Instituto Nacional De Enfermedades Neoplasicas Research Articles

Frequency of IKZF1 Deletions in a Peruvian Population with B-Cell Acute Lymphoblastic Leukemia

Frequency of IKZF1 Deletions in a Peruvian Population with B-cell Acute Lymphoblastic Leukemia Background: B-cell Acute Lymphoblastic Leukemia (B-ALL) is an aggressive disease with worse outcomes in older patients, and latino ethnicity. Additionally, Latino populations are at higher risk of developing B-ALL.IKZF1is an essential lymphoid transcription factor with deletions (ΔIKZF1)implicated in treatment failure and relapses. We aimed to evaluate the frequency ofIKZF1deletions in a cohort of Peruvian patients with newly diagnosed B-ALL. Methods: We collected diagnostic bone marrow samples from 41 consecutive patients with B-ALL diagnosed between 2015-2019 at Instituto Nacional de Enfermedades Neoplasicas (INEN; Lima, Peru). Bone marrow samples were cryopreserved prior to induction treatment. DNA was extracted using High Pure PCR Template Preparation Kit (Roche) at INEN. Samples with adequate DNA were screened forΔIKZF1by multiplex endpoint PCR covering four main deletions - dominant negative Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 IKZF1 deletions at UCL Cancer Insitute (London, UK) using the primers described by Caye et. al. We analyzed outcomes byIKZF1status. Results: Forty-one cases were enrolled during the study period. Clinical characteristics are presented in Table 1. Median age was 20 years[1-63]. Fifteen∆IKZF1cases (37%) were detected (67%BCR-ABL1 negand 33%BCR-ABL1pos).Cases withΔIKZF1were older than those with wild-typeIKZF1(median age 31 vs 13 years, p=0.002). Median presenting white blood count (WBC) was 48 x109/L [R:2-218], with a higher WBC inΔIKZF1compared to wild-type (87 vs 24 x109/L, p=0.001). The most frequent deletion was ∆4-7 (sevenBCR-ABL1 negand threeBCR-ABL1 pos) additional deletions are described in table 2. All patients received intensive 'pediatric-based' treatment, 21 with BFM-2009 and 19 with the CALGB 10403 protocol. CR rates after induction were 67% and 92% for∆IKZF1and wild-type cases, respectively. Eleven (73%) of patients with∆IKZF1subjects (73%) were MRD positive by flow cytometry after induction compared to 11 (44%) among wild-type. At a median follow-up of 2 years EFS was 38% in the∆IKZF1group and 58% in the wild type group, correspond OS was 38% and 58%, respectively. Conclusion: A high frequency of IKZF1 deletions was found in a Peruvian population with B-ALL and was associated with older age and higher presenting white blood counts. Prospective studies with larger Latino population are warranted to confirm this finding. Disclosures No relevant conflicts of interest to declare.

Clinical Characteristics, Immunophenotype and Outcomes of Blastic Plasmacytoid Dendritic Cell Neoplasms in a Peruvian Cohort

Background:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and fatal myeloid malignancy characterized by clonal proliferation of immature plasmacytoid dendritic cells. BDCN has been frequently described in men and age above 60 years, and usually involves the skin and bone marrow. Immunophenotyping is based on CD123+, CD4+ and CD56+ expression and is necessary rule out other myeloid malignancies. Objective: We aimed to describe the clinical characteristics and immunophenotype of BPDCN cases diagnosed at two tertiary Peruvian cancer institutions between 2018-2019. Methods: We retrospectively reviewed medical records of patients diagnosed of BPDCN at two tertiary Peruvian cancer centers (Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru) between 2008 and 2019. Clinical characteristics, treatments, outcomes and immunophenotype by pathology or flow cytometry review, were collected. Patients were classified according to their maturation stage using CD34 and CD117 expression into three subgroups: Immature-Intermediate blastic (IIB-BPDCN; partial expression of CD117 and absence or minimal expression of CD34), mature (M-BPDCN; absence of CD34 and CD117) and unknown(U-BPDCN). Overall survival (OS) and event-free survival (EFS) curves were estimated using the Kaplan-Meier method and compared with the Log-rank test to determine the impact of immunophenotype. Results: Thirty-eight cases were included during the study period. The median age at diagnosis was 38 years (7-82), only six (16%) were older than 65 years, and a notorious female predominance (F/M ratio: 1.7:1) was observed. Twenty-four cases had CD34/117 expression available and were classified according to the maturation stage in IIB-BPDCN (13) and M-BPDCN(11), additionally 14 cases had unknown stage (U-BPDCN). Table 1 summarizes clinical characteristics, treatment and outcomes according to their immunophenotype. Bone marrow infiltration was more frequent in immature phenotypes (92% IIB-BPDCN vs 73% M-BPDCN, p=0.001), as well as skin infiltration was more common in mature phenotype (72% vs 31%, p=0.008). CNS infiltration at diagnosis was 15% and 55% in IIB-BPDCN and M-BPDCN, respectively. Sixteen patients received treatment based on ALL-like protocols, 8 AML-like, 5 CHOP-like and 9 patients only palliative care. At 5 years median follow-up, median EFS and OS was 12 and 16 months, respectively. IIB-BPDCN had the lowest survival (4 months EFS and 6 months OS). Conclusions: We describe a Peruvian cohort of BPDCN patients with younger age at diagnosis and female predominance than reported previously by other series, however further studies in Latino population are required to confirm these results. Immature phenotypes based on CD34 and CD117 expression were associated with high rate of bone marrow infiltration and fatal outcomes. New successful target therapies must be warranted for this rare and fatal condition. Disclosures No relevant conflicts of interest to declare.

