STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP).

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Recommendations for detection, prioritization, and treatment of thoracic oncology patients during the COVID-19 pandemic: the THOCOoP cooperative group.

The world currently faces a pandemic due to SARS-CoV-2. Relevant information has emerged regarding the higher risk of poor outcomes in lung cancer patients. As such, lung cancer patients must be prioritized in terms of prevention, detection and treatment. On May 7th, 45 experts in thoracic cancers from 11 different countries were invited to participate. A core panel of experts regarding thoracic oncology care amidst the pandemic gathered virtually, and a total of 60 initial recommendations were drafted based on available evidence, 2 questions were deleted due to conflicting evidence. By May 16th, 44 experts had agreed to participate, and voted on each of the 58 recommendation using a Delphi panel on a live voting event. Consensus was reached regarding the recommendations (>66 % strongly agree/agree) for 56 questions. Strong consensus (>80 % strongly agree/agree) was reached for 44 questions. Patients with lung cancer represent a particularly vulnerable population during this time. Special care must be taken to maintain treatment while avoiding exposure.

Nefrolitiasis de infección: caso clínico / Nephrolithiasis of infection: clinical case

Se presenta un caso de litiasis de infección, conocida con el nombre de cálculos de estruvita y asociado a una enfermedad metabólica subyacente y diabetes mellitus tipo 2 de reciente debut, el cual se manifestó con oliguria e infección, como resultado de una obstrucción urinaria bilateral parcial. El paciente de 48 años de edad, con antecedentes de cardiopatía isquémica, hipertensión arterial y de expulsar cálculos de riñón, consultó su caso el 21 de enero de 2009. Manejaba cifras de creatinina, glicemia y acido úrico normales anterior al ingreso y estas tuvieron un comportamiento ascendente durante la obstrucción, excepto el ácido úrico. En el diagnóstico aportaron datos de interés la ecografía renal y de próstata, la Uro-TAC y gammagrafía renal con MAG-3. El diagnóstico diferencial incluyó toda causa extrínseca e intrínseca, esta última relacionada con cálculos, coágulos o papila renal necrosada, que provocaran alteración al libre flujo urinario. Se estableció como patrones de buena evolución, la recuperación del volumen urinario, la normalización de la glucemia y creatinina, así como la permanencia del urocultivo negativo. El manejo terapéutico motivó a la utilización de la nefrolitotomía percútanea como una de las opciones que ofrecen los procederes endorulógicos, además del control de las enfermedades de base, lo que resultó una favorable evolución del caso.

A clinical case of lithiasis of infection is presented, known as calculi of struvite associated to an underlying metabolic disease and diabetes mellitus type-2 of recent onset, with oliguria and infection as a result of a partial bilateral urinary infection. A 48 years-old patient having medical records of ischemic heart disease, hypertension and expulsion of kidney stones attended to the office in January 21, 2009 presenting normal values of creatinine, glycemia and uric acid before the admission; these values increased during the obstruction, except the uric acid. Renal and prostate imaging, the Uro-Computerized axial tomography and renal scintigraphy with MAG-3 showed data of interest. Differential diagnosis included extrinsic and intrinsic causes, the last one related to calculi, clots or renal necrotic papilla causing disorder of the free urinary flow. Patterns of good progress were established: recovery of the urinary volume, normal levels of glycemia and creatinine and a permanent negative uroculture. Therapeutic management motivated the use of percutaneous nephrolithotomy as one of the choices for endourologic procedures, as well as the control of the underlying diseases, being favorable for a good progress of the case.