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1.
N Z Med J ; 134(1545): 47-59, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34788271

RESUMO

AIMS: To describe the systemic treatments in patients with de novo metastatic breast cancer (dnMBC, initial metastatic diagnosis) and recurrent metastatic breast cancer (rMBC). METHODS: Women diagnosed with dnMBC and rMBC in 2010-2017 were identified. Adjusted odds ratios of receiving systemic treatments were estimated by logistic regression model. Cox proportional hazards regression was used to estimate adjusted hazard ratio of breast cancer-specific mortality by treatments. RESULTS: The adjusted odds ratio of having chemotherapy and trastuzumab (for human epidermal growth factor receptor 2 positive (HER2+) disease) for Pacific women was 0.43 and 0.13 compared to European women. Patients receiving chemotherapy had improved survival for HER2+ non-luminal and triple negative metastatic breast cancer (MBC) (hazard ratios: 0.30, 0.66). Those with endocrine therapy was associated with better survival for luminal A and luminal B HER2+ MBC (hazard ratio: 0.25, 0.26). Trastuzumab was associated with superior survival in luminal B HER2+ and HER2+ non-luminal disease (hazard ratio: 0.34, 0.40). CONCLUSIONS: Pacific women with MBC were less likely to receive chemotherapy and trastuzumab than non-Pacific women. Chemotherapy was associated with improved survival in HER2+ non-luminal and triple negative MBC. Endocrine therapy improved survival in luminal A and luminal B HER2+ disease. Trastuzumab was associated with improved survival in luminal B HER2+ and HER2+ non-luminal disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Nova Zelândia
4.
Anticancer Res ; 41(10): 5107-5116, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593461

RESUMO

BACKGROUND/AIM: We evaluated local control and toxicity in patients receiving radiotherapy associated with immune check point inhibitors and analyzed which oligometastatic disease setting benefits the most from local ablation in terms of advantage in overall survival. PATIENTS AND METHODS: We retrospectively identified 60 oligoprogressive patients treated with a PD-1 inhibitor in association with radiotherapy on the site of progression (119 lesions). RESULTS: After a median follow-up of 11.7 months (range=1-39 months), we observed complete response (CR) in 45/119, partial response (RP) in 42/119, and stable disease (SD) in 30/119 patients. Nine radionecrotic events occurred. Two patients experienced grade 3 toxicities and 32 patients reported grade 2 toxicities. The number of radiologically evident metastatic organs in patients who received concomitant PD-1 inhibitors and radiotherapy showed a significant increase in survival (respectively, 73% after 12 months and 47% after 24 months) in patients with 0-3 metastatic organs compared to those with more than 3 organ sites involved (p<0.0001). CONCLUSION: Radiotherapy associated with PD-1 inhibitors is overall safe and efficacious. Patients eligible for intensification of local treatments should have less or equal to 3 metastatic organ sites.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Neoplasias/mortalidade , Radiocirurgia/mortalidade , Terapia Combinada , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias/patologia , Neoplasias/terapia , Prognóstico , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos , Taxa de Sobrevida , Testes de Toxicidade
5.
Medicina (Kaunas) ; 57(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684036

RESUMO

Background and objective: Although transarterial chemoembolization (TACE) has been the commonest local modality for hepatocellular carcinoma (HCC), incomplete repsonse occurs especially for tumors with a large size or difficult tumor accessment. The present meta-analysis assessed the efficacy and feasibility of external beam radiotherapy (EBRT) as a salvage modality after incomplete TACE. Materials and Methods: We systematically searched the PubMed, Embase, Medline, and Cochrane databases. The primary endpoint was overall survival (OS), and the secondary endpoints included the response ratem toxicity of grade 3, and local control. Results: Twelve studies involving 757 patients were included; the median of portal vein thrombosis rate was 25%, and the pooled median of tumor size was 5.8 cm. The median prescribed dose ranged from 37.3 to 150 Gy (pooled median: 54 Gy in *EQD2). The pooled one- and two-year OS rates were 72.3% (95% confidence interval (CI): 60.2-81.9%) and 50.5% (95% CI: 35.6-65.4%), respectively; the pooled response and local control rates were 72.2% (95% CI: 65.4-78.1%) and 86.6 (95% CI: 80.1-91.2%) respectively. The pooled rates of grade ≥3 gastrointestinal toxicity, radiation-induced liver disease, hepatotoxicity, and hematotoxicity were 4.1%, 3.5%, 5.7%, and 4.9%, respectively. Local control was not correlated with intrahepatic (p = 0.6341) or extrahepatic recurrences (p = 0.8529) on meta-regression analyses. Conclusion: EBRT was feasible and efficient in regard to tumor response and control; after incomplete TACE. Out-field recurrence, despite favorable local control, necessitates the combination of EBRT with systemic treatments. *Equivalent dose in 2 Gy per fraction scheme.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/terapia , Taxa de Sobrevida , Resultado do Tratamento
6.
Int J Gynaecol Obstet ; 155 Suppl 1: 45-60, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34669196

