Instituto Nacional De Enfermedades Neoplasicas Research Articles

Unveiling Melanoma: A Deep Dive into Disparities at a Latin-American Cancer Institute.

The worldwide incidence of melanoma has increased in the last 40 years. Our aim was to describe the clinic-pathological characteristics and outcomes of three cohorts of patients diagnosed with melanoma in a Latin-American cancer institute during the last 20 years. We evaluated three retrospective patient cohorts diagnosed with melanoma at Instituto Nacional de Enfermedades Neoplasicas (INEN), a public hospital in Lima, Peru, for the years 2005-2006, 2010-2011, and 2017-2018. Survival rate differences were assessed using the Log-rank test. Overall, 584 patients were included (only trunk and extremities); 51% were male, the mean age was 61 (3-97) years, and 48% of patients resided in rural areas. The mean time to diagnosis was 22.6 months, and the mean Breslow thickness was 7.4 mm (T4). Lower extremity was the most common location (72%). A majority of the patients (55%) had metastases at the time of presentation, with 36% in stage III and 19% in stage IV. Cohorts were distributed as 2005-2006 (n=171), 2010-2011 (n=223), and 2017-2018 (n=190). No immunotherapy was used. Cohort C exhibited the most significant increase in stage IV diagnoses (12.3%, 15.7%, 28.4%, respectively; p<0.01). The median overall survival rates at the three-year follow-up demonstrated a decline over the years for stages II (97%, 98%, 57%, respectively; p<0.05) and III (66%, 77%, 37%; p<0.01). There has been a worsening in the incidence of late-stage metastatic melanoma in Peru throughout the years, coupled with a significant decline in overall survival rates. This is underscored by the fact that half of the population lives in regions devoid of oncological access.

Soft tissue sarcomas: Disease burden and health system response in Peru.

e23557 Background: The management of soft tissue sarcomas (STS) presents a challenge in Peru, with a fragmented health system and few centers specialized in sarcoma care. There is no national cancer registry, which does not allow us to have a real view of the most prevalent types. Our aim was to determine the incidence in Instituto Nacional de Enfermedades Neoplásicas (INEN) and to know the real care capacity of cancer centers nationwide. Methods: A retrospective study was carried out in INEN between 2009 and 2015 to know the incidence of STS. Also, a survey was carried out to determine the real capacity of diagnosis and treatment care of cancer centers located in different regions of our country. Results: We were able to determine the anatomopathological diagnosis in 1804 (100%) patients. 52,1% were male (n = 899). Median age was 43 years (15-96). The most frequent sarcoma was undifferentiated pleomorphic sarcoma with 482 patients(27.9%), followed by liposarcoma in 269 (15,6%) and leiomyosarcoma in 159 (9%). The most common primary location was the limbs with 892 patients (51.7%), followed by the abdomen and pelvis with 423 (24.5%), and the least common was the head and neck with 207 patients (12%), followed immediately by the thorax with 205 patients (11.9%). According to the region of origin, 551 (31.9%) patients came from the northern region, 175 (10.1%) from the south, 35 (2%) from the east, 308 (17.8%) from the central region, and 658 (38.1%) from Lima and Callao. We obtained responses from 20 oncology centers of the Ministry of Health along 12 regions operating nationwide. Eight (40%) oncology centers are located in Lima and twelve (60%) in the rest of Peru. 100% (n = 20) of centers have medical oncologists, 70% (n = 14) have surgical oncologists, 65% (n = 13) have traumatologist and pathologist. About capacity of resolution: 100% (n = 20) perform direct biopsy of soft tissue tumors and 60% (n = 12) perform image-guided biopsies; regarding pathology, 95% (n = 19) performed morphological approach and 45% (n = 9) immunohistochemistry studies. 100% (n = 20) can perform ultrasound studies, 95% (n = 19) tomography, and 35% (n = 7) magnetic resonance imaging. 90% (n = 17) accomplish radical surgeries and 60% (n = 12) limb sparing surgeries. 85% (n = 17) enforce chemotherapy treatment. Only 50% (n = 10) have a radiotherapy service. 25% (n = 5) hold multidisciplinary meetings continuously while 40% (n = 8) hold them occasionally for complex cases. Only 8 oncology centers (out of a total of 20) have all the services to care for the complexity of a patient with soft tissue sarcoma, the majority (n = 3) located in Lima. Conclusions: Nearly 1,800 patients have been diagnosed in this reference institution in a period of 5 years, however it represents an underestimation of the real incidence. Cancer centers that can provide complete care for patients with soft tissue sarcomas are scarce, creating a gap in care for this pathology.

