Improved recurrence-free survival with ARCON for anemic patients with laryngeal cancer.
OBJECTIVE
Anemia is associated with poor tumor control. It was previously observed that accelerated radiotherapy combined with carbogen breathing and nicotinamide (ARCON) can correct this adverse outcome in patients with head and neck cancer. The purpose of this study was to validate this observation based on data from a randomized trial.


METHODS
Of 345 patients with cT2-4 laryngeal cancer, 174 were randomly assigned to accelerated radiotherapy and 171 to ARCON. Hemoglobin levels, measured before treatment, were defined as low when <7.5 mmol/L for women and <8.5 mmol/L for men. The hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies. Data were analyzed 2 years after inclusion of the last patient.


RESULTS
Pretreatment hemoglobin levels were available and below normal in 27 of 173 (16%) accelerated radiotherapy and 27 of 167 (16%) ARCON patients. In patients with normal pretreatment, hemoglobin levels treatment with ARCON had no significant effect on 5-year loco-regional control (LRC, 79% versus 75%; P = 0.44) and disease-free survival (DFS, 75% vs. 70%; P = 0.46) compared with accelerated radiotherapy. However, in patients with low pretreatment, hemoglobin levels ARCON significantly improved 5-year LRC (79% vs. 53%; P = 0.03) and DFS (68% vs. 45%; P = 0.04). In multivariate analysis including other prognostic factors, pretreatment hemoglobin remained prognostic for LRC and DFS in the accelerated radiotherapy treatment arm. No correlation between pretreatment hemoglobin levels and pimonidazole uptake was observed.


CONCLUSIONS
Results from the randomized phase III trial support previous observations that ARCON has the potential to correct the poor outcome of cancer patients with anemia (ClinicalTrials.gov number, NCT00147732).
Authors' Affiliations: Department of Radiation Oncology; Department of Oto-Rhino-Laryngology and Head & Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht; Departments of Radiation Oncology and Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam; Department of Radiation Oncology, University Medical Center Groningen, Groningen; Department of Radiation Oncology (MAASTRO), Maastricht University Medical Centre, Maastricht; and Department of Clinical Oncology, Leiden University Medical Centre, Leiden, the Netherlands.
Geert O
GO
Janssens
Saskia E
SE
Rademakers
Chris H
CH
Terhaard
Patricia A
PA
Doornaert
Hendrik P
HP
Bijl
Piet
P
van den Ende
Alim
A
Chin
Robert P
RP
Takes
Remco
R
de Bree
Ilse J
IJ
Hoogsteen
Johan
J
Bussink
Paul N
PN
Span
Johannes H
JH
Kaanders
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000150:complications*; D015415:Biomarkers; D002245:Carbon Dioxide / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000150:complications* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000627:therapeutic use*; D010100:Oxygen / Q000627:therapeutic use*; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011878:Radiotherapy; D016896:Treatment Outcome
D015415:Biomarkers; D006454:Hemoglobins; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen