OC-0632 Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer

Purpose or Objective Lymphopenia during radiotherapy (RT) has an adverse effect on patient’s quality of life and can be life threatening. However, the relationship between RT dose and lymphopenia is still unknown. This work utilized data mining to identify anatomical regions where the received dose is correlated with lymphopenia. A predictive model of lymphopenia is also proposed. Material and Methods 562 lung cancer patients treated with curative intent RT were used as a development set. All patients had baseline lymphocytes ≥ 0.5x109 /L. A Cox model was used to assess prognostic factors of overall survival. Next, two matched groups were defined - patients with and without lymphopenia ≥ G3 (lymphocytes at nadir < 0.5x109 /L according to CTCAE v4.0) - based on planning target volume (PTV), baseline lymphocytes, prescribed dose, and histology. The purpose of matching was to eliminate tumor effects and improve data mining sensitivity. Following matching, 386 patients remained and image-based data mining was used to identify regions where dose correlates significantly with lymphopenia ≥ G3. For that purpose, dose matrices (equivalent dose at 2 Gy/fraction, α/β=10) were aligned using registration of the planning CT images to one reference patient. Then, mean dose distributions were obtained for the two groups and organs of significance were detected. For these organs, various dose parameters were collected and those having the highest correlation with lymphocytes at nadir were selected for analysis. Multivariate analyses were conducted for the full development set by employing the identified dose parameters, along with non-dosimetric parameters significant in univariate analysis (p < 0.05). Finally, the model was validated on 301 esophageal cancer patients. Results Cox regression showed that lymphopenia ≥ G3 in addition to age, PTV, performance status, and RT duration was an independent factor predicting overall survival in lung cancer (Figure 1). The heart, lung, and thoracic vertebrae showed regions where the difference in dose between the matched groups, with and without lymphopenia ≥ G3, was significant. Mean dose to the heart and lung, and V20 of the thoracic vertebrae (volume receiving >20 Gy) correlated most with lymphocyte counts at nadir in the matched set. A model including RT duration, baseline lymphocytes, vertebrae V20, and mean heart dose was then chosen following backward elimination (Table 1). The Hosmer-Lemeshow test, based on deciles of risk, indicated that the model was a good fit. Accuracy and C-statistics of the model in the development set was 75% and 0.82 and in the validation set was 75% and 0.76, respectively. Conclusion Lymphopenia ≥ G3 during RT is a significant risk factor for survival in lung cancer patients and careful management is thus required e.g. by minimizing vertebrae V20 and mean heart dose in order to limit irradiation of stem cells and blood pool. If dose constraints cannot be met, more frequent monitoring of lymphocyte counts during therapy and use of prophylactic antibiotics are recommended.