Clinical and outcome patterns in epithelial ovarian cancer (EOC) within a Latin American cohort.

e23308 Background: Epithelial Ovarian Cancer (EOC) is an heterogenous disease which is usually diagnosed inadvanced stages. Despite the advent of new therapies, the outcomes for this disease remain poor in certain scenarios. We describe the clinical features and survival outcomes in a developing country. Methods: Retrospective study based on case review of women with newly diagnosed EOC between 2015 and 2017 at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima- Peru. Descriptive analysis was conducted for clinical characteristics, epidemiological factors and treatment. PFS was calculated from the date of diagnosis until the first documented progression and OS from the date of diagnosis to death. Both were calculated using the Kaplan Meier curve. Results: 234 patients were included, the most common histology subtype was high grade serous carcinoma (47,5%), followed by mucinous (15.9%) and clear cell carcinoma (15.4%). Median age was 55.7 yo (range 19-88). Breast and ovarian cancer family history were reported in 3.8% and 3.0%, respectively. 35.8% of patients were overweight, and 12.5% were obese. Most patients (61.5%) were diagnosed at advanced disease (III-IV) and the most common site of metastasis was liver (43.6%) and lung/pleural (28.2%). BCRA testing was performed only in 6% of patients, and 4/14 patients had a pathologic mutation. Ca125 was elevated in 86.2% of patients. Regarding treatment, all patients with early stage disease (I-II) underwent surgical staging. For advanced stage disease, 47.6% (69/145) of patients underwent upfront surgery and 41.4% (60/145) received platinum-based chemotherapy in neoadjuvant setting; 57.3% (35/61) of these patients achieved optimal secondary cytoreduction. With a median follow up of 74,4 months, median PFS was 32.61 months (0.6-474) and global median OS was 58.13 months. Median OS for early disease (I-II) was not reached and for advanced disease (III-IV) was 33.73 months. Survival rate at 5y for all stages was 45.2%; 60.8% and 28.4% for early and advanced disease, respectively. Conclusions: These findings highlight the prevalence of high-grade serous carcinoma and the significance of advanced-stage diagnosis in the survival outcomes. In the era of targeted therapies, the lack of access to BRCA detection tests restricts therapeutic options and, consequently, hinders responses in this group of patients.

Abstract PO5-06-05: DISCORDANCE BETWEEN HORMONE RECEPTORS AND HER2 STATUS IN BREAST CANCER PATIENTS RELAPSE

Abstract Introduction: Breast cancer (BC) is a heterogeneous disease, and during its progression, the tumor phenotype can undergo changes that are often associated with a poor prognosis. In this study, we aim to compare the discordance in estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression between primary and recurrent/metastatic lesions. Methods: This study is a retrospective analysis of 132 non-advanced breast cancer patients who experienced confirmed recurrence/metastasis at the Instituto Nacional de Enfermedades Neoplasicas between 2011 and 2022. Descriptive analysis was conducted to assess the expressions of ER, PgR, HER-2, and Ki-67 in primary and metastatic breast cancer, as well as clinical variables. Normality tests, including Kolmogorov-Smirnov and Shapiro-Wilk, were performed. The paired samples Wilcoxon test was used to determine significant differences between primary and recurrent/metastatic tumors. Additionally, Spearman's rank correlation coefficient was employed to evaluate the relationships of expression discordance. Results: Fifty-nine percent of patients presented locoregional recurrence, while 41% presented visceral metastasis. In the primary tumor, ER and PR expression were found in 63.6% and 55.3% of cases, respectively. HER2 status was determined as 0 (36.3%), +1 (22%), +2 (14.4%), +3 (26.5%), and not determined (0.8%) by IHC. For the recurrent/metastatic tumor, ER and PR expression were found in 59% and 34% of cases, respectively. HER2 status was determined as 0 (27.3%), +1 (19.7%), +2 (25%), +3 (25%), and not determined (3%). The median Ki-67 levels were 37% in the primary tumor and 40% in the recurrent/metastatic tumor. Significant differences were found for ER (p=0.014), PR (p&amp;lt; 0.001), and HER2 (p=0.019), but not for Ki-67 percentage (p=0.139). The discordance rates of ER, PR, HER2, and Ki-67 expression were 27.9%, 47.7%, and 26.3%, respectively. Conclussions: Discordance in hormone receptor expression between primary and recurrent/metastatic tumors is a common phenomenon, with ER showing a discordance rate of 27.9% and PR showing a higher rate of 47.7%. HER2 status also displayed significant discordance, with a 26.3% rate of discordant expression between primary and recurrent/metastatic tumors. The findings from this study emphasize the dynamic nature of breast cancer and the importance of comprehensive evaluation of biomarker expression in both primary and recurrent/metastatic tumors, to choose the best treatment options. Citation Format: Katia Roque, Iris Otoya, Natalia Valdivieso, Zaida Morante, Hugo Fuentes, Silvia Neciosup, Henry Gómez, Jorge Cotito, Gonzalo Ziegler, Estefania Peña, Tatiana Vidaurre, Ramon Andrade de Mello, Carlos Castañeda. DISCORDANCE BETWEEN HORMONE RECEPTORS AND HER2 STATUS IN BREAST CANCER PATIENTS RELAPSE [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-05.

Survival according to the site of metastasis in triple-negative breast cancer patients: The Peruvian experience.

