Treatment/Prognosis Flashcards
What is the most important modality in the management of thymomas?
Sg is the mainstay of Tx, with complete resection being the primary goal. The outcome is fully dependent on the extent and completeness of the resection, regardless of stage or histology. Surgical clips can help identify areas difficult to resect or possible residual Dz. It may even be reasonable to resect pleural mets since prolonged survival is possible.
What is the usual approach for the surgical management of thymomas?
Median sternotomy, but more extensive resections may be required depending on the stage at presentation, including partial or total pneumonectomy or pericardiectomy.
In a thymoma pt with MG, what should be done preoperatively?
Signs + Sx should be controlled medically prior to undergoing surgical resection.
How is thymic carcinoma generally managed?
If possible, max Sg → CRT postoperatively. If inoperable, consider induction therapy with chemo, RT, or combination CRT.
When is adj radiotherapy a reasonable indication for the management of thymic malignancies?
Adj radiotherapy should be considered with AJCC stages II–III (Masaoka stage III), ≥ R1 resection, or any thymic carcinoma.
Is adj radiotherapy necessary for an AJCC stage I (Masaoka stage I or II) thymic malignancy after complete resection?
Masaoka stage I thymoma pts likely do not benefit from PORT; however the decision making is more controversial for Masaoka stage II pts. The Tx paradigm that some institutions have adopted is to do adj radiotherapy for more aggressive histology, specifically Masaoka stage IIA + WHO B3 histology or Masaoka stage IIB + WHO B2–B3 histology given that these combinations purport higher risk for recurrence. (Geo et al., J Thorac Oncol 2013; Chen et al., IJROBP 2010)
A Chinese trial randomized 29 Masaoka stage I thymoma pts to Sg-alone vs. Sg + PORT and failed to show differences in outcome as pts had 92% vs. 88% survival at 10 yrs, respectively. (Zhang et al., Chin Med J 1999)
Tx has been historically recommended for Masaoka stage II based on a classic review (Curran W et al., JCO 1988) that included 103 pts with thymomas, finding that pts without PORT had ↑ LR (6 of 19 pts for stage II) vs. no LR in PORT (0 of 1 pt for stage II, 0 of 4 pts for stage III).
However, most recently, Massachusetts General Hospital (Mangi A et al., Ann Thorac Surg 2002) and Japanese series (Haniuda M et al., Ann Surg 1996) showed that PORT may not be necessary after complete resection for stage II pts. Haniuda et al. specifically demonstrated that stage II thymoma with macroscopic adherence to the pleura did benefit from PORT (LR 36% vs. 0%), but PORT was not useful for microscopic invasion of the pleura or pericardium. (Ann Surg 1996)
Meta-analysis (Korst RJ et al., Ann Thorac Surg 2009): 1981–2008 systematic review of 13 studies, 592 pts, ∼42% had Sg + PORT. The LR rate did not benefit from PORT for stages II–III thymoma (OR 0.87 for both stages II–III, p = 0.69).
SEER database (Forquer et al., IJROBP 2009): 901 pts from 1973–2005; 92% thymoma, 8% TC; localized Dz in 274 pts, regional Dz in 626 pts. 5-yr OS benefited from Sg + PORT for regional Dz (76% vs. 66%, p = 0.01); for localized Dz, Sg alone was more favorable (98% vs. 91% [PORT], p = 0.03).
JART database (Omasa M et al., Cancer 2015): A large series of 2,835 pts from 32 Japanese institutions 1991–2010 had Sg, 32% had PORT. PORT for Masaoka stage II–III thymoma showed no benefit in RFS or OS. PORT for stage II–III thymic carcinoma showed better RFS but not OS.
National Cancer Database analysis (Jackson et al., J Thorac Oncol 2017): One of the largest series included 4,056 pts of which 49% rcvd PORT. Improved OS seen with PORT, specifically for thymoma Masaoka stage IIB or positive margins. Stage I–IIA thymomas did not reach statistical significance. PORT also associated with improved OS for thymic carcinomas.
What should the postop target volume include?
The postop target volume should include the entire bed of resection and any involved organs. It is imperative to have a preop CT scan available to help delineate tumor bed volumes. Also, information from operative and pathology reports may help determine areas that might have had adherent, invasive Dz. For high-risk Dz, consider elective LN coverage.
What are the RT doses used for the postop management of thymic malignancies?
Depends on the extent of resection:
If R0: 45–54 Gy
If R1: 55–60 Gy
If R2: 60–70 Gy
Is there a role for proton radiation therapy for Tx of thymic malignancies?
Reasonable to consider given organs at risk, though there is very limited data.
A small study of 4 thymoma pts in the adj setting demonstrated favorable clinical toxicity with grade 1 (n = 3) and grade 2 (n = 2) radiation dermatitis. Proton plans were associated with sparing of organs at risk, specifically lower mean lung (4.6 vs. 8.1 Gy), esophageal (5.4 vs. 20.6 Gy), and heart (6.0 vs. 10.4 Gy) doses when compared to analogous IMRT plans. (Parikh et al., Clin Lung Cancer 2016)
A prospective study of 27 thymoma and thymic carcinoma cases in the adj and definitive setting using proton radiation therapy demonstrated favorable LC (100% at 2 yrs) and OS (94% at 3 yrs). No pts experienced grade ≥3 toxicity. Acute grade 2 toxicities were limited to dermatitis (37%), fatigue (11%), esophagitis (7%), and pneumonitis (4%). (Vogel et al., Radiother Oncol 2016)
When should postop concurrent chemo be considered with RT for the management of thymic malignancies?
Per NCCN 2018, thymoma with gross residual Dz (R2 resection) or thymic carcinoma with R1–R2 resection.
What are some management approaches for unresectable thymic tumors?
Management approaches for unresectable thymic tumor:
Induction chemo → RT only
Induction chemo → Sg → PORT
Induction RT/CRT → Sg → ± more RT
What are the results of definitive RT for unresectable thymic tumors?
RT can be used as the sole modality, with 5-yr OS 50%–87%. Sg should be done whenever possible, however, since resectability is still the most important prognostic factor.
Given the good response rates seen with platinum-based chemo, what is the current preferred Tx paradigm for unresectable thymic malignancy?
Unresectable thymic malignancy Tx paradigm:
Chemo → RT (no Sg). (Loehrer PJ et al., JCO 1997) Cisplatin/doxorubicin/cyclophosphamide (PAC) 2–4 cycles → RT to ≥54 Gy to primary + regional LN. 5-yr OS was 53%.
Chemo → Sg (if possible) → PORT. (MDACC: Shin DM et al., Ann Int Med 1998) 3 cycles induction chemo (Cytoxan/Adriamycin/cisplatin [CAP] + prednisone) → max Sg → RT. 7-yr f/u showed 100% OS and 73% DFS.
What RT dose can be used for the neoadj management of unresectable thymomas?
24–30 Gy with chemo → Sg → then consideration for more RT depending on resection status.
What are the 1st-line combination chemo regimens used for the management of thymic malignancies?
CAP +/- prednisone; VP-16/ifosfamide/cisplatin (VIP); cisplatin/VP-16 (EP); carboplatin/Taxol; cisplatin/Adriamycin/vincristine/Cytoxan (ADOC); Cytoxan/Adriamycin/vincristine/prednisone (CHOP)
