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1.
Anticancer Res ; 41(10): 5123-5130, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593463

RESUMO

BACKGROUND/AIM: The impact of venous resections and reconstruction techniques on morbidity after surgery for pancreatic cancer (PDAC) remains controversial. PATIENTS AND METHODS: A total of 143 patients receiving pancreatoduodenectomy (PD) for PDAC between 2013 and 2018 were identified from a prospective database. Morbidity and mortality after PD with tangential resection versus end-to-end reconstruction were assessed. RESULTS: Fifty-two of 143 (36.4%) patients underwent PD with portal venous resection (PVR), which was associated with longer operation times [398 (standard error (SE) 12.01) vs. 306 (SE 13.09) min, p<0.001]. PVR was associated with longer intensive-care-unit stay (6.3 vs. 3.8 days, p=0.054); morbidity (Clavien-Dindo classification (CDC) grade IIIa-V 45.8% vs. 35.8%, p=0.279) and 30-day mortality (4.1% vs. 4.2%, p>0.99) were not different. Tangential venous resection was associated with similar CDC grade IIIa-IV (42.9% vs. 50.0%, p=0.781) and 30-day mortality rates (3.5% vs. 4.1%, p=0.538) as segmental resection and end-to-end venous reconstruction. CONCLUSION: Both tangential and segmental PVR appear feasible and can be safely performed to achieve negative resection margins.


Assuntos
Adenocarcinoma/cirurgia , Veias Mesentéricas/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/mortalidade , Veia Porta/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/mortalidade , Procedimentos Cirúrgicos Vasculares/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Margens de Excisão , Veias Mesentéricas/patologia , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Veia Porta/patologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
2.
Anticancer Res ; 41(10): 5065-5069, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593456

RESUMO

BACKGROUND/AIM: Many patients with head-and-neck cancer are scheduled for irradiation. This study was performed to determine the frequency of and risk factors for pre-radiotherapy sleep disturbances in these patients. PATIENTS AND METHODS: A total of 103 patients with head-and-neck cancer scheduled for radiotherapy were included in this retrospective study. Eighteen characteristics were evaluated including timing of start of radiotherapy relative to COVID-19 pandemic; age; gender; Karnofsky performance score; Charlson comorbidity index; history of another malignancy; family history of malignancy; distress score; number of emotional, physical or practical problems; request for psychological support; tumor site and stage; upfront surgery; planned chemotherapy; and brachytherapy boost. RESULTS: The frequency of pre-radiotherapy sleep disturbances was 42.7%. This was significantly associated with age ≤63 years (p=0.049), Karnofsky performance score ≤80 (p=0.002), Charlson comorbidity index ≥3 (p=0.005), history of another malignancy (p=0.012), emotional (p=0.001) or physical (p<0.001) problems, and request for psychological support (p=0.002). CONCLUSION: Sleep disturbances were frequent in patients assigned to radiotherapy of head-and-neck cancer. Recognizing risk factors for sleep disturbance helps identify patients requiring psychological support.


Assuntos
Neoplasias de Cabeça e Pescoço/psicologia , Neoplasias de Cabeça e Pescoço/radioterapia , Transtornos do Sono-Vigília/psicologia , COVID-19/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Transtornos do Sono-Vigília/epidemiologia
3.
Anticancer Res ; 41(10): 5165-5169, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593468

RESUMO

BACKGROUND/AIM: Many patients with prostate cancer receive definitive or adjuvant radiotherapy. This study aimed to identify the frequency of sleep disturbances and corresponding risk factors prior to radiation treatment. PATIENTS AND METHODS: Data of 48 patients assigned to local or loco-regional irradiation for prostate cancer were retrospectively analyzed for pre-radiotherapy sleep disturbances. Fifteen characteristics were analyzed including age, performance status, comorbidity, history of previous malignancy, distress score, (emotional, physical or practical) problems, prostate-specific antigen, primary tumor stage, Gleason-score, upfront androgen deprivation therapy (ADT), treatment volume, brachytherapy, and COVID-19 pandemic. RESULTS: Pre-radiotherapy sleep disturbances were reported by 20.8% of patients and significantly associated with distress scores ≥4 (p<0.0001) and ≥3 physical problems (p=0.0001). Trends were found for Karnofsky performance score ≤80 (p=0.095), Gleason score 7b-9 (p=0.079), and ADT (p=0.067). CONCLUSION: Pre-radiotherapy sleep disturbances were less common in prostate cancer patients than in other cancer patients. Risk factors were identified that can help identify patients requiring psychological support prior to radiotherapy.


