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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.
BMJ Open ; 12(9): e058107, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104135

RESUMO

INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world setting to improve survival of people with GBM. Initial experimental arms are evaluating the effectiveness of interventions in newly diagnosed GBM (ndGBM). This study will compare maximal surgical resection followed by chemoradiotherapy plus adjuvant chemotherapy for 6 months with the addition of (1) 'neoadjuvant' chemotherapy beginning as soon as possible after surgery and/or (2) adjuvant chemotherapy continued until progression within the same study platform. METHODS AND ANALYSIS: MAGMA will establish a platform for open-label, multiarm, multicentre randomised controlled testing of treatments for GBM. The study began recruiting in September 2020 and recruitment to the initial two interventions in MAGMA is expected to continue until September 2023.Adults aged ≥18 years with ndGBM will be given the option of undergoing randomisation to each study intervention separately, thereby giving rise to a partial factorial design, with two separate randomisation time points, one for neoadjuvant therapy and one for extended therapy. Patients will have the option of being randomised at each time point or continuing on with standard treatment.The primary outcome for the study is overall survival from the date of initial surgery until death from any cause. Secondary outcomes include progression-free survival, time to first non-temozolomide treatment, overall survival from each treatment randomisation, clinically significant toxicity as measured by grade 3 or 4 adverse events and health-related quality-of-life measures. Tertiary outcomes are predictive/prognostic biomarkers and health utilities and incremental cost-effectiveness ratio.The primary analysis of overall survival will be performed separately for each study intervention according to the intention to treat principle on all patients randomised to each study intervention. ETHICS AND DISSEMINATION: The study (Protocol version 2.0 dated 23 November 2020) was approved by a lead Human Research Ethics Committee (Sydney Local Health District: 2019/ETH13297). The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBER: ACTRN12620000048987.


Assuntos
Glioblastoma , Adolescente , Adulto , Australásia , Quimiorradioterapia , Quimioterapia Adjuvante , Glioblastoma/terapia , Humanos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Cochrane Database Syst Rev ; 9: CD012246, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36111784

RESUMO

BACKGROUND: With an estimated 570,000 new cases reported globally in 2018, and increasing numbers of new cases in countries without established human papillomavirus (HPV) vaccination programmes, cervical cancer is the third most common cancer in women worldwide. The majority of global disease burden (around 85%) is in low-and middle-income countries (LMICs), with estimates of cervical cancer being the second most common cancer in women in such regions. As it commonly affects younger women, cervical cancer has the greatest impact on years of life lost (YLL) and adverse socioeconomic outcomes compared to all other cancers in women. Management of cervical cancer depends on tumour stage. Radical hysterectomy with lymphadenectomy is the standard primary treatment modality for International Federation of Gynecology and Obstetrics (FIGO) stage (2019) 1B1 to 1B3 disease. However, for larger primary tumours, radical hysterectomy is less commonly recommended. This is mainly due to a high incidence of unfavourable histopathological parameters, which require adjuvant concurrent chemoradiotherapy (CCRT) (chemotherapy given with radiotherapy treatment). CCRT is the standard of care and is widely used as first-line treatment for cervical cancer considered to be not curable with surgery alone (i.e.those with locally advanced disease). However, a sizable cohort of women managed with primary CCRT will have residual disease within the cervix following treatment. Debulking' hysterectomy to remove (debulk) the primary tumour in locally advanced disease, prior to CCRT, may be an alternative management strategy, avoiding the potential need for surgery for residual cervical disease following CCRT, which may be more extensive, or have increased morbidity due to CCRT. However, this strategy may subject more women to unnecessary surgery and its inherent risks. OBJECTIVES: To assess the efficacy and harms of debulking hysterectomy (simple or radical) followed by chemoradiotherapy (CCRT) versus CCRT alone for FIGO (2019) stage IB3/II cervical cancer. SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 4), MEDLINE via Ovid (1946 to 12 April 2021) and Embase via Ovid (1980 to 12 April 2021). We also searched other registers of clinical trials, abstracts of scientific meetings and reference lists up to 12 April 2021. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), quasi-RCTs or non-randomised studies (NRSs) comparing debulking hysterectomy followed by CCRT versus CCRT alone for locally advanced FIGO (2019) stage IB3/II cervical malignancy. DATA COLLECTION AND ANALYSIS: We applied Cochrane methodology, with two review authors independently assessing whether potentially relevant studies met the inclusion criteria. We planned to apply standard Cochrane methodological procedures to analyse data and risk of bias. MAIN RESULTS: We did not find any evidence for or against debulking hysterectomy followed by CCRT versus CCRT alone for FIGO (2019) stage IB3/II cervical cancer. We did not identify any studies assessing the validity of debulking hysterectomy for these women.  AUTHORS' CONCLUSIONS: There was no evidence for or against debulking hysterectomy followed by CCRT versus CCRT alone for FIGO (2019) stage IB3/II cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Quimiorradioterapia/métodos , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Histerectomia/métodos , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
4.
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
6.
In Vivo ; 36(5): 2473-2480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099090

