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1.
Breast Dis ; 43(1): 223-229, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968038

RESUMO

BACKGROUND: Neuro-Behcet's disease (NBD) is a variant of Behcet's disease (BD). To our knowledge, there have been no previous reports on concurrent NBD in breast cancer patients undergoing chemotherapy. CASE PRESENTATION: Our patient had a history of BD and was asymptomatic. She was diagnosed with human epidermal growth factor receptor 2-positive breast cancer by core needle biopsy and was administered neoadjuvant chemotherapy. After four courses, in addition to the aggravation of the existing adverse events, headache, fever, dysarthria, and muscle weakness in the upper left and lower extremities appeared. On admission, she was diagnosed with acute NBD, and steroid therapy was initiated. After her symptoms improved gradually, she was discharged. Then, she underwent mastectomy and axillary lymph node dissection for breast cancer. Trastuzumab and pertuzumab plus tamoxifen were administered postoperatively. Two years postoperatively, no recurrence of breast cancer and NBD was noted. CONCLUSION: When chemotherapy is administered to breast cancer patients with a history of BD, it is necessary to select chemotherapy with as few adverse events as possible and to continue with treatment while paying attention to the risk of NBD.


Assuntos
Síndrome de Behçet , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Receptor ErbB-2/metabolismo , Mastectomia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trastuzumab/uso terapêutico , Trastuzumab/efeitos adversos , Pessoa de Meia-Idade , Tamoxifeno/uso terapêutico , Tamoxifeno/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Adulto
2.
Arq Bras Cir Dig ; 37: e1810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38958346

RESUMO

BACKGROUND: Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor. AIMS: To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting. METHODS: The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded. RESULTS: Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%). CONCLUSIONS: The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.


Assuntos
Adenocarcinoma , Quimiorradioterapia Adjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Pessoa de Meia-Idade , Masculino , Feminino , Quimioterapia Adjuvante , Estudos Retrospectivos , Brasil/epidemiologia , Idoso , Adenocarcinoma/terapia , Adenocarcinoma/cirurgia , Adulto , Prognóstico , Programas Nacionais de Saúde , Gastrectomia , Terapia Neoadjuvante , Resultado do Tratamento , Estadiamento de Neoplasias , Assistência Perioperatória
3.
FASEB J ; 38(13): e23784, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38953567

RESUMO

To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle fiber size, satellite cells, and myonuclei. Women with stage I-III breast cancer were randomly assigned to a strength training group (ST, n = 23) performing supervised heavy-load strength training twice a week during chemotherapy, or a usual care control group (CON, n = 17). Muscle strength and body composition were measured and biopsies from m. vastus lateralis collected before the first cycle of chemotherapy (T0) and after chemotherapy and training (T1). Muscle strength increased significantly more in ST than in CON in chest-press (ST: +10 ± 8%, p < .001, CON: -3 ± 5%, p = .023) and leg-press (ST: +11 ± 8%, p < .001, CON: +3 ± 6%, p = .137). Both groups reduced fat-free mass (ST: -4.9 ± 4.0%, p < .001, CON: -5.2 ± 4.9%, p = .004), and increased fat mass (ST: +15.3 ± 16.5%, p < .001, CON: +16.3 ± 19.8%, p = .015) with no significant differences between groups. No significant changes from T0 to T1 and no significant differences between groups were observed in muscle fiber size. For myonuclei per fiber a non-statistically significant increase in CON and a non-statistically significant decrease in ST in type I fibers tended (p = .053) to be different between groups. Satellite cells tended to decrease in ST (type I: -14 ± 36%, p = .097, type II: -9 ± 55%, p = .084), with no changes in CON and no differences between groups. Strength training during chemotherapy improved muscle strength but did not significantly affect body composition, muscle fiber size, numbers of satellite cells, and myonuclei compared to usual care.


