Short-course radiotherapy for rectal cancer: real-world evidence in Argentina.

Background: Short-course radiotherapy (SCRT) of 25 Gy in five daily fractions is a recommended strategy in the neoadjuvant setting for resectable locally advanced rectal cancer (LARC), as well as in cases of metastatic disease for local control. There is scarce information regarding the use of SCRT for patients who have received nonoperative management. Objectives: To describe the characteristics of patients who received treatment with SCRT for LARC and metastatic rectal cancer, toxicity, and the approach after radiation treatment. Methods: This is a retrospective analysis of all patients who underwent SCRT for rectal cancer at the Alexander Fleming Institute from March 2014 to June 2022. Results: In total, 44 patients were treated with SCRT. The majority were male (29, 66%), with a median age of 59 years (interquartile range 46-73). Most patients had stage IV disease (26, 59.1%), followed by LARC (18, 40.9%). Most lesions were located in the middle rectum (30, 68%). The majority of LARC patients underwent SCRT followed by consolidation chemotherapy (ChT) (16/18, 89%), while most patients with metastatic disease underwent SCRT followed by consolidation ChT (14/26, 53.8%). A clinical complete response (cCR) was documented in 8/44, 18.2% of patients. Most patients with LARC and cCR were managed by a watch and wait approach (5/18, 27.7%). Local recurrence was observed in LARC cases (2/18, 11.1%). Patients who underwent SCRT following consolidation ChT were more likely to have adverse events (AEs) than those undergoing induction ChT following SCRT (11/30, 36.7% versus 3/12, 25%, p = 0.02). Conclusion: In a subgroup of patients diagnosed with LARC and treated with SCRT followed by ChT, surgical treatment could be omitted after they achieved a cCR. Local recurrence was similar to that reported in a previous study. SCRT is a reasonable option for local disease control in stage IV disease, yielding low toxicity rates. Therefore, decisions must be made by a multidisciplinary team. Prospective studies are necessary to reach further conclusions.

Atypical pattern of response in rectal cancer after neoadjuvant pembrolizumab treatment: a case report, literature review, and proposed management model.

Background: Immunotherapy is the first-line treatment in patients with advanced microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC). Although immune checkpoint inhibitors (ICIs) for locally advanced rectal cancer (LARC) are not yet a standard, the results are very encouraging and raise the question of whether patients with clinical complete response (cCR) could receive nonoperative management (NOM). However, different patterns of response have challenged management strategies. Case Description: A 34-year-old woman diagnosed with dMMR LARC started treatment with capecitabine 2,000 mg/m2 on day 1 to 14 and oxaliplatin 130 mg/m2 on day 1 and every 21 days. Magnetic resonance imaging (MRI), performed three cycles later, showed local progression of the primary rectal lesion, which at that time had new peritoneal reflex involvement. A new hepatic lesion in segment V was observed. Due to disease progression, she was administered pembrolizumab 200 mg every 21 days. After three cycles, a discordant radiological response was observed on a new MRI scan that showed a complete response of the liver lesion and magnetic resonance tumor regression grade (mrTRG) 1 in the rectum. However, new involvement of the mesentery and enlargement of the regional lymph nodes (LNs) were also evident. A new colonoscopic biopsy was performed, showing no cancerous cells. She underwent surgery on the rectum and liver lesion. Pathology showed a complete response of the rectal wall and liver lesion, but 1 of 22 LNs was positive for adenocarcinoma (ypT0 N1 M0). The patient continued on pembrolizumab, and 14 months after surgery, she had not relapsed. Conclusions: Neoadjuvant immunotherapy for rectal cancer requires new recommendations for the assessment of clinical response. Pseudoprogression should be ruled out as an atypical response before deciding on surgical treatment. We propose an algorithm to address pseudoprogression in this setting.

Implementation of a virtual multicenter gastrointestinal tumor board to reduce cancer disparities in Argentina.

Given the increasing complexity of cancer care, multidisciplinary tumor boards have become essential in daily clinical oncology practice. The Project Extension for Community Healthcare Outcomes (ECHO) initiative developed an innovative telementoring model using a "hub and spoke" design consisting of a team of experts (hub) that offers a full service to multiple participants (the spokes) during regularly scheduled sessions discussing patients' clinical cases. The Alexander Fleming Cancer Institute in Buenos Aires was the first hub in Latin America to implement Project ECHO for gastrointestinal tumors. In our 3-year experience, 80 patients from 37 centers were evaluated within Project ECHO and a range of three to five cases were discussed in each meeting. From our perspective, the impact of this novel approach was a remarkable strategy to reduce care disparities by equalizing access to high-quality medical knowledge in a multidisciplinary environment for medical discussions. Additionally, it was shown to have a cost-effective impact directly on the patients and the local health system, since relevant costs were saved after unnecessary treatments, studies and travel expenses were avoided.

