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1.
Anticancer Res ; 42(4): 2095-2104, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35347033

RESUMO

BACKGROUND/AIM: The standard of treatment for esophageal cancer with adjacent organ invasion (T4) has not been established. We retrospectively analyzed the clinical outcomes of radiotherapy (RT) in elderly and younger patients with T4 esophageal cancer. PATIENTS AND METHODS: Sixty-nine patients with T4 esophageal cancer who underwent RT at the Kanagawa Cancer Center between January 2014 and November 2020 were included in this study. Patients aged ≥70 years were defined as the elderly group and those aged <70 years were defined as the younger group. The total dose of RT was set at 60 Gy in 30 fractions. Chemotherapy combined with 5-fluorouracil and cisplatin was administered concurrently with RT in general. The overall survival (OS) rate was estimated using the Kaplan-Meier method. Adverse events were assessed using CTCAE v4.0. RESULTS: The median survival time (MST) of the elderly group (n=35) was 21.5 months, and the OS rates at 1, 3, and 5 years were 63.7%, 31.3%, and 15.6%, respectively. The MST of the younger group (n=34) was 12.5 months, and the OS rates at 1, 3, and 5 years were 52.2%, 29.4%, and 29.4%, respectively. No significant difference in OS was observed between the two groups (p=0.767). Toxicities were not significantly different between the two groups except for thrombocytopenia and esophageal fistula (p=0.012 and p=0.022, respectively). CONCLUSION: The clinical outcomes of RT for T4 esophageal cancer in elderly patients were generally similar to those in the younger group.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Humanos , Estudos Retrospectivos
2.
Acta Biochim Pol ; 69(3): 625-632, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36070433

RESUMO

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is an ideal treatment for advanced head and neck squamous cell carcinoma (HNSCC). The performance of CCRT induces severe toxicities in HNSCC patients and decreases the quality of life (QOL). Maitake D-Fraction is proteoglycan which has anti-tumor function associated with its immunomodulatory capacity. The polysaccharides of Maitake also have anti-radiation effect in radiation therapy during cancer treatment. This research aimed to illustrate Maitake D-Fraction effects on CCRT-associated adverse events and QOL. METHODS: During CCRT, Maitake capsules were taken orally 3 times a day, each time 4 capsules, one hour before meals. QOL were analyzed by EORTC QLQ-C30-Chinese version and EORTC QLQ-HandN-35-Chinese version. 141 patients were recruited and divided into an intervention group and a placebo group. RESULTS: Frequencies of severe CCRT-associated adverse events in intervention group were less than in placebo group. Global QOL score in intervention group was higher than in placebo group 5 weeks post treatment. The proportion of patients returning to baseline global QOL score at 6-month was increased by Maitake D-Fraction administration. CONCLUSION: In conclusion, this randomized clinical trial demonstrated that in advanced laryngeal and pharyngeal cancer patients, the oral administration of Maitake D-Fraction alleviated CCRT-related adverse events and deterioration in QOL.


Assuntos
Grifola , Neoplasias de Cabeça e Pescoço , Neoplasias Faríngeas , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/radioterapia , Polissacarídeos , Proteoglicanas/uso terapêutico , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço
3.
In Vivo ; 36(5): 2400-2408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099141

RESUMO

BACKGROUND/AIM: Neoadjuvant concurrent chemoradiotherapy (CCRT) for esophageal cancer is often overwhelming due to its toxic effects. This study aimed to establish a prognostic indicator based on pretreatment albumin and neutrophil-to-lymphocyte (NLR) ratio score (ANS) in comparison to the Prognostic Nutritional Index (PNI) in patients with esophageal cancer. PATIENTS AND METHODS: A total of 123 patients who received neoadjuvant CCRT for esophageal cancer were prospectively and consecutively recruited between August 2016 and December 2017 from three medical institutes in Taiwan. Patients were assigned to ANS 0, 1, and 2 groups based on their pretreatment albumin and NLR values. ANS and PNI performances were compared for prediction of survival outcome. RESULTS: Compared with ANS 0 (39 patients) and ANS 1 (51 patients), ANS 2 (33 patients) cases showed worse overall survival (hazard ratio=2.96; 95% confidence interval=1.45-6.05; log-rank p=0.003; hazard ratio=3.79; 95% confidence interval=1.79-8.02, p<0.001, respectively). ANS had better performance in overall survival evaluation and discrimination ability than PNI and individual albumin and NLR. Patients in the ANS 0, 1, and 2 had radiotherapy incompletion rates of 2.6%, 3.9%, and 18.2%, respectively, and chemotherapy incompletion rates of 5.1%, 7.8%, and 30.3%, respectively. Patients in the ANS 2 group were significantly associated with a higher incidence of infection (30.3%) than those in the ANS 0 (10.3%) and ANS 1 groups (9.8%). CONCLUSION: Pre-treatment ANS was significantly associated with CCRT safety profiles, CCRT completion rate, and survival outcome in patients with esophageal cancer with excellent performance compared to PNI and NLR.