Evidence regarding differences in survival associated with the site of metastasis in triple-negative breast cancer (TNBC) remains limited. Our aim was to analyze the overall survival (OS), distant relapse free survival (DRFS), and survival since the diagnosis of the relapse (MS), according to the side of metastasis. This was a retrospective study of TNBC patients with distant metastases at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru) from 2000 to 2014. Prognostic factors were determined by multivariate Cox regression analysis. In total, 309 patients were included. Regarding the type of metastasis, visceral metastasis accounted for 41% and the lung was the most frequent first site of metastasis (33.3%). With a median follow-up of 10.2 years, the 5-year DRFS and OS were 10% and 26%, respectively. N staging (N2-N3 vs. N0, HR = 1.49, 95%CI: 1.04-2.14), metastasis in visceral sites (vs. bone; HR = 1.55, 95%CI: 0.94-2.56), the central nervous system (vs. bone; HR = 1.88, 95% CI: 1.10-3.22), and multiple sites (vs. bone; HR = 2.55, 95%CI:1.53-4.25) were prognostic factors of OS whereas multiple metastasis (HR = 2.30, 95% CI: 1.42-3.72) was a predictor of MS. In terms of DRFS, there were no differences according to metastasis type or solid organ. TNBC patients with multiple metastasis and CNS metastasis have an increased risk of death compared to those with bone metastasis in terms of OS and MS.

Brain Metastasis in Triple‐Negative Breast Cancer

Background. Breast cancer is an important cause of cancer‐related death in women worldwide and represents the second most frequent cause of brain metastases after lung cancer. The aim of this study was to determine the characteristics and outcomes of triple‐negative breast cancer (TNBC) patients with brain metastasis (BM). Methods. We retrospectively reviewed a cohort of patients diagnosed with TNBC at the “Instituto Nacional de Enfermedades Neoplasicas” (period 2000–2014) to evaluate patients who developed BM. Survival rates were assessed by the Kaplan–Meier method, and prognostic factors were identified with the Cox regression analysis. Results. Of a total of 2007 TNBC patients, 193 (9.62%) developed BM. Of these, 169 stages I–III patients with a median age of 45 years (range:21–78) were included. The stage in this cohort was 4 (2.4%) clinical stage (CS) I, 23 (13.6%) with CS II and 142 (84.0%) with CS III. Most of these patients presented ECOG ≥2 (68.6%). The most common symptom was headache (74.0%), followed by nausea‐vomiting (46.7%). Imaging showed that 80 patients (53.0%) had ≥1 metastatic brain lesion. Regarding the treatment of BM in this cohort, 132 patients (84.6%) received radiotherapy (RT), 2 (1.5%) surgery, and 6 (4.5%) surgery plus RT. The overall survival (OS) rate of BM was 59.8%, 37.3%, and 15.0% at 3, 6, and 12 months, respectively. A multivariate analysis showed RT to be the only factor with a positive impact on the OS of BM (hazard ratio (HR) = 0.48, 95% confidence interval (CI):0.30‐0.77, and p = 0.002), while ECOG ≥2 was associated with a worse OS (HR = 1.69, 95%CI:1.15–2.48, and p = 0.007). Conclusion. Despite the poor prognosis of TNBC patients who develop BM, RT showed a benefit in OS rates, while ECOG ≥2 was the only prognostic factor associated with a worse OS. These results may be useful for multidisciplinary teams for treatment planning in patients with TNBC and BM.

Core needle biopsy of breast tumours: comparison of diagnostic performance between surgery and radiology services at a national cancer centre in Latin America.

Breast pathology is a very common reason for medical attention. Tissue diagnosis is usually obtained with core needle biopsy which could be performed by breast surgeons or interventional radiologists. Our aim was to assess the comparison of diagnostic performance between the two services. A retrospective, descriptive and cross-sectional study was carried out on patients who had breast pathology at Instituto Nacional de Enfermedades Neoplasicas in 2019. Descriptive analyses, sensitivity and specificity were calculated using the R program version 4.2.3. From 1,082 patients with breast tumours who underwent core needle biopsy (CNB) during 2019, 782 cases were included. Breast surgeons performed 462 CNBs and radiologists performed 320 CNBs. The 87.5% were palpable tumours and 525 breast carcinomas were identified in the final pathology. The diagnostic performance showed that the sensitivity and specificity were greater than 95% and 98%, respectively. The waiting time in both showed that >95% underwent a CNB before 2 months. The breast surgery service performed the majority of the biopsies in less than 1 week since the indication of the execution of the CNB compared to the radiology service (90% versus 36%). Both hospital services, breast surgery and radiology, are efficient in determining an accurate diagnosis using CNB. However, the breast surgery service performs CNB in a shorter time interval. Breast surgical oncologists are encouraged to perform CNB if there are understaffed radiology services to expedite the diagnosis and treatment of breast cancer patients.

Obesity after Induction Is Associated with Poor Overall Survival in Adults with Acute Lymphoblastic Leukemia: Results from a Peruvian Adaptation of the CALGB10403 Protocol

