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.

HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer.

PURPOSE: Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC. METHODS: Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0. RESULTS: In total, 855 HER2-negative patients were identified. The median follow-up was 59 months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (p = 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (p = 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (p = 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (p = 0.23) for TNBC HER2-low/HER2-0. CONCLUSION: Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.

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.

Prognostic impact of platinum sensitivity in ovarian carcinoma patients with brain metastasis.

BACKGROUND: Brain metastasis (BM) is a rare event in ovarian cancer patients. The current prognostic scores that have been used for other tumors do not account for specific characteristics of ovarian cancer, such as platinum sensitivity. METHODS: This retrospective cohort study examined patients with ovarian carcinoma and BM who were treated at a single institution from January 2007 to December 2017. Clinical data on the diagnosis of BM and follow-up were collected. Cox regression was used to evaluate prognostic factors for overall survival (OS). RESULTS: Of 560 patients, 26 presented with BM. Eight patients were treated with surgery, 15 with whole-brain radiotherapy (RT), and 5 with stereotactic RT, and 4 patients received systemic treatment at the diagnosis of BM. The median OS was 10.8 months. The following factors were associated with OS: platinum-sensitive recurrence (HR 0.34, 95% CI 0.12-0.99; p = 0.049), higher number of previous treatment lines (HR 1.57, 95% CI 1.12-2.19; p = 0.008), ECOG performance status (HR 2.52, 95% CI 1.24-5.09; p = 0.010), and longer interval from initial diagnosis to BM (p = 0.025). Notably, the number of brain metastasis, the largest tumor size, and progression outside of the CNS were not related to survival. Platinum sensitivity was not associated with any of the classic prognostic factors in brain metastasis patients such as number or size of brain metastasis or disease progression outside the CNS strengthening the hypothesis of the importance of platinum sensitivity to the prognosis of ovarian cancer patients with BM. CONCLUSIONS: The factors related to the biological behavior of the ovarian cancer such as platinum sensitivity at the time of BM diagnosis, fewer number of previous treatment lines and interval from initial diagnosis were associated with survival in ovarian cancer patients with BM, while factors that are usually related to survival in BM in other cancers were not associated with survival in this cohort of ovarian cancer patients. The small number of patients did not allow us to exclude the prognostic role of these former factors that were not associated with survival in the present cohort.

Circulating Tumor Cells as Cancer Biomarkers in the Clinic.

It is believed that the development of metastatic cancer requires the presence of circulating tumor cells (CTCs) , which are found in a patient's circulation as rare abnormal cells comingled with billions of the normal red and white blood cells. The systems developed for detection of CTCs have brought progress to cancer treatment. The molecular characterization of CTCs can aid in the development of new drugs, and their presence during treatment can help clinicians determine the prognosis of the patient. Studies have been carried out in patients early in the disease course, with only primary tumors, and the role of CTCs in prognosis seems to be as important as it is in patients with metastatic disease. The published studies on CTCs have focused on their prognostic significance, their utility in real-time monitoring of therapies, the identification of therapeutic and resistance targets, and understanding the process of metastasis . The analysis of CTCs during the early stages, as a "liquid biopsy," helps to monitor patients at different points in the disease course, including minimal residual disease, providing valuable information about the very early assessment of treatment effectiveness. Finally, CTCs can be used to screen patients with family histories of cancer or with diseases that can lead to the development of cancer. With standard protocols, this easily obtained and practical tool can be used to prevent the growth and spread of cancer. In this chapter, we review some important aspects of CTCs , surveying the disease aspects where these cells have been investigated.

The Value of Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer and Application of a Prognostic Score.

