Abstract Purpose Mutations in the Kirsten rat sarcoma viral (KRAS) oncogene constitute a significant driver of lung adenocarcinoma, present in 10–40% of patients, which exhibit heterogeneous clinical outcomes, mainly driven by concurrent genetic alterations. However, characterization of KRAS mutational subtypes and their impact on clinical outcomes in Latin America is limited. Methods A cohort study was conducted at the National Cancer Institute (INCan) of Mexico. Individuals with advance-staged of adenocarcinoma and KRAS mutations, detected by next-generation sequencing, having undergone at least one line of therapy were included for analysis. Clinical and pathological characteristics were retrieved from institutional database from June 2014 to March 2023. Results KRAS was identified in fifty-four (15.6%) of 346 patients, among which 50 cases were included for analysis. KRAS G12D (n = 16, 32%) and KRAS G12C (n = 16, 32%) represented the most prevalent subtypes. KRAS G12D mutations were associated with female ( p = 0.018), never smokers ( p = 0.108), and concurrences with EGFR (25.0% vs. 17.6%, p = 0.124) and CDKN2A (18.8% vs. 14.7%, p = 0.157). KRAS G12D patients showed a better ORR (66.6% vs. 30.0%; OR 4.66, 95% CI 1.23–17.60, p = 0.023) and on multivariate analysis was significantly associated with better PFS (HR 0.36, 95% CI 0.16–0.80; p = 0.012) and OS (HR 0.24, 95% CI 0.08–0.70; p = 0.009). Conclusions To our knowledge, this study represents the first effort to comprehensively characterize the molecular heterogeneity of KRAS-mutant NSCLC in Latin American patients. Our data reinforce the current view that KRAS-mutated NSCLC is not a single oncogene-driven disease and emphasizes the prognostic impact of diverse molecular profiles in this genomically defined subset of NSCLC. Further validation is warranted in larger multicenter Latin American cohorts to confirm our findings.
Accumulated evidence indicates that patients with lung cancer are a vulnerable population throughout the pandemic. Limited information is available in Latin America regarding the impact of the pandemic on medical care. The goal of this study was to describe the clinical and social effect of COVID-19 on patients with thoracic cancer and to ascertain outcomes in those with a confirmed diagnosis.
Mutations in STK11 (STK11Mut) and, frequently co-occurring, KEAP1 mutations (KEAP1Mut) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics.This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients' tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11Wt/KEAP1Wt population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B).Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRASMut + STK11Mut, KRASMut + STK11Mut + KEAP1Mut, STK11Mut + KEAP1Mut, and KRASMut + KEAP1Mut, respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRASWt (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRASMut cases (p = 0.047). Tumors with KRASMut + KEAP1Mut had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3-5.4), slightly longer in those with KEAP1mut 6.1 months versus STK11Mut 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 ≥ 50% (30.9 months), and different from those with PD-L1 1-49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11Mut 14.2 months versus STK11Wt 27.0 months (p = 0.0001)] or KEAP1 [KEAP1Mut 12.0 months versus KEAP1Wt 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS.This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS.
Background: Small cell lung cancer (SCLC) represents 13-15% of all primary lung neoplasms and is characterized by its rapid growth rate and the rapid development of distant metastases.Objectives: The ovjective of the study was to guide and standardize the treatment of extensive disease SCLC in Mexico based on national and international clinical evidence.Material and methods: This document was developed as a collaboration between the National Cancer Institute and the Mexican Society of Oncology in compliance with international standards.An interdisciplinary group was formed, including medical oncologists, oncological surgeons, thoracic surgeons, radiation oncologists, and methodologists with experience in systematic reviews of the literature and clinical practice guidelines.Results: A consensus was reached, both by the Delphi method and in remote meetings, of extensive disease recommendations resulting from work questions.The scientific evidence that answers each of these clinical questions was identified and critically evaluated, before being incorporated into the body of evidence of the Guide.Conclusions: This Clinical Practice Guide provides clinical recommendations for the management of extensive disease of SCLC to contribute to the decision-making process of the clinicians involved with its management in our country, hoping that this will contribute to improving the quality of clinical care in these patients.