Assuntos
Neoplasias da Mama , Força Muscular , Treinamento Resistido , Células Satélites de Músculo Esquelético , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Treinamento Resistido/métodos , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Pessoa de Meia-Idade , Adulto , Quimioterapia Adjuvante , Composição Corporal , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/fisiologia , Terapia Neoadjuvante , Idoso
4.
Minerva Surg ; 79(4): 470-480, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38953759

RESUMO

Locally advanced extraperitoneal rectal cancer represents a significant clinical challenge, and currently, the standard treatment is based on neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection with total mesorectal excision (TME). In the last 30 years, its management has undergone significant changes due to the improvement of complementary radio- and chemotherapy treatments, the improvement of minimally invasive surgical approaches and the diffusion of organ-sparing approaches, such as nonoperative management, commonly called "watch and wait" (NOM) and local excision (LE), in highly selected patients who achieve a major or complete response to neoadjuvant CRT. This review aimed to critically examine the efficacy and oncological safety of NOM and LE compared to those of standard TME in rectal cancer patients after neoadjuvant CRT. Both the pros and cons of these approaches were strictly analyzed, providing a comprehensive and critical overview of these novel management strategies for rectal cancer.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Neoplasias Retais/terapia , Neoplasias Retais/radioterapia , Humanos , Conduta Expectante , Quimiorradioterapia , Resultado do Tratamento , Quimiorradioterapia Adjuvante
5.
Cancer Immunol Immunother ; 73(9): 177, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954046

RESUMO

Paclitaxel and anthracycline-based chemotherapy is one of the standard treatment options for breast cancer. However, only about 6-30% of breast cancer patients achieved a pathological complete response (pCR), and the mechanism responsible for the difference is still unclear. In this study, random forest algorithm was used to screen feature genes, and artificial neural network (ANN) algorithm was used to construct an ANN model for predicting the efficacy of neoadjuvant chemotherapy for breast cancer. Furthermore, digital pathology, cytology, and molecular biology experiments were used to verify the relationship between the efficacy of neoadjuvant chemotherapy and immune ecology. It was found that paclitaxel and doxorubicin, an anthracycline, could induce typical pyroptosis and bubbling in breast cancer cells, accompanied by gasdermin E (GSDME) cleavage. Paclitaxel with LDH release and Annexin V/PI doubule positive cell populations, and accompanied by the increased release of damage-associated molecular patterns, HMGB1 and ATP. Cell coculture experiments also demonstrated enhanced phagocytosis of macrophages and increased the levels of IFN-γ and IL-2 secretion after paclitaxel treatment. Mechanistically, GSDME may mediate paclitaxel and doxorubicin-induced pyroptosis in breast cancer cells through the caspase-9/caspase-3 pathway, activate anti-tumor immunity, and promote the efficacy of paclitaxel and anthracycline-based neoadjuvant chemotherapy. This study has practical guiding significance for the precision treatment of breast cancer, and can also provide ideas for understanding molecular mechanisms related to the chemotherapy sensitivity.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Piroptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Humanos , Piroptose/efeitos dos fármacos , Feminino , Terapia Neoadjuvante/métodos , Camundongos , Animais , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Gasderminas
6.
World J Surg Oncol ; 22(1): 178, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971793

RESUMO

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.


Assuntos
Axila , Neoplasias da Mama , Excisão de Linfonodo , Terapia Neoadjuvante , Neoplasia Residual , Biópsia de Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/diagnóstico por imagem , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Adulto , Biópsia de Linfonodo Sentinela/métodos , Idoso , Neoplasia Residual/cirurgia , Neoplasia Residual/patologia , Linfonodos/patologia , Linfonodos/cirurgia , Linfonodos/diagnóstico por imagem , Seguimentos , Prognóstico , Metástase Linfática , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Viabilidade
7.
Med Oncol ; 41(8): 197, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980546

RESUMO

Neoadjuvant chemotherapy (NAC) improves overall survival in muscle-invasive bladder cancer (MIBC). Older patients often do not receive NAC due to its potential toxicities. We examined treatment patterns of elderly MIBC patients as well as impact of NAC on survival in this population. The National Cancer Database was queried from 2006 to 2019 for stage T2-T4a MIBC patients ≥ 80 years old. Treatment exposures (extirpative surgery; chemotherapy; radiation) were ascertained. Kaplan-Meier survival curves were generated based on treatment modalities (no treatment; radiation only; chemotherapy only; chemoradiation; surgery only; NAC with surgery). Multivariable Cox proportional hazards regression assessed associations with overall survival (OS). The cohort included 16,391 patients (mean age 86 years); 51% received treatment. MIBC treatment was less common with advancing age; patients receiving NAC then surgery were younger and had lower comorbidity scores. From 2006 to 2019, more patients received chemoradiation, while rates of NAC rose modestly. Median OS for the NAC with surgery group was 48 months versus 9 months for the no treatment group. Log-rank tests showed significantly improved survival in the NAC with surgery group compared to the surgery only group, while Cox proportional hazards regression analysis showed highest survival benefit in the NAC with surgery group. Only half of elderly MIBC patients received treatment, with fewer undergoing curative intent. NAC with surgery was associated with the greatest survival benefit. While our findings should be taken in the context of potential selection bias and patient preferences, they support NAC as part of shared-decision making regardless of age.