RESUMO

BACKGROUND/AIM: Previous evaluation of the safety and clinical efficacy of re-irradiation for pelvic recurrence of rectal cancer after preoperative chemoradiotherapy (PCRT) and rectal surgery is insufficient. We evaluated the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for pelvic recurrence of rectal cancer after PCRT. PATIENTS AND METHODS: We reviewed the medical records of patients treated with C-ion RT between August 2011 and December 2021 and analyzed the data of seven consecutive patients. The probabilities of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: The median follow-up duration after C-ion RT initiation was 30.9 months. Five patients received 73.6 Gy [relative biological effectiveness (RBE)] in 16 fractions, and two patients received 57.6 Gy (RBE) in 12 fractions. All patients completed C-ion RT as scheduled. Two-year estimated OS, LC, and PFS rates after C-ion RT initiation were 100%, 83.3%, and 28.6%, respectively. No patients developed grade ≥3 acute toxicity. Regarding late toxicities, one patient who received Gore-Tex sheets as a spacer before C-ion RT developed grade 3 colon perforation, and then developed a grade 3 urinary tract disorder. One patient developed grade 2 peripheral neuropathy. CONCLUSION: C-Ion RT showed favorable local efficacy with minimal toxicity. C-Ion RT might be an effective treatment option for pelvic recurrence of rectal cancer after PCRT even when re-irradiation of the pelvis is required.


Assuntos
Reirradiação , Neoplasias Retais , Carbono , Quimiorradioterapia , Humanos , Pelve , Reirradiação/efeitos adversos , Reirradiação/métodos , Neoplasias Retais/radioterapia , Estudos Retrospectivos
7.
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
9.
BMC Cancer ; 22(1): 957, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068495

RESUMO

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/análogos & derivados , Quimiorradioterapia/métodos , Ensaios Clínicos Fase II como Assunto , Fluoruracila/uso terapêutico , Humanos , Leucovorina , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Compostos Organoplatínicos , Qualidade de Vida , Neoplasias Retais/patologia , Resultado do Tratamento
10.
Contrast Media Mol Imaging ; 2022: 8676787, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082064

