Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma.

OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma

SUMMARY OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

Palliative chemotherapy outcomes in patients with ECOG-PS higher than 1.

PURPOSE: Although patients with incurable disease and Eastern Cooperative Oncology Group performance status (ECOG-PS ≥ 2) are underrepresented in clinical trials, they are frequently offered palliative chemotherapy (pCT) in daily clinical practice in order to improve symptoms and quality of life. In this case-control retrospective analysis, our goal was to identify factors associated with poorer survival and lack of benefit of pCT in this population. PATIENTS AND METHODS: We evaluated 2,514 patients who died between August 2011 and July 2012 in an academic cancer care institution and its hospice. A total of 301 patients with solid tumours and ECOG-PS ≥ 2 at prescription of pCT were selected for this case-control retrospective analysis. Cases were defined as patients who survived less than 90 days after the first cycle of first line pCT, and controls were those who had a longer survival. RESULTS: 142 cases and 159 controls were included. Cases were more likely to experience grade ≥ 3 toxicity (43% versus 28%; p = 0.005), die of toxicity (16% versus 6%; p < 0.001) and not be offered best supportive care (BSC) only (47% versus 71%; p < 0.001). Median overall survival was 204 among controls and 34 days in cases (hazard ratio = 0.177; 95%, confidence interval = 0.015-0.033, p < 0.001). Logistic regression analysis identified ECOG-PS > 2 (odds ratio (OR) = 2.3, p = 0.044) and serum creatinine (sCr) > 1 mg/dL (OR = 11.2, p < 0.001) as independent predictors of 90-day mortality. CONCLUSIONS: The independent predictors of short survival (less than 3 months) after initiation of pCT in this population were ECOG-PS > 2 and elevated sCr. Therefore, patient selection is crucial, as pCT may be deleterious in ECOG-PS ≥ 2 pts.

Carboplatin-based chemoradiotherapy in advanced cervical cancer: an alternative to cisplatin-based regimen?

OBJECTIVE: To evaluate the results of treatment with cisplatin or carboplatin concomitant with radiotherapy (RT) in cases of locally advanced cervical cancer (CC). METHODS: This study is a retrospective analysis of medical records of 184 patients with cervical cancer stage IIB-IVA who were treated at Instituto do Câncer do Estado de São Paulo from May 2008 to December 2012. All patients received complete pelvic region external-beam RT with weekly cisplatin (cis-RT, 40mg/m(2); n=159) or carboplatin (carbo-RT, AUC 2; n=25), followed by high-dose-rate intracavitary brachytherapy (HDR-ICBT). Primary endpoint was progression free survival; secondary endpoints were overall survival and overall response rate, which includes complete and partial responses. RESULTS: Five or more chemotherapy cycles were administered to 87.3% and 84% of the cis-RT- and carbo-RT- treated patients, respectively (p=0.749). Estimated 3-years progression free survival was 59% in the cis-RT group vs 40% in the carbo-RT group (p=0.249). Estimated 3-years overall survival was 70% in the cis-RT group vs 68% in the carbo-RT group (p=0.298). Overall response rate (95.3% cis-RT vs 95.4% carbo-RT; p=0.911) and grade ≥3 toxic effects (8.5% cis-RT vs 11.8% carbo-RT; p=0.757) were similar. In multivariate analysis, only the overall response rate was a significant predictor of survival. CONCLUSIONS: Patients with advanced cervical cancer who are treated with carbo-RT have similar 3-years overall survival, progression free survival, overall response rate, and toxic effects when compared to cis-RT-treated patients. Carbo-RT may be an alternative treatment in patients that cannot receive cisplatin.

Definitive chemoradiotherapy for advanced cervical cancer: should it be different in the elderly?