Liquid biopsy for KRAS, NRAS and BRAF mutation testing in advanced colorectal cancer patients: the Argentinean experience.

Objective: To analyze the frequency of KRAS, NRAS and BRAF hotspot mutations in circulating tumor DNA (ctDNA) from patients with metastatic colorectal cancer (mCRC). Methods: Observational, descriptive and retrospective study in mCRC patients with available ctDNA-based genotype of KRAS, NRAS and BRAF. Results: The frequencies of plasma mutations for KRAS, NRAS and BRAF were 34% (± 7), 4% (± 3) and 4% (± 3), respectively. Median overall survival of plasma-tested RAS/BRAF-mutated patients was 26.6 months (95% CI: 14.4-not estimable [NE]), while RAS/BRAF wild-type patients did not reach the median survival during follow-up. Median progression-free survival for RAS/BRAF wild-type and RAS/BRAF-mutated patients was 12 (95% CI: 7-NE) and 4 months (95% CI: 4-NE), respectively. Conclusion: Our work supports the utility of KRAS, NRAS and BRAF analysis in liquid biopsy from mCRC patients.

The LEGACy study: a European and Latin American consortium to identify risk factors and molecular phenotypes in gastric cancer to improve prevention strategies and personalized clinical decision making globally.

BACKGROUND: Gastric Cancer (GC) is the fourth most deadly cancer worldwide. Enhanced understanding of its key epidemiological and molecular drivers is urgently needed to lower the incidence and improve outcomes. Furthermore, tumor biology in European (EU) and Latin American (LATAM) countries is understudied. The LEGACy study is a Horizon 2020 funded multi-institutional research approach to 1) detail the epidemiological features including risk factors of GC in current time and 2) develop cost-effective methods to identify and integrate biological biomarkers needed to guide diagnostic and therapeutic approaches with the aim of filling the knowledge gap on GC in these areas. METHODS: This observational study has three parts that are conducted in parallel during 2019-2023 across recruiting centers from four EU and four LATAM countries: Part 1) A case-control study (800 cases and 800 controls) using questionnaires on candidate risk factors for GC, which will be correlated with clinical, demographic and epidemiological parameters. Part 2) A case-control tissue sampling study (400 cases and 400 controls) using proteome, genome, microbiome and immune analyses to characterize advanced (stage III and IV) GC. Patients in this part of the study will be followed over time to observe clinical outcomes. The first half of samples will be used as training cohort to identify the most relevant risk factors and biomarkers, which will be selected to propose cost-effective diagnostic and predictive methods that will be validated with the second half of samples. Part 3) An educational study, as part of our prevention strategy (subjects recruited from the general public) to test and disseminate knowledge on GC risk factors and symptoms by a questionnaire and informative video. Patients could be recruited for more than one of the three LEGACy studies. DISCUSSION: The LEGACy study aims to generate novel, in-depth knowledge on the tumor biological characteristics through integrating epidemiological, multi-omics and clinical data from GC patients at an EU-LATAM partnership. During the study, cost-effective panels with potential use in clinical decision making will be developed and validated. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: Part 1: NCT03957031 . Part 2: NCT04015466 . Part 3: NCT04019808 .

Implementation of a molecular tumour board in LATAM: the impact on treatment decisions for patients evaluated at Instituto Alexander Fleming, Argentina.

BACKGROUND: The role of the molecular tumour board (MTB) is to recommend personalised therapy for patients with cancer beyond standard-of-care treatment. A comprehensive molecular analysis of the tumour in a molecular pathology laboratory is important for all targeted therapies approaches. Here we report the 1-year experience of the Instituto Alexander Fleming Molecular Tumour Board. PATIENTS AND METHODS: The MTB of the Instituto Alexander Fleming was launched in December 2019 in a monthly meeting. In each interactive monthly session, five cases were presented and discussed by the members. These cases were referred by the treating oncologists. The MTB recommendations were sent to each physician individually, and to the rest of the meeting participants. This was discussed with the patients/families by the treating oncologist. The final decision to choose therapy was left to the treating physicians. Of the 32 patients presented at MTB, 28 (87.5%) had potentially actionable alterations and only 4 (12.5%) had no actionable mutation. Six (19%) patients received a local regulatory agency approved drug recommendation, nine (28%) patients received an off-label approval treatment recommendation and three (9%) patients did not receive the treatment due to access and reimbursement of the drug. CONCLUSION: In most of the cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. Molecular-guided extended personalised patient care is effective for a small but clinically significant proportion of patients in challenging clinical situations. We believe that the implementation of a MTB is feasible in the Latin America (LATAM) region.