Prognostic Value of DNA Ploidy By Flow Cytometry for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Peruvian Cohort Study

Background: B-cell Acute Lymphoblastic Leukemia (B-ALL) represents an aggressive malignancy but highly curable in children. Currently, pediatric collaborative clinical trials have reported survival rates that exceed 90%, and DNA ploidy by flow cytometry (FC) has been pointed for risk stratification and prognosis in these clinical trials. However, its generalized use remains controversial as few studies reported no impact in real-world populations. We aimed to evaluate prognostic value of DNA ploidy measured by FC in a large cohort of Peruvian children with B-ALL. Methods: We evaluated prospectively DNA-ploidy by FC in bone marrow diagnostic samples from newly diagnosed children (<15 years) with B-ALL treated at Instituto Nacional de Enfermedades Neoplasicas (Lima-Peru) between 2017-2019. DNA-ploidy was evaluated using Propidium Iodide and calculated as the mean ratio between fluorescence of pathologic B blasts and normal marrow cells. Ploidy categories were established based on previous reports of DNA-index(DI): Diploid + Low-Hyperdiploidy (DLH; DI: 0.95 - 1.15), hypo-diploid (HD; DI<0.95) and High-hyperdiploidy (HH; DI>1.15), and recalculated using maximally selected rank statistics. Samples were analyzed in a FacsCanto II flow cytometer (BD) and Infinicyt software (Cytognos). All patients received BFM-2009 protocol and had minimal residual disease evaluation at the end of IA and IB induction. Minimal residual disease (MRD) was evaluated with FC using a detection threshold of 0.0025% and considering positive ≥0.01%. Survival curves (event-free and overall survival) were estimated using the Kaplan-Meier method and compared with the Log-rank test. Results: A total of 192 children were included (2 HD, 141 DLH and 49 HH cases according to DNA ploidy by FC). Clinical characteristics and outcomes are shown in Table 1. Median age at diagnosis was 5 years (Range:1-14), 10 years for HD, 6 and 3 years for DLH and HH, respectively (p=0.002). F/M ratio was 1:1.3 for all cases, but 1:2 in HH group. Most karyotypes (62%) had unsatisfactory or poor-quality result, 29% were considered normal, and only 9 hyperdiploidy and 2 hypodiploidy cases were detected by conventional karyotyping. Regarding genetics, 21 TEL/AML, 19 E2A/PBX1 and 9 BCR/ABL cases were detected by multiplex-PCR and most balanced alterations had DLH subtype and only one HD case had TEL/AML. MRD positivity after Induction IA was 35% without difference between groups (50% HD, 36% DLH and 31% HH, p=0.77), however after Induction IB, MRD was positive in 50% of HD, 12% of DLH and 5% of HH (p=0.048). At eight-teen months of follow-up, one relapse was seen in HD cases, and 11% DLH and 10% in HH. Median EFS and OS was not reached, however one-year EFS and OS were 86% for both without significant differences between groups. Multivariate analysis showed that MRD positivity remains as the principal independent prognostic factor and ploidy by DNA did not show any impact in terms of MRD, EFS and OS. Conclusion: High-Hyperdiploidy by DNA ploidy was associated to better MRD negativity rate after induction IB but without impact in short-term EFS and OS. DNA ploidy did not represent a prognostic factor in our study cohort, however long-term follow-up is warranted. Additionally, a better genetic risk stratification is necessary to improve outcomes in Latino high-risk population. Disclosures No relevant conflicts of interest to declare.

Impact of the Delayed Initiation of Adjuvant Chemotherapy in the Outcome of Triple Negative Breast Cancer

BackgroundAdjuvant chemotherapy decreases the recurrence risk and improves survival rates; however, it is unclear whether a delayed initiation is associated with adverse outcomes, especially in triple negative breast cancer (TNBC). In this study, we evaluated the influence of the time to start adjuvant chemotherapy (TTC) in the outcomes of TNBC. Patients and MethodsWe retrospectively analyzed 15 years of data from patients with TNBC who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). TTC was categorized into 4 groups: ≤ 30, 31 to 60, 61 to 90, and ≥ 91 days. We evaluated overall survival (OS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were used to identify prognostic factors. ResultsIn total, 687 patients were included. The mean age at diagnosis was 49.1 years (SD, 11.8 years), and most (62.6%) patients had pathologic stage T2. The median TTC was 48.1 days (SD, 27.4 days); 189 (27.5%) received chemotherapy ≤ 30 days; 329 (47.9%), between 31 and 60 days; 115 (16.7%), between 61 and 90 days; and 54 (7.9%) in ≥ 90 days. In the multivariate analysis, a TTC between 31 and 60 days (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.17-2.72), 61 and 90 days (HR, 2.38; 95%CI, 1.43-3.97), and ≥ 91 days (HR, 2.45; 95% CI, 1.32-4.55) was associated with an increased mortality in contrast with a TTC < 30 days. Although a TTC between 31 and 60 days, 61 and 90 days, and ≥ 91 days was associated with an increased risk of DRFS (HR, 1.86; 95% CI, 1.24-2.79; HR, 2.34, 95% CI, 1.42-3.867; and HR, 3.16; 95% CI, 1.78-5.61, respectively). ConclusionA delaying in TTC ≥ 30 days was associated with poorer outcomes. Our data suggest that several efforts should be conducted to avoid a delayed TTC in patients with TNBC.

