Systemic immune mediators reflect tumour-infiltrating lymphocyte intensity and predict therapeutic response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer (BC). Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumour-infiltrating lymphocytes (TILs) in pre-treated tumour tissue samples and the likelihood of achieving pCR. Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery. We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders versus non-pCR, with area under the curve (AUC) values of 0.64-0.80. We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0.72-0.82). Last, performing a progression-free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long- and short-survival groups based on high and low production of the cytokines, respectively. Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy. Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival.

Prognostic value of response evaluation based on breast MRI after neoadjuvant treatment: a retrospective cohort study.

OBJECTIVE: To investigate the impact of response evaluation after neoadjuvant chemotherapy (NAC) in breast cancer patients, assessed by both magnetic resonance imaging (MRI) and pathology, on disease-free survival (DFS). METHODS: This single-center, retrospective cohort study included consecutive breast cancer patients who underwent NAC and preoperative breast MRI. Resolution of invasive carcinoma in the breast and axilla was defined as complete pathological response (pCR). Radiological complete response (rCR) was defined as the absence of abnormal enhancement in the tumor site. Kaplan-Meier estimator was used to estimate the disease-free survival on 60 months. Cox regression analysis was used to estimate hazard ratio (HR) values. RESULTS: In total, 317 patients were included with a mean age of 47.3 years and a mean tumor size of 39.8 mm. The most common immunophenotype was luminal (44.9%), followed by triple-negative (26.8%). Overall, 126 patients (39.7%) had an rCR, while 119 (37.5%) had pCR; the radiological and pathological responses agreed in 252 cases (79.5%). During follow-up, patients who had rCR and pCR had a better DFS curve compared to patients with non-rCR and non-pCR, while those who had rCR or pCR presented an intermediate curve (Log-rank p = 0.003). Multivariate analysis showed a higher risk of recurrence in patients with non-rCR and non-pCR (HR: 5,626; p = 0.020) and those who had a complete response on MRI or pathology only (HR: 4,369; p = 0.067), when compared to patients with rCR and pCR. CONCLUSIONS: The association of MRI and pathological responses after NAC might better stratify the risk of recurrence and prognosis in breast cancer patients. KEY POINTS: • Association of response evaluation after neoadjuvant chemotherapy by pathology and MRI allows better stratification of prognosis. • Complete response to neoadjuvant chemotherapy on pathology and MRI was related to better disease-free survival. • Complete response on MRI or pathology only had a greater risk of recurrence.

The Impact of Addition of Consolidation Chemotherapy to Standard Cisplatin-Based Chemoradiotherapy in Uterine Cervical Cancer: Matter of Distant Relapse.

BACKGROUND: Treatment of advanced uterine cervical cancer has advanced little in the last 15 years. Although two phase III trials showed survival benefit with the addition of consolidation chemotherapy (CT) after cisplatin-based chemoradiotherapy (RTCT), it is not considered standard of care. We aimed to evaluate the benefit of consolidation CT compared to no additional treatment in patients treated with RTCT. METHODS: This is a retrospective study including 186 patients with FIGO stage IB2, IIA2, or IIB to IVB (paraaortic lymph nodes only) uterine cervical cancer who were treated with standard RTCT alone or RTCT followed by consolidation CT. Overall survival (OS), progression free survival (PFS), and the risk of distant and local relapses were compared between the two treatment groups. RESULTS: At 3 years OS was 91% versus 82.3% (p=0.027), PFS 84.3% versus 54.4% (p=0.047), and distant metastasis free survival (DMFS) 80.4% versus 62.5% (p=0.027) in favor of the consolidation CT group. Multivariate analysis confirmed the benefit of consolidation CT. There was no difference in locoregional free survival (LRFS). Positive lymph node was related to a higher risk of distant relapse. In the lymph node positive subgroup consolidation CT resulted in longer OS (p=0.050), PFS (p=0.014), and DMFS (p=0.022); in the lymph node negative subgroup there was no benefit from consolidation CT. CONCLUSIONS: Use of consolidation CT resulted in longer OS and PFS, mostly due to control of distant relapses. Patients at higher risk of distant relapse showed the greatest benefit. This data generates a hypothesis that could help to better select patients to consolidation CT.

