Leukemia/Lymphoma

Question 1

What is the size cut-off in axial dimensions to define bulky disease as used in recent DLBCL clinical trials (e.g. RICOVER-60, UNFOLDER)?

A. ≥ 5 cm
B. ≥ 7.5 cm
C. ≥ 10 cm
D. ≥ 12 cm

Answer 1

B. ≥ 7.5 cm

The definition of bulky disease has evolved from use of X-ray based definitions of maximum “Mass to Thoracic Ratio” >33% to CT scan based definition of the above ratio at T5-6 vertebral level of > 0.35, or nodal mass with maximal dimension >10cm. Recent clinical trials use a cut-off of ≥ 7.5 cm which was also adapted in the latest versions of NCCN guidelines. This size is also important in helping to select patients which may benefit with the addition of consolidative radiotherapy after R-CHOP chemotherapy.

Question 2

What dose is considered the standard of care based on findings from the FORT randomized phase 3 non-inferiority trial for indolent follicular and marginal zone lymphoma?

A. 4 Gy in 2 Fx
B. 10 Gy in 5 Fx
C. 24 Gy in 12 Fx
D. 36 Gy in 18 Fx

Answer 2

C. 24 Gy in 12 Fx

This trial help establish the use of 24 Gy in 12 fractions as a standard for follicular lymphoma with 4 Gy in single fraction as a reasonable alternative. The complete response was 68% in the 24 Gy arm vs 49% in the 4 Gy arm across all patients. After median follow-up of 26 months, the HR for time to local progression was 3.42 (95% CI: 2.10-5.57, p< 0.001) in favor of the 24 Gy group. There was no difference in overall survival.

Question 3

Which of the following is included in the International Myeloma Working Group diagnostic criteria for solitary plasmacytoma?

A. Presence of CRAB (hypercalcemia, renal insufficiency, anemia, bone lesions)
B. Bone marrow involvement < 10%
C. Normal skeletal survey (except for primary site of disease)
D. PET scan showing hyperactive lesions

Answer 3

C. Normal skeletal survey (except for primary site of disease)

All others (CRAB, PET scan showing multiple lesions, and bone marrow involvement) would not make it solitary plasmacytoma. Bone marrow less than 10% would be called solitary plasmacytoma with minimal marrow involvement. Thus, the best answer is C.

Question 4

What was the main finding in the randomized trial that compared of 1-5 Fx vs. 10-20 Fx for multiple myeloma?

A. Most patients experienced pain relief, although complete pain response occurs in <10% of the patients
B. Most patients experienced pain relief, with nearly all patients achieving complete pain response
C. Bone recalcification was expected for >90% of patients
D. Longer dose fractionation had higher rate of motor function improvements in patients with cord compression

Answer 4

D. Longer dose fractionation had higher rate of motor function improvements in patients with cord compression

A randomized trial of 1-5 vs. 10-20 fractions demonstrated that longer course regimens achieved higher rates of motor function improvement at 6 (67% vs. 43%; P=.043) and 12 months (76% vs. 40%; P=.003).

Question 5

According to the German Hodgkin Study Group, what is the clinical stage of a Hodgkin lymphoma patient with involvement of the ipsilateral cervical and supraclavicular nodal regions?

A. I
B. II
C. III
D. IV

Answer 5

A. I

According to the German Hodgkin Study Group, the left cervical and supraclavicular lymph node regions are considered to be one lymph node region.

Question 6

What was the MOST common Deauville score on interval PET after ABVD in the UK NCRI RAPID trial for patients with Hodgkin lymphoma?

A. 1
B. 2
C. 3
D. 4

Answer 6

A. 1

52.7% of patients achieved a Deauville score of 1 after ABVD, which was the most common score.

Question 7

In the HD10 trial, what was the finding of dose deintensification using less chemotherapy and lower RT with regards to PFS and OS?