Background:Acute lymphoblastic leukemia (ALL) is a lymphoid malignancy with wide racial disparities. Indeed, ALL is more frequently diagnosed among the Latino population who classically achieve lower remission rates and experience worse survival than other racial and ethnic groups. Several high-risk features including genetic polymorphisms and metabolic issues have been implicated in Latino ethnicity, including obesity. A high body mass index (BMI) at different stages of treatment represents a well-known risk factor in several prospective studies mainly based on white populations. It is unclear whether these findings are consistent in other racial and ethnic unrepresentative groups. We aimed to evaluate the effect of BMI at the end of induction on the overall survival (OS) of Latino adults with ALL. Methods:We conducted a retrospective cohort study among adult patients diagnosed with ALL in an academic cancer center (Instituto Nacional de Enfermedades Neoplasicas - INEN) from 2017 to 2019, with follow-up through July 2023. The INEN is a national tertiary referral center in Lima-Peru that provides leukemia treatment for approximately 85% of the insured population in Peru. Patients aged 20-65 who successfully achieved complete remission after 4 weeks of intensive induction treatment were included. Patient data were manually abstracted from the medical records. BMI was classified as underweight, healthy weight, overweight and obese according to the CDC and WHO recommendations. Vital status was ascertained with the National Vital Registry. The Kaplan-Meier method and the Log-rank test were used to estimate OS probabilities. Multivariable Cox regression was used to evaluate the effect of BMI on OS, adjusting for sex, age, risk, and immunophenotype. Results: Of 784 patients identified in the electronic records of the INEN, we excluded 578 because they didn't achieve complete remission, yielding 206 patients for analysis. The median age at diagnosis was 33 years, most were aged 20-40 years old (68%), and female (54%). 160 (78%) were ALL-B Ph- and 126 (61%) corresponded to the high-risk stratification. At the end of the induction, 119 patients presented a healthy weight (58%), 49 (24%) overweight, 26 (13%) obese, and 12 (6%) underweight (Table 1). With a median follow-up of 55 months, the median OS was 18 months (95% CI: 16-23), and the 5-year OS was 23% for all patients. The 5-year OS was lower in patients with obesity (12%), followed by patients with overweight (20%), healthy weight (26%), and underweight (33%), as evidenced by the Kaplan-Meier curve (Figure 1, p=0.036). In the multivariable analysis, obesity (p-value=0.006) was associated with an increased risk of all-cause mortality (adjusted Hazard Ratio [aHR]: 1.93; 95% CI: 1.21-3.08). A very high-risk disease was also associated with poor OS (aHR:2.69; 95% CI: 1.15-6.26) (Table 1). Conclusion: This study identified that obesity at the end of induction is associated with inferior OS among Peruvian patients who achieved complete remission. Our real-world findings should be validated in prospective studies including other Latino populations to recommend the feasibility of weight reduction strategies.

Chemotherapy Response and Toxicities in Older Adults with Hodgkin Lymphoma

INTRODUCTION Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by high-rate responses to conventional chemotherapy (CT). However, older adults are usually undertreated and develop poor outcomes, mainly due to their limited functional status, comorbidities and toxicities concerns. We evaluated the characteristics and outcomes of patients with HL older than 65 years in a real-life limited setting. METHODS We performed a retrospective study based on medical records review of newly diagnosed HL between 2004 and 2019 at Instituto Nacional de Enfermedades Neoplasicas (INEN, Lima- Peru). The initial treatment options were classified into three categories: (1) Curative CT regimen, (2) palliative treatment, or (3) no treatment. The staging was done according to Ann Arbor Staging Classification and response were defined by RECIST criteria in patients who received at least 3 courses of CT. RESULTS 73 patients were included. Median age was 73 years (range 65- 88y). Among the patients, 61% were male, and the remaining 39% were female. Majority of the patients (61%) presented B symptoms. The details of the presentation features are shown in Table 1. The most common histology was classic HL mixed cellularity (46%); although it could not be determined in 19% of patients. At diagnosis, 86% (n=63) of patients had an ECOG performance status of 0-2. Bulky disease was present in 20% of patients (n=15), and 15% (n=11) had visceral involvement. 26% were classified as early-stage (stage I-II), while 74% had advanced disease (stage III-IV). Regarding treatment, 67.1% (n=49) of the patients received curative CT with ABVD or AVD regimen. A smaller proportion, 4.1% (n= 3), received palliative treatment, and 28.7% (n=28) did not receive any treatment. In patients who received curative CT, 13 patients only received 1 or 2 courses of CT and were subsequently excluded from the analysis. 47% (17/36 patients) achieved complete response, 41.6% partial response (15/36 patients) and 11.1% had progression disease (4/36 patients). In this group of patients, the most common adverse effects observed were hematologic toxicity (22.2%). Additionally, one patient presented pneumonia, and three patients developed pneumonitis. Two patients who presented pneumonitis experienced treatment-related mortality (Table 2). CONCLUSIONS In conclusion, this study provided insights into the characteristics and treatment outcomes of older adults with classic Hodgkin lymphoma. The results suggest that curative chemotherapy with ABVD or AVD regimen is the most common treatment approach, with a significant proportion of patients achieving complete response. However, treatment-related adverse effects, particularly pneumonitis, were noted, warranting careful monitoring and management during the treatment process. Further research and careful assessment of treatment protocols are necessary to improve the outcomes and quality of life for this patient population.

