Impact of Targeted Therapy on the Survival of Patients With Advanced-Stage Non-small Cell Lung Cancer in Oncosalud - AUNA.

BACKGROUND: Lung cancer is still a prevalent and fatal neoplasm in developing countries. In the last decades, chemotherapy (CHT) maintenance occupied an important role in the treatment, as well as targeted therapies. We aimed to evaluate the survival impact of targeted therapy in advanced lung cancer at a private Peruvian institution (Oncosalud - AUNA). METHODS: We reviewed retrospectively medical records of patients with advanced-stage non-small cell lung cancer (NSCLS) (clinical stage III-IV) who received CHT and maintenance treatment with target therapy (TT) or CHT. The impact was assessed by progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method, and comparisons of survival curves were performed using log-rank or Breslow test and Cox model. RESULTS: The median age of the patients was 65 years. Clinical characteristics, as well as the treatment type, showed no significant difference between the two groups. The maintenance schedule in those receiving CHT was generally pemetrexed (70%) and in those receiving TT was erlotinib (60.7%). In patients receiving TT, the median PFS was 13 months compared to 7 months in those receiving CHT; likewise, the median OS was 45 and 17 months, respectively. The PFS and OS curves showed significant differences (P < .05), achieving a better survival in subjects treated with TT. CONCLUSION: Progression-Free Survival and OS were superior in patients who received targeted therapy than those treated only with CHT, the 2 years rate of PFS and OS was nearly double to those who received only CHT-based treatments.

Lymph node ratio as best prognostic factor in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy.

Although lymph node status (ypN) is one of the most important prognostic factors of survival, the lymph node ratio (LNR) has emerged as an equitable factor. We aimed to compare the prognostic value of both ypN and LNR in patients with residual triple-negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC). This was a retrospective cohort study of patients treated in a tertiary care center during the period 2000-2014. We stratified the population based on LNR (≤0.20, 0.20-0.65, and >0.65) and ypN (N1, N2, and N3) status. The overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier curves and the log-rank + test. We further compared patient mortality and disease recurrence using multivariate Cox regression analysis. We evaluated 169 patients with a median follow-up of 87 months. At 2 years of follow-up, patients with low-risk LNR compared to those with moderate and high risk had a higher PFS (54% vs 31% vs 18%, respectively; P < .001) and OS (74% vs 64% vs 45%, respectively; P < .001). Moreover, ypN1 patients compared to ypN2 and ypN3 showed similar results in PFS (53% vs 35% vs 19%, respectively; P = .001) and OS (73% vs 69% vs 43%, respectively; P < .001). Compared to the low-risk population, patients with moderate (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.41-8.71) and high risk (HR: 6.90; 95% CI: 2.29-20.77) had a worse PFS. Regarding OS, moderate-risk (HR: 2.85; 95% CI: 1.10-7.38) and high-risk patients (HR: 6.48; 95% CI: 2.13-19.76) showed considerably worse outcomes. On the other hand, ypN staging was not associated with PFS or OS in the multivariate analysis. The LNR is a better prognostic factor of survival than ypN. The LNR should be considered in the stratification of risk after NAC in patients with TNBC.

Reverse total shoulder arthroplasty for acute proximal humeral fracture: comparison to open reduction-internal fixation and hemiarthroplasty.

BACKGROUND: Significant controversy surrounds optimal treatment of displaced 4-part proximal humeral fractures. Reverse total shoulder arthroplasty (RTSA) has recently been proposed as an alternative to hemiarthroplasty (HA) and open reduction-internal fixation (ORIF). Several authors have questioned the additional implant cost for RTSA. The purpose of this study was to compare outcomes and cost of RTSA, HA, and ORIF. MATERIALS AND METHODS: We prospectively evaluated patients who underwent RTSA for displaced 3- and 4-part proximal humeral fractures and then retrospectively developed age- and sex-matched control groups with 3- and 4-part proximal humeral fractures who underwent HA and ORIF. Range of motion including active forward elevation and external rotation and time to achieve active forward elevation >90° were recorded. American Shoulder and Elbow Surgeons (ASES), Short-Form 12-item (SF-12), and Simple Shoulder Test (SST) scores were recorded. In addition, treatment cost was assessed by Medicare data and implant list prices. RESULTS: This study enrolled 27 patients; 9 underwent RTSA, 9 HA, and 9 ORIF. Minimum follow-up was 1 year. No significant differences were seen in SST, ASES, or SF-12 scores. Significantly more patients achieved >90° of active forward elevation after RTSA (P = .012). RTSA provided significant cost savings to Medicare compared with HA and ORIF (P = .002.) CONCLUSION: In this case-control study, RTSA appears to provide superior range of motion earlier and more predictably than HA and ORIF, with significant cost savings to Medicare.

