Adrenal metastases in lung cancer: clinical implications of a mathematical model

Abstract

Adrenal gland metastases are common in lung cancer. It is well recognized that aggressive treatment of solitary adrenal metastases leads to improved outcomes but the exact nature of adrenal deposits is not well understood. Controversy exists as to the routing of cancer cells to the adrenal gland with some believing that this transmission is lymphatic, in contrast to the more generally accepted theory of hematogenous spread. Recently published mathematical modeling of cancer progression strongly supports the lymphatic theory. With that in mind, we performed a literature review to look for biological plausibility of simulation results and believe that evidence supports the contention that metastases to the adrenal gland can be routed by means of lymphatic channels. This could explain improved survival for patients in whom solitary adrenal metastases are managed aggressively with surgical or radiation modalities. We are calling for clinical trials prospectively testing this hypothesis.

Figure 1

Figure 1a. Metastatic tumor distribution for primary lung cancer from DiSibio and French data set. 163 primary lung cancer autopsies; 619 metastatic tumors; 59 adrenal metastases. Histogram is normalized so that sum of areas is one. Figure 1b. Mean first-passage times to other organs associated with a collection of random walkers leaving the primary lung tumor. Adrenal is the first visited site after lymph nodes.Times are normalized so that regional lymph nodes is unity, others are scaled to it. Figure 1c. Mean first-passage times to other organs associated with a collection of random walkers leaving the primary breast tumor. Adrenal is the seventh visited site. Times are normalized so that regional lymph nodes is unity, others are scaled to it. Figure 1d. Mean first-passage times to other organs associated with a collection of random walkers leaving the primary colon tumor. Adrenal is the sixth visited site.Times are normalized so that regional lymph nodes is unity, others are scaled to it. Figure 1e. Mean first-passage times to other organs associated with a collection of random walkers leaving the primary bladder tumor. Adrenal is the sixth visited site.Times are normalized so that regional lymph nodes is unity, others are scaled to it. Figure 1f. Mean first-passage times to other organs associated with a collection of random walkers leaving the primary prostate tumor. Adrenal is the sixth visited site. Times are normalized so that regional lymph nodes is unity, others are scaled to it.