Assuntos
Terapia Neoadjuvante , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/mortalidade , Feminino , Estudos Retrospectivos , Masculino , Terapia Neoadjuvante/métodos , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Invasividade Neoplásica , Estimativa de Kaplan-Meier
8.
Sci Rep ; 14(1): 14986, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951620

RESUMO

Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the association between a biochemical relapse (only the elevation of CA125) and an image-identified relapse to predict the relapsed lesions better. 162 patients who achieved complete clinical response were enrolled from women diagnosed with stage I-IV serous ovarian, tubal, and peritoneal cancers from January 2013 to June 2019 at our center. The CA125 level of 2 × nadir was defined as the indicator of image-identified relapse (P < 0.001). Compared to CA125 level exceeding 35 U/ml, the 2 × nadir of CA125 improve the sensitivity of image-identified relapse (84.9% vs 67.4%, P < 0.001); the 2 × nadir value can act as an earlier warning relapse signal with a longer median time to image-identified relapse (2.7 vs. 0 months, P < 0.001). Of the relapsed population, there was no difference of CA125 changing trend between the neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) group after initial treatment. Compared with 35 U/ml, CA125 reaching 2 × nadir during the follow-up process might be a more sensitive and early relapse signal in patients with serous OvCa. This criterion may help guide patients to be recommended for imaging examination to detect potential relapse in time.


Assuntos
Antígeno Ca-125 , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Humanos , Feminino , Antígeno Ca-125/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Recidiva Local de Neoplasia/sangue , Idoso , Adulto , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/diagnóstico , Biomarcadores Tumorais/sangue , Terapia Neoadjuvante , Estudos Retrospectivos , Proteínas de Membrana
9.
World J Surg Oncol ; 22(1): 175, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951795

RESUMO

PURPOSE: The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy and construct a nomogram model. METHODS: All enrolled subjects of the SEER database were randomly assigned to the training and testing group in a ratio of 3:2. The patients of Tangdu Hospital were seemed as validation group. Univariate cox regression analysis, lasso regression and random forest survival were used to screen variables related to the survival of advanced CRC patients received neoadjuvant therapy in the training group. Area under curves were adopted to evaluate the 1,3,5-year prediction value of the optimal model in three cohorts. Calibration curves were drawn to observe the prediction accuracy of the nomogram model. Decision curve analysis was used to assess the potential clinical value of the nomogram model. RESULTS: A total of 1833 subjects were enrolled in this study. After random allocation, 1055 cases of the SEER database served as the training group, 704 cases as the testing group and 74 patients from our center as the external validation group. Variables were screened by univariate cox regression used to construct a nomogram survival prediction model, including M, age, chemotherapy, CEA, perineural invasion, tumor size, LODDS, liver metastasis and radiation. The AUCs of the model for predicting 1-year OS in the training group, testing and validation group were 0.765 (0.703,0.827), 0.772 (0.697,0.847) and 0.742 (0.601,0.883), predicting 3-year OS were 0.761 (0.725,0.780), 0.742 (0.699,0.785), 0.733 (0.560,0.905) and 5-year OS were 0.742 (0.711,0.773), 0.746 (0.709,0.783), 0.838 (0.670,0.980), respectively. The calibration curves showed the difference between prediction probability of the model and the actual survival was not significant in three cohorts and the decision curve analysis revealed the practice clinical application value. And the prediction value of model was better for young CRC than older CRC patients. CONCLUSION: A nomogram model including LODDS for the prognosis of advanced CRC received neoadjuvant therapy was constructed and verified based on the SEER database and single center practice. The accuracy and potential clinical application value of the model performed well, and the model had better predictive value for EOCRC than LOCRC.