Subpopulation treatment effect pattern plot analysis: a prognostic model for distant recurrence-free survival to estimate delayed adjuvant chemotherapy initiation effect in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease associated with a poor prognosis. Delaying in time to start adjuvant chemotherapy (TTC) has been related to an increased risk of distant recurrence-free survival (DRFS). We aimed to develop a prognostic model to estimate the effects of delayed TTC among TNBC risk subgroups. We analyzed 687 TNBC patients who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). Database was randomly divided to create a discovery set (n=344) and a validation set (n=343). Univariate and multivariate Cox regression models were performed to identify prognostic factors for DRFS. Risk stratification was implemented through two models developed based on proportional hazard ratios from significant clinicopathological characteristics. Subpopulation treatment effect pattern plot (STEPP) analysis was performed to determine the best prognostic cut-off points for stratifying TNBC subgroups according to risk scores and estimate Kaplan-Meier differences in 10-year DRFS comparing TTC (≤30 vs.>30 days). In univariate analysis, patients aged ≥70 years (HR=4.65; 95% CI: 2.32-9.34; p=<0.001), those at stages pT3-T4 (HR=3.28; 95% CI: 1.57-6.83; p=0.002), and pN2-N3 (HR=3.00; 95% CI: 1.90-4.76; p=<0.001) were notably associated with higher risk. STEPP analysis defined three risk subgroups for each model. Model N°01 categorized patients into low (score: 0-31), intermediate (score:32-64), and high-risk (score: 65-100) cohorts; meanwhile, Model N°02: low (score: 0-26), intermediate (score: 27-55), and high (score: 56-100). Kaplan-Meier plots showed that in the discovery set, patients with TTC>30 days experienced a 17.5% decrease in 10-year DRFS rate (95%CI=6.7-28.3), and the impact was more remarkable in patients who belong to the high-risk subgroup (53.3% decrease in 10 years-DRFS rate). Similar results were found in the validation set. We developed two prognostic models based on age, pT, and pN to select the best one to classify TNBC. For Model N°02, delayed adjuvant chemotherapy conferred a higher risk of relapse in patients ≥70 years and who were characterized by pT3/T4 and pN2/N3. Thus, more efforts should be considered to avoid delayed TTC in TNBC patients, especially those in high-risk subgroups.

Testicular GERM cell tumors treatment outcome in a national cancer institution in Peru.

e17031 Background: Testicular germ cell tumor (TGCT) is the most common neoplasm in young men and the incidence has been increasing over the last few decades, especially among Hispanic men. Multidisciplinary management is associated with excellent oncological outcomes. Here, we describe the treatment outcome of TGCT patients treated in single institution in Peru. Methods: We conducted a retrospective study of TGCT treated at Instituto Nacional de Enfermedades Neoplasicas from 2016 to 2019. Clinical and pathological data were collected from medical records. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and compared with long-rank test. A level of p &lt; 0.05 was considered significant. The statistical package SPSS v19 was used for the data analysis. Results: 221 patients were identified, 56% were non-seminomatous (NS) and 44% were seminomatous (S). Orchiectomy was performed in 94% of patients, only 6% underwent orchiectomy after chemotherapy. In both groups, the treatment regimens were: BEP (Bleomycin/Etoposide/cisplatin) 90%, Carboplatin 8.1% and EP (Etoposide/Cisplatin) 1.8%. 42 (21%) of patients receive rescue therapy, being the most frequent TIP (paclitaxel/ifosfamide/cisplatin). In NS patients, 5-year PFS was superior in good risk compared with poor risk (100% vs. 86%, p = 0.028) and for tumor markers level, S0 was superior to S3 (100% vs. 82%, p = 0.008). In S, 5-year PFS was no significant in any of groups of analysis. With a median follow-up of 57 months, OS in NS was 91%, 83% and 81% in 12, 36 and 60 months, respectively and OS in S was 96%, 87% and 87% in 12, 36 and 60 months, respectively. The analysis of 5-year OS according to clinical stage and risk stratification are shown in the Table 1. Only 2 patients received high-dose chemotherapy and still in complete response. Conclusions: Despite the high incidence of advanced TGCT, our patients had excellent survival results; being lower in those with CS III (both NS and S groups), poor risk and S3 for NS, and intermediate risk for S. Multidisciplinary management in a high volume institution is important for better outcomes in our patients. [Table: see text]

Real-world efficacy of nivolumab in Peruvian patients with advanced melanoma.

e18849 Background: Malignant melanoma in Latin American (LATAM) population has aggressive features as higher rates of Acral lentiginous (ALM) subtype and shorter survival. Immunotherapy has improved prognosis among patients with cutaneous melanoma; however, there is scarce reports of the effectiveness in LATAM population. We describe our experience with management and survival of Peruvian patients with advanced melanoma treated whit nivolumab. Methods: A retrospective study based on cases review evaluated the efficacy of nivolumab. Eligible patients were metastatic, recurrent or unresectable malignant melanoma undergoing treatment with nivolumab as first-line for at least 3 consecutive months between 2020 and February 2021 in two institutions (Instituto Nacional de Enfermedades Neoplasicas, Oncosalud). Clinical pathologic features and immune inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI)) were evaluated. Efficacy was measured as progression-free survival (PFS), objective response rate (ORR), Clinical benefit rate (CBR) and overall survival (OS). A p &lt; 0.05 value (SPSS) will be considered for a significant difference. Results: 57 patients were analyzed; median age was 63 yo (range 34-83); 59.6% were female. 77.2% had a Zubrod 0-1. Regarding histology, 37% (n = 21) had acral subtype, 38% (n = 22) non-acral, 17% (n = 10) mucosal and 8% (n = 4) unknown primary (UP). 81.1% had negative BRAF mutation status, and the median lactate dehydrogenase (LDH) level was 257 U/L (130-1281). 63.2% had visceral metastasis, the most common site being lung (42%) and liver (9%). Central nervous system (CNS) metastases was reported in 5%. After a median follow-up was 25 months, the median OS reported was 51.43 months (95% CI, 14.23-88.62). Median OS was 28.93 for acral melanoma (95% CI, 14.66-43.19) and not reached for other subtypes. Median PFS was 7.93 months (95% CI, 2.49-13.36); 4.93, 14.73 and 5.26 months in patients with acral, non-acral and mucosal melanoma, respectively. A significant difference was founded in OS (p = 0.024) and PFS (p = 0.001) between acral and non-acral melanoma. ORR was reached in 28.1% of patients; 19%, 31.8% and 20% in acral, non-acral and mucosal subtype, respectively. However, global CBR was 64.9%, with the higher and lower rate for non-acral (81.82%) and mucosal melanoma (50%). The overall incidence of immune related adverse effects (irAEs) was 69.5%, the most common were skin reactions (14%), followed by asthenia (12%); not grade 3-4 AEs were reported. Regarding immune inflammatory blood markers, no association between PFS with NLR (p = 0.49), PLR (p = 0.3) and PNI (p = 0.71) were founded. Conclusions: Nivolumab showed efficacy in improving OS for patients with advanced melanoma, however ALM had shorter OS and PFS. No prognostic immune blood markers were reported. New biomarkers are necessary, especially in acral melanoma.