A. Improved PFS and no change in OS
B. Decreased PFS and no change in OS
C. No detriment to PFS and OS
D. No detriment to PFS and improved OS

Answer 7

C. No detriment to PFS and OS

The long-term outcomes from the GHSG HD10 trial showed that excellent outcomes persisted among the de-intensified arm of ABVD x 2 + 20 Gy with no significant difference versus the other arms. 10-year progression free survival was 87.2% and 10-year overall survival was 94.1%.

Question 8

What is the principle toxicity of concern when using low dose rates during TBI for acute leukemia?

A. Myocarditis
B. Enteritis
C. Hepatitits
D. Pneumonitis

Answer 8

D. Pneumonitis

TBI delivered with low dose rate is intended to reduce the risk of pneumonitis.

Question 9

What is the recommended dose for definitive RT for a stage I MALT of the left parotid gland?

A. 24 Gy
B. 36 Gy
C. 45 Gy
D. 50.4 Gy

Answer 9

A. 24 Gy

24 Gy is the recommended dose for MALT of left parotid gland. Other doses would be too high. MALT is radiosensitive, and low doses of RT can achieve excellent long-term control.

Question 10

What is the minimum RT dose for a patient with Stage I NK/T-cell Lymphoma?

A. 24 Gy
B. 36 Gy
C. 40 Gy
D. 50.4 Gy

Answer 10

D. 50.4 Gy

Dose response over 50.4Gy has been demonstrated in many studies.

Question 11

What parameter provides prognostic information for patients with follicular lymphoma (FLIPI index)?

A. Extranodal site
B. ESR
C. Age ≥ 60 years
D. “B” symptoms

Answer 11

C. Age ≥ 60 years

All other choices are prognostic factors for early-stage classical HL, not FL. Age ≥ 60 years is part of the FLIPI for follicular lymphoma.

Question 12

Which translocation or chromosomal aberration is associated with a failure of antibiotic therapy for H. pylori eradication in gastric MALT?

A. t(10;14)
B. t(11;18)
C. Chromosomal hyperdiploidy
D. t(9;22)

Answer 12

B. t(11;18)

The presence of translocation t(11:18) is a feature associated with poor response to H.pylori eradication for gastric MALT. All others are not related to gastric MALT.

Question 13

What is the risk of progression of solitary bone plasmacytoma to multiple myeloma in 10 years?

A. <10%
B. 10 - 30%
C. 31 - 50%
D. 60 - 90%

Answer 13

D. 60 - 90%

Many patients (> 50%) with solitary bone plasmacytoma will develop multiple myeloma in 10 years. Thus, the correct answer is D.

Question 14

What is the minimum recommended RT dose to treat a patent with a 2 cm solitary bone plasmacytoma of the left femur?

A. 35 Gy
B. 45 Gy
C. 50.4 Gy
D. 54 Gy

Answer 14

A. 35 Gy

Per ILROG guidelines, the recommended dose is 35-40 Gy for solitary plasmacytoma that is less than 5 cm.

Question 15

What is the BEST estimate of the increased risk of secondary solid cancer after allogeneic SCT conditioned with myeloablative TBI among pediatric patients age <10 years of age at the time of transplant?

A. 15-fold increase
B. 35-fold increase
C. 55-fold increase
D. 75-fold increase

Answer 15

C. 55-fold increase

In a large multi-institutional cohort of over 28,000 allogeneic transplant recipients the risk of developing a solid malignancy was examined. Using a competing risk analysis, the cumulative incidence of developing a solid cancer was 1% at 10 years, 2.2% at 15 years and 3.3 % at 20 years. For all transplant patients studied, the development of an invasive second cancer was twice the rate expected. The risk of invasive sold cancer development was strongly related to the age of the transplant recipient as well as exposure to RT. Most patients in the study received doses of 10 Gy or more. Pediatric patients < 10 years of age had a 55-fold increase risk of developing a solid cancer, however for patients 30 years or older, no increased risk was observed.

Question 16

Which TBI regimen would be expected to have the same risk of secondary solid cancer as a chemotherapy alone conditioning regimen?

