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Current challenges in the treatment of gliomas:The molecular era

World Journal of Clinical oncology 2024年第8期15卷 982-986页

作者： Castalia Fernández Juan Zafra-Martín Felipe Couñago department of Radiation oncology GenesisCare MadridMadrid 28043Spain department of Radiation oncology Hospital Universitario Vithas La MilagrosaGenesisCareMadrid 28010Spain department of Radiation oncology Hospital Universitario San Francisco de AsísGenesisCareMadrid 28002Spain department of Radiation oncology Hospital Universitario Virgen de la VictoriaMálaga 29010Spain

Gliomas originate from glial cells in the central nervous *** 80%-85%of malignant brain tumors in adults are *** most common central nervous system tumor in children is low-grade pediatric *** was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral *** characterization has led to better diagnostic and prognostic staging,which in turn has increased the precision of *** efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with ***,improvements in survival have been ***,clinical guidelines,as well as the article by Mohamed et al accompanying this editorial piece,are adapting treatment recommendations(surgery,chemotherapy,and radiotherapy)according to diagnosis and prognosis guided by molecular ***,this paves the way for the design of clinical trials with new therapies,which is especially important in pediatric gliomas.

关键词： Gliomas Chemotherapy Radiotherapy Isocitrate dehydrogenase-type mutant Pediatric gliomas Astrocytoma Oligodendroglioma 1p/19q-codeleted

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Phase Ⅱ trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/CDKN2A

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5518-5527页

作者： Javier Martin-Broto Jeronimo Martinez-Garcia David SMoura Andres Redondo Antonio Gutierrez Antonio Lopez-Pousa Javier Martinez-Trufero Isabel Sevilla Roberto Diaz-Beveridge Maria Pilar Solis-Hernandez Amancio Carnero Marco Perez David Marcilla Jesus Garcia-Foncillas Pablo Romero Javier Fernandez-Jara Daniel Lopez-Lopez Ivan Arribas Nadia Hindi Health Research Institute-Fundación Jiménez Díaz University hospital Universidad Autónoma de Madrid(IIS-FJDUAM)28040MadridSpain medical oncology department Fundación Jimenez Diaz University Hospital28040MadridSpain General de Villalba University hospital 28400MadridSpain medical oncology department University Hospital Virgen de la Arrixaca30120MurciaSpain department of medical oncology Hospital Universitario La Paz-IdiPAZP.Castellana26128046MadridSpain Hematology department University Hospital Son Espases07120MallorcaSpain medical oncology department Sant Pau Hospital08025BarcelonaSpain medical oncology department University Hospital Miguel Servet50009ZaragozaSpain Investigación Clínica y Traslacional en Cáncer/Instituto de Investigaciones Biomédicas de Malaga(IBIMA)/hospitales Universitarios Regional y virgen de la victoria de Malaga MalagaSpain medical oncology department Hospital Universitari i Politècnic La Fe46026ValenciaSpain medical oncology department Central University Hospital of Asturias33011OviedoSpain Instituto de Biomedicina de Sevilla(IBiS HUVRCSICUS)41013SevillaSpain Pathology department Virgen del Rocio University Hospital41013SevillaSpain Radiology department Fundación Jimenez Diaz University Hospital28040MadridSpain Computational Medicine Platform Fundación progreso y salud(FPS)Hospital Virgen del Rocío41013SevilleSpain Bioinformatics in Rare Diseases(BiER).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER) FPSHospital Virgen del RocioSevillaSpain Universitat de València-ERI-CES 46010ValenciaSpain

Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 ***4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK *** investigators of this study found that CDK4 overexpression,while not of CDKN2A,was the most consistent predictive factor for palbociclib efficacy in *** adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed CDK4,but not CDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudraCT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this *** was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at *** 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%CI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 *** median PFS and overall survival were 4.2(95%CI 3.6–4.8)and 12(95%CI 8.7–15.4)months,*** research showed a significant correlation between CDK4 mRNA and protein *** was active in a variety of sarcoma subtypes,selected by CDK4/CDKN2A,and deserves further investigation in the sarcoma context.

关键词： CDKN2A sarcoma CDK4

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Adjuvant Taxanes in Breast Cancer: A Critical Re-appraisal

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Journal of Cancer Therapy 2011年第3期2卷 317-321页

作者： Alfonso Sanchez-Munoz Nuria Ribelles Emilio Alba medical oncology department Hospital Clinico Universitario Virgen de la VictoriaMalaga.Spain.