Assuntos
Neoplasias Esofágicas , Terapia Neoadjuvante , Albuminas , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/terapia , Humanos , Linfócitos , Neutrófilos , Avaliação Nutricional , Prognóstico
4.
BMJ Open ; 12(8): e051594, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008072

RESUMO

Epidermal growth factor receptor (EGFR) is a therapeutic target in nasopharyngeal carcinoma (NPC). The optimal combined modality of optimal combined modality of anti--EGFR monoclonal antibodies, induction chemotherapy (ICT), concurrent chemotherapy and radiotherapy for NPC remains poorly defined. None of previous studies have developed subsequent treatment strategies on the basis of stratification according to the efficacy following ICT plus anti-EGFR mAbs. This study aims to increase treatment intensity for patients with poor efficacy of ICT and reduce treatment toxicity for patients with favourable efficacy of ICT by assessing whether the efficacy of this treatment regimen is non-inferior to ICT plus concurrent chemoradiotherapy (historic controls). INTRODUCTION: METHODS AND ANALYSIS: Pathology-confirmed WHO type II/III NPC patients at clinical stage III-IVA (eighth American Joint Committee on Cancer/Union for International Cancer Control staging system) will be included in the study. They will receive ICT plus nimotuzumab (NTZ), followed by radiotherapy plus NTZ or concurrent chemoradiotherapy plus NTZ (stratified based on the efficacy of ICT plus NTZ). The primary endpoint is 3-year failure-free survival rate; while the secondary endpoints are 3-year overall survival rate, distant metastasis-free survival rate and locoregional recurrence-free survival rate, and short-term remission rate of tumour and treatment toxicity. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. Our findings will be disseminated in a peer-reviewed journal. Implementation strategies are in place to ensure privacy and confidentiality of participants. TRIAL REGISTRATION NUMBER: ChiCTR2000041139.


Assuntos
Antineoplásicos , Neoplasias Nasofaríngeas , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Humanos , Quimioterapia de Indução , Estudos Multicêntricos como Assunto , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/terapia , Estadiamento de Neoplasias , Estudos Prospectivos
5.
J Neurooncol ; 159(3): 665-674, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35932358

RESUMO

INTRODUCTION: The treatment of glioma with temozolomide chemoradiotherapy predisposes patients to pneumocystis pneumonia (PCP). Because PCP is a rare outcome, very little is known about specific clinical risk factors for its development in patients with glioma. METHODS: We performed a population-based retrospective cohort study of glioma patients undergoing temozolomide chemoradiotherapy 2005 to 2019 in Ontario, Canada. We compared clinical features of patients who did not versus did develop PCP within one year of chemoradiotherapy. We examined the overall survival of patients by PCP status. RESULTS: There were 5130 patients with glioma treated with temozolomide chemoradiotherapy. Ultimately, 38 patients (0.74%) were diagnosed with PCP within 1 year of chemoradiotherapy. Most (71%) infections occurred between 0-90 days and 29% occurred between 91-365 days. Median survival was 12.3 months in patients who did not develop PCP and 8.6 months in those who did develop PCP (P < 0.001). Trough 90-day lymphocyte counts were lower in the PCP group. When the lymphocytes fell below 0.19 × 109/L (or 0.25 × 109/L among patients without PCP prophylaxis), the risk of PCP was > 3.5%. CONCLUSIONS: Pneumocystis pneumonia is rare in glioma patients who receive temozolomide chemoradiotherapy. Infection is associated with shorter survival and the development of lymphopenia. Reserving PCP prophylaxis for patients whose lymphocyte counts drop below 0.25 × 109/L may be a reasonable strategy.