RESUMO

Purpose: In head and neck squamous cell carcinoma (HNSCC), the early diagnosis and efficient detection of recurrences and/or residual tumor after treatment play a very important role in patient's prognosis. Positron emission tomography (PET) using 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) has become an established method for the diagnosis of suspected recurrence in head and neck carcinomas. In particular, integrated PET/MRI imaging that provides optimal soft tissue contrast and less dental implant artifacts compared to PET/CT is an intriguing technique for the follow-up imaging of HNSCC patients. The aim of this study was to evaluate the benefit of PET/MRI compared to PET/CT in post-treatment follow-up imaging of HNSCC patients. Methods: This retrospective observational cohort study consists of 104 patients from our center with histologically confirmed HNSCC. All patients received chemoradiotherapy (CRT) and underwent 18F-FDG-PET/CT (n = 52) or 18F-FDG-PET/MRI (n = 52) scan 12 weeks after the end of treatment. Image analysis was performed by two independent readers according to a five-point Likert scale analysis. Results: PET/MRI was more sensitive (1.00 vs. 0.77) than PET/CT in the detection of locoregional recurrence. PET/MRI also had better negative (1.00 vs. 0.87) predictive values. AUCs for PET/MRI and PET/CT on patient-based analysis were 0.997 (95% CI 0.989-1.000) and 0.890 (95% CI 0.806-0.974), respectively. The comparison of sensitivity, AUCs, and negative predictive values revealed a statistically significant difference, p < 0.05. In PET/CT, false-negative and positive findings were observed in the more advanced disease stages, where PET/MRI performed better. Also, false-negative findings were located in the oropharyngeal, laryngeal, and nasopharyngeal regions, where PET/MRI made no false-negative interpretations. Conclusion: Based on these results, PET/MRI might be considered the modality of choice in detecting locoregional recurrence in HNSCC patients, especially in the more advanced stages in the oral cavity, larynx, or nasopharynx.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
11.
Medicine (Baltimore) ; 101(36): e30170, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086700

RESUMO

BACKGROUND: To evaluate the role and safety of endostar in cervical cancer by comparing the efficacy and adverse reactions of endostar combined with concurrent chemoradiotherapy in patients with locally advanced cervical carcinoma. METHODS: The quality of the included literature was evaluated by searching the database for the comparison of endostar combined with concurrent radiotherapy and chemotherapy in cervical cancer patients; objective response rate (ORR) and disease control rate (DCR) were used as the main outcome indicators, and statistical analysis was performed using RevMan5.3 and State15.3 software. RESULTS: A total of 13 studies were included in this study, including 1057 patients with locally advanced cervical cancer, suggesting that endostar combined with chemoradiotherapy can significantly improve the objective response rate (ORR: odds ratio 3.88, 95% confidence interval 2.77-5.45, P < .00001) and disease control rate (DCR: odds ratio 4.43, 95% confidence interval 2.78-7.04; P < .00001), and there was no significant increase in treatment-related adverse reactions. CONCLUSIONS: In this meta-analysis, endostar combined with concurrent chemoradiotherapy significantly improved ORR and DCR in patients with locally advanced cervical cancer without increasing toxicity. However, this study only analyzed the short-term efficacy of endostar, and its influence on overall survival and progression-free survival needs to be further verified in large randomized controlled trials with long-term follow-up.


Assuntos
Neoplasias do Colo do Útero , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/uso terapêutico , Endostatinas , Feminino , Humanos , Proteínas Recombinantes , Neoplasias do Colo do Útero/tratamento farmacológico
12.
Clin Lab ; 68(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36125156

RESUMO

BACKGROUND: The goal was to investigate the prognostic values of metastatic lymph node number (MLNn) and ratio (MLNr) for gastric neuroendocrine carcinoma (GNEC) patients treated by neoadjuvant chemoradiotherapy combined with total resection of lesser curvature. METHODS: Seventy-three patients were admitted between August 2018 and August 2021 to receive neoadjuvant chemoradiotherapy combined with total resection of lesser curvature were retrospectively analyzed. The indicators of lymph node involvement, including pathological N (pN) stage, MLNn, MLNr, and metastatic lymph node station (MLNs), and other clinicopathological data were analyzed. RESULTS: Of the 54 eligible patients, 44 (81%) had lymph node metastasis. The median survival time of the whole cohort was 63.2 months (14 - 153 months), and the 3- and 5-year survival rates were 88.9% and 47.9%, respectively. The medians of lymph nodes, MLNn, and MLNr were 19 (10 - 56), 5 (1 - 21), and 25% (6% - 100%), respectively. Cox regression analysis showed that pN1 (p = 0.0266), MLNn > 2 (p = 0.0091), MLNr > 0.1 (p = 0.0031), MLNs = 2 (p = 0.0119) and distant metastasis (p = 0.0021) were independent influencing factors for prognosis. CONCLUSIONS: In addition to pN stage, the indicators of metastatic lymph node involvement, including MLNn, MLNr, and MLNs are significant predictors for the survival of patients with GNEC, and distant metastasis is also a key prognostic factor. These indicators are crucial supplements to survival factors and can improve the risk classification of GNEC patients.