Purpose: Several studies have reported a positive impact for taxanes in adjuvant breast cancer (BC) treatment in terms of reduced recurrence and mortality. However the impact of the magnitude on overall survival (OS) remains partially controversial. Methods: We examined the impact of taxane-containing adjuvant therapy for patients with early BC on OS, based on the number of deaths and on the calculated number of patients who need to be treated with taxanes to avoid one death (NNT). We classified patients in three different groups according to whether taxanes were administered concurrently or sequentially, and whether all treatment arms had the same or different duration. Results: 1) Taxanes in combination therapy: 8258 patients (4373 with taxanes and 3885 without taxanes), with 723 OS events. Overall survival for taxane-treated patients was 92.7% versus 89.6% for patients not receiving taxanes. NNT was 33. 2) Sequential treatment of unequal duration in the treatment arms: 14,228 patients (7970 with taxanes and 6256 without). Overall survival in taxane-treated patients was 86% compared with 83.2% for patients not receiving taxanes. NNT was 44. 3) Sequential treatment and similar duration in treatment arms: 9511 women (5093 with taxanes and 4418 without). Overall survival in patients treated with taxanes was 87% versus 85% in patients not receiving taxanes. NNT was 50. When the results of all these trials were considered together, the NNT stands at 43 patients. Conclusion: Taxanes afford a modest increase in overall survival in BC patients regardless of how they are given. Translational trials may well help to improve patient selection in the future.

关键词： Taxanes Adjuvant Chemotherapy Early Breast Cancer

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21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer

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四川生理科学杂志 2021年第10期43卷 1756-1756页

作者： Kevin Kalinsky From the Winship Cancer Institute at Emory University Atlanta (K.K.) Southwest oncology Group Statistics and Data Management Center (W.E.B. D.L.L. J.M.) and the University of Washington School of Medicine–Seattle Cancer Care Alliance (J.R.G.) — both in Seattle the University of Texas M.D. Anderson Cancer Center Houston (F.M.-B. D.T. G.N.H.) Loyola University Chicago Maywood IL (K.S.A.) the University of Michigan Ann Arbor (D.F.H. A.F.S.) Dana–Farber Cancer Institute Boston (N.U.L.) Mayo Clinic Jacksonville FL (E.A.P.) Fox Chase Cancer Center Philadelphia (L.J.G.) and the University of Pittsburgh Pittsburgh (P.R.) — both in Pennsylvania BC Cancer–Vancouver Cancer Centre Vancouver (S.K.L.C.) and Juravinski Cancer Centre at Hamilton Health Sciences Hamilton ON (S.D.-T.) — both in Canada ugci medical oncology hospital virgen de la victoria Instituto de Investigación Biomédica de Málaga Malaga (E.A.) Instituto de Investigación Sanitaria Gregorio Marañón Centro de Investigación Biomédica en Red Cáncer–Instituto de Salud Carlos III Universidad Complutense Madrid (M.M.) Hospital Universitario Virgen del Rocío Seville (M.R.-B.) Institut Català d’Oncologia Barcelona (M.G.-G.) Hospital Clínico Universitario de Valencia Biomedical Research Institute Investigación del Hospital Clínico de la Comunidad Valenciana Valencia (B.B.) and Centro Oncológico de Galicia A Coruña (M.R.-V.) — all in Spain Institut Gustave Roussy (S.D.) and Institut Curie (J.-Y.P.) Paris Institut Curie–Centre Réné Huguenin Saint-Cloud (E.G.C.B.) and Centre Antoine Lacassagne Nice (J.-M.F.) — all in France Mater Misericordiae University hospital Dublin (C.M.K.) Instituto Nacional de Cancerología de México Mexico City (C.H.A.-S.) the National Cancer Center Korea Goyang-si (E.-S.L.) and Asa Medical Center University of Ulsan College of Medicine Seoul (K.-H.J.) — both in South Korea Exact Sciences Redwood City CA (S.S.) the University of Kansas medical Center Kansas City (P.S.) and Yale University New Haven CT

Background:The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive,human epidermal growth factor receptor 2(HER2)-negative,axillary lymphnode-negative breast *** women with positive lymph-node disease,the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is ***:In a prospective trial,we randomly assigned women with hormone-receptor-positive,HER2-negative breast cancer,one to three positive axillary lymph nodes,and a recurrence score of 25 or lower(scores range from 0 to 100,with higher scores indicating a worse prognosis)to endocrine therapy only or to chemotherapy plus endocrine(chemoendocrine)*** primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence *** end points included distant relapse-free survival.

关键词： chemotherapy Breast Cancer

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