Assuntos
Glioma , Pneumonia por Pneumocystis , Quimiorradioterapia/efeitos adversos , Glioma/tratamento farmacológico , Glioma/terapia , Humanos , Ontário , Pneumonia por Pneumocystis/etiologia , Estudos Retrospectivos , Temozolomida/efeitos adversos
6.
Anticancer Res ; 42(9): 4511-4515, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36039419

RESUMO

BACKGROUND/AIM: Organ-sparing treatment is increasingly used for bladder cancer, particularly for patients with significant comorbidities or advanced age. The upcoming treatment can cause distress and sleep disturbances. This study investigated pre-radiotherapy sleep disturbances in these patients. PATIENTS AND METHODS: Twenty-two patients with bladder cancer scheduled for local or loco-regional radiotherapy were retrospectively evaluated. Sixteen characteristics were analyzed for sleep disturbances including age, sex, performance score, comorbidities, previous malignancy, distress score, emotional problems, physical problems, treatment situation, treatment intent, current primary tumor and nodal stage, distant metastasis, treatment volume, concurrent chemotherapy, and Coronavirus Disease 2019 pandemic. RESULTS: Eleven patients (50.0%) reported sleep disturbances that were significantly associated with distress scores ≥5 (p=0.035). Trends were found for age ≤75 years (p=0.183), ≥2 emotional problems (p=0.183), ≥5 physical problems (p=0.064), and distant metastasis (p=0.090). CONCLUSION: Half of the patients reported pre-radiotherapy sleep disturbances. Risk factors facilitate identification of patients requiring psychological support.


Assuntos
COVID-19 , Transtornos do Sono-Vigília , Neoplasias da Bexiga Urinária , Idoso , COVID-19/complicações , COVID-19/terapia , Quimiorradioterapia/efeitos adversos , Humanos , Estudos Retrospectivos , Sono , Transtornos do Sono-Vigília/etiologia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
7.
PLoS One ; 17(8): e0271242, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35930539

RESUMO

OBJECTIVES: To compare the survival and complications of neoadjuvant chemoradiation (NCRT) versus neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC). METHODS: We conducted a systematic literature search of the PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, Wanfang Data, CBM, and VIP databases from inception to November 2021. Meta-analyses were performed using RevMan (version 5.3) and Stata version 15.0. RESULTS: A total of 18 studies were included, which involved 3137 patients, The results of the metaanalysis showed that the pathological complete remission rate (odds ratio [OR] = 5.21, 95% confidence interval [CI]: 2.85-9.50, p<0.00001) and complete tumor resection rate (OR = 2.31, 95% CI: 1.57-3.41, p<0.0001) in the NCRT group were significantly better than those in the NCT group. Our meta-analysis results showed that 1-, 3-, and 5-year survival rates (1-year overall survival [OS]: OR = 1.51, 95% CI: 1.11-2.05, p = 0.009; 3-year OS: OR = 1.73, 95% CI: 1.36-2.21, p<0.0001; 5-year OS: OR = 1.61, 95% CI: 1.30-1.99, p<0.00001) in the NCRT group were significantly higher than those in the NCT group. NCRT can lead a significant survival benefit compared with NCT and there was no significant difference between the two neoadjuvant treatments in terms of postoperative complications. CONCLUSION: The use of NCRT in the treatment of patients with ESCC patients showed significant advantages in terms of survival and safety relative to the use of NCT.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Células Epiteliais , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Esofagectomia/efeitos adversos , Humanos , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos
8.
Technol Cancer Res Treat ; 21: 15330338221118188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35950239

RESUMO

Introduction: In the adjuvant setting for cervical cancer, classical risk factors for postoperative radiochemotherapy have been established. However, data on laboratory changes during therapy and the prognostic value of serological markers are limited and further knowledge is needed to optimize the toxic trimodal regimen. Methods: We retrospectively identified 69 women who underwent weekly postoperative radiochemotherapy with 40 mg/m2 of cisplatin for cervical cancer between 2010 and 2021 at a single center. Laboratory parameters were recorded before, at each cycle and after radiochemotherapy. Kaplan-Meier and log-rank analyses were used to calculate and compare survival, groups were compared using the Mann-Whitney U, χ2, and variance tests. Results: With a median follow-up of 17.7 months, the 1- and 5-year local control rates were 94.0% and 73.7%, respectively, with significantly better rates for more chemotherapy cycles and negative resection margins. Only 68.1% of patients completed all cycles. The most common reasons for early discontinuation were persistent asymptomatic leukopenia in women aged ≤ 50 years, and limiting infections in women aged > 50 years. Leukopenia was more likely to occur after the third cycle. Significantly worse survival was observed for post-radiochemotherapy elevated C-reactive-protein and lactate dehydrogenase levels, low pre-radiochemotherapy nutritional index, and raised C-reactive-protein-levels; the latter were also predictable for local control. The Glasgow prognostic score did not reliably predict survival. Conclusion: Incomplete application of simultaneous chemotherapy leads to inferior local control, and age-dependent limiting factors should be identified at an early stage. In addition to classical risk factors, serological markers (C-reactive-protein, lactate dehydrogenase, nutritional index) show prognostic significance.