BACKGROUND: Cervical cancer (CC) is the second most common cancer in Brazilian women, and approximately 10% of cases occur in elderly patients (pts). In this age group, disease is usually diagnosed in more advanced stages and oncological therapies are usually less intensive, due to comorbidities and impaired performance status. METHODS: Retrospective analysis of pts ≥65 years old with CC admitted at a Brazilian University Cancer Center from August 2008 to February 2012. We performed a descriptive analysis of baseline performance status (PS), disease stage (FIGO), histology, body mass index (BMI), treatment received and overall survival, using the Kaplan-Meier method. RESULTS: 900 medical records were analyzed and 75 pts (8%) fulfilled the inclusion criteria. Median age was 73.4 years old (±5.5 years). Squamous cell carcinoma (SCC) was the most common histology (71 pts, 94.7%). 67 (89.3%) had PS 0 or 1 and 52 pts (69.3%) were eutrophic (BMI 18.5-25 kg/m(2)). At presentation, disease staging consisted of 18 pts (24%) stage I, 35 pts (46.7%) stage II, 8 pts (10.7%) stage III, 12 pts (16%) stage IVa and 2 pts (2.7%) stage IVb. 24 pts (32%) underwent surgery (hysterectomy, adnexectomy, pelvic and paraaortic lymphadenectomy). Adjuvant treatment with radiotherapy (RT) was performed in 13 pts (total dose of external RT in pelvis ranged from 39.6 to 45 Gy, parametrial boost ranged from 14 to 20 Gy and 4 inserts from 7 to 7.5 Gy of brachytherapy); 8 of them received concomitant platinum-based chemotherapy (CT). 30 pts underwent definitive CRT, 17 definitive RT, 1 palliative CT and 3 best supportive care. In the CRT group, 18 pts received cisplatin (CDDP 40 mg/m(2)/w/6w) and 12 carboplatin (AUC 2/w/6w). During definitive CRT, treatment was discontinued in 39% of pts who received CDDP and 25% of pts who received carboplatin, all due to treatment toxicities. CDDP was associated with more nefrotoxicity (5 pts, 28%) than carboplatin (1 pt, 8.3%). The CDDP group also presented more radiodermatitis and stroke. However, myelosuppression and diarrhea were similar in both groups. After a 26.1-month follow-up, median OS was not reached. CONCLUSIONS: Despite advanced age, more than 60% of pts underwent complete CRT treatment. Thus, age should not be the only factor to guide therapeutic decisions in CC. Carboplatin was better tolerated than CDDP in CRT group, but prospective trials are necessary to evaluate the best treatment option in this population.

Antiepileptic drug prophylaxis in primary brain tumor patients: is current practice in agreement to the consensus?

The role of antiepileptic drugs (AED) prophylaxis in primary brain tumor (PBT) seizure-naïve patients remains unclear. Additionally, AED are associated with severe side effects, negative impact on cognition and drug interactions. Little is known about current practice regarding prophylactic AED use in PBT. We investigated its use in a tertiary care cancer center. We reviewed medical records of 260 patients registered in our center between 2008 and 2012, focusing on prophylactic AED use. A descriptive analysis was performed with SPSS IBM version 20.0. Median age was 44.5 years (11-83). Most patients had ECOG PS ≤1 (76.4 %). Among 141 seizure-naïve patients, 70.2 % received an AED as primary prophylaxis (PP). Most commonly used drugs as PP were phenytoin (85.9 %), carbamazepine (6.1 %) and phenobarbital (5.1 %). In only 14 patients (14.1 %) AEDs were eventually discontinued, in a median time of 5.9 months (1.1-76.8 m). AED were used as PP in 60 % of low-grade gliomas, 73.3 % of anaplastic gliomas and 93.9 % of glioblastoma patients. Twenty-seven patients (27.3 %) on PP presented seizures, generally associated with tumor progression. Of the 42 seizure-naïve patients not receiving AED prophylaxis, only two presented seizures, which occurred during or within the first week post-radiotherapy. In this cross-sectional study, prophylactic AED use in PBT was extremely high. Postoperatively, AED were discontinued in a minority of patients, mostly after a prolonged period. Current prophylactic AED use patterns in PBT are not in accordance with established guidelines.