cHL?
\>50
54
NCCN defines bulk as X cm for cHL
10 cm
55
What is ABVD?
Adrimycin
Bleomycin
Vinblastine
Dacarbazine
56
How is ABVD given?
D1 and D15 of 28 day cycle
57
What are the toxicities of ABVD?
A=cardiomyopathy
B=pulm fibrosis
V=neuropathy and alopecia
D=cytopenia, vomiting, hepatotox
58
What is BEACOPP
B=Bleomycin
E=etoposide
A=adriamycin
C=cyclophosphamide
O=vincristine
P=procarbazine
P=prednisone
59
What is ICE?
Ifosfamide
Carboplatin
Etoposide
60
After classifying patient as favorable/unfavorable cHL, what is next step?
Decide if preference for a chemo only strategy or if combined modality is the intent of treatment
61
How to decide if good candidate for CMT?
Age
Sex
Disease distribution
FHx
Comorbidities
62
Treatment approach for early stage favorable disease
* PET adapted strategy
* Start with 2 cycles of ABVD --\> PET
* If Deauville 1 or 2
* 20 Gy ISRT
* 1-2 cycles ABVD (per RAPID)
* If Deauville 3
* 20 Gy ISRT (if very favorable)
* 1 cycle ABVD --\> 30 Gy
* AVD x 4
* If Deauville 4 or 5 --\> 2 more cycles of ABVD --\> PET
* If D1-3: ISRT 30 Gy
* If D4-5: Biopsy --\>
* neg --\> ISRT 30 Gy
* Pos --\> salvage ICE
63
What is the advantage of CMT for early stage favorable cHL
Randomized trials show EFS benefit of 7-10%
We cannot omit RT even if PET negative after ABVDx2 without decrement in PFS
64
Which patients should not be managed with 2 ABVD --\> 20 Gy
ESR \< 50
\< 3 nodal areas
No extranodal disease
No bulky mediastinal mass
65
Management of early stage unfavorable disease
* ABVD x 2 --\> PET CT
* Deauville 1-3
* ABVD x 2 --\> 30 Gy ISRT
* AVD x 4 (RATHL)
* Deauville 4-5: escBEACOPP x 2 --\> PET/CT
* Deauville 1-3
* escBEACOPP x 2
* ISRT 30 Gy
* Deauville 4-5 --\> biopsy
* negative --\> 30 Gy ISRT
* positive --\> ICE
66
Outcomes for early stage favorable cHL
5 year EFS: 93%
5 year OS: 98%
67
Outcomes for early stage unfavorable cHL
5 year EFS: 85%
5 year OS: 95%
68
Approach to advanced stage cHL
* ABVD x 2 --\> PET CT
* If Deauville 1-3: AVD x 4 (per RATHL)
* If D4-5: escBEACOPP x3 --\> PET/CT
* D1-3: eBEACOPP x1
* D4-5: biopsy
* neg: eBEACOPP x1
* pos: r/r
69
When should RT be used for advanced stage cHL
Consolidation ISRT to residual sites (PR) after 6 cycles of chemo) especially if bulky or extranodal
No role for consolidation if CR to ABVD
No role for consolidation if eBEACOPP used
70
How many patients with early stage cHL will relapse?
10-20%
71
How many patients with advanced stage cHL will relapse
30-40%
72
How to approach relapsed cHL
Biopsy
ICE chemo x2 cycles
RT consolidation (150 x 20 BID)
HDT+AutoSCT
73
What is the risk of second cancers for cHL patient?
20-30% over 30 years
74
Risk of breast cancer in cHL survivors
15-20% at 30 years
4x SIR
75
What is marker pattern of NLPHL?
CD 20+
CD 45+
76
Best treatment for NLPHL early stage
ISRT alone
30 Gy standard
36 Gy if bulky
77
How to contour NLPHL ISRT
ISRT alone typically so generous margins
Go 2-5 cm sup/inf around affected nodal areas depending on the site
78
What is the relapse pattern for NLPHL?
Late, distant and possibility of transformation
79
What is rate of transformation for NLPHL
30% at 20 years
80
How to do post treatment imaging for cHL?