9114 Background: Hypoxia has been associated with chemo-radioresistance secondary to Vascular Endothelial Growth Factor Receptor induced by Hypoxia Induced Factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in cell lines, and this may have anti-angiogenic, pro-apoptotic, and anti-efflux effects. Particularly, EGFR mutated (EGFRm) tumor cell lines have been shown to overexpress both VEGF and HIF. In this phase II study, we evaluated the effect of transdermal NTG on intracranial objective response rate (iORR), intracranial progression-free survival (ICPFS), and overall survival (OS) of NSCLC patients with BM. Methods: We performed an open-label, phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. iORR and ICPFS were evaluated by MRI by two independent, blinded radiologists. Nitroglycerin was administered using a transdermal 36 mg patch, which released 10 mg in 24 hours with a rest interval of 12 hours from Monday-Friday throughout WBRT administration (10 days). Results: Fifty patients were allocated to the control group, while 46 were allocated to the experimental group (NTG); among these 26 (55.3%) had EGFRm in the control group and 21 (44.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response when compared to controls (56.6% vs. 43.5%; p = 0.024). Additionally, patients who received NTG in addition to WBRT had an independently prolonged ICPFS compared with those who received WBRT alone (27.7 vs. 9.6; HR: 0.470 [95%CI: 0.24-0.89]; p = 0.021). PFS was also positively impacted (HR: 0.519 [95%CI: 0.27-0.98]; p = 0.043). The benefit in terms of iORR and ICPFS (HR: 0.38 [95%CI: 0.16-0.91]; p = 0.030) was particularly important in the EGFRm patient subgroup. No differences were observed in OS. A significantly higher rate of vomiting presented in the NTG arm of the study ( p= 0.016). Conclusions: The concurrent administration of NTG and chemo-radiotherapy improves iORR and ICPFS among NSCLC patients with BM. The benefit is particularly significant in the EGFRm patient subgroup. Clinical trial information: NCT04338867.
623 Background: Standard of care for advanced NSGCTs is BEP (bleomycin, etoposide, cisplatin). Social, epidemiologic and economic factors can impact drug availability. In our institution, the COVID-19 pandemic limited accessibility to several antineoplastic drugs, including bleomycin. This analysis describes the frequency of BEP modifications and its impact in prognosis of intermediate (IP) and poor (PP) NSGCT treated at the National Cancer Institute in Mexico. Methods: Retrospective observational study performed from 2018 to 2022. Clinical characteristics and chemotherapy modifications were retrieved from electronic charts. Survival curves were built with Kaplan-Meier method and compared log-rank test to demonstrate effects of different clinicopathological variables on survival. Statistically significant variables in univariate analysis were included in multivariate Cox regression. Results: 179 patients included. Median age 23 (16-56). 33% had IP and 66% PP; 32% had non-pulmonary visceral metastases (NPVM). 60% had at least one dose modification. Median dose of bleomycin was 67.5 IU (IQR, IU 0-90) per cycle. 42% of patients received the full-dose of bleomycin (Bleo360) dose. 55.8% of bleomycin modifications were due to drug shortage. 