Investigating Object Translation in Room-scale, Handheld Virtual Reality.

Handheld devices have become an inclusive alternative to head-mounted displays in virtual reality (VR) environments, enhancing accessibility and allowing cross-device collaboration. Object manipulation techniques in 3D space with handheld devices, such as those in handheld augmented reality (AR), have been typically evaluated in table-top scale and we currently lack an understanding of how these techniques perform in larger scale environments. We conducted two studies, each with 30 participants, to investigate how different techniques impact usability and performance for room-scale handheld VR object translations. We compared three translation techniques that are similar to commonly studied techniques in handheld AR: 3DSlide, VirtualGrasp, and Joystick. We also examined the effects of target size, target distance, and user mobility conditions (stationary vs. moving). Results indicated that the Joystick technique, which allowed translation in relation to the user's perspective, was the fastest and most preferred, without difference in precision. Our findings provide insights for designing room-scale handheld VR systems, with potential implications for mixed reality systems involving handheld devices.

Molecular-guided therapy for the treatment of patients with relapsed and refractory childhood cancers: a Beat Childhood Cancer Research Consortium trial.

BACKGROUND: Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make real­time treatment decisions for children with relapsed/refractory solid tumors. METHODS: Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors. Tumor samples were sent for tumor/normal whole-exome (WES) and tumor whole-transcriptome (WTS) sequencing, and the genomic data were used in a multi-institutional MTB to make real­time treatment decisions. The MTB recommended plan allowed for a combination of up to 4 agents. Feasibility was measured by time to completion of genomic sequencing, MTB review and initiation of treatment. Response was assessed after every two cycles using Response Evaluation Criteria in Solid Tumors (RECIST). Patient clinical benefit was calculated by the sum of the CR, PR, SD, and NED subjects divided by the sum of complete response (CR), partial response (PR), stable disease (SD), no evidence of disease (NED), and progressive disease (PD) subjects. Grade 3 and higher related and unexpected adverse events (AEs) were tabulated for safety evaluation. RESULTS: A total of 186 eligible patients were enrolled with 144 evaluable for safety and 124 evaluable for response. The average number of days from biopsy to initiation of the MTB-recommended combination therapy was 38 days. Patient benefit was exhibited in 65% of all subjects, 67% of neuroblastoma subjects, 73% of CNS tumor subjects, and 60% of rare tumor subjects. There was little associated toxicity above that expected for the MGT drugs used during this trial, suggestive of the safety of utilizing this method of selecting combination targeted therapy. CONCLUSIONS: This trial demonstrated the feasibility, safety, and efficacy of a comprehensive sequencing model to guide personalized therapy for patients with any relapsed/refractory solid malignancy. Personalized therapy was well tolerated, and the clinical benefit rate of 65% in these heavily pretreated populations suggests that this treatment strategy could be an effective option for relapsed and refractory pediatric cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02162732. Prospectively registered on June 11, 2014.

Potential Biotechnological Applications of Venoms from the Viperidae Family in Central America for Thrombosis.

Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent's total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications.

Suprascapular nerve entrapment isolated to the spinoglenoid notch: surgical technique and results of open decompression.