Characteristics of fungemia in a peruvian referral center: 5-year retrospective analysis.

Retrospective descriptive study carried out to determine the characteristics of fungemia in 285 cancer patients hospitalized from 2012 to 2016 at the Instituto Nacional de Enfermedades Neoplásicas (INEN). Demographic, clinical and microbiological information was evaluated. Fungemia by C. albicans predominated in patients with solid tumors and without neutropenia, while those caused by C. tropicalis predominated in patients with hematological neoplasia and neutropenia. C. tropicalis was the agent isolated in most cases (47.0%). Fungemia increased over time in patients without neutropenia. Fungemia caused by C. albicans increases with age in patients with solid tumors without neutropenia. It is concluded that fungemia are mainly caused by C. tropicalis in patients with hematological neoplasia with neutropenia and by C. albicans in patients with solid tumors without neutropenia. In addition, fungemia in patients without neutropenia increases over time; and those caused by C. albicans increase with age in patients with solid tumors without neutropenia.

Abstract PR05: A genetic variant at 6q25 associated with estrogen receptor-negative breast cancer subtypes in Peruvian breast cancer patients

Abstract Background: We have previously identified a genetic variant, rs140068132, which has a strong protective effect on breast cancer risk. This variant is located near the estrogen receptor 1 gene (ESR1) on chromosome 6q25, a locus which has been repeatedly implicated in breast cancer risk. Women who carry two copies of the protective variant (GG) have 60-70% reduction in risk of developing breast cancer compared to women with none. The G variant has relatively high frequency in Latin American women (up to 23% in the 1000 Genomes Project Peruvians); it is only common in people of Indigenous American ancestry and almost absent in all other populations. We investigated whether the rs140068132-A/G polymorphism is associated with a specific breast cancer subtype among Peruvian women with breast cancer. Methods: Blood samples and clinical data were collected from 441 women with breast cancer at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru. Genotypic profiles were generated using the Affymetrix Precision Medicine Research Array. Four major breast cancer subtypes were identified based on immunohistochemical markers (luminal A, luminal B, triple-negative, and human epidermal growth factor receptor 2 (HER2) overexpressing). Quality control of the genotyped data was performed in PLINK. Genetic ancestry was determined for each individual using ADMIXTURE. ANOVAs were performed on the proportion of genetic ancestry and disease subtype. PLINK was used to perform a binary logistic regression on the rs140068132 variant and ER status (ER-negative versus-ER positive), with age and genetic ancestry as covariates. Results: The breast cancer patients analyzed have the following average ancestry proportions: 77.3% Indigenous American, 17.4% European, 3.8% African and 1.5% East Asian. The frequency of the G allele in the Peruvian breast cancer patients is 14% (compared to 23% in healthy individuals from the 1000 Genomes Project). We found that the G allele of rs140068132 was associated with ER-negative status among cases (OR = 0.6443, P = 0.086) for both HER2 overexpressing and triple-negative. We also examined the proportions of ancestry in relation to subtypes of disease. The proportion of Indigenous American ancestry was associated with the HER2 overexpressing subtype (P = 0.06), with an average Indigenous American ancestry among these patients of 83.1% compared to 77.3% among all patients. The proportion of African ancestry was higher in women with the triple-negative subtype, with an average African ancestry of 4.8% among patients with the triple-negative subtype compared to a 3.8% average among all patients, but this trend was not statistically significant (P = 0.21). Conclusions: The lower frequency of the variant in Peruvian breast cancer cases is consistent with a protective effect in this population. We have confirmed that the protective effect of the rs140068132 variant is stronger for ER-negative subtypes. Additional analyses are under way in a larger sample of Peruvian breast cancer patients. This abstract is also being presented as Poster C051. Citation Format: K.M. Marker, T. Vidaurre, L.I. Tamayo, J.N. Vásquez, R. Meza Florez, S. Casavilca, M. Calderon, J.E. Abugattas, H.L. Gómez, H.A. Fuentes, C.L. Monge Pimentel, S. Song, D. Cherry, S. Huntsman, D. Hu, E. Ziv, L. Fejerman. A genetic variant at 6q25 associated with estrogen receptor-negative breast cancer subtypes in Peruvian breast cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr PR05.

Tomographic characteristics of solid-pseudopapillary neoplasms (Frantz tumor).

Solid-pseudopapillary neoplasms (SPN), or Frantz tumor, is a rare, low-grade neoplasm that occurs mainly in young women. It was described in 1959 by Virginia Frantz and constitutes 0.2-2.7 % of all pancreatic tumors. Computed tomography (CT) plays an important role in the diagnosis of this pathology of scarce reporting. The objective of the present study is to describe the epidemiological and tomographic characteristics of the SPN in the Instituto Nacional de Enfermedades Neoplásicas (INEN) of Peru. Descriptive cross-sectional study performed with medical records of all patients diagnosed with SPN between 2004 and 2014. The variables described were tumor size, location, shape, borders, thickness of the capsule, composition, calcifications and uptake of contrast. The categorical variables were expressed in absolute and relative frequencies; while the numerical variables were described with median and interquartile deviation (ID). Statistical support STATA Version 12.0 was used. Of all pancreatic cystic tumors (PCT), 51.9% corresponded to confirmed cases of TSP. The median age was 23.5 years. The isolated location in the head predominated (33.3%); the most frequent mixed location was body and tail (16.7%); diameter was more frequent between 5.1-10 cm and the content of the majority was predominantly solid. 30.0% of the NSP presented calcifications. Most cases of INP SPN (2004-2014) have similar characteristics to those reported in the international literature.

