Lugano April 2018 - European Society for Medical Oncology · 2018. 12. 3. · Everolimus for the...
Transcript of Lugano April 2018 - European Society for Medical Oncology · 2018. 12. 3. · Everolimus for the...
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ESMO Preceptorship Programme
Pulmonary large-cell neuroendocrine carcinoma
causing Cushing’s syndrome
Ioanna Gazouli MD, MSc
Athens General Hospital "Korgialenio-Benakio National Red Cross"
Large-cell neuroendocrine lung cancer– Lugano– April 2018
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ESMO PRECEPTORSHIP PROGRAMME
DISCLOSURE OF INTEREST
None
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ESMO PRECEPTORSHIP PROGRAMME
Case presentation 56 yo Caucasian female, ex-smoker
Medical history:
colon adenocarcinoma (pT3,pN0,M0) moderately differentiated (2 yrs before presentation)
-treated by partial colectomy plus dissection of 24 unaffected lymph nodes plus adjuvant chemotherapy and radiotherapy
-no evidence of recurrent disease up to presentation
2 small rectal polyps, both endoscopically dissected during follow up colonoscopy
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ESMO PRECEPTORSHIP PROGRAMME
Clinical presentation
-fatigue, weakness,
depression
-moon face
-obesity, truncal fat
deposition
-arterial hypertension
(SBP~150mmHg)
-decreased limb muscle
strength (4/5)
-limb edema
Laboratory findings
-hypokaliemia (K+:2.2-2.5mEq/lt) refractory to PO/IV potassium administration
-blood sugar>200mg/dl (HbA1C 5.8)
-CA 19-9:74,468 u/ml
(a-FP 5.6 ng/ml, CEA 16ng/ml)
-24h urine free cortisol: >1,953μg
-evening salivary cortisol: 37μg/dl
Morning values
dexamethasone suppression test
ACTH 501 pg/ml 674 pg/ml
Cortisol 89 mcg/dl 105 mcg/dl
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ESMO PRECEPTORSHIP PROGRAMME
Ectopic Cushing syndrome?
10-20% of ACTH-dependent Cushing
ectopic ACTH sources
NETs (mainly bronchial carcinoids): 3–54.8% (most frequent source in recent pts series)
SCLC: 3.3–50% (most frequent cause in early pts series)
thymic carcinoids: 5–42%
pancreatic NETs: 7.5–25%
Pheochromocytomas: 2.5–25%
medullary thyroid carcinomas: 2–8%
occult tumors: 12–36.5%
(Davi’ et al., 2017)
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ESMO PRECEPTORSHIP PROGRAMME
Work-up
abdominal CT/MRI:
-multiple liver lesions
(up to 1.8cm)
-bilateral adrenal gland
enlargement
thoracic CT:
- bilateral fibroatelectatic
changes in both lungs
-enlarged hilar lymph nodes
(up to 2 cm)
Liver lesions biopsy:
-Morphology
pulmonary large-cell
neuroendocrine carcinoma
with necrosis and
marked mitotic activity
Ki67~40%
-Immunohistochemistry
EMA+, TTF-1+, CEA+, CDX2-
NEN markers: Chromogranin+,
Synaptophysin+, CD56+
ACTH staining…?
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ESMO PRECEPTORSHIP PROGRAMME
Possibly enlightening tests
o 80-90% of NETs
express somatostatin
receptors (Fisseler-Eckhoff and Demes, 2012)
o Pulmonary LNECs
have been shown
in vivo to express
somatostatin receptors
by radionuclide
scintigraphy* (Nocuń et al., 2011, Filosso et al., 2005)
111In-DTPA-octreotide scan
68Galium-dotatate-PET/CT
-Sensitivity and specificity>90%
-more sensitive than CT &
octreoscan
-possible therapeutic implications(Gabriel et al., 2007, Srirajaskanthan et al., 2010,
Deppen et al., 2016)
FDG-PET/CT
-may reveal poorly differentiated
tumours (Oberg et al., 2012)
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ESMO PRECEPTORSHIP PROGRAMME
Treatment and follow up
Patient was started on metyrapone and
spironolactone PO
=>potassium values restored to normal range
Patient was referred to medical oncologist
Anti-neoplastic treatment considered to be of no
benefit
Patient succumbed to her disease ~3mo after
initial presentation
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ESMO PRECEPTORSHIP PROGRAMME
Treatment opportunities…
somatostatin analogs: octreotide iv or lanreotide sc
everolimus: prolonged median PFS (11 vs 3.9mo)
in RADIANT-4, compared to placebo (Yao et al., 2016)
177Lu-DOTATATE: safely administered in pts with
advanced/metastatic pulmonary NET=> objective response in
12/19 pts, symptomatic response in 15/19 pts
1yr OS: 95%, 4yr OS 39% (Parghane et al., 2017)
platinum/cisplatin: (similarly to SCLC) ORR 73% and
OS 16.5mo, superior to NSCLC regimens
- nonetheless LCNEC ≠ SCLC
-LCNEC’s chemosensitivity is not well established (Hiroshima and Mino-Kenudson, 2017)
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ESMO PRECEPTORSHIP PROGRAMME
Remarkable points
Liver metastatic lesions with pulmonary large cell carcinoma features, in the absence of prominent lung primary
➢ NETs account for 1% of tumours of occult primary
➢ No primary is identified in 13% of NETs
CA19-9 elevation with no evidence of GI malignant disease, recurrent or new primary
➢ Could it be a rectal NET? 29% of all GEP-NETs (Rodrigues et al.,2015)
➢ Could it be a colonic LCNEC? reported incidence 0.2% (Bernick et al.,2004)
2 distinct malignancies in the same patient
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ESMO PRECEPTORSHIP PROGRAMME
Literature1. Davi’, M., Cosaro, E., Piacentini, S., Reimondo, G., et al. (2017). Prognostic factors in ectopic Cushing’s syndrome due to neuroendocrine tumors: a multicenter
study. European Journal of Endocrinology, 176(4), pp.451-459.
