Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer: study design.
BACKGROUND
Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires.


METHODS
This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived ≥8 years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses.


CONCLUSIONS
Evaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors.


BACKGROUND
Registered at the Dutch Trial Registry (NTR): NTR4961 .
Department of Gastroenterology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Lisanne S
LS
Rigter
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Manon C W
MC
Spaander
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Leon M
LM
Moons
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Tanya M
TM
Bisseling
Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Berthe M P
BM
Aleman
Department of Hematology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jan Paul
JP
de Boer
Department of Hematology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Pieternella J
PJ
Lugtenburg
Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Cecile P M
CP
Janus
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
Eefke J
EJ
Petersen
Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Judith M
JM
Roesink
Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
John M M
JM
Raemaekers
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Richard W M
RW
van der Maazen
Department of Gastroenterology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Annemieke
A
Cats
Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Eveline M A
EM
Bleiker
Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Petur
P
Snaebjornsson
Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Beatriz
B
Carvalho
Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Iris
I
Lansdorp-Vogelaar
Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Katarzyna
K
Jóźwiak
Division of Biological Stress Response, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Hein
H
Te Riele
Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Gerrit A
GA
Meijer
Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Flora E
FE
van Leeuwen
Department of Gastroenterology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands. m.v.leerdam@nki.nl.
Monique E
ME
van Leerdam
D000236:Adenoma / Q000139:chemically induced / Q000175:diagnosis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D024221:Antineoplastic Protocols; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000175:diagnosis*; D003362:Cost-Benefit Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D055088:Early Detection of Cancer / Q000191:economics* / Q000379:methods; D005243:Feces / Q000737:chemistry; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D007120:Immunochemistry; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000175:diagnosis*; D011344:Procarbazine / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D012107:Research Design; D017741:Survivors; D055815:Young Adult
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011344:Procarbazine
Carcinogenesis; Colonoscopy; Colorectal neoplasia; Hodgkin lymphoma; Stool (DNA) test; Surveillance