OBJECTIVES: Secondary cytoreductive surgery (SCS) is an option for treating patients with recurrent ovarian cancer. Three ongoing randomized trials are comparing SCS plus chemotherapy with chemotherapy alone, and few comparative studies have been published. MATERIALS AND METHODS: We performed a retrospective review of data on 209 patients with recurrent ovarian carcinoma who were treated at a single institution from 2000 to 2013. We analyzed prognostic factors in the recurrence setting to determine the value of SCS in a multivariate model, including propensity score, by prognostic group. RESULTS: In the univariate analysis, younger than 65 years, personal or family history of breast or ovarian cancer, stage I-II at diagnosis, residual disease 10 mm or less after primary debulking surgery, performance status 1 or less, CA125 less than 100, only 1 metastatic site of recurrence, platinum-free interval of more than 12 months, and SCS correlated with better overall survival. In the multivariate model, including propensity score, SCS remained associated with a 66% decrease in the risk of death (hazard ratio, 0.34; 95% CI, 0.15-0.76, P = 0.008). Secondary cytoreductive surgery was also linked to longer progression-free survival (hazard ratio, 0.50; 95% CI, 0.30-0.84, P = 0.008). There was no evidence of a benefit of SCS in patients with unfavorable prognosis (P for interaction = 0.654). CONCLUSIONS: Our results confirm the benefit of SCS in progression-free survival and overall survival in the recurrent setting and suggest that it exists not only for patients with a good prognosis.

Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery and the Risk of Platinum Resistance in Epithelial Ovarian Cancer.

BACKGROUND: Interval debulking surgery (IDS) is an option for treating patients with advanced ovarian carcinoma. Two randomized trials have shown similar survival rates for primary debulking surgery (PDS) and IDS. One of the concerns with IDS is the potentially higher risk of inducing platinum resistance when treating patients with greater disease volume. METHODS: A retrospective review of data on 237 patients with stage IIIC and IV ovarian carcinoma who were treated at a single institution from 2000 to 2013. We analyzed the association of IDS with time to first platinum resistant relapse (TTPR); platinum-resistant disease at first relapse, defined as a platinum-free interval (PFI) after first-line chemotherapy of <6 months; and overall response rate (ORR) to chemotherapy at first platinum-sensitive relapse. RESULTS: The TTPR was 60 months, and the median TTPR was longer for the PDS (80.8 months) versus IDS group (39.3 months; p = 0.012) and for patients with residual disease (RD) ≤10 mm (80.8 months) compared with those with RD >10 mm (26.1 months; p < 0.001). In the multivariate analysis, IDS [hazard ratio (HR) 1.92; p = 0.009] and RD >10 mm (HR 1.65; p < 0.001) retained an increased risk of developing platinum-resistant disease. IDS was not associated with a greater risk of PFI <6 months at first relapse, and the ORR to platinum-based chemotherapy at first platinum-sensitive relapse was 87.2 % for patients who were treated with PDS compared with 68.0 % for those who underwent IDS (p = 0.051). CONCLUSIONS: IDS correlates with a higher risk of the development of platinum resistance.

Risk of metastasis in BRCA2 carriers diagnosed with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown. METHODS: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death. RESULTS: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574). CONCLUSIONS: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: a GBECAM multicenter retrospective study.

Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers.

Combined endocrine and targeted therapy in luminal breast cancer.

Introduction: For decades, endocrine therapy has been the cornerstone of management for luminal breast cancer. Despite the substantial benefit derived by patients from endocrine therapy, primary and secondary resistances to endocrine therapy are serious clinical issues.Areas covered: Today, in the advanced setting, three distinct classes of targeted agents mTOR, CDK 4/6, and PI3K inhibitors, are approved for use. CDK 4/6 inhibitors have improved outcomes substantially, changing the natural history of advanced luminal breast cancer. Current studies seek to bring CDK 4/6 inhibitors to the early setting. This review will cover all available data on target therapy combinations with endocrine therapy for both the early and advanced settings, including approved drugs and agents in development.Expert opinion: Combined endocrine and target therapy has changed the landscape in advanced disease. In early disease, it is possible to have a large impact, particularly in patients with higher risk of relapse. Trials like ADAPTCYCLE seek to leverage neoadjuvant data to de-escalate treatment, substituting chemotherapy for CDK 4/6 inhibitors. In advanced diseases, studies such as PADA-1 point toward a future in which ctDNA will be used to define management before clinical progression occurs.