Incidence of Infusion Site Reactions in Peripheral Fosaprepitant Infusions.

Fosaprepitant is administered intravenously to treat chemotherapy-induced nausea and vomiting. To verify the incidence of infusion site reactions and the relationship among risk factors, a quantitative retrospective cohort study was undertaken. The study included patients seen between October 2013 and February 2014. Fifty-seven patients were included in the study, and there were 105 infusions among them. Infusion site reactions were identified in 42 (40%) cases. Risk factors identified by the study included age (P < .001), insertion at the back of the hand and wrist (P < .001), and first fosaprepitant administration (P < .001). The study found evidence of a higher incidence of infusion site reactions than was reported in the package insert.

Factors correlated with peritoneal carcinomatosis and survival in patients with gastric cancer treated at a single institution in Brazil.

BACKGROUND: Gastric cancer is the second leading cause of death due to cancer worldwide and is particularly prevalent in Brazil. Promising new therapeutic agents have already shown activity in some gastrointestinal malignancies and their role in gastric cancer will need to be evaluated. Determining the prognostic factors of survival for patients with gastric cancer can help in identifying patients with a worse prognosis after treatment with the current chemotherapeutic regimens. METHODS: A retrospective chart review of 186 patients diagnosed with gastric cancer and treated at a single institution in Brazil from January 1994 to December 2004 was carried out. Univariate and multivariate analyses were performed to identify patient- and tumor-related characteristics associated with peritoneal metastasis at diagnosis and with overall survival. RESULTS: Of the 186 patients, 76 were alive at the time of this analysis. The median survival for all patients was 30.1 months. Two independent factors associated with the presence of peritoneal metastasis at diagnosis were identified by multivariate analysis: signet-ring cell type (odds ratio [OR], 10.8; 95% confidence interval [CI], 3.1 to 37.5), and visceral metastasis (OR, 51.8; 95% CI, 12.4 to 215.4). The prognostic factors for poor survival were tumor stage T3 or T4 (hazard ratio [HR], 1.87; 95% CI, 1.09 to 3.22) and visceral metastasis (HR, 4.98; 95% CI, 3.02 to 8.20). CONCLUSION: Two factors correlated with peritoneal metastasis and two prognostic factors for survival were identified. These findings may contribute to clinical decision-making, treatment tailoring, and the design of future trials.

Predictors of peritoneal carcinomatosis in patients with gastric cancer treated at a single institution in Brazil.

BACKGROUND: Peritoneal carcinomatosis is a common pattern of recurrence in gastric cancer and is associated with a poor prognosis. Determining predictive factors for peritoneal recurrence can help the selection of patients suitable for more aggressive treatment strategies. METHODS: A retrospective chart review of 162 patients diagnosed with gastric cancer with no peritoneal carcinomatosis and treated at a single institution in Brazil from January 1994 to December 2004 was carried out. Univariate and multivariate analyses were performed to identify patient and tumor-related characteristics associated with the development of peritoneal metastasis. RESULTS: Twenty-three (14.2%) patients developed peritoneal carcinomatosis. Three independent factors associated with the development of peritoneal metastasis were identified by multivariate analysis: signet-ring cell histology (odds ratio [OR] = 4.9; P = 0.018), the presence of vascular invasion (OR = 4.8; P = 0.022), and the presence of visceral metastasis at diagnosis (OR = 5.1; P = 0.011). Tumor stages T3 or T4 showed a trend towards significance (P = 0.062). CONCLUSIONS: Patients with gastric cancer presenting with signet-ring histology, vascular invasion, or visceral metastasis appear to be at higher risk for the development of peritoneal carcinomatosis.