systemic therapy of thymic malignancies€¦ · journal of thoracic oncology. 5(10):s260-s265,...
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Systemic therapy of Thymic Malignancies
Tim Benepal
Consultant Medical Oncologist
St Georges Hospital
October 2018
What is it ?
2
What does it do ?
3
+ve
Selection
-ve
Selection
AIREImmature
T-Cells
Mature
T-Cells
Cell 2016 166, 582-595DOI: (10.1016/j.cell.2016.06.024)
Copyright © 2016 The Authors Terms and Conditions
Problem 1
5
Copyright © 2011 Journal of Thoracic Oncology. Published by Lippincott Williams & Wilkins. 6
Engels, Eric A.
Journal of Thoracic Oncology. 5(10):S260-S265, October 2010.
doi: 10.1097/JTO.0b013e3181f1f62d
What exactly does the word Thymoma mean ?
Table 1
TABLE 1. World Health Organization (WHO) Pathologic Classification of Thymoma
Copyright © 2011 Journal of Thoracic Oncology. Published by Lippincott Williams & Wilkins. 8
The Management of Thymoma: A Systematic Review and Practice Guideline
Falkson, Conrad B.; Bezjak, Andrea; Darling, Gail; Gregg, Richard; Malthaner, Richard; Maziak, Donna E.; Yu, Edward; Smith, Christopher A.; McNair, Sheila; Ung, Yee C.; Evans, William K.; the Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-Based CareJournal of Thoracic Oncology. 4(7):911-919, July 2009.doi: 10.1097/JTO.0b013e3181a4b8e0
◆Increasing proportion of lymphocytes with increasing pathological Subtype
◆Thymic carcinoma no lymphocytes , but invasive epithelial cells
9
Is there a staging system ?
Clinical Presentation ?
The Rule of Thirds?
13
Figure 1
FIGURE 1. Fifty-seven-year-old previously healthy man imaged with a chest radiograph after a motor vehicle accident. Posterior-anterior (A) chest radiograph demonstrates a mass (curved arrow) abutting and inseparable from the heart confirmed to be in the anterior mediastinum (black arrows) on the lateral chest radiograph (B). Contrast-enhanced chest computed tomography (CT) (C) revealed a 12 cm mass (T) compressing the lateral wall of the right ventricle. Biopsy confirmed this to be a thymoma. H, heart.
Copyright © 2011 Journal of Thoracic Oncology. Published by Lippincott Williams & Wilkins. 14
Imaging Thymoma
Marom, Edith M.
Journal of Thoracic Oncology. 5(10):S296-S303, October 2010.
doi: 10.1097/JTO.0b013e3181f209ca
Figure 3
FIGURE 3. Sixty-one-year-old woman imaged for staging of a newly discovered early breast cancer. Posterior-anterior chest radiograph (A) shows thickening of the anterior junction line (black arrowheads) confirmed on the lateral chest radiograph (B) to represent an anterior mediastinal mass (curved white arrow) anterior to but separate from the ascending aorta (black arrowhead). Contrast-enhanced chest computed tomography (CT) (C) confirmed the presence of a well-demarcated lobulated anterior mediastinal mass (straight white arrow) confirmed at surgery to represent an invasive thymoma (stage II).
Copyright © 2011 Journal of Thoracic Oncology. Published by Lippincott Williams & Wilkins. 15
Imaging Thymoma
Marom, Edith M.
Journal of Thoracic Oncology. 5(10):S296-S303, October 2010.
doi: 10.1097/JTO.0b013e3181f209ca
Thymoma Associated Myasthenia Gravis
◆ 1/3 Patients with Thymomas
◆ Never occurs in thymic carcinomas
◆ Is predominantly associated with Ab to Ach receptors
◆Increases with pathological subtype
16Thomas C, JCO Vol 17, No 7 (July), 1999: pp 2280-2289
Immune DysfunctionAcute Pericarditis
Addisons Disease
Agranulocytosis
Alopecia Areata
Cushings
Haemolytic Anaemia
Limbic Encephalitis
Myocarditis
Neuromyotonia
Nephrotic Syndrome
Panhypopituitarism
Pernicious Anaemia
Polymyosotis
Rheumatiod Arthritis
Sarcoidosis
Scleroderma
Sensorimotor Radiculopathy
Stiff persons Syndrome
Thyroiditis
Ulcerative Colitis
17Thomas C, JCO Vol 17, No 7 (July), 1999: pp 2280-2289
Problem 2
18
The Role of Surgery?
19
The Role of DXT?
20
What about the traditional poisons?