Abstract P1-10-22: Predictive biomarkers of survival after neoadjuvant chemotherapy for breast cancer

Abstract Introduction: The use of neoadjuvant chemotherapy (NAC) has become the standard of care in non-metastatic breast cancer patients meaning an improvement of tumor regression rates with a high impact on survival especially in patients who achieve pathological complete response (pCR). Predictive biomarkers of survival acquire more relevance in the setting of patients who don’t achieve complete response allowing us to design strategies based on the response evaluation. This study aimed to evaluate the predictive value of the NAC response represented by residual cancer burden (RCB) and tumor-infiltrating lymphocytes in residual disease (RD TILs). Methods: We analyze non-metastatic breast cancer patients diagnosed at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru who received NAC and were under surgery from 2016 to 2019, we performed a prospective evaluation of RCB and the level of stromal RD TILS by hematoxylin and eosin (H&amp;E), CD-3 and CD-8 by immunohistochemistry in a subgroup of patients, we choose the median of percentage as a cut-off. Epidemiologic and clinic-pathological data were collected from clinical files. Survival analysis was calculated by using Kaplan-Meier method. Results: During the study period, we analyzed 271 NAC cases, median of age of diagnosis was 51 years, most common molecular subtype was Luminal B (56.5%) followed by Triple Negative (24.4%), 124 (45.8%) patients were at clinical stage IIIB followed by 54 (19.9%) IIB. 226 (83.4%) patients didn’t achieve pCR, most of them achieved RCB class III (40.6%) followed by RCB class II (37.6%). Among these we evaluated RD TILs in 42 patients. 54.8% of patients had RD TILs level greater than 30%, 53.3% had CD-3 level greater than 60% and 51.2% a level of CD-8 greater than 40%. Median PFS was 42 months (range 15.6 - 68) and estimated 3-years OS was 95.5%. We found significative difference between the RCB class and PFS (p=0.001) and OS (p=0.035), no differences between the level of stromal RD TILs, CD-3 or CD-8 with PFS or OS was found. Conclusion: Results from this cohort provide evidence for the benefit of NAC, in this setting RCB had a significative predictive value for breast cancer recurrence and survival, however, the level of RD TILs, CD-3 and CD-8 didn’t show differences on survival maybe by the number of cases. This work was supported by CONCYTEC (contract No. 198-2015-CONCYTEC) Keywords: Breast cancer, Neoadjuvant, Residual cancer burden, TILs, progression-free survival. Citation Format: Marco Galvez-Nino, Katia Roque, Luis Angel Bernabe, Miluska Castillo, Joselyn Sanchez, Maria Landa Baella, Gabriela Calderon, Miguel De la Cruz, Jorge Dunstan, Julio Abugatas, Jose Cotrina, Carlos Castaneda, Henry Gomez. Predictive biomarkers of survival after neoadjuvant chemotherapy for breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-22.

TransAnal Total Mesorectal Excision (TaTME) in Peru: Case series

IntroductionDescribe and demonstrate the feasibility and safety of TaTME in short term outcomes in the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Peru. Materials and methodsCase series with retrospective and prospective data collection of patients with middle and inferior rectal cancer who underwent TaTME between January 2015 and March 2020. Patients and tumor characteristics, operative details, postoperative complications and pathological results were analyzed. ResultsNineteen patients were included. The median age was 56 years old (range 40–69). Ten were female. The median distance from the anal verge was 4 cm (range 3–6) and 17 cases were located in the inferior rectum. Eleven patients with clinical stage III. Thirteen (68.4%) patients received neoadjuvant treatment. There was no conversion to open surgery reported. Ten (52.6%) cases had intersphincteric resection and 18 (94.7%) had primary coloanal anastomosis, 13 (72.2%) of them with hand-sewn. All patients had a diversion with ileostomy. The median operative time was 330 min (range 270–480). Median postoperative hospital stay of 5 days (range 3–18). The overall rate of postoperative complication was 21.1%, two cases (10.5%) had anastomotic leakage and mortality was present in one (5.3%) patient. 94.5% had an optimal TME specimen, only one case (5.3%) had positive circumferential resection margin and positive distal margin. The median tumor size in the specimen was 4 cm (range 2–11) and nine (47.4%) patients had ypT3 on pathology. ConclusionTaTME is a safe and feasible technique with good pathological results.

Lung Cancer in the Young.

Median age at diagnosis of lung cancer is 70years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients. We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software. We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36years (range 14-40years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2months. The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.

Implementation of the Peripherally Inserted Central Venous Catheter for Patients with Hematological Malignancies in a Peruvian Cancer Center