RESUMO

Endometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Since The Cancer Genome Atlas defined four molecular subgroups of endometrial cancers, the molecular factors are increasingly used to define prognosis and treatment. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (and increasingly sentinel node biopsy) enables identification of lymph node-positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant therapy is used for Stage I-II patients with high-risk factors and Stage III patients; chemotherapy is especially used in non-endometrioid cancers and those in the copy-number high molecular group characterized by TP53 mutation. In advanced disease, a combination of surgery to no residual disease and chemotherapy with or without radiotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease-free interval.


Assuntos
Neoplasias do Endométrio , Recidiva Local de Neoplasia , Quimioterapia Adjuvante , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/terapia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Útero/patologia
7.
World J Surg Oncol ; 19(1): 305, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663341

RESUMO

BACKGROUND: Some clinical researchers have reported that patients with cCR (clinical complete response) status after neoadjuvant chemoradiotherapy (nCRT) could adopt the watch-and-wait (W&W) strategy. Compared with total mesorectal excision (TME) surgery, the W&W strategy could achieve a similar overall survival. Could the W&W strategy replace TME surgery as the main treatment option for the cCR patients? By using the meta-analysis method, we evaluated the safety and efficacy of the W&W strategy and TME surgery for rectal cancer exhibiting cCR after nCRT. METHODS: We evaluated two treatment strategies for rectal cancer with cCR after nCRT up to July 2021 by searching the Cochrane Library, PubMed, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Clinical data for primary outcomes (local recurrence, cancer-related death and distant metastasis), and secondary outcomes (disease-free survival (DFS) and overall survival (OS)) were collected to evaluate the efficacy and safety in the two groups. RESULTS: We included nine studies with 818 patients in the meta-analysis, and there were five moderate-quality studies and four high-quality studies. A total of 339 patients were in the W&W group and 479 patients were in the TME group. The local recurrence rate in the W&W group was greater than that in the TME group in the fixed-effects model (OR 8.54, 95% CI 3.52 to 20.71, P < 0.001). The results of other outcomes were similar in the two groups. CONCLUSION: The local recurrence rate of the W&W group was greater than that in the TME group, but other results were similar in the two groups. With the help of physical examination and salvage therapy, the W&W strategy could achieve similar treatment effects with the TME approach. TRIAL REGISTRATION: Protocol registration number: CRD42021244032 .


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Recidiva Local de Neoplasia/terapia , Prognóstico , Neoplasias Retais/terapia , Conduta Expectante
8.
J Pak Med Assoc ; 71(Suppl 5)(8): S75-S78, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34634021

RESUMO

OBJECTIVE: To study the frequency of the thigh, hip and groin soft tissue sarcomas and retrospectively analyse the management, treatment results, and outcomes of these uncommon malignant tumours, in a tertiary care hospital of the city of Karachi. Methodology: Data of soft tissue tumours registered from 2017-2018 was retrieved during January 2019 to March 2019 from Aga Khan University Hospital, Karachi bone and soft tissue tumour registry. A retrospective review was performed and all soft tissue tumour cases treated with surgical intervention (with adjuvant /neoadjuvant therapy) or palliative intention were included. RESULTS: Total 119 cases of soft tissue tumours (STS) were identified out of which 85 were malignant cases (sarcomas) while 30 were benign. On presentation 84 (70.6%) were primary cases. On topographical distribution, there were 25 patients who had hip, groin and thigh sarcoma. Of these, 15 were males and 10 were females. As treatment, neo-adjuvant radiation was done in 4 (16%) patients and adjuvant chemo/radio therapy was given to 13 (52%) patients. Wide margin excision was performed in 19 (76%) patients and 4 (16%) had amputation. Reconstruction was offered to 3 (12%) patients. In post-surgical complications, 1 (4%) patient had wound infection. On final surgical histopathology, majority of the sarcomas were liposarcomas, myxofibrosarcoma, synovial sarcoma and Leiomyosarcoma. Post-surgery recurrence occurred in 7 (28%) patients. Overall survival was 76%. CONCLUSIONS: In treatment of soft tissue sarcoma, limb salvage is an achievable option and survival results are also good.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Feminino , Virilha , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Sarcoma/epidemiologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/terapia , Centros de Atenção Terciária , Coxa da Perna , Resultado do Tratamento
10.
J Hematol Oncol ; 14(1): 161, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627333