Assuntos
Neoplasias Colorretais , Terapia Neoadjuvante , Nomogramas , Programa de SEER , Humanos , Masculino , Feminino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Programa de SEER/estatística & dados numéricos , Terapia Neoadjuvante/estatística & dados numéricos , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/mortalidade , Pessoa de Meia-Idade , Taxa de Sobrevida , Seguimentos , Prognóstico , Idoso , Metástase Linfática , Estadiamento de Neoplasias , Adulto , Estudos Retrospectivos
10.
Breast Cancer Res ; 26(1): 107, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951909

RESUMO

PURPOSE: HER3, a member of the EGFR receptor family, plays a central role in driving oncogenic cell proliferation in breast cancer. Novel HER3 therapeutics are showing promising results while recently developed HER3 PET imaging modalities aid in predicting and assessing early treatment response. However, baseline HER3 expression, as well as changes in expression while on neoadjuvant therapy, have not been well-characterized. We conducted a prospective clinical study, pre- and post-neoadjuvant/systemic therapy, in patients with newly diagnosed breast cancer to determine HER3 expression, and to identify possible resistance mechanisms maintained through the HER3 receptor. EXPERIMENTAL DESIGN: The study was conducted between May 25, 2018 and October 12, 2019. Thirty-four patients with newly diagnosed breast cancer of any subtype (ER ± , PR ± , HER2 ±) were enrolled in the study. Two core biopsy specimens were obtained from each patient at the time of diagnosis. Four patients underwent a second research biopsy following initiation of neoadjuvant/systemic therapy or systemic therapy which we define as neoadjuvant therapy. Molecular characterization of HER3 and downstream signaling nodes of the PI3K/AKT and MAPK pathways pre- and post-initiation of therapy was performed. Transcriptional validation of finings was performed in an external dataset (GSE122630). RESULTS: Variable baseline HER3 expression was found in newly diagnosed breast cancer and correlated positively with pAKT across subtypes (r = 0.45). In patients receiving neoadjuvant/systemic therapy, changes in HER3 expression were variable. In a hormone receptor-positive (ER +/PR +/HER2-) patient, there was a statistically significant increase in HER3 expression post neoadjuvant therapy, while there was no significant change in HER3 expression in a ER +/PR +/HER2+ patient. However, both of these patients showed increased downstream signaling in the PI3K/AKT pathway. One subject with ER +/PR -/HER2- breast cancer and another subject with ER +/PR +/HER2 + breast cancer showed decreased HER3 expression. Transcriptomic findings, revealed an immune suppressive environment in patients with decreased HER3 expression post therapy. CONCLUSION: This study demonstrates variable HER3 expression across breast cancer subtypes. HER3 expression can be assessed early, post-neoadjuvant therapy, providing valuable insight into cancer biology and potentially serving as a prognostic biomarker. Clinical translation of neoadjuvant therapy assessment can be achieved using HER3 PET imaging, offering real-time information on tumor biology and guiding personalized treatment for breast cancer patients.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-3 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico por imagem , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Receptor ErbB-3/metabolismo , Receptor ErbB-3/genética , Estudos Prospectivos , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Tomografia por Emissão de Pósitrons/métodos
11.
Pathol Oncol Res ; 30: 1611817, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957347

RESUMO

The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante/métodos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Prognóstico
12.
Front Immunol ; 15: 1394497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947323

RESUMO

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.


Assuntos
Cistadenocarcinoma Seroso , Citocinas , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/mortalidade , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/terapia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/diagnóstico , Citocinas/sangue , Pessoa de Meia-Idade , Idoso , Terapia Neoadjuvante , Fenótipo , Procedimentos Cirúrgicos de Citorredução , Biomarcadores Tumorais/sangue , Gradação de Tumores , Prognóstico , Resultado do Tratamento , Adulto
13.
Front Immunol ; 15: 1405146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947338

RESUMO

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Aprendizado de Máquina , Terapia Neoadjuvante , Tomografia Computadorizada por Raios X , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Masculino , Feminino , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Imunoterapia/métodos , Nomogramas , Resultado do Tratamento , Adulto , Radiômica
14.
Cancer Immunol Immunother ; 73(9): 182, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967817

RESUMO

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Instabilidade de Microssatélites , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Idoso , Adulto , Reparo de Erro de Pareamento de DNA , Quimioterapia Adjuvante/métodos , Seguimentos
15.
BMC Cancer ; 24(1): 789, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956544

