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1.
Br J Cancer ; 127(7): 1289-1295, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35840733

RESUMO

BACKGROUND: During the COVID pandemic, there was a paucity of data to support clinical decision-making for anticancer treatments. We evaluated the safety of radical treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection. METHODS: Using descriptive statistics, we report on the characteristics and short-term clinical outcomes of patients undergoing radical cancer treatment during the first COVID-19 wave compared to a similar pre-pandemic period. RESULTS: Compared to 2019, the number of patients undergoing radical treatment in 2020 reduced by: 28% for surgery; 18% for SACT; and 10% for RT. Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy and 2% biological therapy. A similar proportion of RT was delivered in 2019 and 2020 (53% vs. 52%). Oncological outcomes were also similar to pre-COVID-19. The COVID-19 infection rates were low: 12 patients were positive pre surgery (1%), 7 post surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19-related deaths were reported. CONCLUSIONS: Whilst there were fewer patients receiving radical anticancer treatments, those who did receive treatment were treated in a safe environment. Overall, cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.


Assuntos
COVID-19 , Neoplasias , COVID-19/epidemiologia , Humanos , Imunoterapia , Londres/epidemiologia , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Pandemias
3.
Int J Radiat Oncol Biol Phys ; 108(4): 1019-1029, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32585332

RESUMO

PURPOSE: Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H2O2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action. METHODS AND MATERIALS: Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H2O2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H2O2 was mixed in 1% sodium hyaluronate gel (final H2O2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis. RESULTS: Compliance with H2O2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1ß, IL-4, and MIP-1α with tumor response. CONCLUSIONS: Intratumoral H2O2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.


Assuntos
Neoplasias da Mama/terapia , Quimiorradioterapia/métodos , Peróxido de Hidrogênio/administração & dosagem , Oxidantes/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/sangue , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/terapia , Quimiocina CCL3/sangue , Fracionamento da Dose de Radiação , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Peróxido de Hidrogênio/efeitos adversos , Injeções Intralesionais/efeitos adversos , Injeções Intralesionais/métodos , Interleucina-1beta/sangue , Interleucina-4/sangue , Irradiação Linfática , Masculino , Pessoa de Meia-Idade , Oxidantes/efeitos adversos , Medição da Dor , Dor Processual/induzido quimicamente , Radiodermite/patologia , Pele/efeitos dos fármacos , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Ultrassonografia de Intervenção , Viscossuplementos/administração & dosagem
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