Assuntos
Neoplasias da Próstata/psicologia , Neoplasias da Próstata/radioterapia , Transtornos do Sono-Vigília/psicologia , Idoso , COVID-19/epidemiologia , Humanos , Masculino , Prevalência , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Transtornos do Sono-Vigília/epidemiologia
4.
Anticancer Res ; 41(9): 4407-4410, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475061

RESUMO

BACKGROUND/AIM: Many patients with gynecological malignancies receive postoperative radiotherapy, which can lead to fear and sleep disorders. We aimed to identify the prevalence of and risk factors for sleep disorders. PATIENTS AND METHODS: Sixty-two patients assigned to radiotherapy for gynecological malignancies were retrospectively evaluated. Seventeen characteristics were analyzed for associations with pre-radiotherapy sleep disorders including age, Karnofsky performance score, Charlson comorbidity index, history of additional malignancy, family history of gynecological cancer, distress score, emotional, physical or practical problems, tumor site/stage; chemotherapy, treatment volume, brachytherapy, and the COVID-19 pandemic. RESULTS: The prevalence of pre-radiotherapy sleep disorders was 46.8%. Sleep disorders were significantly associated with Charlson comorbidity index ≥3 (p=0.012), greater number of physical problems (p<0.0001), and advanced primary tumor stage (p=0.005). A trend was found for greater number of emotional problems (p=0.075). CONCLUSION: Pre-radiotherapy sleep disorders are common in patients with gynecological malignancies, particularly in those with specific risk factors. Patients should be offered early psychological support.


Assuntos
Neoplasias dos Genitais Femininos/radioterapia , Neoplasias dos Genitais Femininos/cirurgia , Radioterapia Adjuvante/métodos , Transtornos do Sono-Vigília/epidemiologia , Adulto , Braquiterapia , COVID-19/epidemiologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/psicologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Estudos Retrospectivos , Fatores de Risco , Transtornos do Sono-Vigília/etiologia , Resultado do Tratamento
5.
Anticancer Res ; 41(9): 4439-4442, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475066

RESUMO

BACKGROUND/AIM: Radiotherapy and radiochemotherapy are common treatments for rectal and anal cancer. Anticipation of treatment may cause distress and sleep disorders. This study aimed to identify risk factors for sleep disorders. PATIENTS AND METHODS: In 42 patients with rectal or anal cancer scheduled for radiotherapy, 16 characteristics were analyzed for associations with pre-radiotherapy sleep disorders including age, gender, performance score, comorbidity, patient's or family history of additional cancer/melanoma, distress score, emotional/physical/practical problems, tumor site and stage, surgery and relation to COVID-19 pandemic. RESULTS: Overall prevalence of pre-radiotherapy sleep disorders was 42.9%. Sleep disorders were significantly associated with Karnofsky performance score 60-80 (p=0.044), Charlson comorbidity index ≥3 (p=0.0012), distress score 6-10 (p=0.00012), and more emotional (p=0.0012), physical (p=0.0004) or practical (p=0.033) problems. A trend was found for female gender (p=0.061). CONCLUSION: Sleep disorders were common in patients with rectal or anal cancer scheduled for radiotherapy. Risk factors can help identify patients requiring psychooncological support already prior to the start of radiotherapy.


Assuntos
Neoplasias do Ânus/radioterapia , Neoplasias do Ânus/cirurgia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Transtornos do Sono-Vigília/epidemiologia , Idoso , Neoplasias do Ânus/patologia , Neoplasias do Ânus/psicologia , COVID-19/epidemiologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Neoplasias Retais/patologia , Neoplasias Retais/psicologia , Caracteres Sexuais , Transtornos do Sono-Vigília/etiologia , Resultado do Tratamento
6.
In Vivo ; 35(5): 2763-2770, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410966