88% who received Bleo360 didn´t have other chemotherapy drug modifications (p<.001). Median Progression Free Survival (mPFS) was 17.4 months (95% Confidence Interval (CI), 11.8-23.1). Median Overall Survival (mOS) was 73.6 months (95% CI, 20.6-126.7). Univariate and multivariate analysis are described in the table. Conclusions: Oncology drug shortages may have serious consequences for patient’s survival. In our cohort the dose-modifications of bleomycin had a deleterious impact in the survival of IP/PP NSGCTs patients. Policy modifications and stakeholders awareness is paramount to decrease shortage of “vintage” oncological therapies. Univariate and multivariate analysis. Univariate Multivariate Variable PFS HR(IC 95%) p OS HR(IC 95%) p PFS HR(IC 95%) p OS HR(IC 95%) p IPPP 0.34(0.21-0.56) <0.0001 0.3(0.2-0.5) 0.0001 Ref.2.4(1.4-4.2) 0.002 Ref.2.8(1.5-5.5) 0.002 NPVMNoYes 0.53(0.36-0.78) 0.001 0.5(0.4- 0.9) 0.011 Ref.1.3(0.9-2) 0.2 Ref.1.1(0.7-1.9) 0.6 Bleo360YesNo 0.6(0.66-0.98) 0.04 0.63(0.39-1.0) 0.06 Ref.1.3(0.9-2.0) 0.1 Ref.1.3(0.8-2.1) 0.3 Log Tumor MarkerFavorableUnfavorable 0.51(0.30-0.84) 0.009 Ref.2.1(1.2-3.7) 0.008 Ref.1.6(0.9-2.9) 0.1
34 Background: Prostate cancer represents a strong economic and social burden in the world. Imaging, pathology report and prostate specific antigen are the cornerstone for decision making. PSMA imaging with PET/CT has demonstrated superiority over conventional imaging, however, its availability is limited in countries with emerging economies. 99mTc-based imaging is widely used and has been favored by the development of new inhibitors targeting PSMA. Methods: We analyzed retrospectively 119 men with a histopathological diagnosis of prostate cancer obtained through transrectal biopsy or with clinical suspicion due to elevated PSA levels and physical examination findings. 68 were classified as high-risk and 51 as very high-risk, and referred for staging with [99mTc]Tc-iPSMA SPECT/CT between July 2022 and July 2024. The waiting times for initiating treatment were compared with a strategy based on PET/PSMA. Also number of lesions in patients with dual imaging with [99mTc]Tc-MDP and [99mTc]Tc-iPSMA was analyzed and assessed the changes in intention to treat. Results: Mean age of patients was 69.2 y/o (range 55-89 y/o), mean PSA level of staging group was 78.5 ng/mL (range 28.5-1667 ng/mL). Waiting time for a [99mTc]Tc-iPSMA was 7.2 days (+/- 1.5 days) versus 67.5 days (+/- 11.8 days) for [18F]F-iPSMA PSMA-1007. An additional study was required in 15.1% (n=18) of patients (n=13 PET/CT [18F]F PSMA-1007, 5 abdominal magnetic resonance). 36 patients had dual studies, observing 108 lesions with [99mTc]Tc-iPSMA and 114 with [99mTc]Tc-MDP, 6 with PSMA and 12 with MDP did not show anatomical changes. These findings did not modify the clinical stage or treatment intention. Overall, 590 lesions were identified in 119 patients, 101 in prostate, 267 in bone (diffuse disease in bone was considered as a single lesion), 135 in regional lymph nodes, and 87 in non-regional lymph nodes. Size range of lymph nodes detected were 0.5 mm to 25 mm. The change in management occurred in 23% patients (n=28); the changes were from ADT alone to doublet (ADT and Docetaxel) (n=11), from Radiotherapy to the pelvis to ADT + Docetaxel (n=8), from Radiotherapy to the pelvis to triplet (ADT+ Docetaxel + ARPi) (n=5), from ADT + RT to surgery (n=2), from ADT alone to ADT + SBRT (n=2). Conclusions: [99mTc]Tc-iPSMA SPECT/CT is an efficient alternative tool to [18F]F-iPSMA PSMA-1007, the results provide sufficient information to allow a significant change in intention to treat, significantly reducing waiting times, especially in countries where equipment availability PET is limited. These results support the development of public policies that promote the use of this type of radiopharmaceuticals to expand access to the new generation imaging modality and provide a benefit in the clinical management of prostate cancer especially in countries with low PET/CT infrastructure.