COVID-19 pandemic impact on the oncology care using a virtual survey in Peru.

e18738 Background: Advocacy programs in oncology has shown to improve outcomes through education, patient empowerment and civil society awareness, enabling better actions and efforts for patient care, especially in COVID-19 era. We present the results of a virtual survey conducted with the support of a Peruvian advocacy program for cancer patients in COVID-19 pandemic. Methods: In October 2020, a Peruvian Advocacy Program at Instituto Nacional de Enfermedades Neoplasicas (INEN) (“Club de la Mama”) formed by advocates and supported by a team of health professionals developed a virtual survey between October 2020 and July 2021 with the purpose of evaluating the impact of interruption of diagnosis or oncological treatment, detect a degree of anxiety/depression due to quarantine and provide information on the response of the oncological institution to the pandemic; from the patient’s perspective. This virtual survey includes: alternative treatment options, degree of anxiety/depression, early access to medical prescription, mode of appointment and quality of care. Patients answered the survey anonymously via web promoted on social networks (Facebook/ WhatsApp) and person-to-person diffusion. Results: A total of 244 patients were included, 78.7% females. Most of patients (86.5%) were from Lima and 86.9% had public insurance. 16.8% of patients had COVID-19 in the period of time evaluated. According to education level, 50.8% were superior, 37.7% high school, 10.7% elementary school and 0.8% illiterate. The most common cancer type was breast (36.1%), followed by hematologic (27.9%) and cervical (7.0%). The most common modality of care was in-person (73%), followed by telemedicine (15%) and only 2% not received medical consult. Regarding the degree of depression: 39% were mild, 14% moderate, 12% moderate-severe, 5% severe and 30% none. The most common degree of anxiety was 42% mild, 16% moderate, 12% severe, and 30% no degree. The most frequent reasons for not attending to hospital were unavailability of appointments (31%), followed by fear to COVID-19 (26%), geographic (10%) and difficulty in transportation (9.0%). The appointment cancellation/postponement time [reported in days] was: 18.0% not canceled, 16% [ &lt; 15], 14% [15-30], 19% [30-60], 10% [60-90], 23% [ &gt; 90]. Of the patients with surgical indication, 72% did not undergo surgery. Regarding prescription, 83% of patients received oncologic treatment, 10% did not received, and the remaining 7% answered that they did not need medication. Quality of care: 18% were considered excellent, 67% good, 10% fair, and 5% poor. Conclusions: Although the survey showed higher degrees of anxiety/depression in patients and longer cancellation/postponement/medication changes during COVID-19 pandemic, there was a significant adherence of medicine prescription, with no negative impact on the perception of quality of oncology care.

Cryptococcosis in non-HIV/non-transplant hematological patients: A 12-year retrospective clinical analysis in a Peruvian referral cancer center.

e19536 Background: Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in non-HIV/non-transplant oncohematological patients. Methods: We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2018. We exclude HIV and transplant recipients patients. Results: During the 12-year study period, among 14908 individuals with hematological malignancies (HM), a total of 21 cases of cryptococcosis were identified, representing an incidence rate of 1.41 per 1000 HM diagnosed in our center. Non-Hodgkin lymphoma (NHL) (47.6%), acute leukemias (23.8%), multiple myeloma (19.1%), and Hodgkin lymphoma (9.5%). Three cases of adult T-cell leukemia/lymphoma were identified. The sub-group analysis showed that NHL (7.35 per 1000 NHL) and Multiple myeloma (4.59 per 1000 MM) had the highest incidence rates. Regarding the clinical presentation, the time between the diagnosis of cryptococcosis and HM was 42 (18–161) days. Cryptococcal fungemia and antigenemia was the most frequent diagnosis (85.7%), followed by pulmonary (52.4%) and central nervous system (38.1%) involvement. At the time of the diagnosis of cryptococcosis, 61.5% were receiving chemotherapy, 53.9% were in the induction phase, and 7.7% were on maintenance therapy. The use of immunosuppressants and chemotherapy within a month of the diagnosis of cryptococcosis was the most common risk factor (90.5%). Regarding the subanalysis performed between the different types of malignancies (NHL versus other HM), age at admission (p = 0.02), site of cryptococcosis presentation (p = 0.01), and lymphocyte count at admission (p = 0.01) were statistically different between these groups. In the NHL subgroup, there was less involvement of the lungs and higher fungemia (p = 0.01). The overall survival (OS) of our cohort at 15 and 120 days was 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other HM was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82). Conclusions: Our cohort characterized the distinct clinical presentation, risk factors, and outcomes of cryptococcal infection in hematologic malignancies subgroups. NHL was the HM with the worst prognosis and the highest incidence rate. [Table: see text]