RESUMO

BACKGROUND/AIM: Being scheduled for radiotherapy can cause emotional distress. This study aimed to identify risk factors in 338 patients assigned to radiotherapy for breast cancer. PATIENTS AND METHODS: Nineteen potential risk factors including the COVID-19 pandemic were investigated for associations with the six emotional problems included in the National Comprehensive Cancer Network Distress Thermometer. RESULTS: Worry and fears were significantly associated with age ≤60 years; sadness with age and Karnofsky performance score (KPS) <90; depression with KPS and Charlson Comorbidity Index ≥3; loss of interest with KPS. Trends were found for associations between sadness and additional breast cancer/DCIS, Charlson Index and chemotherapy; between depression and additional breast cancer/DCIS, treatment volume and nodal stage N1-3; between nervousness and additional breast cancer/DCIS, mastectomy and triple-negativity; between loss of interest and Charlson Index, family history of breast cancer/DCIS, invasive cancer, chemotherapy, and treatment volume. The COVID-19 pandemic did not increase emotional problems. CONCLUSION: Several risk factors for emotional problems were identified. Patients with such factors should receive psychological support well before radiotherapy.


Assuntos
Neoplasias da Mama , COVID-19 , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Pandemias , Radioterapia Adjuvante/efeitos adversos , SARS-CoV-2
7.
J Surg Oncol ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416792

RESUMO

BACKGROUND: Guidelines recommended for resection of oral cancer define a free margin of ≥5 mm as clear and safe (R0). This statement was questioned recently based on the assumption that different surgical margins may hold different risk categories. The aim of this study was to investigate the impact of stratification of the surgical margins on the survival outcome of patients with oral cancer. METHODS: In a cohort of 753 patients, the hazard ratio for local recurrence-free survival (LRFS), overall survival (OS), and oral cancer-specific survival (OCSS) were estimated for R0 resection, the close margin of 1-4 mm, involved resection borders but with free frozen sections. Competing risk factors were considered in the statistical regression model. RESULTS: One hundred seventy-three (23%) patients developed local recurrence and 316 (42%) died in the 5 follow-up years. There was a gradual improvement in the LRFS, OCSS, OS with the increase of clear margin. OS showed a similar tendency. CONCLUSION: Not all patients with an R0cm status carry the same risk for impaired LRFS, OCSS, and OS. Their risk to develop recurrence is higher than those patients with R0 ≥5 mm but stratified risk management can be recommended according to the presented results.

8.
In Vivo ; 35(4): 2253-2260, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182504

RESUMO

BACKGROUND/AIM: The anticipation of radiotherapy can cause distress and sleep disorders, which may be aggravated by the COVID-19 pandemic. This study investigated sleep disorders in a large cohort of patients with breast cancer before and during the pandemic. PATIENTS AND METHODS: Twenty-three characteristics were retrospectively analyzed for associations with pre-radiotherapy sleep disorders in 338 patients. Moreover, 163 patients presenting before and 175 patients presenting during the COVID-19 pandemic were compared for sleep disorders. RESULTS: Sleep disorders were significantly associated with age ≤60 years (p=0.006); high distress score (p<0.0001); more emotional (p<0.0001), physical (p<0.0001) or practical (p<0.0001) problems; psycho-oncological need (p<0.0001); invasive cancer (p=0.003); chemotherapy (p<0.001); and hormonal therapy (p=0.006). Sleep disorders were similarly common in both groups (prior to vs. during the pandemic: 40% vs. 45%, p=0.38). CONCLUSION: Although additional significant risk factors for sleep disorders were identified, the COVID-19 pandemic appeared to have no significant impact on sleep disorders in patients scheduled for irradiation of breast cancer.


Assuntos
Neoplasias da Mama , COVID-19 , Transtornos do Sono-Vigília , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Pandemias , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2 , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia
9.
In Vivo ; 35(4): 2283-2288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182507

RESUMO

BACKGROUND/AIM: Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer. Options for palliative treatment include systemic agents and radiotherapy. Selection of a radiation regimen should consider the patient's survival prognosis. This study aimed to identify prognostic factors of survival after palliative radiotherapy for cSCC of the head-and-neck. PATIENTS AND METHODS: Ten factors were analyzed for survival in 12 patients including age, gender, tumor site, histological grade, primary tumor stage, lymph node involvement, distant metastases, upfront surgery, radiation dose and completion of radiotherapy. RESULTS: On univariate analysis, improved survival was significantly associated with lower histological grade (better differentiation) (p=0.022), no distant metastases (p=0.040) and completion of radiotherapy (p=0.014). In the multivariate analysis, lower histological grade (risk ratio=6.05, p=0.100) and completion of radiotherapy (risk ratio=4.87, p=0.115) showed trends. CONCLUSION: Predictors of survival were identified that can help design individual treatments. Patients require optimal supportive care as completion of radiotherapy was associated with better survival.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Pescoço , Estadiamento de Neoplasias , Cuidados Paliativos , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia
10.
Anticancer Res ; 41(6): 3055-3058, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083297