Assuntos
Leucopenia , Neoplasias do Colo do Útero , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Cisplatino , Intervalo Livre de Doença , Feminino , Humanos , Lactato Desidrogenases , Leucopenia/tratamento farmacológico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
9.
Cochrane Database Syst Rev ; 8: CD010260, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35994243

RESUMO

BACKGROUND: This is an update of the Cochrane Review published in Issue 4, 2015. Cervical cancer is one of the most frequent cause of death from gynaecological cancers worldwide. Many new cervical cancer cases in low-income countries present at an advanced stage. Standard care in Europe and the US for locally advanced cervical cancer (LACC) is chemoradiotherapy. In low-income countries, with limited access to radiotherapy, LACC may be treated with chemotherapy and hysterectomy. It is not certain if this improves survival. It is important to assess the value of hysterectomy with radiotherapy or chemotherapy, or both, as an alternative. OBJECTIVES: To determine whether hysterectomy, in addition to standard treatment with radiotherapy or chemotherapy, or both, in women with LACC (Stage IB2 to III) is safe and effective compared with standard treatment alone. SEARCH METHODS: We searched CENTRAL, MEDLINE via Ovid, Embase via Ovid, LILACS, trial registries and the grey literature up to 3 February 2022. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that compared treatments involving hysterectomy versus radiotherapy or chemotherapy, or both, in women with LACC International Federation of Gynecology and Obstetrics (FIGO) Stages IB2 to III. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We independently assessed study eligibility, extracted data and assessed the risk of bias. Where possible, we synthesised overall (OS) and progression-free (PFS) or disease-free (DFS) survival in a meta-analysis using a random-effects model. Adverse events (AEs) were incompletely reported and we described the results of single trials in narrative form. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: From the searches we identified 968 studies. After deduplication, title and abstract screening, and full-text assessment, we included 11 RCTs (2683 women) of varying methodological quality. This update identified four new RCTs and three ongoing RCTs. The included studies compared: hysterectomy (simple or radical) with radiotherapy or chemoradiotherapy or neoadjuvant chemotherapy (NACT) versus radiotherapy alone or chemoradiotherapy (CCRT) alone or CCRT and brachytherapy. There is also one ongoing study comparing three groups: hysterectomy with CCRT versus hysterectomy with NACT versus CCRT. There were two comparison groups for which we were able to do a meta-analysis. Hysterectomy (radical) with neoadjuvant chemotherapy versus chemoradiotherapy alone Two RCTs with similar design characteristics (620 and 633 participants) found no difference in five-year OS between NACT with hysterectomy versus CCRT. Meta-analysis assessing 1253 participants found no evidence of a difference in risk of death (OS) between women who received NACT plus hysterectomy and those who received CCRT alone (HR 0.94, 95% CI 0.76 to 1.16; moderate-certainty evidence). In both studies, the five-year DFS in the NACT plus surgery group was worse (57%) compared with the CCRT group (65.6%), mostly for Stage IIB. Results of single trials reported no apparent difference in long-term severe complications, grade 3 acute toxicity and severe late toxicity between groups (very low-quality evidence). Hysterectomy (simple or radical) with neoadjuvant chemotherapy versus radiotherapy alone Meta-analysis of three trials of NACT with hysterectomy versus radiotherapy alone, assessing 571 participants, found that women who received NACT plus hysterectomy had less risk of death (OS) than those who received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93; I2 = 0%; moderate-quality evidence). However, a significant number of participants who received NACT plus hysterectomy also had radiotherapy. There was no difference in the proportion of women with disease progression or recurrence (DFS and PFS) between NACT plus hysterectomy and radiotherapy groups (RR 0.75, 95% CI 0.53 to 1.05; I2 = 20%; moderate-quality evidence). The certainty of the evidence was low or very-low for all other comparisons for all outcomes. None of the trials reported quality of life outcomes. AUTHORS' CONCLUSIONS: From the available RCTs, we found insufficient evidence that hysterectomy with radiotherapy, with or without chemotherapy, improves the survival of women with LACC who are treated with radiotherapy or CCRT alone. The overall certainty of the evidence was variable across the different outcomes and was universally downgraded due to concerns about risk of bias. The certainty of the evidence for NACT and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate. The same occurred for the comparison involving NACT and hysterectomy compared with CCRT alone. Evidence from other comparisons was generally sparse and of low or very low-certainty. This was mainly based on poor reporting and sparseness of data where results were based on single trials. More trials assessing medical management with and without hysterectomy may test the robustness of the findings of this review as further research is likely to have an important impact on our confidence in the estimate of effect.