Comparison of hormonal receptor expression and HER2 status between circulating tumor cells and breast cancer metastases.

OBJECTIVES: Breast cancer (BC) is the most common neoplasm in women. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as there are discrepancies in these patterns between primary tumors and metastases in up to 40% of the cases. Circulating tumor cells (CTCs) are related to BC outcomes and could potentially be an alternative to the invasive procedures of metastasis rebiopsy. ISET® technology is not currently employed to detect CTCs in patients with BC. Emerging data support that the characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-ß plays a role in BC progression and invasiveness. Thus, in this study, we aimed to compare ER, PR, and HER2 expression in primary tumors, CTCs, and metastases and evaluate TGF-ß type 1 receptor (TGF-ß RI) expression in CTCs as prognostic factor for progression free survival (PFS) and overall survival (OS). METHODS: This prospective study was conducted at the A.C. Camargo Cancer Center, Brazil. Blood samples were processed in ISET® (Isolation by SizE of Tumors, Rarecells, France) before computed tomography-guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/metastases (medical records). RESULTS: Of the 39 patients initially included, 27 underwent both biopsies of metastases and blood collection and were considered for analysis. The concordance rates for ER, PR, and HER2 expression between primary tumors and metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern of protein expression in all triple-negative (TN) tumors (92.5%, 81.5% and 96.2% respectively) (p<0.0001) was observed. When metastases/CTCs were classified as TN/non-TN, CTCs showed high specificity (93%), accuracy (84.2%), and negative predictive value (88%). The median OS of patients without TGF-ß RI expression in CTCs was 42.6 versus 20.8 months for TGF-ß RI expression-positive ones (p>0.05). CONCLUSION: The role of CTCs detected by ISET has not yet been established in BC. Here, we suggest that this methodology may be useful to evaluate metastasis in non-TN cases as well as TGF-ß RI expression in CTCs, which may impact patient survival. Due to sample limitations, future studies must focus on specific BC subtypes and an expansion of the cohort.

Genetic Landscape of Male Breast Cancer.

Male breast cancer (MBC) is now considered molecularly different from female breast cancer (FBC). Evidence from studies indicates that common genetic and epigenetic features of FBC are not shared with those diagnosed in men. Genetic predisposition is likely to play a significant role in the tumorigenesis of this rare disease. Inherited germline variants in BRCA1 and BRCA2 account for around 2% and 10% of MBC cases, respectively, and the lifetime risk of breast cancer for men harboring BRCA1 and BRCA2 mutations is 1.2% and 6.8%. As for FBC, pathogenic mutations in other breast cancer genes have also been recently associated with an increased risk of MBC, such as PALB2 and CHEK2 mutations. However, while multigene germline panels have been extensively performed for BC female patients, the rarity of MBC has resulted in limited data to allow the understanding of the magnitude of risk and the contribution of recently identified moderate penetrance genes of FBC for MBC predisposition. This review gathers available data about the germline genetic landscape of men affected by breast cancer, estimated risk associated with these genetic variants, and current guidelines for clinical management.

Retrospective analysis of the role of cyclin E1 overexpression as a predictive marker for the efficacy of bevacizumab in platinum-sensitive recurrent ovarian cancer.

