Dose and calcifications predict overall survival in NSCLC patients receiving RT

Dr. Joseph Delano Fule Robles
19 Oct 2018

Investigators from the University of Manchester, Manchester, UK recently demonstrated a significant interaction between volume of identified calcifications and their mean radiotherapy (RT) dose in predicting survival in patients with non-small-cell lung cancer (NSCLC).

The study, presented at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) 2018, was performed with 1,072 NSCLC patients treated with 55 Gy in 20 fractions. The method was developed to automatically segment calcifications within the heart, the aortic arch and the surrounding areas. 3D planning was performed using well-established image processing algorithms.  [Osorio A, et al, WCLC 2018 abstract OA01.03]

“Shape analysis was also included to enhance regions that look like vessels [tubular] or those that look like plates,” added study investigator Dr Alan McWilliam from the Division of Clinical Cancer Sciences, University of Manchester, Manchester, UK.

Calcifications were verified using CT scans under the guidance of both radiologists and cardiologists. The study  found 82 percent of the calcifications with 9 percent of the calcifications incorrectly classified.

Survival analysis showed that patients with interaction between calcification and RT dose fare worse than those who do not show such interaction (hazard ratio [HR], 1.006; 95 percent confidence interval [CI], 1.001 to 1.010; p=0.03). The multivariate survival analysis identified tumour size (continuous, p<0.0001) and the interaction of calcification volume and their mean dose (continuous, p=0.029) as significant.

“The results show us that the presence of calcifications may have an impact on patient survival especially if calcifications around the heart are irradiated,” explained McWilliam.

Interactions with patient age (HR, 1.007; 95 percent CI, 0.999 to 1.016; p=0.08), calcification volume (HR, 0.95; 95 percent CI, 0.87 to 1.04; p=0.57) or dose to calcification (HR, 0.99; 95 percent CI, 0.99 to 1.00; p=0.27), however, were found to be not significant.

Further directions of the study include improvements to identify calcifications in the descending thoracic aorta and validation of the methodology by utilizing 4D-CT and using larger datasets of patients. Moreover, the group plans to improve the sensitivity and specificity of the test. However, contrast is an issue.

They are also proposing to have a more comprehensive calculation of the calcifications of the thorax by obtaining Coronary Artery Calcification or Agaston scores.

A study in 1,101 lung cancer patients treated with curative-intent RT showed that higher doses (ie, more than 8.5 Gy) is significantly associated with worse patient survival (p<0.001). [Eur J Cancer 2017;85:106-113]

More than 50 percent of lung cancer patients were reported to often present with three or more comorbid conditions.  Emerging evidence also showed that cardiac events were relatively common after high-dose thoracic RT and were independently associated with both heart dose and baseline cardiac risk. [J Clin Oncol 2017;35:1387-1394]

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