RESUMO
INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Consenso , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Espanha , Equipe de Assistência ao Paciente , Técnica Delphi , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: Lung cancer is one of the most prevalent cancers and the leading cause of cancer death. Advanced non-small cell lung cancer (aNSCLC) patients frequently harbor mutations that impact their survival outcomes. There are limited data regarding the prognostic and predictive significance of these mutations on survival outcomes in the real-world setting. METHODS: This observational retrospective study analyzed de-identified electronic medical records from the Flatiron Health Clinico-Genomic and FoundationCore® databases to identify patients with aNSCLC who initiated first-line immune checkpoint inhibitors (ICI; alone or in combination) or chemotherapy under routine care between 2016 and 2021. The primary objectives were to assess the prevalence of non-actionable mutations and to determine their association with overall survival (OS). Real-world progression-free survival (rwPFS) and real-world response (rwR) were investigated as secondary exploratory outcomes. RESULTS: Based on an assessment of 185 non-actionable mutations in 2999 patients, the most prevalent mutations were TP53 (70%), KRAS (42%), CDKN2A/B (31%), and STK11 (21%). STK11, KEAP1, and CDKN2A/B mutations were significantly associated with lower rwR, shorter rwPFS and OS. KRAS mutations were clinically associated with shorter rwPFS in CIT-treated patients. Subgroup analysis revealed that fast progressors were significantly more likely to harbor STK11, KEAP1, and CDKN2A/B mutations. Accordingly, long-term survivors (LTS) showed a significantly lower prevalence of these mutations. CONCLUSION: Our results provide evidence on the prognostic value of STK11, KEAP1, and CDKN2A/B mutations in patients with aNSCLC. Further research is required to better understand the implications of these findings on patient management and future trial design and treatment selection.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mutação , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Masculino , Feminino , Prognóstico , Idoso , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidor p16 de Quinase Dependente de Ciclina/genética , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Idoso de 80 Anos ou mais , Adulto , Taxa de SobrevidaRESUMO
Lung cancer (LC) is the most common cause of cancer death worldwide mostly due to the low survival rate: 75% of cases are identified in advanced stages. In this study, the list of useful biomarkers to make an early diagnosis using liquid biopsies was expanded. A total of 30 samples of LC were analyzed to define potential miRNA biomarkers in liquid biopsies for LC. The biomarkers have been identified in interaction networks miRNA-mRNA. The potential biomarkers have been then validated in large cohorts. A total of 15 candidate miRNAs, that regulate the repression of 30 mRNAs, have been identified as a specific functional interaction network for squamous carcinoma, while the specific functional interaction network of adenocarcinoma consists of four candidate miRNAs that seem to handle the repression of five mRNA. Inspection of expression levels in larger cohorts validates the usefulness of the 11 candidates as biomarkers in liquid biopsies. The 11 candidate miRNAs found could be utilized to form diagnostic predictive biomarkers for LC in liquid biopsies.
Assuntos
Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , RNA Mensageiro/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pulmão , Biópsia LíquidaRESUMO
UNLABELLED: Objective. We conducted this phase II trial to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods. ELIGIBILITY CRITERIA: stage IV NSCLC, Performance status =/< 2, adequate renal, hepatic and bone marrow function. Treatment consisted on: VNR 25 mg/m(2) plus gemcitabine 1000 mg/m(2), on days 1 and 8 of each 21-day cycle, followed by docetaxel 36 mg/m(2) weekly until progression or unacceptable toxicity. Results. 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types were: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patients (5%) and squamous cell carcinoma in 12 patients (57%). The majority of the patients had and ECOG PS of 1. Eight patients (38%) did not complete six cycles of gemcitabine-navelbine. The median number of cycles of gemcitabine-navelbine was 4 (range 2-6) Of the 13 patients (61%) who completed six cycles of gemcitabine-navelbine, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3- 16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6-25 months). The median survival time (MST) was 7.9 months, and the 1-year survival was 30%, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patients (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with docetaxel, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with docetaxel. Conclusion. The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Taxoides/administração & dosagem , Vimblastina/análogos & derivados , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Desoxicitidina/administração & dosagem , Docetaxel , Feminino , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Fatores de Tempo , Vimblastina/administração & dosagem , Vinorelbina , GencitabinaRESUMO
Renal cell carcinoma is an uncommon tumor in adults. Metastasis in the nasal fossa is rare, and can become apparent as a result of repeated epistaxis. We report a patient with renal cell carcinoma presenting with epistaxis secondary to a metastasis in the right nasal fossa. The primary tumor was treated with nephrectomy and the nasal fossa metastasis was treated successfully with embolization, chemoimmunotherapy, surgery, and radiotherapy. The presence of repeated epistaxis may very occasionally be the first symptom of renal cell carcinoma, and systemic treatment combined with local treatment may enable adequate control of the disease.