* Document CR by PET w/i 3 months of finishing treatment
* Then CT N/CAP q6 months x 2 years
81
Outcomes for NLPHL
10 year OS \>90%
10 year RFS 75%
82
What is the marker pattern for DLBCL
CD20+
CD45+
83
What is the chemo regimen for DLBCL?
R-CHOP
84
What is RCHOP
R-rituximab
C-cyclophosphamide
H-doxorubicin
O-vincristine
P-prednison
85
How often is RCHOP given
Typically q3w
86
What is the prognostication score for DLBCL?
R-IPI
87
What are the IPI factors?
**Think APLES**
A-Age \>60
P-ECOG 2+
L-elevated LDH
E-2+ extranodal sites
S-stage III/IV
88
How to work up a DLBCL patient
* H&P
* Imaging: PET, ?MRI
* Labs: CBC, COMP, LDH, Hep serologies
* Path: excisional bx, bone marrow bx, LP if high risk
* Develop risk category using IPI
* Decide if chemoimmunotherapy or CMT
89
What is 4 year OS for DLBCL IPI 0
94%
90
What is 4 year OS for IPI 1-2
80%
91
What is 4 year OS for IPI 3-5
55%
92
What is bulk for DLBCL?
7.5 cm
93
What is the approach to stage I/II non bulky DLBCL?
* Options
* RCHOP alone to 4-6 cycles
* Combined modality
* RCHOP x3-4 followed by ISRT
94
What is the dose of RT for combined modality therapy for DLBCL?
If CR: 30 Gy
If PR: 36-40 Gy
If no chemo: 45-50 Gy
95
What is the benefit of Rituximab for DLBCL?
About 10% improvement in OS
96
What is the management of early stage bulky DLBCL
6 cycles RCHOP +/- RT
30 Gy if CR
36 Gy if PR
97
What is the limitation of the UNFOLDER data?
No interim PET imaging
Unclear if CR actually needs RT?
98
What are aggressive variant DLBCL
* Double hit
* Triple hit
* Burkitt like features
* Very high IPI
99
How to appoach aggressive variant DLBCL
6 cycles R-da-EPOCH
30 Gy if CR to bulky or extranodal sites
100
How to approach stage III/IV DLBCL
6 cycles of RCHOP
Consider consolidation RT to sites of bulk, skeletal, PR
101
How does RT help for DLBCL of the elderly
Improves EFS, PFS, OS for elderly patients getting 6 cycles of RCHOP for sites of initial bulk and extralymphatic involvement
102
What is an open question about consolidation of DLBCL
If bulky but PET CR at the end of therapy still requires consolidation (subject of OPTIMAL 60 study)
103
Which DLBCL cases should get CNS prophylaxis
IPI\>4
testicular
parameningeal involvement
HIV
adrenal/kidney involvement
consider for high risk histologies (double/triple hit)
104
What is the preferred CNS prophylaxis
IT MTX x 4-8 cycles
105
What is the treatment of testicular DLBCL
* Orchiectomy
* 6 cycles RCHOP
* IT MTX prophylaxis (4-8 cycles)
* RT to contralateral testicle (30 Gy/15 fx)
106
What is the treatment of bone lymphomas
RCHOP x 3-4
Consolidation RT to 30-36 Gy if CR (prechemo volume using MRI)
107
What is the treatment of gastric DLBCL?
RCHOP x 3
Repeat endoscopy
30 Gy/15 fx if CR
More chemo --\> RT if PR
108
What is a palliative dose regimen for DLBCL
3 Gy x 10-13
4 Gy x 7
109
What virus associated with Burkitt
EBV
110
What virus associated with splenic MZL
HCV
111
What associated with cutaneous MALT
Lyme disease
112
What infection associated with ocular MALT
chlamydia psittaci
113
What are the path hallmarks of MCL
Cyclin D+
t11:14 associated with activation of BCL1
114
How to treat localized MCL?
* RCHOP x 6 cycles +/- ISRT if PR
* RT alone to 36 Gy
115
What is approach to treat advanced stage MCL?
