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

Br J Cancer. 2017 Jul 25;117(3):306-314. doi: 10.1038/bjc.2017.177. Epub 2017 Jun 20.

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-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-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 (Padditivity=0.004).

Conclusions: Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bleomycin / therapeutic use
  • Colon*
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / etiology
  • Diaphragm
  • Doxorubicin / therapeutic use
  • Female
  • Follow-Up Studies
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / radiotherapy*
  • Humans
  • Male
  • Mechlorethamine / therapeutic use
  • Middle Aged
  • Neoplasms, Radiation-Induced / epidemiology*
  • Neoplasms, Radiation-Induced / etiology
  • Neoplasms, Second Primary / epidemiology*
  • Neoplasms, Second Primary / etiology
  • Netherlands / epidemiology
  • Prednisone / therapeutic use
  • Procarbazine / administration & dosage*
  • Procarbazine / therapeutic use
  • Rectum
  • Risk Factors
  • Survivors
  • Vinblastine / therapeutic use
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antineoplastic Agents
  • Bleomycin
  • Procarbazine
  • Mechlorethamine
  • Vincristine
  • Vinblastine
  • Doxorubicin
  • Prednisone

Supplementary concepts

  • MOPP protocol
  • MOPP-ABV protocol