BACKGROUND: Entrapment of the suprascapular nerve (SSN) at the spinoglenoid notch (SGN) specifically affects the infraspinatus, and isolated external rotation (ER) weakness can result. We describe the technique of open SSN decompression at the SGN for infraspinatus involvement and report the results of a consecutive series. MATERIALS AND METHODS: Twenty-nine shoulders underwent SSN decompression at the SGN. The mean age was 44 years (range, 15-69 years), and the mean follow-up was 4.3 years (range, 1-7 years). On manual muscle testing, ER strength was abnormal in all patients: 2/5 in 3, 3/5 in 21, and 4/5 in 5. The mean preoperative American Shoulder and Elbow Surgeons (ASES) score was 48 (range, 23-83). Atrophy of the infraspinatus was visible or palpable in 72% of shoulders. Magnetic resonance imaging showed ganglion cysts at the SGN in only 20.7% of shoulders. RESULTS: Of the patients, 19 (66%) regained full ER strength, 9 (31%) improved to 4/5, and 1 (3%) had ER strength of 3/5. The mean ASES score improved to 75 (range, 60-100) (P < .05). Of 29 shoulders, 23 (79%) showed improved ER strength within 1 week of surgery. All ganglion cyst cases regained full ER strength within a mean of 6 weeks. In all cases, ER strength improved by at least 1 full strength grade. DISCUSSION: A ganglion cyst is not necessary to produce SSN compression at the SGN. SSN compression at the SGN can present as an isolated entity or can occur in conjunction with rotator cuff pathology or a ganglion cyst. An index of suspicion, physical examination, magnetic resonance imaging, and electromyography confirm the diagnosis. The described operative approach detaches no muscle and allows rapid recovery, and in all cases, ER strength improved to normal or by 1 full grade.

Temporal Variation of Treatment Patterns and Survival Outcomes of Triple-Negative Breast Cancer Patients: A Real-World Experience From 2000 to 2014.

BACKGROUND: Previous studies have reported a higher prevalence of triple-negative breast cancer (TNBC) in US Hispanic/Latina populations. However, survival outcomes and treatment approaches over time in Latin American females are scarcely reported. We aimed to evaluate the temporal variation in treatment patterns and overall survival (OS) outcomes of females with TNBC according to cancer stage. MATERIALS AND METHODS: We performed a single-center retrospective cohort study on 1840 females from 2000 to 2014. Patients were classified in 3 calendar periods (2000-2004, 2005-2009, and 2010-2014). The Kaplan-Meier method and multivariable regression analyses were employed. RESULTS: Stage III cancer was identified in half of the population. Five-year OS estimates for cancer stages I, II, and IV remained unchanged across all calendar periods. However, we found worsening 5-year OS estimates in stage III females (49% in 2000-2004 and 31% in 2010-2014; P < .001). Despite increased uptake of overall use of neoadjuvant therapy in stage III females, the time from diagnosis to treatment initiation (P = .013) and time to complete the planned cycles (P < .001) increased over time. Fifty-sex percent of stage IV patients were untreated. Females aged ≥70 years were less likely to receive treatment. CONCLUSIONS: Survival estimates were lower than those reported in high-income countries. Most females were diagnosed with advanced disease, and the OS for stage III females worsened over time. Our outcomes show difficulties in delivering timely neoadjuvant therapy in an overwhelmed healthcare system. Public health authorities should improve screening practices, develop regional clinical guidelines, and expand trial enrollment.

Outcomes of HTLV-1 Carriers with Diffuse Large B-Cell Lymphoma: A Single-Center Retrospective Matched Cohort Study.

BACKGROUND: The human T-cell lymphotropic virus type 1 (HTLV-1) is associated with aggressive diseases, such as adult T-cell leukemia/lymphoma (ATLL). However, less is known on the impact of HTLV-1 infection in non-ATLL hematologic malignancies. We aimed to investigate if HTLV-1 carriers with diffuse large B-cell lymphoma (DLBCL) have worse survival outcomes than non-HTLV-1 carriers. MATERIALS AND METHODS: We performed a single-center retrospective cohort study by matching HTLV-1 carriers to non-carriers based on age, sex, Ann Arbor stage, and year of diagnosis. Our outcomes of interest were overall survival (OS) and progression-free survival (PFS). The Kaplan-Meier method was used to estimate OS and PFS between carriers and non-carriers. We fitted multivariate Cox regression models to assess the mortality and recurrence/disease progression risk of HTLV-1 infection. RESULTS: A total of 188 patients, 66 with HTLV-1 infection and 122 without HTLV-1, were included in the study. HTLV-1 carriers had higher extranodal involvement than non-carriers (47% vs. 27%, P = .010). With a median follow-up of 78 months (95% CI: 41-90 months), HTLV-1 carriers had a similar 5 year OS (41% vs. 42%, P = .940) and PFS (34% vs. 32%, P = .691) compared to non-carriers. In the multivariate Cox analysis, HTLV-1 infection was not associated with worse OS (aHR: 0.98, 95% CI: 0.64-1.50) or PFS (aHR: 0.90, 95% CI: 0.60-1.34). CONCLUSION: HTLV-1 carriers with DLBCL did not have worse survival outcomes compared to non-carriers. Our results suggest that clinicians should follow standard guidelines for DLBCL management on HTLV-1 seropositive patients.