Assuntos
Neoplasias do Colo do Útero , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Histerectomia , Terapia Neoadjuvante/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia
10.
Dis Markers ; 2022: 6707821, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990252

RESUMO

Background: Linc00312 is downregulated in nasopharyngeal carcinoma (NPC) and associates with poor treatment efficacy. Genetic variations are the main cause of individual differences in treatment response. The objective of this study is to explore the relationship between genetic variations of linc00312 and the risk of chemoradiotherapy induced toxic reactions in NPC patients. Methods: We used a bioinformatics approach to select 3 single nucleotide polymorphisms (SNPs) with regulatory feature in linc00312 (rs12497104, rs15734, and rs164966). 505 NPC patients receiving chemoradiotherapy with complete follow-up data were recruited. Genotyping was carried out by MassARRAY iPLEX platform. Univariate logistic and multivariate logistic regression were used to analyze the risk factors responsible for toxic reactions of NPC patients. Results: Our result demonstrated that linc00312 rs15734 (G > A) was significantly associated with severe leukopenia in NPC patients underwent chemoradiotherapy (AA vs. GG, OR = 3.145, P = 0.029). In addition, the risk of severe leukopenia was remarkably increased to 5.635 times (P = 0.034) in female with rs15734 AA genotype compared to male with rs15734 GG genotype. Moreover, patients with rs12497104 (G > A) AA genotype showed a 67.5% lower risk of thrombocytopenia than those with GG genotype (P = 0.030). Remarkably, the younger patients (age < 47) with rs12497104 AA genotype displayed a 90% decreased risk of thrombocytopenia compared with older patients (age ≥ 47) carrying rs12497104 GG genotype (P = 0.030). Conclusions: Genetic variations of linc00312 affect the risk of chemoradiotherapy induced hematotoxicity in nasopharyngeal carcinoma patients and may serve as biomarkers for personalized medicine.


Assuntos
Quimiorradioterapia , Leucopenia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , RNA Longo não Codificante , Biomarcadores , Estudos de Casos e Controles , Quimiorradioterapia/efeitos adversos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Leucopenia/induzido quimicamente , Leucopenia/genética , Masculino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Fatores de Risco , Trombocitopenia
11.
Lancet Oncol ; 23(9): 1189-1200, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35952709

RESUMO

BACKGROUND: TGF-ß is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-ß blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-ß type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer. METHODS: This was an investigator-initiated, single-arm, phase 2 study done in two medical centres in Portland (OR, USA). Eligible patients had previously untreated, locally advanced, rectal adenocarcinoma, stage IIA-IIIC or IV as per the American Joint Committee on Cancer; Eastern Cooperative Oncology Group status 0-2; and were aged 18 years or older. Participants completed two 14-day courses of oral galunisertib 150 mg twice daily, before and during fluorouracil-based chemoradiotherapy (intravenous fluorouracil 225 mg/m2 over 24 h daily 7 days per week during radiotherapy or oral capecitabine 825 mg/m2 twice per day 5 days per week during radiotherapy; radiotherapy consisted of 50·4-54·0 Gy in 28-30 fractions). 5-9 weeks later, patients underwent response assessment. Patients with a complete response could opt for non-operative management and proceed to modified FOLFOX6 (intravenous leucovorin 400 mg/m2 on day 1, intravenous fluorouracil 400 mg/m2 on day 1 then 2400 mg/m2 over 46 h, and intravenous oxaliplatin 85 mg/m2 on day 1 delivered every 2 weeks for eight cycles) or CAPEOX (intravenous oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks for four cycles). Patients with less than complete response underwent surgical resection. The primary endpoint was complete response rate, which was a composite of pathological complete response in patients who proceeded to surgery, or clinical complete response maintained at 1 year after last therapy in patients with non-operative management. Safety was a coprimary endpoint. Both endpoints were assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02688712, and is active but not recruiting. FINDINGS: Between Oct 19, 2016, and Aug 31, 2020, 38 participants were enrolled. 25 (71%) of the 35 patients who completed chemoradiotherapy proceeded to total mesorectal excision surgery, five (20%) of whom had pathological complete responses. Ten (29%) patients had non-operative management, three (30%) of whom ultimately chose to have total mesorectal excision. Two (67%) of those three patients had pathological complete responses. Of the remaining seven patients in the non-operative management group, five (71%) had clinical complete responses at 1 year after their last modified FOLFOX6 infusion. In total, 12 (32% [one-sided 95% CI ≥19%]) of 38 patients had a complete response. Common grade 3 adverse events during treatment included diarrhoea in six (16%) of 38 patients, and haematological toxicity in seven (18%) patients. Two (5%) patients had grade 4 adverse events, one related to chemoradiotherapy-induced diarrhoea and dehydration, and the other an intraoperative ischaemic event. No treatment-related deaths occurred. INTERPRETATION: The addition of galunisertib to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer improved the complete response rate to 32%, was well tolerated, and warrants further assessment in randomised trials. FUNDING: Eli Lilly via ExIST program, The Providence Foundation.


