Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

Anna M van Eggermond; Michael Schaapveld; Cécile Pm Janus; Jan Paul de Boer; Augustinus Dg Krol; Josée M Zijlstra; Richard Wm van der Maazen; Leontien C Kremer; Monique E van Leerdam; Marieke Wj Louwman; Otto Visser; Marie L De Bruin; Berthe Mp Aleman; Flora E van Leeuwen

doi:10.1038/bjc.2017.177

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

Anna M van Eggermond, Michael Schaapveld, Cécile Pm Janus, Jan Paul de Boer, Augustinus Dg Krol, Josée M Zijlstra, Richard Wm van der Maazen, Leontien C Kremer, Monique E van Leerdam, Marieke Wj Louwman, Otto Visser, Marie L De Bruin, Berthe Mp Aleman, Flora E van Leeuwen

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Abstract

Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m â '2 was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m â '2 procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (P additivity =0.004).Conclusions:Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.

Originalsprog	Engelsk
Tidsskrift	B J C
Vol/bind	117
Udgave nummer	3
Sider (fra-til)	306-314
Antal sider	9
ISSN	0007-0920
DOI	https://doi.org/10.1038/bjc.2017.177
Status	Udgivet - 25 jul. 2017

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van Eggermond, A. M., Schaapveld, M., Janus, C. P., de Boer, J. P., Krol, A. D., Zijlstra, J. M., van der Maazen, R. W., Kremer, L. C., van Leerdam, M. E., Louwman, M. W., Visser, O., De Bruin, M. L., Aleman, B. M., & van Leeuwen, F. E. (2017). Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors. B J C, 117(3), 306-314. https://doi.org/10.1038/bjc.2017.177

van Eggermond, AM, Schaapveld, M, Janus, CP, de Boer, JP, Krol, AD, Zijlstra, JM, van der Maazen, RW, Kremer, LC, van Leerdam, ME, Louwman, MW, Visser, O, De Bruin, ML, Aleman, BM & van Leeuwen, FE 2017, 'Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors', B J C, bind 117, nr. 3, s. 306-314. https://doi.org/10.1038/bjc.2017.177

@article{9b3d69da05a24b6b8647074c77235b62,

title = "Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors",

abstract = "Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m {\^a} '2 was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m {\^a} '2 procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (P additivity =0.004).Conclusions:Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.",

keywords = "Adult, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Bleomycin, Colon, Colorectal Neoplasms, Diaphragm, Doxorubicin, Female, Follow-Up Studies, Hodgkin Disease, Humans, Male, Mechlorethamine, Middle Aged, Neoplasms, Radiation-Induced, Neoplasms, Second Primary, Netherlands, Prednisone, Procarbazine, Rectum, Risk Factors, Survivors, Vinblastine, Vincristine, Young Adult, Journal Article",

author = "{van Eggermond}, {Anna M} and Michael Schaapveld and Janus, {C{\'e}cile Pm} and {de Boer}, {Jan Paul} and Krol, {Augustinus Dg} and Zijlstra, {Jos{\'e}e M} and {van der Maazen}, {Richard Wm} and Kremer, {Leontien C} and {van Leerdam}, {Monique E} and Louwman, {Marieke Wj} and Otto Visser and {De Bruin}, {Marie L} and Aleman, {Berthe Mp} and {van Leeuwen}, {Flora E}",

year = "2017",

month = jul,

day = "25",

doi = "10.1038/bjc.2017.177",

language = "English",

volume = "117",

pages = "306--314",

journal = "The British journal of cancer. Supplement",

issn = "0007-0920",

publisher = "nature publishing group",

number = "3",

}

TY - JOUR

T1 - Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

AU - van Eggermond, Anna M

AU - Schaapveld, Michael

AU - Janus, Cécile Pm

AU - de Boer, Jan Paul

AU - Krol, Augustinus Dg

AU - Zijlstra, Josée M

AU - van der Maazen, Richard Wm

AU - Kremer, Leontien C

AU - van Leerdam, Monique E

AU - Louwman, Marieke Wj

AU - Visser, Otto

AU - De Bruin, Marie L

AU - Aleman, Berthe Mp

AU - van Leeuwen, Flora E

PY - 2017/7/25

Y1 - 2017/7/25

N2 - Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m â '2 was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m â '2 procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (P additivity =0.004).Conclusions:Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.

AB - Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m â '2 was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m â '2 procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (P additivity =0.004).Conclusions:Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.

KW - Adult

KW - Antineoplastic Agents

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Bleomycin

KW - Colon

KW - Colorectal Neoplasms

KW - Diaphragm

KW - Doxorubicin

KW - Female

KW - Follow-Up Studies

KW - Hodgkin Disease

KW - Humans

KW - Male

KW - Mechlorethamine

KW - Middle Aged

KW - Neoplasms, Radiation-Induced

KW - Neoplasms, Second Primary

KW - Netherlands

KW - Prednisone

KW - Procarbazine

KW - Rectum

KW - Risk Factors

KW - Survivors

KW - Vinblastine

KW - Vincristine

KW - Young Adult

KW - Journal Article

U2 - 10.1038/bjc.2017.177

DO - 10.1038/bjc.2017.177

M3 - Journal article

C2 - 28632726

SN - 0007-0920

VL - 117

SP - 306

EP - 314

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

IS - 3

ER -

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

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