A. 2 Gy in 1 Fx
B. 4 Gy in 1 Fx
C. 12 Gy in 6 Fx
D. 14.4 Gy in 12 Fx

Answer 16

A. 2 Gy in 1 Fx

Early studies examining the risk of secondary solid cancers have suggested an increased risk of malignancies among patients treated with higher RT doses (Curtis RE et al NEJM 1997). Recent regimens have utilized chemotherapy alone or low TBI doses for allogeneic stem cell transplant in an effort to reduce treatment related morbidity and mortality. Among a cohort of just under 5,000, 1-year allogeneic HCT survivors with a median follow up of 12.5 years, myeloablative chemotherapy alone was associated with a two-fold higher risk of secondary cancer compared to the general population (Baker et al). The secondary malignancy risk for low-dose TBI (2-4.5 Gy) was comparable to chemotherapy alone regimens. The risk was the greatest for survivors that received high-dose unfractionated (6-12 Gy) or very high dose fractionated TBI (14.4 – 17.5 Gy). Fractionated TBI to 6-12 Gy was also associated with an increased risk of second cancer as compared to chemotherapy alone conditioning.

Question 17

Blocking of which organ during TBI improves OS after allogeneic SCT?

A. Kidney
B. Liver
C. Testes
D. Lung

Answer 17

D. Lung

Pulmonary toxicity can occur as an acute or late complication of TBI. Many studies have shown that the dose rate of RT delivery, the TBI fraction size as well as the total dose administered to the lung influences the severity of pulmonary toxicity after RT. Inferior overall survival has been seen in several studies. Reduction in lung dose can be accomplished with lung shielding to keep the total dose to the lung lower than 8-10 Gy.

Question 18

What is the optimal treatment approach to maximize disease control in a patient with favorable risk, non-bulky Hodgkin lymphoma?

A. ABVD alone
B. ABVD + consolidative RT
C. Brentuximab vedotin + AVD
D. ABVD + high dose chemotherapy

Answer 18

B. ABVD + consolidative RT

To date, three randomized trials, UK Rapid, EORTC H10F and GHSG HD16 have demonstrated that among non-bulky favorable risk stage I/II Hl patients, progression free survival is improved with combined modality therapy (ABVD followed by consolidative RT) as compared to ABVD alone. Extended follow up for these studies is lacking, therefore the impact of modern RT on secondary malignancy and cardiac morbidity is unknown. However, if the priority of frontline therapy is optimized disease control, combined modality therapy is the preferred treatment based on published randomized data. Brentuximab (A) is a novel antibody-drug conjugate targeting CD30. Recently the phase 3 ECHELON-1 study has demonstrated superior PFS for A+AVD as compared to ABVD as initial therapy for patients with advanced stage III/IV classical HL (and not limited stage HL) (Straus et al).

Question 19

Which factor is associated with hypothyroidism after combined modality therapy for HL?

A. V25 of the thyroid
B. Age at the time of RT
C. ABVD chemotherapy
D. Large thyroid gland

Answer 19

A. V25 of the thyroid

Several dosimetric factors have been associated with the development of RT related hypothyroidism after treatment for HL. Among patients treated with 3D conformal and IMRT both V25 (cutoff of 63.5%) and V30 (cutoff of 62%) are influential (Cella et al, Pinnix et al). Age does not appear to influence the risk of RT induced hypothyroidism (Vogelius et al). Patients treated with ABVD alone have negligible risk of hypothyroidism (Bethge et al). Patients with small thyroid glands (less and 11.2 ml) are at greater risk of RT related hypothyroidism and likely require stricter criteria (Pinnix et al).

Question 20

Which of the FDA approved radioimmuno-labeled agents has a beta and gamma emission?

A. Ibritumomab tiuxetan
B. Tositumomab
C. 223Ra dichloride
D. Lintuzumab

Answer 20

B. Tositumomab

Tositumomab is labeled with I-131, which has both beta and gamma emission. The gamma emissions allows for imaging, and the longer half-life of 8 days allows for delayed imaging as well as multiple imaging time points after injection for dosimetry calculations. Therefore, I-131 is often used for RIT with antibodies. Xofigo is an alpha emitter used to treat bone disease. Lintuzumab is an antibody used to treat AML and was abandoned when phase IIb failed to show increased survival.