Background: A central venous access is essential during active treatment for most patients with hematological malignancies, and historically, the central inserted venous catheter (CVC) has been the preferred option in clinical practice. In the last years, the peripheral inserted central catheter (PICC) has increasingly been used as an alternative to CVC with less incidence of catheter related infections (CRI). Our aim was to compare the incidence of documented catheter related infections and mortality for patients with PICC versus CVC. Methods: We prospectively enrolled patients who were candidates for PICC implantation from March 2018 to February 2019, and matched them with a CVC candidate patient. PICC patients were followed at our PICC line program and CVC patients with their primary oncologist team as per institutional protocol. All patients received intensive treatment at a public tertiary cancer center in Lima-Peru (Instituto Nacional de Enfermedades Neoplasicas). Results: We included 94 cases during the study period (44 PICC and 50 CVC cases), median age was 39 years and M:F ratio was 2:1. In the PICC group, main diagnoses were acute leukemias (46%), Lymphomas (22%) and Multiple Myeloma (16%), on the other hand, in the CVC group, acute leukemias (72%), lymphoma (16%) and multiple myeloma (8%). Mean length of catheterization was 40 and 24 days for PICC and CVC, respectively. The incidence of documented CRI was lower in PICC group (12.6 versus 3.1 per 1000 days for CVC and PICC, respectively), showing a risk reduction of 75% of bacteremia (RR: 0.25, 95%CI 0.1-0.6, p&lt;0.01). Mortality rate was 20% and 14% in CVC and PICC groups, respectively (p=0.4). Conclusion: PICC represents a safe and effective alternative to CVC for patients with hematological malignancies in a limited source setting. An alarming high incidence of catheter related infections was noted in this study. Disclosures No relevant conflicts of interest to declare.

P2.15-12 Epidemiology of Thymic Epithelial Tumors: 22-Year Experience from a Single-Institution

Thymic epithelial tumors (TETs) represents a heterogeneous group of rare neoplasms that represent, however, the most common entity of the anterior mediastinum. Epidemiological data and treatment options for these neoplasms are very limited. Retrospective study of TET diagnosed at Instituto Nacional de Enfermedades Neoplasicas (INEN) in Lima, Peru, from 1996 to 2018. Clinicopathological data was retrieved from clinical files. All cases were reviewed by a pathologist and reclassified according to the 2004 WHO classification system. Staging was performed with the Masaoka-Koga Staging System. Treatment and follow-up data were also collected. Survival curves were constructed with the Kaplan-Meier method. 84 patients were included. Median age at diagnosis was 55 years old (range 19 to 84) and 51.8% were female. Most patients (95.2%) were in good status performance (Zubrod 0-2) and 36.5% were smokers. The histological type corresponded to thymoma (T) in 63.9% of cases (n=53) and to thymic carcinoma (TC) in 36.1% of cases. T were of type A, AB, B1, B2 and B3 in 15.8%, 19.7%, 3.2%, 3.9% and 7.9% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was higher in TC (89.6%) than in T (51.1%). The most common treatment modality was systemic chemotherapy for advanced disease in 37.3%. With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (p=0.01). Survival according to different histological types is shown in table 1.Tabled 1Histological typeMedian OS (months)Thymoma A, AB, B1102Thymoma B2 – B316.7Thymic carcinoma12.3 Open table in a new tab The result of this study indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher than expected proportion of T with advanced disease at diagnosis. The reasons behind this finding require further research. Being this a rare disease, collaboration is very important to foster knowledge and to promote prospective and randomized clinical trials focused on classification and treatment.

Abstract 4184: Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru

Abstract There are few Latin American cohorts with available biospecimens that include women of high Indigenous American ancestry. The Peruvian population is characterized by a high degree of Native American (NA) ancestry, with this ancestral component varying between 56 to 100% on average, depending on the region. We have collected 1199 Peruvian samples from the Instituto Nacional de Enfermedades Neoplasicas in Lima. This cohort of patients represents a unique opportunity to study the molecular characteristics of breast cancer in the NA genetic and genomic background. Here we present a basic description of the women in the study and a comparison of tumor subtypes distribution and risk factor information of the patients by place of birth and residence. We explored differences in tumor subtype distribution and risk factors in relation to place of birth or residence in the three main geographical region of Peru. To test differences in proportions we used Chi2 or Fisher-exact tests. To test differences in means for continuous variables we used ANOVA or t-tests. Genetic ancestry was estimated using genome wide genotypes and the program ADMIXTURE. Tumor subtypes were defined using the following criteria: ER+/PR+/HER2- as luminal A, ER+/PR+/HER2+ as luminal B, ER-/PR-/HER2+ as HER2+ and ER-/PR-/HER2- as triple negative. Overall, the patients included in the study were relatively young (50 yrs, SD=11.0). The average number of full-term pregnancies was 3 (SD=1.8), the average age at first pregnancy 22 (SD=5.7) and age at menarche was 13 (SD=1.8). The tumor subtype distribution was 31% of Luminal B tumors, 24% luminal A, 12% HER2 and 12% triple negative and did not differ by place of birth or residence. We found that patients from the Coastal region were heavier and taller than those born in the Andean region (p&amp;lt;0.005). Women born in the Coastal region had the lowest age at menarche and a lower number of full-term pregnancies (p&amp;lt;0.0001). Similar trends were observed when we compared women by place of residence. Patients born in Lima, the Capital of Peru, smoke more (p&amp;lt;0.05), were heavier, had lower age at menarche, lower number of full term pregnancies and were diagnosed at a younger age, compared to women born outside the city (p&amp;lt;0.05). The distribution of NA genetic ancestry also varied by place of birth: patients born outside Lima had higher proportion of NA ancestry (78% SD=0.15 vs. 74%, SD=0.18, p&amp;lt;0.05). The distribution of tumor subtypes among women in the Peruvian breast cancer cohort did not differ by place of birth or residence. However, we found that for some breast cancer risk factors, exposures differed between women from different regions. Finally, given the relatively low observed values for reproductive and lifestyle related exposures and the high proportion of Indigenous American ancestry of Peruvian women, this cohort is likely to be particularly informative to study genetic predisposition to breast cancer. Citation Format: Valentina Zavala, Tatiana Vidaurre, Katie Marker, Jeannie Vásquez, L Tamayo, Renzo Florez, Sandro Casavilca, M Calderon, J Abugattas, H Gómez, H Fuentes, C Monge-Pimentel, S Song, D Cherry, Laura Fejerman. Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4184.