Application of probabilistic models for extreme values to the COVID-2019 epidemic daily dataset.

Worldwide, COVID-19 coronavirus disease is spreading rapidly in a second and third wave of infections. In this context of increasing infections, it is critical to know the probability of a specific number of cases being reported. We collated data on new daily confirmed cases of COVID-19 breakouts in: Argentina, Brazil, China, Colombia, France, Germany, India, Indonesia, Iran, Italy, Mexico, Poland, Russia, Spain, U.K., and the United States, from the 20th of January, 2020 to 28th of August 2021. A selected sample of almost ten thousand data is used to validate the proposed models. Generalized Extreme-Value Distribution Type 1-Gumbel and Exponential (1, 2 parameters) models were introduced to analyze the probability of new daily confirmed cases. The data presented in this document for each country provide the daily probability of rate incidence. In addition, the frequencies of historical events expressed as a return period in days of the complete data set is provided.

An international, multicenter, retrospective study on the positive impact of cutaneous involvement on the clinical outcome of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p < 0.01; 1-year OS 53 vs. 27%, respectively, p = 0.012). Combination zidovudine and interferon-alpha (AZT-IFN) yielded high response rates (overall response, OR = 100%, n = 8; complete response 62.5%) compared to chemotherapy (OR = 33.3%, n = 12/36). In conclusion, cutaneous involvement was associated with better survival in Latin American patients with ATLL. AZT-IFN demonstrated encouraging responses in ATLL patients with cutaneous involvement.

Gastric myeloid sarcoma: A case report.

BACKGROUND: Myeloid sarcoma (MS) is a rare hematologic malignancy defined as an extramedullary tumor of immature granulocytic cells. It can occur as primary or de novo and be associated with myelodysplasia or myeloproliferative neoplasms. The most frequent locations are the skin, lymph nodes and bones. The case of a patient with a diagnosis of primary granulocytic de novo gastric MS is reported. CASE SUMMARY: A 19-year-old female patient with MS, whose abdominal computed tomography showed a bulky tumor of 16.5 cm in the gastric chamber with infiltration in the retroperitoneal, pancreatic and bile duct region; the histological study showed gastric mucosa diffusely infiltrated by mononucleated cells and the immunohistochemistry expressed myeloperoxidase. After receiving induction chemotherapy based on the 3 + 7 regimen (daunorubicin/cytarabine), the patient developed severe hematological toxicity and neutropenic typhlitis which required a prolonged medical treatment. She presented a rapid disease progression. Although she received supportive treatment, the patient died. CONCLUSION: Gastric primary de novo MS is a rare and aggressive course neoplasm, fostering knowledge is very important to decide its management and to promote more approaches focused on understanding this pathology and its particularities in our population.

Real-World Data on Adult T-Cell Leukemia/Lymphoma in Latin America: A Study From the Grupo de Estudio Latinoamericano de Linfoproliferativos.

PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS: We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS: We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone-like regimen (P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION: This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.

Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial.

Although combination BRAF and MEK inhibitors are highly effective for the 40-50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAFV600wt metastatic melanomas.

Genomic and Transcriptomic Analysis of Relapsed and Refractory Childhood Solid Tumors Reveals a Diverse Molecular Landscape and Mechanisms of Immune Evasion.