Assuntos
Neoplasias Gástricas , Quimiorradioterapia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
13.
J Exp Med ; 219(12)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36125780

RESUMO

Lethal intestinal tissue toxicity is a common side effect and a dose-limiting factor in chemoradiotherapy. Chemoradiotherapy can trigger DNA damage and induce P53-dependent apoptosis in LGR5+ intestinal stem cells (ISCs). Gamma-aminobutyric acid (GABA) and its A receptors (GABAAR) are present in the gastrointestinal tract. However, the functioning of the GABAergic system in ISCs is poorly defined. We found that GABAAR α1 (GABRA1) levels increased in the murine intestine after chemoradiotherapy. GABRA1 depletion in LGR5+ ISCs protected the intestine from chemoradiotherapy-induced P53-dependent apoptosis and prolonged animal survival. The administration of bicuculline, a GABAAR antagonist, prevented chemoradiotherapy-induced ISC loss and intestinal damage without reducing the chemoradiosensitivity of tumors. Mechanistically, it was associated with the reduction of reactive oxygen species-induced DNA damage via the L-type voltage-dependent Ca2+ channels. Notably, flumazenil, a GABAAR antagonist approved by the U.S. Food and Drug Administration, rescued human colonic organoids from chemoradiotherapy-induced toxicity. Therefore, flumazenil may be a promising drug for reducing the gastrointestinal side effects of chemoradiotherapy.


Assuntos
Receptores de GABA-A , Proteína Supressora de Tumor p53 , Animais , Bicuculina/farmacologia , Cálcio , Quimiorradioterapia , Flumazenil/farmacologia , Humanos , Intestinos , Camundongos , Espécies Reativas de Oxigênio , Células-Tronco/fisiologia , Proteína Supressora de Tumor p53/genética , Estados Unidos , Ácido gama-Aminobutírico/farmacologia
14.
Radiat Oncol ; 17(1): 158, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104707

RESUMO

BACKGROUND: Many patients with incurable esophageal cancer (ECa) present with dysphagia as their predominant symptom. Currently there is no consensus on how best to initially manage this scenario with multiple therapeutic options available. We aimed to assess the safety and efficacy of using hypofractionated radiotherapy given over a progressively shorter timeframe with concurrent carboplatin and paclitaxel in the management of patients with ECa and dysphagia. METHODS: In this phase I trial we enrolled patients with histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastro-esophageal junction with symptomatic dysphagia from local disease and not for curative treatment. Patients needed to be 18 years or older, have an ECOG performance status of 0-2 and be suitable to receive carboplatin and paclitaxel chemotherapy. Patients were placed in four progressively shorter radiation schedules culminating in 30 Gy in 10 fractions in a step wise manner, all with concurrent carboplatin AUC 2 and paclitaxel 50 mg/m2 chemotherapy delivered weekly with the radiation therapy. The primary endpoint was the development of the dose limiting toxicities (DLTs) esophageal perforation or febrile neutropenia. Secondary endpoints were relief of dysphagia, time to improvement of dysphagia, dysphagia progression free survival and overall survival. RESULTS: Eighteen patients were enrolled in the study between October 2014 and March 2019. There were no DLTs experienced during the trial. The most common grade 3 + acute toxicity experienced by patients were nausea and vomiting (both in 4/18 patients). The most common radiation specific acute toxicity experienced was esophagitis with 67% of patients experiencing grade 1-2 symptoms. All patients experienced improvement in dysphagia. The median time to dysphagia improvement was 3 weeks from the start of chemoradiotherapy (CTRT) (range 2-10 weeks). The median dysphagia free survival was 5.8 months with a median overall survival of 8.9 months. CONCLUSION: Hypofractionated palliative CTRT with 30 Gy/10# of radiation therapy with concurrent weekly carboplatin and paclitaxel chemotherapy is well tolerated and provides a good response in improvement of dysphagia. Further studies need to be undertaken which provide both symptomatic improvement in the primary tumor but also control of the metastatic burden in these patients. CLINICAL TRIAL REGISTRATION: This trial was prospectively registered with www.anzctr.org.au Identifier: ACTRN12614000821695.


