To the editor:

In the recent article by Willett et al.1 on neoadjuvant therapy with bevacizumab (BV) in patients with rectal cancer, treatment effects were ascribed to therapy with the VEGF-specific antibody bevacizumab. However, because patients underwent concurrent treatment with 5-fluorouracil, we wonder if at least a portion of the treatment effects observed at 7 weeks might have been mediated by 5-fluorouracil, either alone or through a potentially synergistic effect of the combination.

In addition, we regretted the absence of information about the marked increase in 18-fluorodeoxyglucose (FGD) uptake in a projection on the cervical spine region of one patient, as shown by the PET scan 6–7 weeks after the end of neoadjuvant therapy (Fig. 1c in ref. 1). Because this finding was not observed in this patient's prior PET examinations, it does not seem appropriate to view it as a mere technical artifact; it appears highly suggestive of a distant metastasis that has grown (and consequently become visible by PET) under bevacizumab combination therapy. Unexpected tumor growth at distant sites linked to treatment targeted at the primary cancer site, such as have been observed in both animal models and cancer patients2, might be due to higher net suppression of growth-inhibiting as compared to growth-stimulating substances secreted from an individual primary tumor. The PET findings in this patient could reflect this sort of adverse effect from bevacizumab–5-fluorouracil combination therapy. Therefore, we would like the authors to comment on the apparent divergent efficacy at the site of the primary tumor as compared to distant locations.

See Reply to “PET concerns in bevacizumab treatment” by Willett et al.