RESUMO

BACKGROUND: MicroRNA-1 (miR-1) is a tumour suppressor that can inhibit cell proliferation and invasion in several cancer types. In addition, miR-1 was found to be associated with drug sensitivity. Circulating miRNAs have been proven to be potential biomarkers with predictive and prognostic value. However, studies of miR-1 expression in the serum of breast cancer (BC) patients are relatively scarce, especially in patients receiving neoadjuvant chemotherapy (NAC). METHODS: Serum samples from 80 patients were collected before chemotherapy, and RT-PCR was performed to detect the serum expression of miR-1. The correlation between miR-1 expression in serum and clinicopathological factors, including pathological complete response (pCR), was analyzed by the chi-squared test and logistic regression. KEGG and GSEA analysis were also performed to determine the biological processes and signalling pathways involved. RESULTS: The miR-1 high group included more patients who achieved a pCR than did the miR-1 low group (p < 0.001). Higher serum miR-1 levels showed a strong correlation with decreased ER (R = 0.368, p < 0.001) and PR (R = 0.238, p = 0.033) levels. The univariate model of miR-1 for predicting pCR achieved an AUC of 0.705 according to the ROC curve. According to the interaction analysis, miR-1 interacted with Ki67 to predict the NAC response. According to the Kaplan-Meier plot, a high serum miR-1 level was related to better disease-free survival (DFS) in the NAC cohort. KEGG analysis and GSEA results indicated that miR-1 may be related to the PPAR signalling pathway and glycolysis. CONCLUSIONS: In summary, our data suggested that miR-1 could be a potential biomarker for pCR and survival outcomes in patients with BC treated with NAC.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , MicroRNAs , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Prognóstico , Adulto , Idoso , Resultado do Tratamento , Regulação Neoplásica da Expressão Gênica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
16.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 691-696, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-38955700

RESUMO

Objective: To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression. Methods: The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected. Results: The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive (P<0.001), Ki-67 index below 35% (P<0.001), well or moderate differentiation (P<0.001) and over the age of 50 (P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions: The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.


Assuntos
Neoplasias da Mama , Metástase Linfática , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Receptor ErbB-2/metabolismo , Feminino , Estudos Retrospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Terapia Neoadjuvante , Hibridização in Situ Fluorescente , Imuno-Histoquímica , Pessoa de Meia-Idade , Adulto , Antígeno Ki-67/metabolismo
17.
J Transl Med ; 22(1): 637, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978099

RESUMO

BACKGROUND: Breast cancer patients exhibit various response patterns to neoadjuvant chemotherapy (NAC). However, it is uncertain whether diverse tumor response patterns to NAC in breast cancer patients can predict survival outcomes. We aimed to develop and validate radiomic signatures indicative of tumor shrinkage and therapeutic response for improved survival analysis. METHODS: This retrospective, multicohort study included three datasets. The development dataset, consisting of preoperative and early NAC DCE-MRI data from 255 patients, was used to create an imaging signature-based multitask model for predicting tumor shrinkage patterns and pathological complete response (pCR). Patients were categorized as pCR, nonpCR with concentric shrinkage (CS), or nonpCR with non-CS, with prediction performance measured by the area under the curve (AUC). The prognostic validation dataset (n = 174) was used to assess the prognostic value of the imaging signatures for overall survival (OS) and recurrence-free survival (RFS) using a multivariate Cox model. The gene expression data (genomic validation dataset, n = 112) were analyzed to determine the biological basis of the response patterns. RESULTS: The multitask learning model, utilizing 17 radiomic signatures, achieved AUCs of 0.886 for predicting tumor shrinkage and 0.760 for predicting pCR. Patients who achieved pCR had the best survival outcomes, while nonpCR patients with a CS pattern had better survival than non-CS patients did, with significant differences in OS and RFS (p = 0.00012 and p = 0.00063, respectively). Gene expression analysis highlighted the involvement of the IL-17 and estrogen signaling pathways in response variability. CONCLUSIONS: Radiomic signatures effectively predict NAC response patterns in breast cancer patients and are associated with specific survival outcomes. The CS pattern in nonpCR patients indicates better survival.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Prognóstico , Pessoa de Meia-Idade , Adulto , Imageamento por Ressonância Magnética , Resultado do Tratamento , Estudos de Coortes , Idoso , Estudos Retrospectivos , Reprodutibilidade dos Testes , Radiômica
18.
Hum Vaccin Immunother ; 20(1): 2370085, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38967227