Assuntos
Quimiorradioterapia , Neoplasias Esofágicas , Neoplasias Gástricas , Carboplatina/uso terapêutico , Transtornos de Deglutição/complicações , Transtornos de Deglutição/terapia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/terapia , Humanos , Paclitaxel/uso terapêutico , Cuidados Paliativos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/terapia
15.
Acta Otolaryngol ; 142(7-8): 634-637, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36089862

RESUMO

BACKGROUND: Chemoradiation therapy is standard practice for hypopharyngeal and laryngeal cancer, but its impact on skin health can cause complications if salvage surgery is required. AIMS/OBJECTIVES: To develop simple objective indices for the early detection of complications following head-and-neck salvage surgery. MATERIAL AND METHODS: Preoperatively and on postoperative days 1, 3, 5 and 7, we measured skin hardness (N), interstitial liquid content (П) and intracellular liquid content (W) as biophysical properties in patients who underwent post-CRT salvage therapy and those who underwent total organ resection without CRT as controls. We then analyzed these data in relation to occurrence of complications. RESULTS: In 11 patients undergoing salvage surgery and 23 controls, complications tended to be higher (p = .54) in the salvage group. N values were significantly higher in the salvage and complication groups on days 5 and 7, П values were higher in the complication group on day 7, and W values were lower in the complication group on day 3 and in the salvage group preoperatively and on days 1 and 5. CONCLUSIONS AND SIGNIFICANCE: N, П and W are useful measurements for the early identification of patients likely to develop complications.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia , Humanos , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento
16.
Curr Oncol ; 29(9): 6342-6349, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36135068

RESUMO

Concurrent chemoradiotherapy (CRT) is regarded as the standard treatment for inoperable esophageal cancers (EC). It is still controversial whether consolidation chemotherapy (CCT) or induction chemotherapy (IC) is beneficial for the patients who received CRT. Therefore, we carried out a retrospective analysis at our institution. A total of 186 inoperable EC patients from 20 October 2017 to 7 June 2021 who have previously received CRT were included in our study. The patients were divided into IC + CRT (n = 52), CCRT (n = 64), and CRT + CCT (n = 70) groups according to whether they received induction chemotherapy, consolidation chemotherapy, or not. We used Kaplan-Meier statistics to analyze their 1-, 2-, and 3-year OS. The median follow-up time for the whole group was 14.15 months. The 1-, 2-, 3- year overall survival (OS) for the CCRT group were 72.2%, 52.5%, and 29.5%, and 50.9%, 37.5%, and 25% for the IC + CRT group (p > 0.05). For the CRT + CCT group,1-, 2-, and 3-year OS were 89.8%, 59.0%, and 42.5% (p < 0.05). Adverse reactions in the three groups were mainly graded 0-3. The difference between the three groups was not statistically significant (p > 0.05). For non-surgical EC patients who received CRT, CCT after CRT but not IC before CRT can improve 1-, 2-, and 3-year OS with a low incidence of associated severe adverse effects. As a result, the addition of consolidation chemotherapy to chemoradiotherapy has significant prognostic advantages for inoperable EC patients.


Assuntos
Quimioterapia de Consolidação , Neoplasias Esofágicas , Quimiorradioterapia , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Quimioterapia de Indução , Estudos Retrospectivos , Taxa de Sobrevida
17.
Cancer Radiother ; 26(6-7): 858-864, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35987811

RESUMO

Despite recent advances, the prognosis of pancreatic adenocarcinomas remains poor, even for patients with resectable tumors. For these latter, new approaches based on neoadjuvant treatment have been developed. Two components are used: chemotherapy and radiation therapy (RT). Indeed, pre-operative RT has many advantages in terms of efficacy and tolerance. It increases notably the chances of subsequent complete tumor resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal. Another crucial question is to know which is the best RT technique: conventional normofractionated chemoradiotherapy or hypofrationated stereotactic body RT?


