Treatment/Prognosis Flashcards
What is the Tx paradigm for resectable MPM?
For stages I–III, resectable MPM Tx paradigm, a combined modality approach is preferred:
- EPP or P/D → chemo → hemithorax radiation therapy (RT) or
- Neoadj chemo → EPP or P/D → hemithorax RT
What is removed with an EPP for MPM?
Parietal and visceral pleura, lung, MNs, pericardium, and ipsi diaphragm, with a graft to prevent herniation of abdominal contents through the diaphragmatic defect. Mediastinal nodal dissection should be done.
What is the Tx paradigm for unresectable MPM, clinical stage IV, or sarcomatoid histology?
For the unresectable scenario (or relative contraindication like for sarcomatoid histology), combination chemo, perhaps with cisplatin/pemetrexed (Alimta), and then re-evaluation for Sg. If remains unresectable, continue chemo, and palliative symptomatic therapy.
What % of MPM pts are surgically resectable at Dx?
<5% of pts are surgically resectable at Dx.
What TNM stage of Dz determines surgical resectability using EPP for MPM?
T1–3N0–1. Therefore, mediastinoscopy to r/o N2–N3 Dz will be important.
What are the chemos of choice for the Tx of MPM?
Preferred Tx includes the combination chemo of choice incorporated into trimodality regimens utilizing antifolate agents such as pemetrexed/cisplatin or gemcitabine/cisplatin. Pemetrexed/cisplatin is based on an RCT (Vogelzang NJ et al., JCO 2003) of unresectable MPM pts to cisplatin vs. pemetrexed/cisplatin. There was improved response rate (17% vs. 41%) and survival (9 mos vs. 12 mos) with pemetrexed/cisplatin. This trial led to FDA approval for use in unresectable Dz. Cisplatin/gemcitabine use is based on several phase II studies.
When is a pleurectomy with decortication (P/D) a preferred procedure over EPP in a pt with MPM?
P/D has traditionally been preferred over extrapleural pneumonectomy (EPP) in pts with more advanced Dz (↑ nodal Dz, areas of local invasion), nonepithelioid or mixed histology, and medically high-risk pts, but since there is no evidence to support a survival benefit of EPP, and given the less morbidity of P/D, P/D is increasingly used in place of EPP. Periop mortality is 2%–5%. LF 44%–73% vs. 13%–40% for EPP. It is unclear which operation is sup oncologically and factors such as tumor histology and distribution, pulmonary function, and availability of adj Tx may be of greater importance for the outcomes of pts.
Is there any evidence that EPP offers survival benefit over P/D?
No, there are no randomized comparisons of EPP vs. P/D, and most retrospective series show no significant advantage of EPP over P/D, if not with greater toxicities. A large series from MSKCC (n = 663) (Flores R et al., J Thorac Cardiovasc Surg 2008) comparing EPP (385) to P/D (278) showed greater operative mortality for EPP (7% vs. 4%), but with reduced LR (33% vs. 65%). However MS was 12 mos for EPP vs. 16 mos for P/D (HR 1.4, p <0.001).
What is the mortality rate of EPP? What is the MS for MPM after EPP?
The mortality rate of EPP ranges from 4%–31% (8% at MDACC) and depends largely on the experience of the center and preop selection. MS in most series is 4–20 mos. Rice et al. reported 10.2-mo OS. If IMRT, 14.2 mos and if LN– and epithelioid, 28 mos. (Ann Thorac Surg 2007)
What study supports adj RT after EPP for MPM?
MSKCC phase II trial with hemithorax RT to 54 Gy after EPP improved LC and OS compared to historical controls (Rusch V et al., IJROBP 2003). 2-yr OS was 33%. MS was 34 mos for stages I–II and 10 mos for later stages.
What study supports the role of trimodality therapy for MPM?