* If aggressive: RCHOP --\> HDT/ASCT
* If indolent: observe
* Palliation: consider 2 Gy x 2
116
What is the translocation hallmark of FL?
t14:18
Overexpresses BCL2
117
What share of NHL is FL?
20%
118
What additional workup needed for FL?
BONE MARROW BX
119
What is the risk of transformation for FL?
3% risk per year
120
How is grade determined for FL?
Number of centroblasts per HPF
121
What is grade 1 FL
0-5 centroblasts pHPF
122
What is grade 2 FL
6-15 centroblasts
123
What is grade 3 FL
\>15 centroblasts
124
How to assess risk for FL?
FLIPI or FLIPI2 score
125
What is FLIPI score?
* NOLASH
* \>4 nodal areas
* LDH elevated
* Age \>60
* Stage III/IV
* Hgb \<12
126
What is FLIPI2 score
HAS NO BM
* Hgb \< 12
* Age \> 60
* Serum beta2 microglob elevated
* Node \>6cm
* BM: bone marrow involvement
127
How many cases of FL are localized
10-30%
128
What is the treatment strategy for localized FL
* ISRT to 24 Gy in 12 fractions
* Can consider addition of ritux or RCVP if more extensive disease
129
Contouring for localized FL
* GTV = involved nodes
* CTV = GTV + 5 cm craniocaudal + 1 cm radially
* PTV = 0.5 - 1 cm pending location
130
Outcomes for localized FL
* 98% response to RT
* 90% local control at 5 years with RT alone
* 75% PFS for stage I
* 50% PFS for stage II at 5 years
131
How to approach stage II noncontiguous
* Chemo-immunotherapy +/- ISRT
* Observation
132
How many FL cases are stage III/IV
70-90%
133
When should we treat stage III/IV FL?
Symptomatic
End organ dysfunction
Cytopenias
Bulky disease
Steady progression
134
Options for treatment of advanced stage FL
* Observation
* Chemoimmunotherapy (R-Benda, RCHOP, Rituximab)
* Low dose RT
135
What is the success rate of 2 Gy x 2
70% local PFS at 5 years
136
What translocation predicts antibiotic resistance for gastric MALT?
t11;18
137
What workup is necessary for suspected gastric MALT?
* Labs: LDH, beta2microglobulin
* H Pylori breath or stool test
* Endoscopy with random biopsies, staining for H Pylori
* Check 11;18 translocation
* PET Scan
138
How to approach Gastric MALT
* If H Pylori positive --\> triple therapy
* Recheck endoscopy in 3 months
* If H Pylori + --\> can try second line antibiotics
* If H Pylori - and persistent MALT --\> ISRT
* If H Pylori negative or if t11;18 positive --\> ISRT
139
How successful is antibiotics for H Pylori + gastric malt?
2/3 of cases are treated
140
What is triple therapy
* PPI
* Amoxicillin 1g BID (or metronidazole 500 mg BID if PCN allergy)
* Clarithromycin 500 mg BID
141
What is the dose of RT for gastric MALT?
30 Gy in 20 fx
142
What should be given with RT for gastric MALT?
PPI
Zofran
NPO 3 hrs before
143
What is contouring strategy for gastric MALT
* GTV: visible tumor and regional nodes
* CTV: whole stomach, duodenal bulb
* ITV
* PTV: CTV + 1.5 cm
* Daily CBCT
144
What is the dose for nongastric MALT?
24 Gy in 12 if definitive
4 Gy in 2 if palliative
145
Contouring approach for orbital MALT (conjunctival)
CTV = Include full conjunctival reflection to fornices
9 MeV with 1 cm bolus
PTV is CTV + 5 mm
146
Contouring approach for orbital MALT (non-conjunctival)
CTV = full orbit
PTV = CTV + 5 mm
Use wedge pair or IMRT, opp lats if bilateral
147
What is the workup for a plasma cell neoplasm?