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Estudos Prospectivos
18.
Cancer Radiother ; 26(6-7): 766-770, 2022 Oct.
Artigo em Francês | MEDLINE | ID: mdl-35995720

RESUMO

Standard care for rectal cancers relies on both tumor (location relative to the sphincter, T and N stage, sphincter involvement) and patients characteristics. Radical surgery (total mesorectal excision) following short-course radiotherapy (RT) or standard chemo-radiotherapy, associated with induction or consolidation chemotherapy (total neoadjuvant treatment), remains the cornerstone of locally advanced rectal cancer (T3cd, T4 and/or N+) treatment. Nevertheless, for early stages, this radical resection could be avoided in favor of conservative approaches combining RT (external, contact, brachytherapy) with or without chemotherapy (concurrent, induction or consolidative), or even be limited, for good responders, to a local excision with view of organ-preservation strategies. This conservative approach could also be offered selectively to patients with complete clinical response after the induction sequence, irrespective of initial tumor characteristics. The Watch and Wait strategy relies on clinical, endoscopic and radiological evaluations, as well as sustained surveillance. Ongoing studies aim to improve response rates, either with chemotherapy intensification, or RT boost dose escalation with brachytherapy or contact-therapy.


Assuntos
Quimiorradioterapia , Neoplasias Retais , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Preservação de Órgãos , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Resultado do Tratamento , Conduta Expectante
19.
Cancer Radiother ; 26(6-7): 884-889, 2022 Oct.
Artigo em Francês | MEDLINE | ID: mdl-36008261

RESUMO

For non-operable, localized esophageal cancer, definitive concurrent chemoradiotherapy is the standard treatment. Currently, the radiation dose recommended is 50 to 50,4Gy. However, the optimal radiation dose remains controversial. Many studies have demonstrated that locoregional failure remains a common failure pattern, most likely to occur within the original gross tumor volume. Several retrospective studies have indicated that higher radiation dose may improve local control and survival while others failed to demonstrate improved oucomes. In three randomized trials (INT0123, ARTDECO, and CONCORDE), dose escalation did not improve locoregional control nor survival, establishing 50Gy as the standard chemoradiation dose for patients who will not undergo surgery. Here, we reviewed the results of dose escalation in the literature in the neoadjuvant and definitive settings.


Assuntos
Neoplasias Esofágicas , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Humanos , Terapia Neoadjuvante , Dosagem Radioterapêutica , Estudos Retrospectivos
20.
Cancer Radiother ; 26(6-7): 871-874, 2022 Oct.
Artigo em Francês | MEDLINE | ID: mdl-36008262

RESUMO

Anal cancer is considered a rare tumor, accounting for 6 % of digestive cancers and about 2000 new cases per year in France. It is mostly diagnosed at a localized stage. For many years, the standard of care for patients with localized disease is an association with radiotherapy and chemotherapy including Mitomycin C and 5-Fluorouracil. There weren't any major changes in the therapeutic management of these tumors despite several phase III studies. However, there is an improvement in patient prognostic. This can be explained by imaging progress, using magnetic resonance imaging and positron emission tomography-computed tomography, permitting better staging and evaluation of disease. Moreover, irradiation modalities changed because of the development of Intensity Modulated Radiotherapy. Actual research focuses on a more personalized strategy according to tumoral stages. Patients with early-stage tumors are potentially over-treated with a risk of chronic digestive toxicities. Several studies are interested in irradiation de-escalation for these patients. On the other hand, treatment results for patients with advanced tumoral stages are disappointing. It seems relevant to propose a therapeutic intensification for these patients, such as dose escalation, association with new therapies like immunotherapy or induction chemotherapy using taxans given promising results at the metastatic stage.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Radioterapia de Intensidade Modulada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia/métodos , Fluoruracila , Humanos , Mitomicina , Estadiamento de Neoplasias , Radioterapia de Intensidade Modulada/métodos
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