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Histologic Remission following Neoadjuvant Immunotherapy in a Patient with Lynch-Syndrome and Primarily Unresectable Relapse of Rectum Carcinoma.

Abstract Clinical History A 43-year-old male patient was diagnosed to have rectum carcinoma cT4N2M0 with underlying Lynch-Syndrome. After initializing neoadjuvant radio-chemotherapy followed by operation, the patient presents with an extensive locoregional relapse within a short time. In order to achieve resectability, a second line treatment with FOLFOXIRI protocol in addition to Bevacizumab was conducted. However, after completing six cycles of this intensiv treatment protocol, the tumour showed further progression. Clinical Course Having no evidence of distance metastasis, we decided to initiate off-label use of Pembrolizumab, a PD-1-receptor inhibitor. Clinical symptoms decreased rapidly and after receiving six cycles, PET/CT imaging showed regression. The side effects were limited to subclinical autoimmune thyroiditis. After re-operation no evidence of malignancy were found in the resectates of exenteration of the pelvis. Currently the patient is capable of working with only limited symptoms. Conclusion Pembrolizumab offers new treatment options for patients with DNA-repair-deficiency mismatch, e. g. Lynch-Syndrome. A phase II study already showed effectiveness in this particular group of patients. The striking and unexpected histo-pathologic results showing full remission should draw attention to the use of Pembrolizumab in neoadjuvant settings.
PMID
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Authors

Mayor MeshTerms

Colorectal Neoplasms, Hereditary Nonpolyposis

Rectal Neoplasms

Keywords
Journal Title deutsche medizinische wochenschrift (1946)
Publication Year Start




PMID- 28564739
OWN - NLM
STAT- MEDLINE
DA  - 20170531
DCOM- 20170622
LR  - 20170622
IS  - 1439-4413 (Electronic)
IS  - 0012-0472 (Linking)
VI  - 142
IP  - 11
DP  - 2017 Jun
TI  - [Histologic Remission following Neoadjuvant Immunotherapy in a Patient with
      Lynch-Syndrome and Primarily Unresectable Relapse of Rectum Carcinoma].
PG  - 842-846
LID - 10.1055/s-0043-101212 [doi]
AB  - Clinical History A 43-year-old male patient was diagnosed to have rectum
      carcinoma cT4N2M0 with underlying Lynch-Syndrome. After initializing neoadjuvant 
      radio-chemotherapy followed by operation, the patient presents with an extensive 
      locoregional relapse within a short time. In order to achieve resectability, a
      second line treatment with FOLFOXIRI protocol in addition to Bevacizumab was
      conducted. However, after completing six cycles of this intensiv treatment
      protocol, the tumour showed further progression. Clinical Course Having no
      evidence of distance metastasis, we decided to initiate off-label use of
      Pembrolizumab, a PD-1-receptor inhibitor. Clinical symptoms decreased rapidly and
      after receiving six cycles, PET/CT imaging showed regression. The side effects
      were limited to subclinical autoimmune thyroiditis. After re-operation no
      evidence of malignancy were found in the resectates of exenteration of the
      pelvis. Currently the patient is capable of working with only limited symptoms.
      Conclusion Pembrolizumab offers new treatment options for patients with
      DNA-repair-deficiency mismatch, e. g. Lynch-Syndrome. A phase II study already
      showed effectiveness in this particular group of patients. The striking and
      unexpected histo-pathologic results showing full remission should draw attention 
      to the use of Pembrolizumab in neoadjuvant settings.
CI  - (c) Georg Thieme Verlag KG Stuttgart . New York.
FAU - Micheel, Anita
AU  - Micheel A
AD  - Bundeswehrkrankenhaus Berlin, Abteilung fur Innere Medizin, Berlin.
FAU - Aigner, Felix
AU  - Aigner F
AD  - Charite - Universitatsmedizin Berlin, Chirurgische Klinik, Campus Virchow
      Klinikum, Berlin.
FAU - Henke, Oliver
AU  - Henke O
AD  - Bundeswehrkrankenhaus Berlin, Abteilung fur Innere Medizin, Berlin.
LA  - ger
PT  - Journal Article
TT  - Histologische Vollremission nach neoadjuvanter Immuntherapie bei einem Patienten 
      mit Lynch-Syndrom und primar inoperablem Rezidiv eines Rektumkarzinoms.
DEP - 20170531
PL  - Germany
TA  - Dtsch Med Wochenschr
JT  - Deutsche medizinische Wochenschrift (1946)
JID - 0006723
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - Antineoplastic Agents/therapeutic use
MH  - *Colorectal Neoplasms, Hereditary Nonpolyposis/pathology/therapy
MH  - Humans
MH  - Immunotherapy
MH  - Male
MH  - Neoadjuvant Therapy
MH  - Neoplasm Recurrence, Local
MH  - Off-Label Use
MH  - *Rectal Neoplasms/pathology/therapy
MH  - Recurrence
COI - Disclosure The authors report no conflicts of interest in this work.
EDAT- 2017/06/01 06:00
MHDA- 2017/06/24 06:00
CRDT- 2017/06/01 06:00
AID - 10.1055/s-0043-101212 [doi]
PST - ppublish
SO  - Dtsch Med Wochenschr. 2017 Jun;142(11):842-846. doi: 10.1055/s-0043-101212. Epub 
      2017 May 31.