THYMOMA
THYMIC CARCINOMA
24
Carbo/Taxol in Thymic Malignancy
S
T
R
A
T
I
F
Y
Thymoma
Thymic
Carcinoma
Carboplatin AUC 6
Paclitaxel 225 mg/m2
Q21 x 646 patients 7 years
PFS/OS
Signal Transduction Pathways Controlled by the Activation of EGFR
Ciardiello F, Tortora G. N Engl J Med 2008;358:1160-1174
Table 1
TABLE 1. Studies Reporting EGFR Expression by Immunohistochemistry in Thymic Malignancies
Copyright © 2011 Journal of Thoracic Oncology. Published by Lippincott Williams & Wilkins. 27
Thymic Tumors: Relevant Molecular Data in the Clinic
Girard, Nicolas
Journal of Thoracic Oncology. 5(10):S291-S295, October 2010.
doi: 10.1097/JTO.0b013e3181f209b9
EGFR Mutations in Thymic Malignancies
• Nearly 200 tumours analysed in the literature
• 3 patients mutations
• 1 reponse to gefitinib
28
EGFR
Mutation
Exon
Thymoma1 L858R Exon 21
Thymoma1 G863D Exon 21
Thymic 2*
Carcinoma* Gefitinib
G719A
L858R
Exon 18
Exon 21
1 Yoh K, Lung Cancer 2008;19:1361-1362
2 Yamaguchi H, Lung Cancer 2006;52:261-262
Rare Cancer
Becomes Front
Page News
C-KIT Expression in Thymic tumours
TABLE 2. Studies Reporting KIT Expression in Thymic Tumors
Copyright © 2011 Journal of Thoracic Oncology. Published by Lippincott Williams & Wilkins. 30
Thymic Tumors: Relevant Molecular Data in the Clinic
Girard, Nicolas
Journal of Thoracic Oncology. 5(10):S291-S295, October 2010.
doi: 10.1097/JTO.0b013e3181f209b9
Sunitinib in thymic tumoursThomas et al, The Lancet Oncology, VOLUME 16, ISSUE 2, P177-186, FEBRUARY 01, 2015
Figure 2. Survival in patients with
thymoma and thymic carcinoma
(A)Progression-free survival and (B)
overall survival.
41 patients
26 Thymic Carcinoma RR 26%
16 Thymoma RR 6%
Lung Cancer. 2016 Jul;97:99-104. doi:
10.1016/j.lungcan.2016.04.024. Epub 2016 May 3.
Sunitinib in patients with advanced thymic
malignancies: Cohort from the French RYTHMIC
network.
Remon J1, Girard N2, Mazieres J3, Dansin E4, Pichon
E5, Greillier L6, Dubos C7, Lindsay CR1, Besse B8.
28 patients
RR 22%
Clinical responses to Sunitinib
Rajan ASCO 2017
PD-1 Expression in Thymic TumoursFig 1. CD8 semiquantitative scoring scheme: Scoring for each specimen took into account the heterogeneity of TIL densities throughout the entire section of each tumor, here showing representative images of 1+ (A), 2+ (B) and 3+ (C) scores for CD8 representing numbers of immuno-labeled TILs per 40X microscopic field in
the range of 1–30, 31–100, and >100, respectively.
Arbour KC, Naidoo J, Steele KE, Ni A, Moreira AL, et al. (2017) Expression of PD-L1 and other immunotherapeutic targets in thymic
epithelial tumors. PLOS ONE 12(8): e0182665. https://doi.org/10.1371/journal.pone.0182665
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182665
Arbour KC, Naidoo J, Steele KE, Ni A, Moreira AL, et al. (2017) Expression of PD-L1 and other immunotherapeutic targets in thymic
epithelial tumors. PLOS ONE 12(8): e0182665. https://doi.org/10.1371/journal.pone.0182665
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182665
Arbour KC, Naidoo J, Steele KE, Ni A, Moreira AL, et al. (2017) Expression of PD-L1 and other immunotherapeutic targets in thymic
epithelial tumors. PLOS ONE 12(8): e0182665. https://doi.org/10.1371/journal.pone.0182665
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182665
Rajan ASCO 2017
Rajan ASCO 2017
Rajan ASCO 2017
Pembrolizumab in Thymic Carcinoma
Giaconne et al The Lancet Oncology VOLUME 19,
ISSUE 3, P347-355, MARCH 01, 2018
Conclusions
• Rare
• Chemo sensitive- Pt/Anthracycline/Carbo Taxol
• Sunitinib active in Thymic Carcinomas
• Role of Immunotherapy
• Surgery when indicated
• PORT more valuable than we think
• DATABASE
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