RESUMO

BACKGROUND: BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations. METHODS: We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial. RESULTS: BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1-2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity (≤ 10-4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months. CONCLUSION: Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800018143.


Assuntos
ADP-Ribosil Ciclase 1/imunologia , Antígeno de Maturação de Linfócitos B/imunologia , Imunoterapia Adotiva/métodos , Mieloma Múltiplo/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Adulto , Idoso , Animais , Antígeno de Maturação de Linfócitos B/antagonistas & inibidores , Linhagem Celular Tumoral , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Masculino , Camundongos , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Mieloma Múltiplo/imunologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia , Receptores de Antígenos Quiméricos/imunologia
11.
Nat Med ; 27(10): 1789-1796, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34608333

RESUMO

Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-based intralesional oncolytic immunotherapy approved for the treatment of unresectable melanoma. The present, ongoing study aimed to estimate the treatment effect of neoadjuvant T-VEC on recurrence-free survival (RFS) of patients with advanced resectable melanoma. An open-label, phase 2 trial (NCT02211131) was conducted in 150 patients with resectable stage IIIB-IVM1a melanoma who were randomized to receive T-VEC followed by surgery (arm 1, n = 76) or surgery alone (arm 2, n = 74). The primary endpoint was a 2-year RFS in the intention-to-treat population. Secondary and exploratory endpoints included overall survival (OS), pathological complete response (pCR), safety and biomarker analyses. The 2-year RFS was 29.5% in arm 1 and 16.5% in arm 2 (overall hazard ratio (HR) = 0.75, 80% confidence interval (CI) = 0.58-0.96). The 2-year OS was 88.9% for arm 1 and 77.4% for arm 2 (overall HR = 0.49, 80% CI = 0.30-0.79). The RFS and OS differences between arms persisted at 3 years. In arm 1, 17.1% achieved a pCR. Increased CD8+ density correlated with clinical outcomes in an exploratory analysis. Arm 1 adverse events were consistent with previous reports for T-VEC. The present study met its primary endpoint and estimated a 25% reduction in the risk of disease recurrence for neoadjuvant T-VEC plus surgery versus upfront surgery for patients with resectable stage IIIB-IVM1a melanoma.


Assuntos
Produtos Biológicos/administração & dosagem , Imunoterapia , Melanoma/terapia , Terapia Neoadjuvante , Adulto , Idoso , Produtos Biológicos/imunologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Humanos , Masculino , Melanoma/genética , Melanoma/patologia , Melanoma/virologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/virologia , Estadiamento de Neoplasias , Terapia Viral Oncolítica/tendências , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia
12.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502216

RESUMO

Background and case: An adolescent male presented with a second mediastinal tumor 1.5 years after treatment of a proven malignant germ-cell tumor in that location. The differential diagnosis included a recurrent germ-cell tumor or a non-germ cell malignancy. Serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were negative. The first biopsy was not informative, and the second biopsy gave a broad differential diagnosis including secondary non-germ cell malignancy using histology and immunohistochemistry. DNA methylation profiling, RNA sequencing, and targeted microRNA371a-3p profiling was subsequently performed, without a supportive result. After resection of the tumor the definitive diagnosis yielded two secondary non-germ cell malignancies in the form of a leiomyosarcoma and a solitary neuro endocrine carcinoma (NEC). In spite of the differences between the molecular profiles of the initial germ-cell tumor, the leiomyosarcoma and large-cell NEC are clonally related, as determined by the presence of identical chromosomal breakpoints. The copy number profiles suggest an initial polyploidization step, followed by various independent chromosomal gains and losses. This case demonstrates that germ-cell tumors must be evaluated carefully, including molecularly, in which the non-germ cell malignancy is negative for miR-371a-3p, both in tissue as well as in serum, in contrast to the primary tumor. We conclude that the patient presented with a primary type II mediastinal GCT and, a year and a half later, followed by a leiomyosarcoma and a large-cell NEC presenting as two secondary somatic-type malignancies clonally related to the original GCT. Conclusions: Malignant germ-cell tumors are known to recur as a somatic-type malignancy in very rare cases. This case report illustrates the challenges faced in defining the nature and clonality of the secondary somatic-type malignancies.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Mediastino/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Adolescente , Humanos , Masculino , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/terapia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/terapia , Prognóstico
13.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502329

