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ESMO Preceptorship Programme
Possible immune-related pneumonitis after
radiotherapy
Miguel Garcia Pardo de Santayana
Hospital Gregorio Marañon, Madrid, Spain
Immuno-Oncology - Zurich (Glattbrugg), 2-3.11.2018
ESMO PRECEPTORSHIP PROGRAMME
Conflicts of interest
� None. I declare that there are no financial conflicts
of interest with regard to this work
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� Woman, seventyyears old
� PS= 1
� Current smoker
� Diagnosis of lungadenocarcinoma stage IVA in 2013
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� She received:
– Carboplatin + paclitaxel + bevacizumab. PFS 9months
– Carboplatin + pemetrexed. PFS 9months
– Vinorelbine. PFS 3months
– Nivolumab as fourth line treatment with Partial Response.
PFS 12months
– Docetaxel. PFS 3months
October 2016: Phase I/II Clinical Trial (ICIs combination)
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� Started October 2016
� Stable disease. 12
cycles, until July 2017
(PFS 9 months).
� July 2017: palliative
thoracic radiotherapy
for minor local
progression, and
continue treatment
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� Long survivor patient (> 4 years of advanced disease)
� Re-treatment with immunotherapy
� No extrathoracic metastases
� Palliative thoracic radiotherapy for control of local
progression in oligometastatic disease
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� October 2017:
pneumonitis
– Asymptomatic
– Radiation pneumonits?
– ICIs are suspended
– Methylprednisolone 1mg /
kg / day
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� Symptoms rapidly
progressed during the 2
weeks after the
diagnosis:
– Fever
– Shortness of breath
� She was admitted to
Medical Oncology Unit
ESMO PRECEPTORSHIP PROGRAMME
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� We rule out infectious causes (BAL cultures included)
� Covered with broadspectrum antibiotics
� High dose methylprednisolone
� We added Infliximab 5mg/kg iv with no improvement
� She finally died 4 weeks after the diagnosis of pneumonitis
ESMO PRECEPTORSHIP PROGRAMME
Images
Week 1 Week 3 Week 4
ESMO PRECEPTORSHIP PROGRAMME
Histopathology
Chronic restrictive pulmonary disease of morphological pattern type: Nonspecific interstitial pneumonia (NSIP), with bilateral diffuse pulmonary involvement.
ESMO PRECEPTORSHIP PROGRAMME
Discussion
� Was thoracic radiotherapy the best option, or were
we too aggressive?
� Do you agree this is a immune-related
pneumonitis? Did the radiotherapy have a synergy
effect in the toxicity?
� What could we have done better? Is infliximab the
best option? Did we add infliximab too late?
ESMO PRECEPTORSHIP PROGRAMME
Discussion
� Combination of immune checkpoint inhibitors and radiotherapy: abscopal effect?
– Radiotherapy (RT) is known to activate several key elements of the immune response and can prime the immune response2,3,4
– However, uncertainties remain regarding a potential synergy resulting in increased toxicities
– Effects of concomitant ICIs with thoracic radiotherapy on pulmonary toxicities is not currently known4
– A particular attention should be paid to the diagnosis and management of these new toxicities associated with immunotherapy specifically in association with radiotherapy4
ESMO PRECEPTORSHIP PROGRAMME
References1. Haanen JBAG, Carbonnel F, Robert C, Kerr K, Peters S, Larkin J, Jordan K.
Management of toxicities from immunotherapy: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2017; 28:
119-142
2. Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint
blockade activate non-redundant immune mechanisms in cancer. Nature 2015;
520: 373–377
3. Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer
immunotherapy. JAMA Oncol 2015;1: 1325–1332.
4. Louvel G, Bahleda R, Ammari S, et al. Immunotherapy and pulmonary toxicities:
can concomitant immune-checkpoint inhibitors with radiotherapy increase the risk
of radiation pneumonitis? Eur Respir J 2018; 51: 1701737
ESMO Preceptorship Programme
Thanks for your attention!