Abstract 5235: Transcriptome-wide study of tumor samples from Peruvian women identifies dysregulated pathways in luminal tumors typically associated with more aggressive disease

Abstract Purpose: Breast cancer incidence and outcomes differ by US census racial/ethnic category. Since large-scale genetic studies of human disease are predominately focused on populations of European ancestry, little is known about breast cancer molecular biology in Hispanic/Latinos which can widen cancer health disparities due to suboptimal translation of discoveries into clinical practice or public health policy. We aim to describe relevant pathways in breast cancer subtype differentiation in breast cancer patients from Peru. Patients and Methods: Formalin fixed paraffin embedded tumor tissues samples were whole exome sequenced for a total of 271 patients, recruited by the Peruvian Breast Cancer Genomics Study (PEGEN-BC) from the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Quality control was conducted to remove genes with low counts. Intrinsic tumor subtypes were classified using the PAM50 method using genefu package in R. Differential gene expression between subtypes was performed by DEseq2 R package and statistical significance was determined using FDR&amp;lt;0.05 for samples with at least log2 1.5-fold change. Pathway analyses were performed to explore differences among the subtypes using GSEA with fgsea package in R. Indigenous American ancestry proportions for participants were estimated using germline genome-wide genotypes and the program Admixture. Results: The mean age of patients was 50 and the median Indigenous American ancestry was 79%. PAM50 classification of the sequenced samples defined 20.2% of tumors as LumA, 27.9% as LumB, 27.1% as HER2, 22.5% as Basal and 2.3% as Normal. Transcriptomic pathway analysis showed that most of the significantly changed pathways were similar to those previously described such as upregulation of high proliferation pathways in LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Top 10 significantly changed pathways show some unique findings: the epithelial-mesenchymal-transition (EMT) pathway is downregulated in Basal, comparing to LumA and HER2 tumors, which is unexpected given that the EMT is associated with stem cell features and poor outcomes. The E2F-targets pathway is upregulated in LumA when comparing to HER2 tumors, but downregulated when compared to Basal tumors. Conclusions: We identified novel pathways associated with breast cancer subtypes in individuals with high Indigenous American ancestry from Peru and are working on testing the robustness of these findings. If our findings are confirmed, results would suggest a more aggressive profile of Luminal subtypes in the studied samples from Peru, with implications for treatment and survival. Citation Format: Chenghuiyun Xu, Valentina A. Zavala-Cordero, Xiaosong Huang, David M. Rocke, Sandro Casavilca-Zambrano, Jeannie M. Navarro-Vásquez, Carlos A. Castañeda, Guillermo Valencia, Zaida Morante, Monica Calderón, Julio E. Abugattas, Henry Gómez, Hugo A. Fuentes, Ruddy Liendo-Picoaga, Jose M. Cotrina, Silvia P. Neciosup, Katia Roque, Jule Vásquez, Luis Mas, Marco Gálvez-Nino, Jovanny Zabaleta, Tatiana Vidaurre, Laura Fejerman. Transcriptome-wide study of tumor samples from Peruvian women identifies dysregulated pathways in luminal tumors typically associated with more aggressive disease. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5235.

Abstract 6753: Non-HIV cryptococcal patients with hematological malignancies: A retrospective analysis of a ten-year study from a Peruvian oncologic center

Abstract Background Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in people with hematological disorders. Methods We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2017. Results During the 11-year study period, a total of 21 cases of cryptococcosis (incidence rate of 13,4 per 1000 hematological malignancies). The time of diagnosis of cryptococcosis since hematologic malignancy diagnosis was 42 (18-161) days. Non-Hodgkin lymphoma (NHL) was the most frequent malignancy (47.6%), followed by leukemias (23.8%), multiple myeloma in (19.1%), and HL (9.5%). Three cases of adult T-cell leukemia/lymphoma associated with HTLV-1 infection were identified in the NHL. Cryptococcemia was the most frequent diagnosis (85.7%) followed by pulmonary (52.4%) and CNS (38.1%) involvement. Regarding clinical presentation, f ever was the most common symptom in meningeal cryptococcosis (76.2%) and dyspnea in pulmonary cryptococcosis (61.9%). The use of immunosuppressant chemotherapy within a month before the diagnosis of cryptococcosis was the most common risk factor. The main characteristics between patients with cryptococcosis and type of neoplasms (NHL vs other hematological neoplasms) such as age at admission, site of presentation of cryptococcosis, and lymphocyte count at admission were different significantly between these groups. In the NHL group, there was less involvement of the lungs. Overall survival (OS) in 15 and 120 days were 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other hematological malignancies was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82). Conclusions CNS cryptococcal infection was more frequent in patients with NHL. Citation Format: Kelly Meza, Luis E. Cuellar. Non-HIV cryptococcal patients with hematological malignancies: A retrospective analysis of a ten-year study from a Peruvian oncologic center. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6753.