Abstract 1589: Breast cancer subtype GWAS in Peruvian breast cancer patients

Abstract Background: We previously investigated genetic ancestry associations with breast cancer subtypes in Peruvian women. We found that women with human epidermal growth factor receptor 2 (HER2) over-expressing tumors had higher Indigenous American ancestry than women with other subtypes. We found a suggestive association between African ancestry and triple negative breast cancer (TNBC). We hypothesized that these associations could be due to the presence of germline variants in the Indigenous American genome or the African genome predisposing women to HER2 over-expression or TNBC respectively. We conducted genome wide association analyses to explore this hypothesis. Methods: Blood samples and clinical data were collected from 1195 women with breast cancer at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru. Genotypic profiles for 821 women were generated using the Affymetrix Precision Medicine Research Array. Four major breast cancer subtypes were identified using immunohistochemical markers (luminal A, luminal B, triple negative, and HER2 over-expressing). Genetic ancestry was determined using ADMIXTURE. Genome wide association analyses were conducted in PLINK. Results: Three polymorphisms with the lowest p values in the TNBC GWAS are of interest. A variant, rs16910137, at 10q26, is located in an intron of the Glutaredoxin 3 gene (GLRX3 or TXNL2, OR = 2.45, P = 8.60*10-07). The protein encoded by this gene may inhibit apoptosis and play a role in cellular growth. It has also been described as a biomarker for TNBC. Our own RNA-seq data for TXNL2 in 52 Colombian women with breast cancer showed that the expression level of this gene is higher in women with triple negative (N=9) compared to luminal tumors (N=43) (P=0.06). The other two variants, rs12327440 and rs13381183, are located in an intron of the Mitogen-Activated Protein Kinase 4 (MAPK4) gene at 18q21 (OR = 0.44 and 1.94 respectively, P = 4.92*10-07 and 7.230*10-06). RNA-seq data for MAPK4 suggestively showed that the expression level is higher in women with TNBC compared to luminal tumors (P=0.18). The variant in the HER2 over-expressing GWAS with the lowest p value, rs11594103, at 10p11 is located upstream of the Enhancer Of Polycomb Homolog 1 (EPC1) gene (OR = 2.38, P = 8.03*10-07). The encoded protein has been linked to apoptosis and DNA repair among other functions and suggested as involved in the activation of metastasis. Conclusions: Our data suggests that a germline variant within the GLRX3/TXNL2 gene might be associated with the risk of developing TNBC compared to other subtypes. This is particularly interesting in the light that previous work suggested that TXNL2 autoantibodies could be biomarker of TNBC. The MAPK4 and EPC1 genes have been previously implicated in multiple types of cancer and our results indicate that they may play a role in the etiology of specific breast cancer subtypes. This supports the importance of conducting genetic association studies in diverse samples. Citation Format: Katie M. Marker, Tatiana Vidaurre, Jeannie Navarro Vasquez, Valentina Zavala, Silvia Serrano Gomez, Lizeth Tamayo, Renzo Meza Florez, S Casavilca, M Calderon, JE Abugattas, Henry Gómez, Hugo Fuentes, CL Monge Pimentel, Sikai Song, Daniel Cherry, Scott Huntsman, Donglei Hu, Elad Ziv, Laura Fejerman. Breast cancer subtype GWAS in Peruvian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1589.

Epidemiology and survival of lung cancer in a Latin American cohort.

e13101 Background: Lung cancer epidemiology and survival data is lacking in LA. This information is relevant for understanding regional cancer burden and for designing targeted interventions for cancer control. Methods: Retrospective analysis of lung cancer cases diagnosed at Instituto Nacional de Enfermedades Neoplasicas (INEN) from 2010 to 2014. Data was manually curated from clinical files. Results: 1384 patients were included. Median age at diagnosis was 64 years old (range 20-92) and 51.6% were females. The histologic type was adenocarcinoma, NOS carcinoma, squamous cell carcinoma and small-cell carcinoma in 72.3%, 12.8%, 9.4% and 3.5% of the cases, respectively. The adenocarcinoma/squamous cell carcinoma ratio was 7.7. Among NSCLC cases, most patients presented with advanced disease. Stage III (9.2%) and IV (85.5%) were the most frequent. With a median follow-up of 71.5 months, median overall survival (OS) was 9.2, 7.7 and 8.1 months for adenocarcinoma, NOS carcinoma and squamous carcinoma, respectively. Five-year OS for stage III was 6% and for stage 4, 4%. Detailed results are shown in the table. Conclusions: The epidemiological profile of lung cancer in Peruvian patients is different from that of other countries with a younger age at diagnosis, a preponderance of females over males and an unexpectedly high frequency of adenocarcinomas. This may be in concordance with the low prevalence of tobacco smoking and the high prevalence of EGFR mutations reported for our population as well as with particular exogenous exposures such as biomass fumes from inhouse cooking. The molecular characterization of this cohort of patients is ongoing. [Table: see text]

Peripheral-blood stem cell transplantation in pediatric recipients in Peru: Experience of a reference center.