Children with treatment-refractory or relapsed (R/R) tumors face poor prognoses. As the genomic underpinnings driving R/R disease are not well defined, we describe here the genomic and transcriptomic landscapes of R/R solid tumors from 202 patients enrolled in Beat Childhood Cancer Consortium clinical trials. Tumor mutational burden (TMB) was elevated relative to untreated tumors at diagnosis, with one-third of tumors classified as having a pediatric high TMB. Prior chemotherapy exposure influenced the mutational landscape of these R/R tumors, with more than 40% of tumors demonstrating mutational signatures associated with platinum or temozolomide chemotherapy and two tumors showing treatment-associated hypermutation. Immunogenomic profiling found a heterogenous pattern of neoantigen and MHC class I expression and a general absence of immune infiltration. Transcriptional analysis and functional gene set enrichment analysis identified cross-pathology clusters associated with development, immune signaling, and cellular signaling pathways. While the landscapes of these R/R tumors reflected those of their corresponding untreated tumors at diagnosis, important exceptions were observed, suggestive of tumor evolution, treatment resistance mechanisms, and mutagenic etiologies of treatment. SIGNIFICANCE: Tumor heterogeneity, chemotherapy exposure, and tumor evolution contribute to the molecular profiles and increased mutational burden that occur in treatment-refractory and relapsed childhood solid tumors.

Correlates of clinical benefit from immunotherapy and targeted therapy in metastatic renal cell carcinoma: comprehensive genomic and transcriptomic analysis.

BACKGROUND: The clinical significance of tumor-specific genomic alterations in metastatic renal cell carcinoma (mRCC) is emerging, with several studies suggesting an association between PBRM1 mutations and response with immunotherapy (IO). We sought to determine genomic predictors of differential response to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) and IO. METHODS: Consecutive patients who underwent genomic profiling were identified; patients receiving either VEGF-TKIs or IO were included. Clinical tumor-normal whole exome sequencing and tumor whole transcriptome sequencing test were performed using a Clinical Laboratory Improvement Amendments (CLIA)-certified assay (Ashion Analytics; Phoenix, Arizona, USA). Genomic findings were compared between patients with clinical benefit (CB; complete/partial response or stable disease for >6 months) and no clinical benefit (NCB) in VEGF-TKI-treated patient cohort and IO-treated patient cohort. RESULTS: 91 patients received genomic profiling and 58 patients received VEGF-TKI and/or IO therapy. 17 received sequenced treatment involving both VEGF-TKI and IO, resulting in 32 patients in the IO cohort and 43 patients in the VEGF-TKI cohort. The most commonly used IO and VEGF-TKIs were nivolumab (66%) and sunitinib (40%). The most frequently detected alterations in the overall cohort were in VHL (64%), PBRM1 (38%), SETD2 (24%), KDM5C (17%) and TERT (12%). TERT promoter mutations were associated with NCB in the IO cohort (p=0.038); transcriptomic analysis revealed multiple differentially regulated pathways downstream of TERT. TERT promoter mutations and PBRM1 mutations were found to be mutually exclusive. While PBRM1 mutations were more prevalent in patients with CB with IO and VEGF-TKIs, no statistically significant association was found. CONCLUSIONS: Our analysis found that TERT promoter mutations may be a negative predictor of outcome with IO and are mutually exclusive with PBRM1 loss-of-function mutations.

Neutrophil-to-lymphocyte ratio predicts early mortality in females with metastatic triple-negative breast cancer.

