Evidence Based Questions Flashcards
What is the Tx paradigm for low-risk stage 4S NB, and which study supports this approach?
Low-risk stage 4S NB Tx paradigm: Bx → supportive care. Chemo and/or RT are reserved for rapidly growing or symptomatic Dz. A subgroup analysis of CCG 3881 showed that supportive care is sufficient for 57% of pts. The protocol resulted in a 5-yr EFS of 86% and an OS of 92%. (Nickerson HJ et al., JCO 2000)
Which studies support the use of observation (without resection) in infants with localized NB without N-myc amplification?
The use of observation (without resection) in infants with localized NB without N-myc amplification was evaluated in the German GPOH trials NB95-S and NB97. Of 93 pts with gross Dz, 44 had spontaneous regression. OS and DMFS were no different from outcomes of pts treated with Sg or chemo in these trials. (3-yr OS 99%, DMFS 94%). (Hero B et al., JCO 2008)
What is the role of RT in the Tx of intermediate-risk NB?
In intermediate-risk pts, RT is typically reserved for those who are symptomatic d/t tumor bulk and are not responding to initial chemo, such as pts with respiratory distress d/t hepatomegaly or with neurologic compromise d/t cord compression. RT is not indicated as a consolidative therapy even with persistent Dz. Indications for RT based on A3961: Symptomatic palliation, viable residual Dz in Tx-refractory pts, and recurrent Dz.
What is the Tx for unfavorable stage 4S (intermediate-risk) Dz?
The Tx is chemo × 8 cycles.
Which targeted agent has recently been demonstrated as promising new adj therapy for high-risk NB?
Promising results have been observed with immunotherapy targeting the surface glycolipid molecule disialoganglioside (GD2). A recent phase III randomized trial showed a significant improvement in EFS and OS for children with high-risk NB receiving chimeric anti-GD2 (ch14.18) combined with cytokines (IL2 and GM-CSF) and isotretinoin after myeloablative consolidation therapy. (Yu AL et al., NEJM 2010)
In low-risk and intermediate-risk NB, what dose of RT is generally used?
In low-risk NB, RT to 21 Gy at 1.5 Gy/fx can be used for Sx that do not respond to chemo. In intermediate-risk NB, if PR to chemo and viable residual Dz after 2nd-look Sg, then RT can be given locally to the primary + 2-cm margin to 24 Gy at 1.5 Gy/fx.
In high-risk NB, what tissues are targeted during RT and to what dose?
Per current COG ANBL0532, high-risk NB pts are treated with RT to their postchemo, preop tumor bed to a total dose of 21.6 Gy in 1.8 Gy/fx if GTR and 36.0 Gy (21.6 Gy to preop GTV → 14.4 Gy boost) if gross residual. Based on pts with residual Dz treated on CCG 3891, 21.6 Gy is also acceptable for high-risk Dz. (Haas-Kogan D et al., IJROBP 2003)
In high-risk NB, should elective nodal RT be given?
No. In high-risk NB, only clinically+ or pathologically+ LN regions are covered in the RT volumes.
What study indirectly demonstrated an RT dose–response in high-risk NB?
A secondary analysis of CCG 3891 found that high-risk NB pts who rcvd 10 Gy local EBRT + 10 Gy TBI as part of a transplant preparation regimen had better LC than pts who did not get TBI (or a transplant) (5-yr LR rate was 22% vs. 52%). These results support the current use of 21.6 Gy in high-risk protocols. (Haas-Kogan D et al., IJROBP 2003)
What study demonstrated the benefits of high-dose chemo → BMT as well as adj cis-retinoic acid in high-risk NB?
In CCG 3891, 379 high-risk NB pts were treated with induction chemo → Sg and 10 Gy to gross residual. Pts were then randomized to 3 cycles of nonmyeloablative chemo vs. myeloablative chemo, TBI, and BMT. Pts underwent secondary randomization to observation vs. cis-retinoic acid × 6 mos. Both the myeloablative chemo and cis-retinoic acid improved OS. 5-yr OS for pts who rcvd both was 59%. (Matthay KK et al., JCO 2009)
What is the appropriate Tx for NB pts with cord compression?
Consider chemo initially for NB-related cord compression. Unresponsive Dz can be treated with Sg or RT.
What is the RT dose and dose/fx used for NB pts being treated for symptomatic cord compression?
For symptomatic cord compression:
- If pt is <3 yo, treat to 9 Gy (1.8 Gy/fx)
- If pt is ≥3 yo, treat to 21.6 Gy (1.8 Gy/fx)
What is the RT dose and dose/fx used for NB pts being treated for symptomatic hepatomegaly?
Symptomatic hepatomegaly is treated to 4.5 Gy (1.5 Gy × 3).
Can the vertebral body be split during RT planning?
No. It is necessary to always cover the full width of the vertebrae to avoid scoliosis.
What is the role of I-131 MIBG in NB?
I-131 MIBG can be used for refractory NB, based on a promising phase II study showing a 36% response rate. (Matthay KK et al., JCO 2007)