Margriet Kwint

Prognostic value of volumetric changes during concurrent chemoradiation 101 5 The median GTV-volume at start of treatment was comparable to the median GTV published in literature (13-15), however we observed a lower GTV-volume reduction compared to other studies (13-15). The reason for this might be our reduced overall treatment time (OTT), since patient were treated with a hypofractionated CCRT regime with an OTT of 32 days (24x2.75Gy) compared to an OTT between 40-51 days (60-74 Gy in 1.8-2Gy/fraction)) in the literature(13-15). Furthermore, different chemotherapy regimens were used. In our institute, daily low-dose Cisplatin is administered as a radio sensitizer, while conventionally weekly or three weekly administrations of high dose chemotherapy are applied and sometimes combined with induction chemotherapy. Moreover, different chemotherapy regimens, radiotherapy-schedules and OTT could have influenced the onset of the DNA damage response system (36, 37). The DNA damage response system determines the radio sensitivity, type and timing of cell death. The vast majority of proliferating tumor cells die at a relatively long interval after irradiation, usually after attempting mitosis 1 or 2 times. Therefore, this could have affect the GTV- change, which could explain the observed differences. In patients with AC and more than the median GTV-change, a tendency towards a worse OS compared to other pathology groups was found. In the LCMM subgroups, the same tendency in association was found; subgroup 3 (the subgroup with the sharpest decrease in volume) showed worse OS compared to the other subgroups. However, this was not statistically significant, probably due to the small number of patients in this subgroup (N=6). This association is in accordance with the study of Brink et al.(13), who found that patients with more GTV-change during treatment showed worse treatment outcomes. Treatment guidelines for CCRT for LA-NSCLC patients are currently based on ‘one-size-fits-all’ standards and there is no risk based distinction on pathology. Previously published literature already reported higher incidences of brain metastases in AC (38-41), a higher incidence of distant metastases in AC and that loco regional failures are more common in SCC (11), underlining that AC and SCC might be two different entities. A possible explanation could be that more aggressive tumors have a higher mitotic rate and are therefore more radiosensitive tumors, resulting in increased tumor regression during treatment. This is comparable to small-cell lung cancer, which is in general very radiosensitive due to the higher mitotic count (rapid growth) and has a poor treatment outcome (42). Therefore, response monitoring during treatment within adenocarcinoma patients might be beneficial and further investigation is needed.