Assuntos
Adenocarcinoma , Segunda Neoplasia Primária , Neoplasias Retais , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Quimiorradioterapia/efeitos adversos , Diarreia/etiologia , Fluoruracila , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Oxaliplatina , Pirazóis , Quinolinas , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Fator de Crescimento Transformador beta
12.
Contrast Media Mol Imaging ; 2022: 2256690, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909587

RESUMO

Even though cytopenia caused by either chemotherapy or radiotherapy is a common complication in cancer patients, chemoradiotherapy remains an essential treatment for the majority of patients. The purpose of this study was to look into the clinical efficacy and cost-effectiveness of recombinant human thrombopoietin (rhTPO) in treating chemo- or chemoradiotherapy-induced grade II, III, and IV thrombocytopenia. From December 2019 to November 2020, 233 lung cancer patients admitted to our hospital with chemotherapy- or chemoradiotherapy-induced thrombocytopenia were enrolled and treated with rhTPO. The study's findings revealed a significant disparity in the use of concurrent chemoradiotherapy in patients with grade II, III, and IV thrombocytopenia. All costs, including rhTPO treatment costs, platelet costs, drug costs, and nondrug costs, tended to rise as the severity of thrombocytopenia increased. In the treatment of chemotherapy or radiotherapy-induced thrombocytopenia, rhTPO has shown good clinical efficacy. In the treatment of grade II thrombocytopenia, rhTPO has a favorable economic evaluation. As a result, early intervention and thrombocytopenia treatment should be provided, which warrants further clinical investigation.


Assuntos
Neoplasias Pulmonares , Trombocitopenia , Quimiorradioterapia/efeitos adversos , Humanos , Contagem de Plaquetas , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Resultado do Tratamento
13.
JAMA ; 328(8): 728-736, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35997729

RESUMO

Importance: Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). Objective: To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. Design, Setting, and Participants: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Interventions: Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). Main Outcomes and Measures: The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Results: Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Conclusions and Relevance: Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02633202.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Cisplatino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/etiologia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos
14.
Klin Onkol ; 35(4): 307-314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35989088

RESUMO

BACKGROUND: Radiotherapy of locally advanced head and neck cancer represents a major clinical challenge. Any treatment intensification aiming at improved treatment outcomes poten-tially results in a higher toxicity. The search for optimal treatment schedule involving conventional or altered fractionation of radiotherapy and the frequency and dose of concomitant cisplatin or other systemic agents has been spanning over several decades. PURPOSE: To evaluate long-term outcomes and toxicity of accelerated chemoradiotherapy of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). PATIENTS AND METHODS: Forty patients with stage III and IVA (TNM, 7th Ed.) LA SCCHN were treated with accelerated radiotherapy with a total dose of 67.5 Gy in 6 weeks delivered with simultaneous integrated boost intensity-modulated radiotherapy (SIB IMRT) and concomitant weekly cisplatin 40mg/m2. Five-year outcomes and early and late toxicity were evaluated. RESULTS: With the median follow-up of 47.8 months, a 5-year locoregional control rate (LCR) was 56.5%, distant control rate (DCR) was 87% and 5-year progression-free survival (PFS) and overall survival (OS) were 37 and 45%, respectively. Cisplatin cumulative dose of 200mg/m2 was administered in 83% of patients. Grade 2 late toxicity with dietary change was observed in 21 (53%) patients. Human papillomavirus (HPV) status determined by p16 immunohistochemistry was the only significant factor in 5-year treatment outcomes analysis with LCR 100 vs. 41% (P < 0.01), DCR 100 vs. 78% (P = 0.154), PFS 80 vs. 23% (P = 0.01) and OS 80 vs. 34% (P = 0.03) for HPV positive oropharyngeal cancer (OPC) and other HPV negative LA SCCHN. CONCLUSION: High proportion of patients with LA SCCHN received an adequate cumulative dose of concurrent cisplatin with accelerated radiotherapy with SIB IMRT. This study demonstrated that chemoradiotherapy with weekly cisplatin resulted in favorable local control rate and survival in patients with HPV+ OPC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Papillomaviridae , Infecções por Papillomavirus/complicações , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
15.
Nihon Shokakibyo Gakkai Zasshi ; 119(8): 768-775, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35944995

