Efficacy of Cancer Chemotherapy in Relation to the Pretreatment Number of Lymphocytes in Patients with Metastatic Solid Tumors

Abstract

The evidence of lymphocytopenia has been demonstrated to predict a poor prognosis in terms of survival in advanced cancer patients. This finding is not surprising because of the fundamental role of lymphocytes in mediating tumor cell destruction. Despite the importance of lymphocytes in the pathogenesis of cancer, there are only few data about the profile and the function of lymphocytes during the various antitumor therapies, and in particular the relation between lymphocyte pretreatment number and response to chemotherapy remains to be established. The present study was performed to evaluate whether the evidence of lymphocytopenia before the onset of treatment may influence the efficacy of chemotherapy in metastatic cancer patients affected by the most frequent tumor types. The study included 183 patients (lung cancer: 89; colorectal cancer: 63; breast cancer: 31), 95 of whom had been previously treated with chemotherapy. The chemotherapeutic regimens consisted of oxaliplatin plus 5-fluorouracil and folates in untreated colorectal cancer, weekly irinotecan in pretreated colorectal cancer, cisplatin plus gemcitabine or etoposide in untreated lung cancer, weekly vinorelbine in pretreated lung cancer, and taxotere in breast cancer patients who had been previously treated with anthracyclines. Lymphocyte count was considered to be abnormally low for values below 1500/mm3. Lymphocytopenia was found in 79/183 (43%) patients, without any significant differences in relation to tumor histology. A complete response (CR) was achieved in 6/104 patients with a normal lymphocyte count and in none of the 79 lymphocytopenic patients. A partial response (PR) was obtained in 39 patients with a normal lymphocyte count and in only eight patients with a low lymphocyte count prior to therapy. Therefore, irrespective of the type of chemotherapy, the objective tumor response rate (CR + PR) in lymphocytopenic patients was significantly lower than in patients with normal pretreatment lymphocyte counts (8/79 vs 45/104; p < 0.001). This study shows that the evidence of lymphocytopenia prior to chemotherapy is associated with a lower efficacy of treatment in terms of objective tumor regression rates in patients with metastatic solid tumors, and suggests that the action of chemotherapy may depend at least in part on an interaction with the antitumor immunity. Pretreatment lymphocyte count may represent a new, simple biological marker to be taken into consideration by oncologists in the chemotherapeutic treatment of metastatic cancer.

Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients

“…Host's immune response to cancer cells is in fact lymphocytedependent and different studies reported association between low or high lymphocyte count and survival. 34, 35 Interestingly, we found in the control group an advantage in term of PFS for patients who presented a high baseline lymphocyte count; Monocytes are attracted in tumor tissue by different chemokines, such as CCL-2 or CCL-5, produced by cancer cells, fibroblasts or immune cells. Once have reached the tumor site, these cells quickly differentiate into tumor-associated macrophages (TAMs).…”

Pro-inflammatory State Portends Poor Outcomes with Stereotactic Radiosurgery for Brain Metastases

“…Specifically, pretreatment lymphopenia has been found to predict a poor response to chemotherapy in the setting of lung, breast and colorectal cancer (8). An elevated pretreatment PLR has been shown to predict poor outcome in the setting of SRS for early-stage NSCLC.…”

“…Pre-treatment markers of systemic inflammation, including an elevated platelet-to-lymphocyte ratio (PLR), elevated neutrophil count, low lymphocyte count and low serum albumin concentration, have been found to predict responses to anti-neoplastic therapies and disease outcomes across multiple different malignancies (5)(6)(7)(8)(9)(10)(11). However, these markers and the role the systemic immune system plays in treatment outcomes in the setting of SRS for brain metastases have yet to be fully evaluated.…”

Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

“…Similarly, pediatric ALL patients with an ALC at day 15 ≥ 350 cells/µL after induction chemotherapy experienced a 6-year overall survival of 87% [19]. [20]. In pediatric patients with Ewing sarcoma that achieved an ALC at day 15 after initial chemotherapy, treatment of ≥500 cells/µL had a 3-year overall survival of 68% compared with 32% for patients with an ALC < 500 cells/µL at day 15 after initial chemotherapy treatment [21,22].…”