The relative benefit of bevacizumab in ovarian cancer (OC) patients is greater the more the disease becomes platinum-resistant. Among other mechanisms of action, antiangiogenic agents may induce homologous recombination deficiency. Cyclin E1 (CCNE1) overexpression is a proposed marker of platinum resistance and is mutually exclusive with deficiency in homologous recombination. In this study, we evaluated the predictive value of CCNE1 expression with regard to the efficacy of bevacizumab. We retrospectively evaluated data from patients with platinum-sensitive recurrent OC who were treated with chemotherapy (CT) plus bevacizumab (Bev group) or CT alone (CT group) at a tertiary cancer centre from 2005 to 2017. The two groups were paired according to histology, platinum-free interval (PFI) and number of previous treatment lines. Progression-free survival (PFS) was compared between groups by log rank test and Cox regression. A total of 124 patients were included, with 62 in each group. The groups were well balanced regarding histology, PFI and number of previous treatment lines. Median PFS (mPFS) was 19.5 months for the Bev group versus 16.0 months for CT group (p = 0.150). By multivariate analysis, the HR for PFS was 2.25 (95% CI: 1.10-4.60) for CCNE1 overexpression. The benefit of bevacizumab was larger in the subgroups of patients with PFI 6-12 months (mPFS 18.6 versus 10.4 months, p = 0.002) and CCNE1 overexpression (mPFS 16.3 versus 7.0 months, p = 0.010). In conclusion, CCNE1 overexpression and PFI may suggest which patients will receive the greatest benefit from bevacizumab. These data, if confirmed by other studies, could help better select patients for antiangiogenic therapy.

Malignant Phyllodes Tumor of the Breast: A Practice Review.

INTRODUCTION: Phyllodes tumor (PT) of the breast, particularly malignant phyllodes tumor (mPT), is a rare fibroepithelial neoplasm. A complex diagnosis is based on pathologic, radiologic, and clinical findings, with controversies about what is the best therapeutic strategy. OBJECTIVE: Our objective was to provide an overview of the clinical, pathologic, and therapeutic aspects of this rare tumor. CONCLUSIONS: mPT is a rare presentation of breast cancer and a challenge in clinical practice. A multidisciplinary approach should take into account some aspects like pathogenic mutations and hereditary syndromes. Oncologic surgery is the fundamental approach, and the use of adjuvant therapies is still controversial due to the lack of clinical trials. Treatment recommendations should be individualized according to patient risk and preferences. Prospective studies are fundamental to clarifying the best treatment for these tumors.

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.

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.

Risk factors for pelvic and distant recurrence in locally advanced cervical cancer.

OBJECTIVE: Despite the benefits of concomitant radiotherapy and cisplatin for locally advanced cervical cancer, recurrence rates remain high. New treatment strategies such as consolidation chemotherapy and different concomitant chemotherapy combinations have been tested in recent years. Identification of the best candidates for each treatment strategy could optimize results. STUDY DESIGN: A retrospective review of data from 127 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics Stages IIB-IVA), treated at a single institution from 2005 to 2014. Risk factors for loco-regional and systemic recurrence, and prognostic factors for overall survival (OS) were analysed using Cox regression. Survival of patients treated with consolidation chemotherapy was compared with survival of patients not treated with consolidation chemotherapy in the role cohort and in a propensity-score-matched cohort. RESULTS: With a median follow-up time of 48.7 months, loco-regional-recurrence-free survival (LRFS), distant-metastasis-free survival (DMFS) and OS at 5 years were 76.6%, 54.0% and 63.0%, respectively. On multivariate analysis, tumour size ≥6 cm was associated with shorter LRFS [hazard ratio (HR) 5.18; 95% confidence interval (CI) 1.45-18.45; p = 0.011], and adenocarcinoma (HR 2.48; 95% CI 1.10-5.57; p = 0.028) and positive lymph nodes (HR 2.21; 95% CI 1.303-4.72; p = 0.041) were associated with shorter DMFS. Tumour size ≥6 cm was associated with shorter OS (HR 2.64; 95% CI 1.09-6.35; p = 0.031). Twenty-two patients were treated with consolidation chemotherapy; on univariate analysis, these patients had longer OS compared with patients who were not treated with consolidation chemotherapy (p = 0.043). In a propensity-score-matched cohort, patients treated with consolidation chemotherapy had longer DMFS and OS compared with patients who were not treated with consolidation chemotherapy, although the difference was not significant. CONCLUSIONS: Different risk factors are associated with loco-regional and distant metastases in patients with locally advanced cervical cancer, and could potentially lead to particular therapeutic strategies. Although the number of patients treated with consolidation chemotherapy in the study cohort was small, they seemed to live longer and to have better control of distant relapse then patients who were not treated with consolidation chemotherapy.

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.