e21530 Background: Stem cell transplantation (SCT) is a curative treatment for children with refractory/relapsed malignancies. However, data on pediatric transplantation in developing countries like Peru is still needed. The aim of this study was to describe and assess the survival and complications of children with neoplastic disease who have received peripheral-blood stem cell transplantation (PBSCT) at a reference center in Peru. Methods: A retrospective longitudinal study was performed by reviewing medical histories of 20 children (≤14 years) with neoplastic disease who underwent related allo- or auto-PBSCT from October 2014 to December 2017 of INEN (Instituto Nacional de Enfermedades Neoplásicas). In the cases of ALL &gt; 3 years, radiotherapy was not part of the conditioning regimen. The Kaplan-Meier method was used to determine the overall survival (OS) and event-free survival (EFS). Data were analyzed using Stata/MP 14.0. Results: We found 13 males and 7 females with a median age of 9.5 years (1-14), of whom 18 received allo-SCT and 2 auto-SCT. Diagnosis: 14 ALL(66.6%), 1 AML(4.7%), 1 NHL(4.7%), 2 biphenotypic leukemia(9.5%), 1 juvenile chronic myelomonocytic leukemia(4.7%) and 1 germ cell tumor(4.7%) who performed two auto-transplants. Complete remission (CR) was achieved before transplantation in 19 cases: 8(38%) 1CR; 8(38%) 2CR and 3(14.2%) 3CR. A median of 7.14x106CD34+/kg (3.97-13.05) (auto- vs allo-; 6.35 vs 7.27) were collected and median time to myeloid engrafment: 11 days. At a median follow-up of 12 months (1-39) the 2-year OS and EFS were 75.7% (95% confidence interval [CI], 38-92%) and 51.6% (95% CI, 22-74%) respectively. Considering only ALL &gt; 3 years, OS and EFS were 51.9% and 45.1%, respectively. Acute graft-versus-host disease (GVHD), chronic GVHD, transplantation-related mortality (TRM) and relapse were 27.7%, 11.1%, 4.7%, and 33.3%, respectively. Conclusions: We are encouraged by this first experience in our country. OS and EFS are comparable with results at the international level. However, survival of children with ALL &gt; 3 years who did not receive radiotherapy is less than international standards. Studies with a higher number of cases and longer follow-up time are needed to reach definitive conclusions.

Invasive fungal infection diagnosis in the Instituto Nacional de Enfermedades Neoplasicas 2013–2015 based on the criteria of EORTC/MSG

In uncertainty quantification, multivariate sensitivity analysis (MSA) extends variance-based sensitivity analysis to cope with the multivariate response, and it aims to apportion the variability of the multivariate response into input factors and their interactions. The first-order and total-effect covariance matrices from MSA, which assess the effects of input factors, provide useful information about interactions among input factors, the order of interactions, and the magnitude of interactions over all model outputs. In this paper, first, we propose and study generalized sensitivity indices (GSIs) using the first-order and total-effect covariance matrices. The new GSIs make use of matrix norms when partial orders such as the Loewner ordering on covariance matrices is not possible, and we obtain the classical GSIs using the Frobenius norm. Second, we propose minimum variance unbiased estimators (MVUEs) of the first-order and total-effect covariance matrices, and third, we provide an efficient estimator of the first-order and total (classical) GSIs. We also derive the consistency, the asymptotic normality, and the asymptotic confidence regions of these estimators. Our estimator allows for improving the GSIs estimates.

Abstract GS2-05: Impact of the delayed initiation of adjuvant chemotherapy in the outcomes of triple negative breast cancer

Abstract Background: Adjuvant chemotherapy decreases the risk of recurrence and improves survival rates but it is unclear whether a delayed initiation is associated with adverse outcomes. Information available is especially scarce for triple negative breast cancer (TNBC) which represents a high-risk group. We evaluated the influence of time to chemotherapy (TTC) on TNBC patient's survival outcomes. Methods: We retrospectively analyzed the data using the medical records of TNBC patients who received adjuvant chemotherapy at Instituto Nacional de Enfermedades Neoplasicas between 2000-2014. TTC was defined as the number of days between surgery and the first dose of chemotherapy. Patients were categorized into 4 groups according to TTC: ≤30, 31-60, 61-90, ≥91 days. We evaluated recurrence-free survival (RFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used. Results: 687 patients were included. Mean age at diagnosis was 49.15 (range, 21-89) and most patients were stage II (60.1%) or III (29.45%). They received either anthracyclines or anthracyclines and taxane-based chemotherapy (96.1%). Median TTC was 41 days. 189 (27.5%) received chemotherapy at or before 30 days; 329 (47.9%), between 31 and 60 days; 115 (16.7%), between 61 and 90 days and; 54 (7.9%) beyond 90 days. Median follow-up was 101 months. 10y-DFS was 81.4%, 68.6%, 70.8% and 68.1% among patients who received chemotherapy ≤30, 31-60, 61-90, ≥91 days, respectively (p=0.005). Accordingly, 10y-OS was 82%, 67.4%, 67.1% and 65.1% among patients who received chemotherapy ≤30, 31-60, 61-90, ≥91 days, respectively (p=0.003). In the multivariate analysis, TTC was an independent prognostic factor for RFS and OS. Patients with TTC of 31-60 days (HR, 1.92; 95% CI, 1.225 to 2.998), 61-90 days (HR, 2.38; 95% CI, 1.354 to 4.172) and ≥91days (HR, 2.47; 95% CI, 1.250 to 4.886); had worse survival compared with those who initiated treatment in the first 30 days after surgery. Patients with TTC of 31-60 days (HR, 1.94; 95% CI, 1.243 to 3.034), 61-90 days (HR, 2.45; 95% CI, 1.402 to 4.265) and ≥91days (HR, 2.79; 95% CI, 1.418 to 5.506); had worse survival compared with those who initiated treatment in the first 30 days after surgery. Conclusion: Delayed initiation of adjuvant chemotherapy in TNBC patients over 30 days is associated with a decrease in RFS and OS rates. The greater the delay, the worse the outcomes. As this represents a feasible opportunity for improvement, every attempt should be made to avoid delayed adjuvant chemotherapy initiation in this high-risk group of patients. Citation Format: Morante Z, Ruiz R, De la Cruz - Ku G, Namuche F, Mantilla R, Lujan MG, Fuentes H, Schwarz J, Aguilar A, Neciosup S, Gomez H. Impact of the delayed initiation of adjuvant chemotherapy in the outcomes of triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-05.