Assuntos
Adenocarcinoma de Células Claras/secundário , Carcinoma de Células Renais/secundário , Neoplasias Renais/diagnóstico , Cavidade Nasal , Neoplasias Nasais/secundário , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Terapia Combinada , Embolização Terapêutica , Epistaxe/etiologia , Evolução Fatal , Fluoruracila/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Nefrectomia , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/terapia , Orquiectomia , Pneumonectomia/métodos , Radioterapia Adjuvante , Proteínas Recombinantes , Neoplasias Testiculares/secundário , Neoplasias Testiculares/cirurgia , Tomografia Computadorizada por Raios X , Vimblastina/uso terapêuticoRESUMO
Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathologic syndrome with characteristic features. The diagnosis of BOOP requires the presence of a combination of pathological, clinical, and radiological features. We report the case of a lung cancer patient with bronquiloalveolar carcinoma (BAC) presenting with BOOP after chemotherapy with docetaxel and gemcitabine producing severe respiratory insufficiency, and simulating a progression of the tumor.
Assuntos
Adenocarcinoma Bronquioloalveolar/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pneumonia em Organização Criptogênica/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma Bronquioloalveolar/induzido quimicamente , Adenocarcinoma Bronquioloalveolar/complicações , Adenocarcinoma Bronquioloalveolar/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pneumonia em Organização Criptogênica/induzido quimicamente , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Pneumonia em Organização Criptogênica/tratamento farmacológico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Diagnóstico Diferencial , Progressão da Doença , Docetaxel , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia , Taxoides/administração & dosagem , Tomografia Computadorizada por Raios X , GencitabinaRESUMO
The median survival in patients with peritoneal carcinomatosis from colorectal adenocarcinoma is,with conventional approaches, only about six months. Combined treatment consisting of maxi-mum cytoreductive surgery plus intraoperative intraperitoneal hyperthermic chemotherapy has been shown, albeit in small non-comparative series, to increase disease-free survival and overall survival, compared with previous series. Further, a randomized trial has demonstrated better results (a median survival of 22.4 months) with cytoreduction plus intraperitoneal chemotherapy compared with conventional chemotherapy. Technical considerations, infrastructure requirements and possible complications imply specialized centres and staff. Surgery consists of peritonectomy of affected areas and fulguration of all macroscopic lesions. Intraperitoneal chemotherapy must reach all parts of the peritoneal cavity and the temperature of the hyperthermic procedure must be maintained between 42-44 degrees C. Three prognostic factors associated with this procedure are: pathologic tumour grade, peritoneal carcinomatosis index, and cytoreductive surgery grade.
Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/terapia , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Terapia Combinada , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Hipertermia Induzida , Período Intraoperatório , Neoplasias Peritoneais/tratamento farmacológico , PrognósticoRESUMO
Primary signet-ring cell carcinoma of the prostate is infrequent and even more so as secondary spread of this pathologic sub-type to the prostate. We describe the sixth reported case with a diagnosis of a secondary signet-ring cell tumour of the prostate secondary to a gastric cancer. Five years post-gastrectomy to resect signet-ring cell carcinoma, we detected a secondary intra-prostatic spread with urinary tract obstruction. The physical appearance of the tumour cells was similar to that of the previously-resected signet-cell carcinoma of the stomach. There were no metastases in other sites and the patient was treated with radiotherapy. When confronted with intra-prostatic signet-ring cell adenocarcinoma it is necessary to distinguish between primary and secondary aetiology since this would reflect in the choice of treatment and prognosis.