RESUMO

A 78-year-old man came to our department because of obstructive jaundice, and was diagnosed as pancreatic head cancer. He underwent chemoradiation therapy. A metal stent was inserted into the common bile duct and the patient was followed up on an outpatient basis. The patient visited our emergency department 46 days after stent insertion due to abdominal pain. The patient was diagnosed with ruptured pseudoaneurysm of the superior pancreaticoduodenal artery by angiography and treated with coil embolization. He died due to sudden deterioration the next day. Pathological autopsy revealed that the cause of the ruptured pseudoaneurysm appeared to be vasculopathy due to radiation therapy.


Assuntos
Falso Aneurisma , Embolização Terapêutica , Hemobilia , Neoplasias Pancreáticas , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/terapia , Autopsia , Quimiorradioterapia/efeitos adversos , Embolização Terapêutica/efeitos adversos , Hemobilia/etiologia , Humanos , Masculino , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/terapia
16.
Biomed J ; 45(3): 522-532, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35817708

RESUMO

BACKGROUND: Stromal cell-derived factor-1α (SDF-1α) is a chemokine associated with tumor progression in various types of cancers. The current study aimed to evaluate whether pre-treatment or kinetics of SDF-1α can predict the prognosis in patients with esophageal squamous cell carcinoma (ESCC) receiving definitive concurrent chemoradiotherapy (CCRT). METHODS: A total of 97 patients with ESCC were identified at Kaohsiung Chang Gung Memorial Hospital between January 2010 and December 2015. Serum concentration of SDF-1α was measured at day 0 (pre-treatment) and chemotherapy day 28 to determine its kinetics and the cut-off level of pre-chemotherapy SDF-1α was 1.5 ng/mL. Two ESCC cell lines, TE1 and KYSE30, were selected to evaluate the function of SDF-1α. RESULTS: Univariate and multivariate analyses showed that pre-treatment SDF-1α ≥ 1.5 ng/mL and an increased SDF-1α level after treatment were significantly associated with worse progression-free survival (p = 0.021 and p = 0.008, respectively) and overall survival (p = 0.005 and p < 0.001, respectively). In addition, patients with pre-treatment SDF-1α ≥ 1.5 ng/mL and increased SDF-1α levels after treatment were found to have poor response to CCRT. Moreover, these cell lines were treated with chemotherapeutic agents (cisplatin or 5-FU) and SDF-1α, alone or in combination. Our in vitro study results showed SDF-1α promoted the proliferation of tumor cells and overcame the cytotoxic effect of chemotherapy (p < 0.001). CONCLUSION: Our study suggested that SDF-1α plays an important role in ESCC disease progression and that pre-treatment SDF-1α level and kinetics of SDF-1α are the independent prognostic factors for ESCC patients receiving definitive CCRT. Periodic determinations of serum SDF-1α level may be valuable to predict prognosis of ESCC in clinical practice.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiocina CXCL12/uso terapêutico , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/etiologia , Humanos , Prognóstico
17.
Sci Rep ; 12(1): 11978, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831424

RESUMO

This retrospective study compared the efficacy and safety of nedaplatin-based chemoradiotherapy and cisplatin-based chemoradiotherapy in stage II-IVa nasopharyngeal carcinoma (NPC) patients. Patients treated with cisplatin-based or nedaplatin-based chemoradiotherapy between January 2012 and December 2015 were evaluated. Survival was estimated by the Kaplan‒Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. A cohort of 538 NPC patients was enrolled. There were no significant differences in the 5-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), or distant metastasis-free survival (DMFS) between the cisplatin and nedaplatin groups. During the whole treatment course, patients in the cisplatin group had higher incidences of grade 3‒4 vomiting and anorexia, while patients in the nedaplatin group had higher incidences of grade 3‒4 leucopenia and mucositis. In terms of late toxicities, patients in the cisplatin group had a higher incidence of xerostomia. In multivariate analysis, T stage, N stage, and clinical stage were prognostic factors for OS, PFS, and DMFS. In subgroup analyses, nedaplatin-based chemotherapy achieved comparable treatment outcomes in specific populations stratified by age, sex, ECOG PS score and clinical stage. Cisplatin and nedaplatin are effective choices for stage II-IVa NPC patients, with a different spectrum of side effects.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Resultado do Tratamento
18.
Thorac Cancer ; 13(16): 2404-2409, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35808894

RESUMO

BACKGROUND: Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited-disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non-inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive-disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD-SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of AP in patients with LD-SCLC. METHODS: Treatment-naive patients with LD-SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m2 /day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m2 /day. RD and MTD will be determined by evaluating toxicities. DISCUSSION: Based on our previous study, the initial dose of AMR 25 mg/m2 is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD-SCLC.


