We analyzed retrospectively the relationships and the prognostic significance of four anatomopathological features (elastosis, fibrosis, necrosis, inflammatory cell reaction) of the primary tumor in a series of 1,457 cases of infiltrating ductal carcinoma observed at our institution from January 1978 to December 1991. Necrosis, elastosis, fibrosis and inflammatory cell reaction were strongly associated among themselves (all p < 0.0001), the only exception being necrosis and elastosis. Necrosis was significantly related to tumor size (odds ratio [OR] = 5.40, p < 0.0001) and tumor grade (OR = 2.22, p < 0.0001). Univariate analysis showed that the presence of necrosis and cell reaction were significantly related to worse survival (p < 0.0001 and p = 0.03, respectively). Multivariate analysis, including the four variables plus nodal status, tumor size, grading, adjuvant therapy, age and first order interactions, revealed that greater tumor size (p < 0.0001), positive nodal status (p < 0.0001), higher histologic grade (p < 0.0001) and presence of inflammatory cell reaction (p = 0.0007) independently worsened survival. On the other hand, adjuvant therapy had a significant independent role in preventing deaths (p = 0.03). The only first-order interaction retained in the model was that between grading and cell reaction (p = 0.002). Cell reaction had a different prognostic behaviour in the groups G1-G2 and G3: in the former group, survival was worse (p = 0.0001) when the inflammatory cell reaction was present. In conclusion, we demonstrate that cell reaction is an independent prognostic factor in the G1-G2 subgroup of patients, and propose a hypothesis as to the role of cell reaction in primary breast cancer.
The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting.We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma.Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10–17) and 31 (28–36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13–22) and an OS of 38 (33–41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20–0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95–9.77; P < 0.01).We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may yield a survival benefit with low costs and no detrimental effects on quality of life.
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