RESUMO

Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calculated using the Demicco risk stratification system (RSS). The results were combined and examined to assess the accuracy of risk stratification and classification. The most common location was in non-extremities; 66% were located in soft tissue or subcutaneous areas and 92.8% in deep locations. On microscopic analysis, 38.1% of tumors revealed hypercellularity with a predominant patternless and/or hemangiopericytic growth pattern; 13.4% had ≥4 mitoses/10HPF; 16.5% showed necrosis, and almost half the tumors showed at least focal myxoid areas. Dedifferentiation was observed in three tumors. Immunomarker expression in SFTs was as follows: CD34 92.9%, CD99 57.1%, Bcl2 67.9%, neuroendocrine markers (at least 1) 25.7%, Desmin 14.3%, CK(AE1/AE3) 3%, Apoptotic Protease Activating Factor (APAF-1) 87% and finally Ki-67 ≥ 10% in 14.4%. The NAB2/STAT6 gene fusion was detected in 50 tumors. After a median follow-up of 90 months, 9.3% recurred, 11.3% metastasized, 10.3% died of disease and 76.2% were free of disease. TERT mutations were detected in 40.6% of the SFTs; the TP53 mutation was detected in 17%, and only 9.3% showed both mutations. According to the Demicco RSS, 6.1%, 11.3% and 82.4% of the tumors were classified as high, intermediate or low-risk of metastasis, respectively. All high-risk tumors had ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10, HTER and/or TP53 mutation and poor evolution. The intermediate risk SFTs with worse evolution displayed the HTER mutation. Almost all low-risk tumors had a favorable evolution, although four showed at least one adverse factor (Ki-67 ≥ 10, ≥4 mitoses/10HPF or high tumor size) and had a worse evolution. An integration of clinical, morphologic, immunohistochemical and molecular findings may improve risk stratification and classification and better predict patient outcome. The unfavorable course seems to be more frequent in high-risk SFTs, although it is not exceptional in low-risk SFTs either; hence, a long-term follow-up is required independently of the assigned risk stratification score. The inclusion of molecular findings in risk stratification systems could improve the precision in the classification of SFTs, especially those of intermediate risk. Future studies will be required to determine the most effective way to incorporate molecular analyses into RSS on SFTs. The coexistence of several adverse factors such as ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10%, mutations in HTER and/or p53 may suggest a closer clinical follow-up regardless of the histological appearance of the tumor.


Assuntos
Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica/métodos , Recidiva Local de Neoplasia/patologia , Medição de Risco/métodos , Tumores Fibrosos Solitários/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Tumores Fibrosos Solitários/classificação , Tumores Fibrosos Solitários/metabolismo , Tumores Fibrosos Solitários/terapia
14.
Head Neck ; 43(12): 3788-3795, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34524729

RESUMO

BACKGROUND: High-grade neuroendocrine carcinoma of the larynx (HG-NECL) is rare and aggressive with limited data regarding response to systemic therapy. We evaluated clinicopathological features, therapeutic approaches, and outcomes in patients with laryngeal or hypopharyngeal HG-NECL. METHODS: Data were retrospectively collected through 1997-2020. Median disease-free (mDFS), progression-free (mPFS), and overall survival (mOS) were estimated using the Kaplan-Meier method. RESULTS: Fifteen patients were identified; most had locoregional (N = 7) or metastatic disease (N = 5). The main curative-intent treatment was chemoradiation concurrent with platinum-based chemotherapy; the rate of complete response was 78%. Most patients (80%) developed recurrence; the mDFS was 13.1 months. For the first-line palliative therapy, the ORR and mPFS were 50% and 3.1 months, respectively. For all patients, the mOS was 17.8 months, and 8.6 months for metastatic disease. CONCLUSION: Laryngeal HG-NEC is associated with high relapse rates and dismal prognosis for those with recurrent/metastatic disease. Novel therapeutic strategies are needed.


