advanced thoracic net clinical cases: prrt in lung nen...advanced thoracic net clinical cases: prrt...
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Advanced Thoracic NET Clinical Cases:
PRRT in Lung NEN
Ulrike Garske-Román MD, PhD
ESMO Preceptorship Prague 2017
Bronchial carcinoidsCycle 1 March 2009 Cycle 7 Oct 2010
Ulrike Garske-Román
Cycle 1 2 3 45 6 7
TTP 71 MonthsSurvival 80+ Months
8e december 2012
Bronchial carcinoids: 13 patients with
advanced disease
Median time to
progression 44
months
Median overall
survival 44
months
Ulrike Garske-Román, Dissertation Uppsala University 2012
Bronchial carcinoids
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Bronchial carcinoids
Median Time to Progression 44 Months
Median Overall Survival 44 Months
Lung NET& PRRT• Sabet, Haug, Eiden et al JNM May 2014,
supplement 1, 394
• 22 patients Bronchial NETs G1&2: 177Lu-DOTA-
octreotate 4 cycles, intended 3 months interval,
mean activity 7,8 GBq
• PFS 31, median OS 42
This publication should have been
mentioned in this place:• Long-term results of PRRT in advanced bronchopulmonary
carcinoid
• Eur J Nucl Med Mol Imaging (2016) 43:441–452• Mariniello, A. Bodei, L, Tinelli, C, Baio, SM, Gilardi, L, Colandrea,
M, Papi, S, Valmadre, G, Fazio, N, Galetta, D, Paganelli, G, Grana, MC
• Retrospective analysis of 114 patients with advanced stages of BPC treated in Milan from 1997-2012, follow-up until 2014 with three different PRRT protocols
• 90Y-DOTATOC vs 177Lu-DOTATATE vs 90Y-DOTATOC+177Lu-DOTATATE
• Rating of objective responses, overall survival (OS) and andprogression-free survival (PFS)
Long-term results of PRRT in advanced bronchopulmonary carcinoidEur J Nucl Med Mol Imaging (2016) 43:441–452
continued
• Median OS (evaluated in 94 patients) 58.8 months
• Median PFS 28 months
• The 177Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses+ minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS.
• The 90Y- DOTATOC+177Lu-DOTATATE protocol provided the highest response rate (38.1 %).
• Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival.
• Patients treated with 90Y- DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity.
Long-term results of PRRT in advancedbronchopulmonary carcinoid
Eur J Nucl Med Mol Imaging (2016) 43:441–452, continued
• Conclusion:
• PRRT proved to be promising in prolonging survival
and delaying disease progression
• Despite the potential selection biases, considering
the risk-benefit ratio, 177Lu-DOTATATE monotherapy
seems the best option for PRRT.
• Our results indicate that the use of PRRT in earlier
stages of the disease could provide a more
favorable outcome.
Leukemia and PRRT: Uppsala experience
• 485 patients with data (++)
• 6 leukemia (bony mets in at least 5)
• 1 ALL: Lung NET, BM mets +, previous temozolomide
• 1 CML: SI-NET(unconfirmed) G2/G3; BM mets +++
• previous temozolomide (4 mo)
• 4 AML:
• 1 Lung: Paraplatin Vepesid before, 3 yearsTemozolomide after PRRT,
• 2 SI-NET ( 1 no chemo; BM mets ++, 1 unknowntreatment),
• 1 EPT (Strepto/ 5FU: intolerance r//t declined kidneyfunction
• Absorbed BM doses: 0.2-0.5 Gy blood dose;
• 0.47-0.64 Gy total accumulated dose
This publication should have been mentioned in this place:
• Eur J Nucl Med Mol Imaging (2015) 42:5–19
• Long-term tolerability of PRRT in 807 patients with
neuroendocrine tumours: the value and limitations
of clinical factors• Bodei, L, Kidd, M, Paganelli, G, Grana, CM, Drozdov, I, Cremonesi, M,
Lepensky, C, Kwekkeboom, DJ, Baum, RP, Krenning, EP, Modlin, IM
• 807 patients studied at IEO Milan (1997-2013)
• 177Lu: 34.4%/ 90Y: 44.4%7 177Lu&90Ycombined (19.5%)/ 2% PRRT
combined with other agents
• Results: Treatment with 90Y and 90Y+177Lu was more likely to result in
nephrotoxicity than treatment with 177Lu alone (33.6 %, 25.5 % and
13.4 % of patients, respectively; p < 0.0001)
Eur J Nucl Med Mol Imaging (2015) 42:5–19continued
• Results: Nephrotoxicity (any grade), transient and persistent, occurred in 279 patients (34.6 %) and was severe (grade 3+4) in 12 (1.5 %).
• …..
• Myelodysplastic syndrome occurred in 2.35 % of patients…... Platelet toxicity grade (…..) and longer PRRT duration (…..) were relevant. Acute leukaemia occurred in 1.1 % of patients (….).
• Myelodysplastic syndrome occurred in 2.35 % of patients … Platelet toxicity grade ….and longer PRRT duration …….were relevant. Acute leukaemia occurred in 1.1 % of patients.
• Conclusion Identified risk factors provide a limited (<30 %) risk estimate even with target tissue dosimetry.
• These data strongly suggest the existence of unidentified individual susceptibilities to radiation-associated disease.
PRRT and chemotherapy• More data need to be collected regarding late
bone marrow toxicity
• Combination of especially alkylating agents or
cisplatinum and radiation (PRRT) reported
problematic
• Brieau et al 2016 (20% 4/20 3 MDS,1 AML) all had
had alkylating agents
• Kesavan et al 2014 (2/65 patients (3%) PRRT with
tem/cap) MDS
Risk factors and open questions
• Presence of BM mets: Can they increase the
stochastic risk? What about small volume disease in
skeleton?
• Early hematotoxicity after treatment: indicator ?
• Bone marrow absorbed doses? Blood doses?
Accumulated activity?
Getting back to PRRT in lung NETs……
• Promising
• A place for 1st line therapy in progressive patients
with advanced disease?
• A randomised study would be nice: against …..???
Open questions!
• The future is yours to ask the
right questions to provide
new concepts and to come
up with new ideas!
The aim of therapy
• Thank you for your attention!
• Hopefully, your stay in
Prague was fruitful!