RESUMO

BACKGROUND/AIM: Patients with advanced squamous cell carcinoma of the head-and-neck (SCCHN) may be assigned to palliative irradiation. A survival score was developed for this group to support treatment personalization. PATIENTS AND METHODS: Seventy-eight patients who received palliative irradiation for SCCHN and had complete data regarding performance score, pre-radiotherapy hemoglobin levels, and main tumor site were included in this retrospective study. Six-month survival rates of these factors were divided by 10 (factor scores) and added for each patient (total patient scores). RESULTS: Total patient scores ranged between 8 and 15 points. Three groups were designed based on the 6-month survival rates, namely 8-9 (n=15), 11-13 (n=36), and 14-15 (n=27) points. Six-month survival rates were 13%, 28%, and 63%, and median survival times were 1, 2, and 11 months (p=0.001). CONCLUSION: A new survival score including three prognostic groups was developed. This new tool can help physicians when designing personalized treatments for patients with SCCHN scheduled for palliative irradiation.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Cuidados Paliativos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Taxa de Sobrevida , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Medicina de Precisão , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
11.
Anticancer Res ; 41(6): 3205-3210, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083316

RESUMO

BACKGROUND/AIM: A considerable number of patients with advanced head-and-neck cancer (SCCHN) receive palliative radiotherapy. This study aimed to identify prognostic factors for survival to facilitate personalized treatment for these patients. PATIENTS AND METHODS: Ninety-two patients receiving palliative radiotherapy for SCCHN were retrospectively analyzed. Fourteen characteristics were evaluated for survival including age, gender, performance score, pre-radiotherapy hemoglobin, tumor site and stage, histologic grade, p16-status, equivalent dose in 2 Gy-fractions (EQD2), completion of radiotherapy, upfront surgery and systemic therapy. RESULTS: On univariate analysis, improved survival was significantly associated with pre-radiotherapy hemoglobin ≥12 g/dl (p=0.003), EQD2 >42.3 Gy (p=0.003) and completion of radiotherapy (p<0.001). In the multivariate analysis, hemoglobin levels remained significant (p=0.024). Trends were found for EQD2 (p=0.057) and completion of radiotherapy (p=0.093). CONCLUSION: Prognostic factors for survival were identified that can facilitate treatment personalization. The fact that higher EQD2 and completion of radiotherapy were associated with improved survival demonstrates the importance of close monitoring and care of these patients during radiotherapy.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Cuidados Paliativos , Radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Humanos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
12.
Anticancer Res ; 41(5): 2489-2494, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952476

RESUMO

BACKGROUND/AIM: Most patients with breast cancer are assigned to radiotherapy, which may cause fears leading to sleep disorders. Very few data are available regarding the prevalence of sleep disorders and corresponding risk factors. PATIENTS AND METHODS: Data of 175 patients with breast cancer presenting for adjuvant radiotherapy were retrospectively analyzed. Twenty-three patient and tumor characteristics were investigated for associations with pre-radiotherapy sleep disorders. RESULTS: Seventy-eight patients (44.6%) stated sleep disorders prior to radiotherapy. These were significantly associated with higher distress score (p<0.0001); greater number of emotional (p<0.0001), physical (p<0.0001) or practical problems (p<0.001); and request for psycho-oncological support (p<0.001). Trends were found for worse performance status (p=0.062) and higher comorbidity index (p=0.059). CONCLUSION: Sleep disorders prior to radiotherapy for breast cancer are common. This applies particularly to patients with risk factors including distress due to emotional, physical or practical problems. These patients should be offered psycho-oncological support as soon as possible.