Assuntos
Carcinoma Neuroendócrino , Neoplasias Laríngeas , Laringe , Carcinoma Neuroendócrino/terapia , Humanos , Hipofaringe , Neoplasias Laríngeas/terapia , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Taxa de Sobrevida
15.
J Surg Oncol ; 124(8): 1451-1458, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34510454

RESUMO

BACKGROUND AND OBJECTIVES: To analyze and evaluate the impact of preoperative transcatheter rectal arterial chemoembolization (TRACE) with concurrent chemoradiotherapy on surgery and prognosis of locally advanced rectal cancer (LARC). METHODS: A total of 118 patients with LARC were enrolled in this nonrandomized prospective study. They were assigned into the experimental group receiving preoperative TRACE with concurrent chemoradiotherapy (TRACE-CRT group, N = 60) and the control group receiving only neoadjuvant chemoradiotherapy (CRT group, N = 58). All patients underwent surgery after their preoperative treatments. RESULTS: All patients successfully completed the surgical operation. No significant differences were found in sphincter preservation rate and R0 resection rate between TRACE-CRT group and CRT group (p > 0.05). No significant differences were found between the two groups in terms of the perioperative indicators and postoperative complications except mean operation time (165.8 vs. 196.6 min, p < 0.001). Local recurrence occurred in 8 and 5 patients, respectively (p > 0.05). Distant metastasis occurred in 5 and 11 patients, respectively (p < 0.05). CONCLUSIONS: Adding TRACE in the preoperative standard treatment for LARC did not increase perioperative complications. In addition, it has the potential advantage of preventing distant metastasis. It is worthy of further application and promotion in clinical practice.


Assuntos
Quimioembolização Terapêutica/mortalidade , Quimiorradioterapia/mortalidade , Recidiva Local de Neoplasia/mortalidade , Cuidados Pré-Operatórios , Neoplasias Retais/mortalidade , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Ensaios Clínicos Controlados não Aleatórios como Assunto , Prognóstico , Estudos Prospectivos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Taxa de Sobrevida
16.
J Hematol Oncol ; 14(1): 140, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34493319

RESUMO

BACKGROUND: In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL). METHODS: Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor. RESULTS: The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56-3.49] and 1.21 [0.56-2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44-1.49] and 0.95 [0.58-1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01-0.07] and 0.08 [0.01-0.67], respectively) and study-specific neurological events (0.16 [0.08-0.33] and 0.05 [0.02-0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor. CONCLUSIONS: After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL. TRIAL REGISTRATION: NCT02631044 and NCT02348216.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Resultado do Tratamento
17.
J UOEH ; 43(3): 355-361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483195

RESUMO

A sufficient dose of radiation is difficult to administer in re-irradiation for local recurrence of cancer after radiotherapy because of the dose limitation to organs at risk. Re-irradiation cases also include radioresistant tumors that are difficult to control locally, and their prognosis is poor in general. The effect of re-irradiation using intensity-modulated radiotherapy (IMRT) has recently been reported to significantly reduce the dose to organs at risk, and the efficacy of hyperthermia has been reported for radioresistant tumors. We report a case of local recurrence after concurrent chemoradiotherapy treated with salvage re-irradiation using IMRT and chemotherapy combined with hyperthermia in a patient with nasopharyngeal carcinoma, and include a discussion of the literature.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Reirradiação , Quimiorradioterapia , Humanos , Hipertermia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos
18.
Abdom Radiol (NY) ; 46(12): 5715-5722, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34476534

