Angiogenesis vs. response after combined chemoradiotherapy of squamous cell head and neck cancer

Oxygen/drug supply to cancer cells is an important factor defining response to radiotherapy and chemotherapy, Although tumor angiogenesis is considere d an important prognostic: marker, its role in the outcome of chemotherapy and radiotherapy is unknown. In the present study we examined the possible correlation of the degree of angiogenesis with response to cytotoxic therap y in locally advanced squamous cell head and neck cancer (HNC). Vascular gr ade (VG) was assessed immunohistochemically using the JC70 monoclonal antib ody (MAb) in tumor specimens from 76 patients treated with platinum/5-fluor ouracil (with or without methotrexate) induction chemotherapy (ICT) (n = 37 ) or concurrent chemoradiotherapy (CCRT) with cisplatin or carboplatin (n = 39). Seventeen of 76 analyzed patients had an overall microvessel score of <11 (VGI), 25/76 of 11-30 (VG2), 16/76 of 31-50 (VG3) and 18/76 of >50 (VG 4), Complete response rate after ICT or after CCRT was higher in cases with an intermediate vascularization (VG2,3). Both local relapse-free and overa ll survival were significantly better in the VG2 group. Patients treated wi th CCRT had a better survival compared to those treated with ICT. This was mainly observed in VGI tumors. Multivariate analysis showed that VG and tre atment modality were independent prognostic factors for local relapse and s urvival, Intratumoral angiogenesis correlation with the cytotoxic therapy o utcome is likely to follow a bell-shaped relation, the response being bette r in cases with an intermediate VG. This may be the consequence of 2 vascul ature-dependent factors, ie., the drug/oxygen availability and the ability of cancer cells to undergo rapid repopulation in optimally oxygenated condi tions. Our pilot study stresses the importance of individualization of ther apy according to VG. Int. J. Cancer 80:810-817, 1999. (C) 1999 Wiley-Liss, Inc.