Análisis mono-intitucional de pacientes con cáncer de cuello uterino tratadas con cirugía de wertheim meigs / Mono-intitutional analysis of patients with cervical cancer treated with surgery of wertheim meigs

El cáncer de cuello uterino (CCU) es la primera causa de muerte por cáncer en la provincia de Misiones. Objetivo primario: evaluación de las pacientes con CCU en estadios tempranos, sometidas a cirugía de Wertheim Meigs (WM). Objetivos secundarios: analizar las características clínico patológicas asociadas a los patrones de eficacia, en términos de SLR-SG y morbilidades. La búsqueda fue multidisciplinaria y activa, se seleccionaron mujeres con diagnóstico de CCU en estadios tempranos, tratadas con cirugía de WM, período 2010-2017. Se registraron datos clínico-patológicos y terapéuticos. Se calculó tasa de recurrencia local-sistémica, SLE y SG. Fuente de datos: RISMI (HC Informatizada), RITA (Registro de tumores), sub-registros de los servicios de ginecología y oncología. Se incluyeron 101 pacientes, edad promedio de 38 años. El 56% (57) se encontraba asintomático al momento del diagnóstico. La vía de abordaje fue laparotomía en el 97% (98), tiempo operatorio promedio 247 minutos. El promedio de días de internación post operatorio fue de 5.3. Ausencia de complicaciones post operatorias en 79% (80). Promedio de ganglios resecados 12, FIGO patológico IB en 42% (43). Realizaron adyuvancia 36% (35). Recurrencias loco-regionales y sistémicas 8% (5), tiempo medio a la recaída 37 meses. Mediana de seguimiento a 3 años: VSE 60% (35), PDSEG 27% (15), tasa de mortalidad específica 11% (6), VCE 6% (3). El CCU en estadios tempranos, diagnosticado y tratado por un grupo multidisciplinario en el Hospital Escuela de Agudos Dr. Ramón Madariaga, presentó patrones de eficacia y tasas de supervivencia enfermedad específica y de mortalidad, similar a las informadas en la literatura (AU)

Cervical cancer (CC) is the leading cause of cancer death in Misiones province. Primary objective: evaluation of patients with CCU in early stages submitted to Wertheim Meigs (WM) surgery. Secondary objectives: clinical pathological characteristics associated with efficacy patterns in terms of SLR-SG and morbidities. The research was multidisciplinary and active, we selected women with CC in early stages, treated with WM surgery, period 2010- 2017. Clinical-pathological and therapeutic data were recorded. Local-systemic recurrence rate, SLE, SG was calculated. Data source: RISMI (HC Computerized), RITA (Tumor Registry), subregistries of gynecology and oncology services. We included 101 patients, mean age 38 years. The 56% (57) were asymptomatic at the time of diagnosis. The approach was laparotomy in 97% (98), mean operative time 247 minutes. The mean number of days of post-operative hospitalization was 5.3. Absence of postoperative complications in 79% (80). Average resected nodes 12. Pathological IB in 42% (43). The 36% (35) performed adjuvancy). Locoregional and systemic recurrences 8% (5), mean time to relapse 37 months. Median followup at 3 years: VSE 60% (35), PDSEG 27% (15), specific mortality rate 11% (6), VCE 6% (3). The CC in early stages, diagnosed and treated by a multidisciplinary group in the Hospital Escuela de Agudos Dr. Ramón Madariaga, presents patterns of efficacy and survival rates, specific disease and mortality, similar to those reported in the literature (AU)

Tratamiento sistémico de las metástasis cerebrales de cáncer de mama / Systemic treatment of brain metastases from breast cancer

El cáncer de mama es el segundo tumor, luego del de pulmón, en número de casos que desarrollan metástasis cerebrales (1). Como los pacientes logran una sobrevida más prolongada, la incidencia ha ido aumentando; este fenómeno se acompaña, también, con una mayor sensibilidad de las imágenes que se utilizan para detectarlas. Se estima que, aproximadamente del 10% al 16% de los pacientes, las presentan a lo largo de la evolución de la enfermedad (2). Varios estudios indican que las metástasis cerebrales de cáncer de mama son más frecuentes en pacientes jóvenes con tumores más grandes y con subtipos histológicos más agresivos, como los triples negativos y los Her2 positivos (3, 5). El pronóstico es malo, sobrevida estimada a 1 y 2 años del 20% y del 2%, respectivamente (6, 7)