Harvard retrospective review (Sugerbaker D et al., J Thorac Cardiovasc Surg 1999) of 183 pts treated with EPP + adj chemo (Cytoxan/Adr/cisplatin [CAP] or carboplatin/Taxol) + RT → adj chemo. Overall, MS was 19 mos; 5-yr OS was 15%. 3 factors predicted for best outcomes: epithelial histology, negative resection margin, and negative extrapleural nodes.
University of Toronto retrospective review (De Perrot M et al., J Clin Oncol 2009): Induction chemo (n = 60) → EPP (n = 45) → Hemithoracic RT to ≥ 50 Gy (n = 30): MS 14 mos, with MS 59 mos and 5-yr DFS 53% if pN0–1.
Name 2 RT techniques used for adj Tx of MPM after EPP.
AP/PA or IMRT to 45–54 Gy, with a boost to 60 Gy for a close/+ margin. Traditional Rx for AP/PA technique: 54 Gy in 1.8 Gy/fx, off-cord at 41.4 Gy. Electrons given concurrently. IMRT is preferred to allow for more conformal high-dose RT. Radiation initiated 3–6 wks after EPP.
Describe the conventional RT field borders for adj RT Tx of MPM after EPP.
Based on Yajnik S et al. (IJROBP 2003): Include scars with bolus in the field and boost if necessary.
Sup: Top of T1
Lat: Flash the skin
Medial: Contralateral edge of vertebral body if MN negative or 1.5–2.0 cm beyond contralateral edge of vertebral body if MN positive for Dz
Inf: Bottom of L2
Need to block critical structures anteriorly and posteriorly from the incidental AP/PA photon beam such as the heart, stomach, and liver and supplement blocked areas with electrons.
An abdominal block to shield liver (right side) or stomach (left side) is present anteriorly and posteriorly throughout Tx with electron supplementation at 1.53 Gy/fx (15% scatter from photon fields under blocks). These blocks extend 1.5 cm from ipsi border of vertebral body to within 2 cm from edge of CW. Blocks are present only where diaphragm abutted the abdominal wall anteriorly/posteriorly, but not where the diaphragm was oblique to the abdominal wall.
For left-sided tumors, the kidney is blocked throughout, and the heart block is present after 19.8 Gy. The spinal cord is blocked after 41.4 Gy by shifting the medial border to the ipsi edge of the vertebral body.
How is IMRT delivered for the adj Tx of MPM?
MDACC experience (Ahamad A et al., IJROBP 2003, 2004), using 13–27 fields with 8–11 angles, with <100 segments/field. Target volume was the entire hemithorax, all surgical clips, all sites of instrumentation, and the ipsi MN; initial dose to 45–50 Gy, with a boost to 60 Gy for a close/+ margin. 2-yr survival was 62%, and 3-yr DFS was 45% for LN–, epithelioid histology. 5 pts with stage I Dz had 3-yr DFS of 100%. Updated outcomes in 86 pts who rcvd IMRT (Gomez DR et al., JTO 2013) showed MS 14.7 mos, 5 grade 5 pulm toxicities. LRR = 16%, DM = 59%.
What is sometimes recommended after a P/D procedure for MPM?
B/c of the high LR rate, adj RT is advocated. At MSKCC, 125 pts were treated with pleurectomy → interstitial RT or EBRT (Gupta V et al., IJROBP 2005). MS was 13.5 mos; 2-yr OS was 23%. Those with epithelioid or earlier-stage Dz did better. <40 Gy, left-sided Dz, use of an implant, or nonepithelioid histology did worse. LC rate was 40%. However, 12 pts developed pneumonitis, 8 pts pericarditis, and 2 pts died from grade 5 toxicity within 1 mo of Tx.
Phase II single arm study (IMPRINT) at MSKCC (Rimner A et al., J Clin Oncol 2016): chemo × 4 cycles (n = 45) → P/D (n = 21) → pleural-based IMRT (50.4 Gy). No grade 4–5 toxicities. MS 23.7 mos, PFS 12.4 mos. Largest prognostic factor was resectability (2-yr OS for resectable Dz 59% vs. 25% for unresectable).