RESUMO

Small cell carcinoma of the esophagus (SCCE) is a rare and highly malignant type of esophageal cancer with no standard treatment, facing challenges of resistance to conventional therapies. This study presents the cases of one extensive-stage and two limited-stage SCCE patients treated with chemoimmunotherapy. The two limited-stage patients underwent surgery post-treatment and experienced notable and enduring positive responses. This represents the first documented application of neoadjuvant chemoimmunotherapy in limited-stage SCCE patients. Additionally, comprehensive immunohistochemical analysis and whole exome sequencing were performed on the case patients. The findings revealed that infiltration of CD8+ T cells and PD-L1 expression in the SCCE tumor were key factors for favorable responses in SCCE patients receiving chemoimmunotherapy.


Assuntos
Carcinoma de Células Pequenas , Neoplasias Esofágicas , Imunoterapia , Terapia Neoadjuvante , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/tratamento farmacológico , Masculino , Imunoterapia/métodos , Pessoa de Meia-Idade , Antígeno B7-H1/metabolismo , Resultado do Tratamento , Idoso , Biomarcadores Tumorais , Linfócitos T CD8-Positivos/imunologia , Feminino , Sequenciamento do Exoma
19.
Breast Cancer Res ; 26(1): 112, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965610

RESUMO

BACKGROUND: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. METHOD: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. RESULTS: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. CONCLUSION: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Ácidos Nucleicos Livres , Terapia Neoadjuvante , Regiões Promotoras Genéticas , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Adulto , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Resultado do Tratamento , Perfilação da Expressão Gênica
20.
Eur J Cardiothorac Surg ; 66(1)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38913852

RESUMO

OBJECTIVES: Unlike the initial plan, some patients with oesophageal squamous cell carcinoma cannot or do not receive surgery after neoadjuvant chemoradiotherapy (nCRT). This study aimed to report the epidemiology of patients not receiving surgery after nCRT and to evaluate the potential risk of refusing surgery. METHODS: We analysed patients with clinical stage T3-T4aN0M0 or T1-T4aN1-N3M0 oesophageal squamous cell carcinoma who underwent nCRT as an initial treatment intent between January 2005 and March 2020. Patients not receiving surgery were categorized using predefined criteria. To evaluate the risk of refusing surgery, a propensity-matched comparison with those who received surgery was performed. Recurrence-free (RFS) and overall survival (OS) was compared between groups, according to clinical response to nCRT. RESULTS: Among the study population (n = 715), 105 patients (14.7%) eventually failed to reach surgery. There were three major patterns of not receiving surgery: disease progression before surgery (n = 25), functional deterioration at reassessment (n = 47), and patient's refusal without contraindications (n = 33). After propensity-score matching, the RFS curves of the surgery group and the refusal group were significantly different (P < 0.001), while OS curves were not significantly different (P = 0.069). In patients who achieved clinical complete response on re-evaluation, no significant difference in the RFS curves (P = 0.382) and in the OS curves (P = 0.290) was observed between the surgery group and the refusal group. However, among patients who showed partial response or stable disease on re-evaluation, the RFS and OS curves of the refusal group were overall significantly inferior compared to those of the surgery group (both P < 0.001). The 5-year RFS rates were 10.3% for the refusal group and 48.2% for the surgery group, and the 5-year OS rates were 8.2% for the refusal group and 46.1% for the surgery group. CONCLUSIONS: Patient's refusal remains one of the major obstacles in completing the trimodality therapy for oesophageal squamous cell carcinoma. Refusing surgery when offered may jeopardize oncological outcome, particularly in those with residual disease on re-evaluation after nCRT. These results provide significant implications for consulting patients who are reluctant to oesophagectomy after nCRT.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Terapia Neoadjuvante , Humanos , Masculino , Feminino , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Pessoa de Meia-Idade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Terapia Neoadjuvante/estatística & dados numéricos , Idoso , Estudos Retrospectivos , Estadiamento de Neoplasias , Pontuação de Propensão , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Quimiorradioterapia
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