Assuntos
Neoplasias da Mama/radioterapia , Radioterapia Adjuvante/efeitos adversos , Transtornos do Sono-Vigília/radioterapia , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/patologia
13.
Anticancer Res ; 41(5): 2495-2499, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952477

RESUMO

BACKGROUND/AIM: Sino-nasal cancer is rare and often diagnosed at advanced stages. Some patients cannot receive curative treatment and are treated with palliative irradiation. We aimed to identify prognostic factors for survival to facilitate treatment personalization for this group. PATIENTS AND METHODS: Twelve patients treated with palliative radiotherapy for locally advanced sino-nasal cancer were retrospectively analyzed for survival. Ten characteristics were evaluated including age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin, tumor site, lymph node involvement, histology, equivalent dose in 2 Gy-fractions, completion of radiotherapy and concurrent chemotherapy. RESULTS: On univariate analysis, KPS ≥70 (p<0.001) and completion of radiotherapy (p<0.001) were significantly associated with better survival. Chemotherapy showed a trend (p=0.097). In the multivariate analysis, KPS ≥70 was significant (p=0.025), and completion of radiotherapy showed a trend (p=0.080). CONCLUSION: KPS is an independent predictor of survival for palliative irradiation of sino-nasal cancer. Patients require close monitoring and care for side effects, since completion of radiotherapy is important for survival.


Assuntos
Neoplasias Nasais/radioterapia , Cuidados Paliativos/métodos , Radioterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Nasais/patologia , Teste de Desfecho Sinonasal
14.
Front Med (Lausanne) ; 8: 640515, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33987192

RESUMO

Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far. Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering. Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies. Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones.

15.
Transl Lung Cancer Res ; 10(3): 1424-1443, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33889520

RESUMO

Background: Neutrophils can play a pro-tumor or anti-tumor role depending on the tumor microenvironment. The effects of concurrent treatment with granulocyte colony-stimulating factor (G-CSF) and radiotherapy (RT) on neutrophils have not yet to be described. Methods: Hypofractionated radiation of 8 Gy ×3 fractions was administered with or without recombinant G-CSF to Lewis lung carcinoma tumor-bearing C57BL/6 model mice. The activation status of cytotoxic T cells in the mice was measured, along with the levels of tumor-associated neutrophils, cytotoxic T cells, and Treg cells. Tumor growth, survival, cytokine expression, and signaling pathways underlying anti-tumor effects of tumor-associated neutrophils after treatment were also studied. To ascertain the effects of concurrent RT and G-CSF on tumor-associated neutrophils, neutrophil depletion was performed. Results: RT affected early neutrophil infiltration, which is the first-line immune response. Subsequently, enhanced accumulation of lymphocytes, particularly CD8 cytotoxic T cells, was observed. Notably, lymphocytic infiltration was inhibited by neutrophil depletion but enhanced by G-CSF treatment. RT generated persistent DNA damage, as evidenced by an accumulation of phosphorylation of histone H2AX (γH2AX), and subsequently triggered inflammatory chemokine secretion. The chemokines CXCL1, CXCL2, and CCL5 were upregulated in both radiation-treated cells and the corresponding supernatants. Neutrophils that were newly recruited after RT improved radiosensitivity by inhibiting epithelial-mesenchymal transition via the reactive oxygen species-mediated PI3K/Akt/Snail signaling pathway, and G-CSF treatment enhanced this effect. Conclusions: The results of this study suggest that RT activates neutrophil recruitment and polarizes newly recruited neutrophils toward an antitumor phenotype, which is enhanced by the concurrent administration of G-CSF. Mesenchymal-epithelial transition induced by reactive oxygen species accumulation plays a major role in this process. Thus, the polarization of tumor-associated neutrophils might play a role in future cancer immunotherapies.

16.
BMC Cancer ; 21(1): 386, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836671

RESUMO

BACKGROUND: Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. METHODS: The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a 'natural' background progression-rate of 10% without radiotherapy (null hypothesis). DISCUSSION: If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. TRIAL REGISTRATION: clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Irradiação Craniana/efeitos adversos , Glioma/complicações , Glioma/patologia , Convulsões/diagnóstico , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/radioterapia , Quimiorradioterapia , Irradiação Craniana/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Eletroencefalografia , Feminino , Glioma/radioterapia , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Convulsões/terapia , Avaliação de Sintomas , Resultado do Tratamento
17.
Anticancer Res ; 41(2): 877-884, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517293