Assuntos
Quimiorradioterapia , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Adulto , Idoso , Antraciclinas , Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Etoposídeo , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/terapia , Adulto Jovem
19.
Cancer Treat Res Commun ; 32: 100604, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35809530

RESUMO

BACKGROUND: Locally advanced rectal cancer (LARC) has a high incidence of local and distant relapse even after adequate treatment. The emerging role of neoadjuvant induction chemotherapy may allow initial down staging of the primary tumor, less toxicity and early treatment of micrometastatic disease followed by chemoradiation with the hope of increased complete response rates before surgery OBJECTIVES: To identify the effect of induction chemotherapy before concurrent chemoradiation (CCRTH) in locally advanced rectal cancer in terms of response and toxicity. Primary end point is assessment of pathological complete response rate after surgery. Secondary end points are disease free survival (DFS) and overall survival (OS) after 3 years follow up. PATIENTS AND METHODS: Patients with MRI based criteria for staging high-risk LARC (T4 tumors, tumors within 2 mm of mesorectal fascia, T3 tumors at or below levators and T2-4 with LN +ve tumors) were included. Thirty-five patients were recruited. Patients received 12 weeks of induction capecitabine/oxaliplatin followed by concomitant capecitabine and conventional 3D-conformal radiotherapy. Surgery was done at least 6 weeks later . RESULTS: Five patients (20.8%) had a pathological complete response (TRG 0) (ypT0N0). Another three patients (12.5%) had near complete pathological response (TRG 1). Regarding OS and pathological complete response corrlelation, it was statistically not significant in relation to patients with incomplete pathological response (p = 1). CONCLUSION: Induction chemotherapy could be a promising option for better response rates either clinical or pathological for high risk LARC patients with acceptable toxicity.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Capecitabina/efeitos adversos , Quimiorradioterapia/efeitos adversos , Humanos , Quimioterapia de Indução , Recidiva Local de Neoplasia/tratamento farmacológico , Segunda Neoplasia Primária/etiologia , Oxaliplatina/uso terapêutico , Neoplasias Retais/patologia , Neoplasias Retais/terapia
20.
Front Immunol ; 13: 952066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874780

RESUMO

Patients with metastatic cancer refractory to standard systemic therapies have a poor prognosis and few therapeutic options. Radiotherapy can shape the tumor microenvironment (TME) by inducing immunogenic cell death and promoting tumor recognition by natural killer cells and T lymphocytes. Granulocyte macrophage-colony stimulating factor (GM-CSF) was known to promote dendric cell maturation and function, and might also induce the macrophage polarization with anti-tumor capabilities. A phase II trial (ChiCTR1900026175) was conducted to assess the clinical efficacy and safety of radiotherapy, PD-1 inhibitor and GM-CSF (PRaG regimen). This trial was registered at http://www.chictr.org.cn/index.aspx. A PRaG cycle consisted of 3 fractions of 5 or 8 Gy delivered for one metastatic lesion from day 1, followed by 200 µg subcutaneous injection of GM-CSF once daily for 2 weeks, and intravenous infusion of PD-1 inhibitor once within one week after completion of radiotherapy. The PRaG regimen was repeated every 21 days for at least two cycles. Once the PRaG therapy was completed, the patient continued PD-1 inhibitor monotherapy until confirmed disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). A total of 54 patients were enrolled with a median follow-up time of 16.4 months. The ORR was 16.7%, and the disease control rate was 46.3% in intent-to-treat patients. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.3 to 4.8), and median overall survival was 10.5 months (95% CI, 8.7 to 12.2). Grade 3 treatment-related adverse events occurred in five patients (10.0%) and grade 4 in one patient (2.0%). Therefore, the PRaG regimen was well tolerated with acceptable toxicity and may represent a promising salvage treatment for patients with chemotherapy-refractory solid tumors. It is likely that PRaG acts via heating upthe TME with radiotherapy and GM-CSF, which was further boosted by PD-1 inhibitors.


Assuntos
Quimiorradioterapia , Segunda Neoplasia Primária , Quimiorradioterapia/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Segunda Neoplasia Primária/terapia , Terapia de Salvação , Resultado do Tratamento , Microambiente Tumoral
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