BACKGROUND: The aim of this study was to determine the utility of the neutrophil-to-lymphocyte ratio (NLR) as a biomarker for predicting early-mortality (<2 years) among females with metastatic triple-negative breast cancer (mTNBC). METHODS: We reviewed 118 medical records of females with mTNBC. The cut-off value for the NLR (<2.5 and ≥2.5) was determined with receiver operating characteristic curves (area under the curve: 0.73; 95% CI: 0.62-0.85). Survival curves were estimated using the Kaplan-Meier method and compared with the Log-rank test. Multivariate Cox regression was used to identify the risk of mortality at two years. Moreover, we performed sensitivity analyses with different cut-off values and a subgroup analysis in females that only received chemotherapy. RESULTS: The median follow-up was 24 months. Females with NLR ≥2.5 had a poor overall survival compared to females with NLR <2.5 (6% vs. 28%, p<0.001) at two years. This outcome remained when we stratified for females that only received chemotherapy (8% vs. 36%, p = 0.001). Multivariate analyses identified NLR ≥2.5 as a poor prognostic risk factor for mortality in the entire population (HR: 2.12, 95% CI: 1.32-3.39) and among females that received chemotherapy (HR: 2.68, 95% CI: 1.46-4.92). CONCLUSION: The NLR is an accessible and reliable biomarker that predicts early mortality among females with mTNBC. Our results suggest that females with high NLR values have poor prognosis despite receiving standard chemotherapy. Health providers should evaluate the possibility to enroll these patients in novel immunotherapy trials.

Breast-conserving surgery vs. total mastectomy in patients with triple negative breast cancer in early stages: A propensity score analysis.

BACKGROUND: Breast-conserving surgery (BCS) as an alternative to total mastectomy (TM) in patients with early-stage triple-negative breast cancer (TNBC) is not widely spread. OBJECTIVE: We aimed to compare the overall survival (OS) and disease-free survival (DFS) between both surgical approaches in early-stage TNBC patients at 10 years. METHODS: We conducted a retrospective cohort study in TNBC female patients with stage I-IIa, treated at a single-center during the period of 2000-2014. We estimated and compared the survival rates with the Kaplan Meier and Long-rank test. Propensity scores were calculated with the generalized boosted regression model and were used in the multivariate Cox regression analysis with the covariate adjustment method. RESULTS: We included 288 patients, 111 in the BCS vs. 177 in the TM group. The median follow-up was 102 months. Moreover, the patients in the BCS group had superior OS (85% vs. 81%, p = 0.56) and DFS (83% vs. 80%, p = 0.42) at 10 years. In the multivariate Cox analysis, BCS decreased the mortality risk (HR: 0.79, 95% CI: 0.37-1.67, p = 0.538), and the locoregional or distant recurrence risk (HR: 0.67, 95% CI: 0.32-1.41, p = 0.294), albeit with no statistical significance. CONCLUSION: BCS is a safe alternative to TM in Latin-American patients with early-stage TNBC.

Triple-negative breast cancer in Peru: 2000 patients and 15 years of experience.

BACKGROUND: Epidemiological studies commonly identify the clinical characteristics and survival outcomes of patients with breast cancer at five years. Our study aims to describe the sociodemographic, clinicopathological characteristics and determine the long-term event-free survival (EFS) and overall survival (OS) of a Peruvian population with triple-negative breast cancer. METHODS: We reviewed the medical records of new cases treated at a single institution in the period 2000-2014. The survival analysis included patients with stages I-IV. Survival estimates at 10 years were calculated with the Kaplan-Meier method and compared with the Log-rank test. We further used multivariate Cox regression analysis to calculate prognostic factors of recurrence and mortality. RESULTS: Among the 2007 patients included, the median age at diagnosis was 49 years (19-95 years). Most patients presented histologic grade III (68.7%), tumor stage II (34.2%), and III (51.0%) at diagnosis. Local and distant relapse was present in 31.9 and 51.4% of the patients, respectively. The most frequent sites of metastasis were the lungs (14.5%), followed by bone (9.7%), brain (9.6%), and liver (7.9%). The median follow-up was 153 months. At 3, 5, and 10 years, the EFS of the population was 55%, 49%, and 41%, respectively, while the OS was 64%, 56%, and 47%, respectively. Moreover, an N3 lymph node status was the most important prognostic factor for both disease relapse (HR: 2.54, 95% CI: 2.05-3.15) and mortality (HR: 2.51, 95% CI: 2.01-3.14) at ten years. An older age and higher T staging were associated with a worse OS, while patients who received radiotherapy and adjuvant chemotherapy had better survival rates. CONCLUSION: The sociodemographic features of Peruvian patients with TNBC are similar to those of other populations. However, our population was diagnosed at more advanced clinical stages, and thus, EFS and OS were lower than international reports while prognostic factors were similar to previous studies.