Prognostic factors in HIV-positive patients with non-Hodgkin lymphoma: a Peruvian experience

BackgroundNon-Hodgkin lymphoma (NHL) is the most common cancer in people with HIV. Although 95% of HIV patients are in developing countries like Peru, the majority of these studies have been conducted in developed countries. In this study we aim to evaluate prognostic factors associated with outcomes in HIV positive patients undergoing systemic therapy for treatment of NHL.MethodsThis retrospective study includes patients with NHL seen in the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 2004 to 2014. Patients were divided into two groups: antiretroviral therapy (ART) -naïve (n = 34) and those previously treated, ART-exposed (n = 13), at the time of diagnosis. All patients received chemotherapy and ART. The medical records were reviewed. Data were analyzed using t-test and chi-square test. Survival curves were estimated by the Kaplan-Meier method and comparison was done by log-rank test. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model.ResultsAll ART-exposed patients were from the capital city (p = 0.039); they had significantly lower hemoglobin levels compared to ART-naïve patients (p = 0.026). The median OS was 47.7 months with a 5-yr OS of 36.1%. The median OS for ART naïve patients was significantly higher than that for ART-exposed patients (57.05 and 21.09 months, respectively; p = 0.018). Advanced stage and low serum albumin were associated with lower OS in both groups. Age > 60 was associated with worse outcomes in the ART-naïve cohort.ConclusionsAdvanced stage, low serum albumin and previous ART treatment were the primary prognostic factors associated with poorer outcomes in patients with NHL and HIV infection. In ART-naïve patients, age > 60 was associated with worse outcomes but in this cohort, older patients still had better overall outcomes than ART-exposed patients.

Abstract 588: Neutrophil to lymphocyte ratio as strongest predictor of early death in metastatic triple negative breast cancer

Abstract Background: Metastatic triple-negative breast cancer (mTNBC) is a heterogeneous disease with poor prognosis where recent studies suggest that the immune system plays a critical role the mechanisms of disease progression and metastasis. In the other hand, a high Neutrophil to Lymphocyte Ratio (NLR) is associated with poor survival in patients diagnosed with several types of cancer. Our aim was to evaluate the prognostic value of NLR in mTNBC. Methods: We retrospectively reviewed 130 patients diagnosed with mTNBC between 2000-2014 at “Instituto Nacional de Enfermedades Neoplasicas”. NLR group was divided in &amp;lt;2.5 and ≥2.5. Sites of metastasis were identified by TAC or magnetic resonance imaging. Survival rates were estimated by the Kaplan-Meier method and differences were calculated by Log-rank test. The Cox Regression was used for prognostic factors. Results: The median age was 50 years (range: 23-92 years). From our study population, 41.2% were premenopausal, and just 10 patients (9.5%) had a breast-ovary cancer familiar background, 62.5% were diagnosed at clinical stage T3-T4 and 86.1% had lymph node involvement. From 130 patients, 41 and 64 had NLR &amp;lt;2.5 and ≥2.5, respectively, while there was no association between characteristics and NLR, only patients with malnutrition had NLR ≥2.5 (9.1% vs 40.8%, p=0.002) and solid organ involvement (62.4% vs 81.3%, p=0.04). Furthermore, lung and bone were the most frequent sites of metastasis. Those patients with lower ratio (&amp;lt;2.5) had better response to chemotherapy (p &amp;lt;0.001). With a median follow-up of 6.25 years, at 1-year OS was lower among patients with NLR ≥2.5 (59% vs 20%, HR: 2.77, 95%CI:1.77-4.33, p&amp;lt;0.001). In addition, at univariate analysis malnutrition also showed an impact on OS (HR: 1.79, 95%CI: 1.20-2.67, p=0.005). At multivariate analysis, between age, T stage, N stage, NLR and solid organ involvement, just NLR was the best and only predictor of worse OS (HR: 3.12, 95%CI:1.94-5.03, p&amp;lt;0.001). Conclusion: In mTNBC, an NLR ≥2.5 was a strong and accessible biomarker of poor OS. Lower values of NLR could help us to predict chemotherapy response. Citation Format: Gabriel A. De la Cruz Ku, Zaida Morante, Joseph Pinto, Jhajaira Araujo, Daniel Enriquez, Eduardo Eyzaguirre, Antonella Saavedra, Maria Lujan, Renato Luque, Cesar Rázuri, Hugo Fuentes, Silvia Neciosup, Henry Gómez Moreno. Neutrophil to lymphocyte ratio as strongest predictor of early death in metastatic triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 588.