2. Sehgal, R., Mchayleh, W., Reider, J., Cheema, A. and Ramanathan, R. (2010). Adenocarcinoma of Colon Presenting As Cushing's Syndrome. Journal of Clinical
Oncology, 28(8), pp.e126-e127.
3. Baldvinsdottir, B., Jonasson, J., Agnarsson, U. and Sigurjonsdottir, H. (2014). Ectopic Cushing Syndrome Due to Colon Cancer With Dual Morphology. Journal of
Endocrinology and Metabolism, 4(5-6), pp.153-154.
4. Onishi R, Sano T, Nakamura Y, et al: Ectopic adrenocorticotropin syndrome associated with undifferentiated carcinoma of the colon showing multidirectional
neuroendocrine, exocrine, and squamous differentiation. Virchows Arch 427:537-541,1996
5. Fisseler-Eckhoff, A. and Demes, M. (2012). Neuroendocrine Tumors of the Lung. Cancers, 4(3), pp.777-798.
6. Nocuń, A., Chrapko, B., Gołębiewska, R., Stefaniak, B. and Czekajska-Chehab, E. (2011). Evaluation of somatostatin receptors in large cell pulmonary
neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy. Nuclear Medicine Communications, 32(6), pp.522-529.
7. Filosso, P., Ruffini, E., Oliaro, A., Rena, O., Casadio, C., Mancuso, M., Turello, D., Cristofori, R. and Maggi, G. (2005). Large-cell neuroendocrine carcinoma of the
lung: A clinicopathologic study of eighteen cases and the efficacy of adjuvant treatment with octreotide. The Journal of Thoracic and Cardiovascular Surgery, 129(4),
pp.819-824.
8. Gabriel, M., Decristoforo, C., Kendler, D., Dobrozemsky, G., Heute, D., Uprimny, C., Kovacs, P., Von Guggenberg, E., Bale, R. and Virgolini, I. (2007). 68Ga-DOTA-
Tyr3-Octreotide PET in Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and CT. Journal of Nuclear Medicine, 48(4), pp.508-518.
9. Srirajaskanthan, R., Kayani, I., Quigley, A., Soh, J., Caplin, M. and Bomanji, J. (2010). The Role of 68Ga-DOTATATE PET in Patients with Neuroendocrine Tumors
and Negative or Equivocal Findings on 111In-DTPA-Octreotide Scintigraphy. Journal of Nuclear Medicine, 51(6), pp.875-882.
10. Deppen, S., Blume, J., Bobbey, A., Shah, C., Graham, M., Lee, P., Delbeke, D. and Walker, R. (2016). 68Ga-DOTATATE Compared with 111In-DTPA-Octreotide
and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. Journal of Nuclear
Medicine, 57(6), pp.872-878.
11. Oberg, K., Hellman, P., Ferolla, P. and Papotti, M. (2012). Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment
and follow-up. Annals of Oncology, 23(suppl 7), pp.vii120-vii123.
12. Yao, J., Fazio, N., Singh, S., Buzzoni, R., Carnaghi, C., Wolin, E., Tomasek, J., Raderer, M., Lahner, H., Voi, M., Pacaud, L., Rouyrre, N., Sachs, C., Valle, J., Fave,
G., Van Cutsem, E., Tesselaar, M., Shimada, Y., Oh, D., Strosberg, J., Kulke, M. and Pavel, M. (2016). Everolimus for the treatment of advanced, non-functional
neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. The Lancet, 387(10022), pp.968-977.
13. Hiroshima K, Mino-Kenudson M. Update on large cell neuroendocrine carcinoma. Translational Lung Cancer Research. 2017;6(5):530-539.
14. Parghane, R., Talole, S., Prabhash, K. and Basu, S. (2017). Clinical Response Profile of Metastatic/Advanced Pulmonary Neuroendocrine Tumors to Peptide
Receptor Radionuclide Therapy with 177Lu-DOTATATE. Clinical Nuclear Medicine, 42(6), pp.428-435.
15. Bernick PE, Klimstra DS, Shia J, et al. Neuroendocrine carcinomas of the colon and rectum. Dis Colon Rectum. 2004;47:163–9.
16. Rodrigues Â, Castro-Poças F, Pedroto I. Neuroendocrine Rectal Tumors: Main Features and Management. GE Portuguese Journal of Gastroenterology.
2015;22(5):213-220. doi:10.1016/j.jpge.2015.04.008.
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ESMO Preceptorship Programme
Thank you for your attention!