Real-world outcomes of anti-EGFR therapy in advanced non-small cell lung cancer EGFR mutated in Peru.

Despite the advances in the management of advanced non-small cell lung cancer (NSCLC), the access to genetic profiling and target therapies remains a challenge in Latin America, even in countries with a higher rate of targetable mutations. The aim of this study is to evaluate the clinical outcomes of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) treatment in a Peruvian real-world setting. This is a retrospective study of recurrent or advanced NSCLC EGFR mutated patients diagnosed and treated with anti-EGFR TKI at Instituto Nacional de Enfermedades Neoplásicas (INEN) between January 1, 2015 to December 31, 2020. The outcomes were objective response rate (ORR), progression free survival (PFS), and overall survival (OS). We identify 613 stage IV or recurrent NSCLC patients who were tested for EGFR mutations and found a pathogenic mutation in 39.5% of patients. Only 51.2% of them received anti-EGFR TKI as institutional treatment. ORR was 58%, after median follow-up of 32 months, the estimated median PFS was 13.9months (11.1-16.7months), and the estimated median OS was 21.7months (18.5-24.9months). No differences were found in PFS according to line of treatment or brain metastases at diagnosis (p=0.46 and p=0.07, respectively), respect to OS there were no differences line of treatment (p=0.12), significant difference were found in presence of brain metastases (p=0.006). Our study demonstrates that erlotinib for advanced NSCLC harboring EGFR-activating mutations is effective even in patients usually excluded from clinical trial, like those previously exposed to one or more lines of chemotherapy or with brain metastases.

The impact of telemedicine on cancer care: real-world experience from a Peruvian institute during the COVID-19 pandemic.

Background: The COVID-19 pandemic caused discontinuities in cancer care (CC) in most countries. Here, the authors describe the real-world impacts of implementing a contingency plan employing telemedicine for CC. Methods: A retrospective study of patients who received CC through telemedicine at the Instituto Nacional de Enfermedades Neoplasicas, Peru, from March 2020 to February 2021 was conducted. Impacts were measured by comparing the amount of CC administered during the pandemic versus the prior year. Results: A total of 16,456 telemedicine visits were carried out. An annual comparative analysis showed a gap of 23% and telemedicine accounted for 27.6% of the total CC during administered during the pandemic. A high (4.50/5) level of patient satisfaction with telemedicine was reported. Conclusion: Telemedicine is an important tool to facilitate the continuity of CC.

Genomic landscape of lung cancer in the young.

BackgroundLung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small cell lung cancer (NSCLC) in young patients and compared it with genetic alterations in older patients.MethodsComparative study of the genomic profile of NSCLC young (≤40 years old) vs older patients (>40 years old) from Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Archival paraffin-embedded tumor samples were profiled with FoundationOne CDx assay to identify short variants alterations (insertions and deletions), copy number variations (CNV), tumor mutational burden and microsatellite instability in 324 driver genes and rearrangements in 28 commonly rearranged genes. A targetable alteration was defined as any alteration in a driver oncogene for which an FDA approved therapy existed at the time of study enrollment.ResultsOverall, 62 tumors were profiled, 32 from young and 30 from older patients. All clinicopathological features (smoking status, clinical stage, and histology) were similar between groups, except for gender (65.6% of females in the younger group vs 40% in the older group, P=0.043). At least one actionable mutation was present in 84.4% and 83.3% in younger and older patients, respectively. Alteration rates in the main genes were: BRAF, 3.1%(n=1) vs 0%; EGFR, 46.9% (n=15) vs 43.3% (n=13); ERBB2, 12.5% (n=4) vs 16.7% (n=5); KRAS, 15.6% (n=5) vs 16.7% (n=5); ALK, 6.3% (n=2) vs 3.3% (n=1); RET, 0.0% vs 3.3% (n=1); ROS1, 3.1% (n=1) vs 3.3% (n=1); NTRK1, 0.0% vs 3.3% (n=1) and MET, 3.1% (n=1) vs 13.3% (n=4). Mean TMB was 4.04 Mut/Mb (SD ± 3.98) for young vs 8.06 Mut/Mb (SD ± 9.84) for older patients (P=0.016). There were not significant differences in CNV, frequency of gene rearrangements, or microsatellites instability.ConclusionNSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological characteristics between younger and older patients and therefore not be applicable to all populations.

LINC-23. Factors influencing outcomes of older children with Medulloblastoma over 15 years in Peru, a resource limited setting

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with Medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997-2013, data from 103 children older than three years with Medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997 – 2008 and 2009 – 2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, while prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The five-year OS was 62% (95% CI: 53 – 74%) while EFS was 57% (95% CI: 48 – 69%). The variables adversely affecting survival were anaplastic histology [compared to desmoplastic; OS: HR=3.4, p=0.03], metastasis [OS: HR=3.5, p=0.01; EFS: HR=4.3, p=0.004], delay in radiation therapy of 31-60 days [compared to ≤30 days; EFS: HR=2.1, p=0.04], and treatment 2009 – 2013 cohort[OS: HR=2.2, p=0.02; EFS: HR=2.0; p=0.03]. CONCLUSIONS: Outcomes for Medulloblastoma at INEN were low compared with HIC. Anaplastic sub-type, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009 - 2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.