Treatment/Prognosis Flashcards
What is the management paradigm for an immunocompetent pt with PCNSL and KPS ≥40?
PCNSL management paradigm: high-dose Mtx (good CNS penetration) based regimen. If CR: consider: high-dose chemo with stem cell rescue, high-dose cytarabine +/– etoposide, or low-dose WRT.
If no CR: WBRT, or consider high-dose cytarabine +/– etoposide, or best supportive care.
What is the management paradigm for a KPS <40?
Give steroids. If KPS improves, chemo, otherwise WBRT (24–36 Gy WBRT then boost to 45 Gy). (NCCN 2018)
What is the 1st intervention in a symptomatic pt after Bx?
The use of high-dose steroids is the 1st intervention in a symptomatic pt after Bx.
If a pt is suspected of harboring PCNSL, why should steroids not be started right away before obtaining a Bx?
Tumor regression (in 90%) with subsequent Bx yielding nondiagnostic results; Bx 1st → start of steroids (upfront steroids only for unstable pts)
How does the RT response differ b/t PCNSL and other types of extranodal NHL?
PCNSL is very radioresistant (5-yr OS is 4%). Extranodal NHL response is 90%.
How did the IELSG determine the prognostic groups that may predict for better survival?
Fererri AJ et al.: 378 pts from 1980–1999, HIV– with CNS lymphoma. All were treated with various regimens (+/– chemo, +/– RT). (JCO 2003)
How do survival outcomes differ b/t CRT and RT alone?
MS is ∼44 mos (CRT) vs. ∼10–18 mos (RT alone). 5-yr OS is 30% (CRT) vs. 5% (RT alone).
What % of pts are long-term survivors?
∼15%–20% long-term survival in contemporary clinical trials of Mtx-based chemo (+/– RT).
What is the outcome of pts with ocular lymphoma?
The outcome of pts with ocular lymphoma is uniformly fatal. MS is only 6–18 mos.
Is cyclophosphamide HCl/doxorubicin/Oncovin/prednisone (CHOP) effective against PCNSL? Is cyclophosphamide HCl/doxorubicin/Oncovin/dexamethasone (CHOD) effective?
No. There is ineffective blood–brain barrier penetration. 3 RCTs, including RTOG 8806 (Schultz C et al., JCO 1996), demonstrated no benefit of CHOP or CHOD.
What pts should be considered for WBRT after chemo and to what dose?
This should be decided based on the response to chemo. In general should be given to younger pts, as WBRT may increase neurotoxicity especially in pts >60 yrs. The dose depends on the response. For CR after chemo, give WBRT 23.4 Gy in 1.8 Gy fx. If
What were the results of the phase II trial on R-MPV f/b reduced-dose consolidative WBRT and cytarabine (Morris PG et al., JCO 2013)?
This was a multicenter phase II study of 52 pts receiving induction rituximab (Rituxan), Mtx, procarbazine, and vincristine (R-MPV) for 5–7 cycles, f/b reduced dose WBRT (23.4 Gy) for a CR or standrad WBRT (45 Gy) for nonCR. 60% had CR and rcvd reduced dose WBRT, with 3-year OS of 87% and 2-yr PFS of 77%. There was min neurotoxicity.
Which study demonstrated that an RT boost is not beneficial for PCNSL?
RTOG 8315 (phase II): WBRT 40 Gy → CD to 60 Gy. MS was 11.5 mos. 80% failed in the boost field.
What does the Memorial MSKCC data demonstrate on the use of high-dose Mtx + WBRT and the relation of age to developing neurotoxicity?
MSKCC data: phase II, 52 pts. MS was 60 mos. High-dose Mtx × 5 cycles (3.5 g/m2) was Alt intrathecal Mtx (12 mg) → procarbazine/vincristine + WBRT 45 Gy → high-dose cytosine arabinoside (Ara-C) (intravenous 3 mg × 2). Of those aged >60 yrs, some did not rcv RT. Survival was the same b/t no RT vs. RT, but DFS was worse if there was no RT. Those >60 yrs who rcvd RT had ↑ risk of neurotoxicity (83%) vs. age <60 yrs (6%). With chemo alone, only 1 pt developed neurotoxicity. (Abrey LE et al., JCO 2000)
In the Abrey study, what was the response rate to pre-RT chemo?
CR 56% and PR 33% (ORR 89%). (Abrey LE et al., JCO 2000)
In RTOG 9310, did 36 Gy (1.2 Gy bid) benefit PCNSL pts when compared to 45 Gy (conventional qd) WBRT?
RTOG 9310 (Fisher B et al., J Neurooncol 2005): no difference in control and survival, but worse neurotoxicity (23% vs. 4%); prospective study of Abrey chemo regimen → 45 Gy vs. 36 Gy bid (if CR to chemo) (63 pts rcvd 45 Gy, and 16 pts rcvd 36 Gy. MS was 37 mos).
What were the results of RTOG 0227?
RTOG 0227 (Glass J et al., JCO 2016) was a phase I/II study of induction chemo with Mtx, rituximab, and TMZ, f/b hyperfractionated WBRT (hWBRT; 36 Gy in 1.2 Gy bid) and subsequent TMZ. In phase I, 13 pts rcvd increasing doses of TMZ, and in phase II, 53 pts were treated. 2-yr OS and PFS of 81% and 64%, respectively, were significantly improved compared to historical controls from RTOG 9310 (see above). 66% had G3/4 toxicity before hWBRT, and 45% had G3/4 toxicity attributed to hWBRT. Cognitive function and QOL improved/stabilized after hWBRT.
What did the RCT of +/- consolidative WBRT by Thiel et al. show (JCO 2010)?
This was a multicenter, randomized phase III, noninferiority trial of 318 pts treated with high-dose Mtx + ifosfamide +/– WBRT. There was no OS difference (32.4 mos WBRT vs. 37.1 mos no WBRT). There was improved PFS in the WBRT arm but neurotoxicity was more common in the WBRT arm (49% vs. 26%).
What are the CR rates with chemo and deferred RT after chemo?
Several phase II trials have tested this approach of chemo with deferred RT, with CR rates ranging from 42% to 61%, and OS from 14 to 55 mos. However some pts did not achieve CR and need WBRT, and even among those with CR, ∼half relapse.
In pts with failure after high-dose Mtx without prior RT, what are the Tx options?
If the response duration >12 mos, options include: re-treating with high-dose Mtx, other systemic therapy, high-dose therapy with stem cell rescue. If the response duration <12 mos, WBRT or involved field RT with/without chemo, or consider high-dose therapy with stem cell rescue.
What is the typical response rate to salvage WBRT for pts failing initial chemo?
CR 37%–58% and PR 21%–37% (Nguyen PL et al., JCO 2005; Hottinger AF et al., Neurology 2007)
What critical volumes need to be covered with WBRT?
The post retina and CNS down to C2 need to be covered.
What volumes are treated with RT if the pt presents with an ocular primary?
WBRT to C2, + bilat orbits with opposed lats to 36 Gy → CD to WBRT + post retina to 45 Gy
How should AIDS+ PCNSL be treated?
The optimal therapy has not been well defined. High-dose Mtx therapy with steroids and antiretroviral therapy has been shown to offer palliation for up to 12–18 mos. In very select pts, can consider rituximab plus high-dose Mtx. WBRT has historically been the standard Tx, which leads to CR rates of 20%–50%, but survival is still very poor, ∼3.5 mos.