* H&P
* Labs
* CBC
* CMP
* Beta2 microglobulin
* Albumin
* LDH
* SPEP
* UPEP
* Protein immunofixation
148
What is the imaging required for new diagnosis of plasma cell neoplasm
* Plain films or skeletal survey
* PET
* MRI/CT of the primary site
149
What is the diagnosis of solitary plasmacytoma
* Negative BM (\<10% of plasma cells)
* Bx proven plasma cell neoplasm
* No more than 1 lesion on imaging
* No end organ damage
* Low IgM or IgA, low serum M spike
150
What is treatment of ossoeus plasmacytoma
ISRT to 46 Gy in 23 fractions
151
Margins for osseous plasmacytoma
CTV: 2 cm
PTV: 0.5 to 1.0
152
What is the preferred treatment of extramedullar plasmacytoma
ISRT to 46 Gy in 23 fractions
Consider treating 1st eschelon nodes (especially if head and neck)
153
What is local control of osseous plasmacytoma
88-100%
154
Risk of transition to MM from osseous plasmacytoma
70%
155
Local control of extramedullary plasmacytoma after RT
80-100%
156
Risk of myeloma after RT-treated extramedullary plasmacytoma
30%
157
Myeloma stage I
B2 microglob \< 3.5
Albumin \> 3.5
Normal LDH
158
Myeloma stage II
Not stage I or III
159
Myeloma stage III
B2microglob \> 5.5 and either
High risk chromosomal abnormalities by FISH OR
High LDH
160
Diagnosis of MM requires
* Plasmacytoma or BM plasma cells \> 10%
* Presence of end organ/tissue impairment
* Anemia (Hgb \<10)
* Hypercalcemia (Ca \> 11)
* Renal insufficiency (Cr \>2)
* Bone lesions - one or more osteolytic lesions \> 5mm
* OR presence of biomarker associated with near inevitable progression to end-organ damage
* \>60% plasma cells in bone marrow
* FLC ration \> 100
* MRI with more than one focal lesion
161
Treatment for MM
* Chemo: bortezomib containing regimens (melphalan)
* VCD - lenalidomide, cyclophosphamide, vincristine
* HDCT+ASCT
* Bisphosphonates
* Palliative RT
162
Dose of RT for palliative lesions MM
20-30 Gy in 3-4 Gy fractions
163
Dose for primary cutaneous follicle center lymphoma
If solitary: 24/12
If diffuse 4/2
164
Control rates for PCFCL
99% CR
20-30% fail in skin
165
Typical margins for skin lymphomas
1.5 cm margin around the wired lesion
Choose electron with penetration to depth of lesion plus 5 mm
Rx to 90% IDL
Place 1 cm bolus, typically 6-9 MEV
166
Dose for primary cutaneous anaplastic large cell lymphoma
36 Gy if solitary
167
Treatment of anaplastic large cell lymphoma
BV-CHP if aggressive and systemic
168
Stage IA MF
Patches, plaques, papules \< 10% BSA
169
Stage IB MF
\>10% BSA
170
Stage IIA MF
N+ or B1 (sezary cells)
171
Stage IIB MF
tumors \> 1cm
172
Stage III MF
confluent erythema \>80%
173
Treatment of localized MF
* Topicals
* RT with electrons
* Consider systemic therapy +/- RT
* Consider TSEB for IB
174
What is response rate to TSEB
CR 80% but 10 year RFS is 10%
175
Palliative dose of RT for localized MF lesion
200 x 6 2-3x per week
176
Curative dose of solitary MF lesion
200 x 10
177
What margin should be used for MF lesions
2 cm
178
Acute toxicities of TSEB
Dermatitis and desquamation
Alopecia
Lymphedema
Nail loss
Anhidrosis
179
Longer term side effects of TSEB
2nd skin cancer
cataracts
edema
chronic xerosis
alopecia
telangiectasia
180
What is the setup for TSEB
* Dual fields with a superior and inferior field angled 18 degrees above and below horizontal
* Treat with 9 MeV
* Treatment behind a Lucite screen to scatter E- and improve surface dose
* Treat all 6 positions single session
181
Dose of TSEB
16-20 Gy
2x per week in 2 Gy fractions
Consider boosting the higher risk areas
182
Treatment of PMBCL
* If 6 cycles of R-da-EPOCH --\> no RT if in CR
* If 6 cycles of RCHOP --\> RT if CR
* 30 GY if CR