RESUMO

BACKGROUND/AIM: Prognosis of patients with unresectable squamous cell carcinomas of the head and neck requires improvement. This retrospective study compared accelerated radiotherapy plus chemotherapy to conventional radiochemotherapy. PATIENTS AND METHODS: Patients received definitive treatment with accelerated radiotherapy plus chemotherapy (group A, n=10) or conventional cisplatin-based radiochemotherapy (group B, n=85). Groups were matched for several patient and tumor characteristics and compared for locoregional control (LRC), overall survival (OS) and toxicities. Additionally, accelerated radiotherapy plus chemotherapy and chemotherapy regimens in group B were compared for LRC and OS. RESULTS: Treatment type had no significant impact on LRC (p=0.98) and OS (p=0.57). In group A, toxicities occurred more often, including grade ≥3 mucositis (p=0.041), grade ≥2 lymphedema (p=0.007) and grade ≥3 leucopenia (p=0.007). Best 2-year LRC (p=0.39) and OS (p=0.015) was achieved with 20 mg/m2 cisplatin days 1-5 every 4 weeks; accelerated radiochemotherapy resulted in second-worst outcomes. CONCLUSION: Given the limitations of this study, accelerated radiotherapy plus chemotherapy provided no significant benefit but increased toxicity compared to conventional radiochemotherapy.


Assuntos
Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/efeitos adversos , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Radioterapia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
Anticancer Res ; 41(1): 379-384, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419834

RESUMO

BACKGROUND/AIM: In a previous study investigating radiotherapy for newly diagnosed glioblastoma multiforme (GBM), significant or almost significant associations with survival were found for performance status, upfront resection, O6-methylguanine-DNA methyl-transferase (MGMT) promoter methylation and unifocal GBM. This study aimed to create a survival score based on these factors. PATIENTS AND METHODS: Most of the 81 patients included received resection of GBM followed by radiochemotherapy (59.4 Gy/33 or 60 Gy/30 fractions). The previously identified predictors of survival were re-evaluated. Factors significantly associated with survival were used for the score. RESULTS: All factors were significantly associated with survival. For each factor, 0 points (less favorable survival) or 1 point (more favorable survival) were assigned and added for each patient. Three groups were designed, 0-1 (n=10), 2 (n=21) and 3-4 points (n=50); 12-month survival rates were 0%, 38% and 78% (p<0.001). CONCLUSION: A new survival score was created for patients requiring radiotherapy for GBM that can improve treatment personalization.


Assuntos
Glioblastoma/mortalidade , Glioblastoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Gerenciamento Clínico , Feminino , Glioblastoma/diagnóstico , Glioblastoma/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Anticancer Res ; 41(1): 477-484, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419846

RESUMO

BACKGROUND/AIM: Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments. PATIENTS AND METHODS: Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities. RESULTS: LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients. CONCLUSION: AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.


Assuntos
Quimiorradioterapia , Fracionamento da Dose de Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Resultado do Tratamento
20.
In Vivo ; 35(1): 411-415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402490

RESUMO

BACKGROUND/AIM: Some patients with unresectable or incompletely resected head-and-neck cancer (SCCHN) cannot tolerate radiochemotherapy. Alternatives are needed that are more effective than conventional radiotherapy alone. PATIENTS AND METHODS: This retrospective study investigated patients irradiated for non-metastatic stage IV SCCHN who could not receive concurrent chemotherapy. Eight patients received accelerated radiotherapy with concomitant boost (group A) and 31 patients conventionally fractionated radiotherapy (group B). Groups were matched for tumor site, gender, age, performance score and histologic grade. RESULTS: Two-year PFS-rates were 63% in group A vs. 41% in group B, and median PFS-times were 36 vs. 10 months (p=0.48). Two-year OS-rates were 88% vs. 37%, and median OS-times were 44 vs. 14 months (p=0.19). Grade ≥2 radiation dermatitis was significantly (p=0.040) more common in group B; other toxicities were similar. CONCLUSION: Accelerated fractionation with concomitant boost appeared superior to conventional fractionation and can be considered for patients with stage IV SCCHN not suitable for radiochemotherapy. Larger studies are needed to confirm these findings.


Assuntos
Neoplasias de Cabeça e Pescoço , Quimiorradioterapia , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
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