RESUMO

PURPOSE: To study the clinical efficacy and safety of transarterial chemoembolization with drug-eluting beads (DEB-TACE) among women with advanced-stage or recurrent cervical cancer. METHODS: This retrospective cohort study enrolled women with cervical cancer who were treated by DEB-TACE between April 3, 2017 and July 12, 2021. Inclusion criteria were pathologic diagnosis of cervical cancer, II-IVa period, being aged 18 to 80 years, patient's inclination of treatment with DEB-TACE, and complete clinicopathologic data. Direct medical cost, hospital stay, resection frequency, treatment responses, adverse events, overall survival, and progression-free survival were investigated. RESULTS: A total of 16 women with cervical cancer were treated by DEB-TACE. DEB-TACE was successfully performed in all patients, with no major complications or adverse events. A total of 10 minor complications were observed in 9 women (56.3%) after the procedure. Seven (43.8%) women experienced mild to moderate post-embolization pain. The tumors decreased 3 and 6 months after the treatment. The frequency of complete response, partial response, stable disease, and progressive disease was 1 (40%), 3 (40%), 12 (15%), and 0 (0%), respectively, resulting in an objective response rate of 25.0% and a disease control rate of 100.0% after 1 month. The median hospital stay was 9.5 days, and the direct medical cost was 5.9 × 104 ¥. The median follow-up time was 4.1 months (interquartile range 2.6-23.7 months). The median overall survival was 19.1 months, and the 1- and 3-year survival rate was 64.9% and 46.4%, respectively. CONCLUSION: DEB-TACE with diamminedichloroplatinum-preloaded beads may be an effective and safe treatment for women with advanced-stage or recurrent cervical cancer.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Preparações Farmacêuticas , Neoplasias do Colo do Útero , Carcinoma Hepatocelular/terapia , Doxorrubicina , Feminino , Humanos , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/terapia
19.
Leuk Res ; 110: 106689, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34592699

RESUMO

INTRODUCTION: Hodgkin's (HL) and non-Hodgkin's (NHL) lymphomas have usually high cure rates. The standard of care for chemosensitive relapsed/refractory lymphoma patients is salvage chemotherapy followed by AHSCT. Due to carmustine and melphalan shortages, alternative pre-AHSCT conditioning regimens with similar tolerance and response were needed. OBJECTIVES: To compare the efficacy and toxicity profile between relapsed/refractory HL and NHL lymphomas given BEAM or BuCyE. METHODS: A retrospective analyses of 122 patients in a Brazilian center was made. OS and PFS were calculated by Kaplan-Meier and compared by log rank. Toxicity and engraftment data were also compared. RESULTS: Most clinical characteristics were similar between groups, although a higher frequency of grade ≥ 2 mucositis (p = .01) was seen in the BuCyE group. No significant difference in OS or PFS were observed between the groups. CONCLUSION: BEAM and BuCyE are well tolerated with similar toxicity profiles and survival outcomes. Therefore, BuCyE conditioning regimen can be considered an alternative to BEAM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Bussulfano/administração & dosagem , Carmustina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Transplante Autólogo , Adulto Jovem
20.
Cancer Sci ; 112(10): 4026-4036, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34382720

RESUMO

Disialoganglioside (GD2)-specific chimeric antigen receptor (CAR)-T cells (GD2-CAR-T cells) have been developed and tested in early clinical trials in patients with relapsed/refractory neuroblastoma. However, the effectiveness of immunotherapy using these cells is limited, and requires improvement. Combined therapy with CAR-T cells and molecular targeted drugs could be a promising strategy to enhance the antitumor efficacy of CAR T cell immunotherapy. Here, we generated GD2-CAR-T cells through piggyBac transposon (PB)-based gene transfer (PB-GD2-CAR-T cells), and analyzed the combined effect of these cells and a MEK inhibitor in vitro and in vivo on neuroblastoma. Trametinib, a MEK inhibitor, ameliorated the killing efficacy of PB-GD2-CAR-T cells in vitro, whereas a combined treatment of the two showed superior antitumor efficacy in a murine xenograft model compared to that of PB-GD2-CAR-T cell monotherapy, regardless of the mutation status of the MAPK pathway in tumor cells. The results presented here provide new insights into the feasibility of combined treatment with CAR-T cells and MEK inhibitors in patients with neuroblastoma.


Assuntos
Antineoplásicos/uso terapêutico , Gangliosídeos/uso terapêutico , Imunoterapia Adotiva/métodos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Neuroblastoma/terapia , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Receptores de Antígenos Quiméricos/uso terapêutico , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Cumarínicos/uso terapêutico , Elementos de DNA Transponíveis , Resistencia a Medicamentos Antineoplásicos , Feminino , Terapia Genética/métodos , Humanos , Camundongos , Camundongos SCID , Mutação , Recidiva Local de Neoplasia/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Linfócitos T , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas ras/antagonistas & inibidores
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