Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
1.
N Engl J Med ; 384(5): 428-439, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33471991

RESUMO

BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Variação Genética , Mutação de Sentido Incorreto , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Risco , Análise de Sequência de DNA , Adulto Jovem
2.
Phys Rev Lett ; 125(14): 141104, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33064506

RESUMO

The 2017 Event Horizon Telescope (EHT) observations of the central source in M87 have led to the first measurement of the size of a black-hole shadow. This observation offers a new and clean gravitational test of the black-hole metric in the strong-field regime. We show analytically that spacetimes that deviate from the Kerr metric but satisfy weak-field tests can lead to large deviations in the predicted black-hole shadows that are inconsistent with even the current EHT measurements. We use numerical calculations of regular, parametric, non-Kerr metrics to identify the common characteristic among these different parametrizations that control the predicted shadow size. We show that the shadow-size measurements place significant constraints on deviation parameters that control the second post-Newtonian and higher orders of each metric and are, therefore, inaccessible to weak-field tests. The new constraints are complementary to those imposed by observations of gravitational waves from stellar-mass sources.

3.
Am J Hum Genet ; 107(5): 837-848, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33022221

RESUMO

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

4.
J Neurooncol ; 148(1): 117-130, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32367436

RESUMO

BACKGROUND: Combined radiochemotherapy followed by maintenance chemotherapy with cisplatin, lomustine and vincristine within the NOA-07 study resulted in considerable short-term toxicity in adult medulloblastoma patients. Here we investigated the long-term impact of this treatment, focusing on neurocognitive functioning and health-related quality of life (HRQoL). METHODS: Neurocognitive functioning and HRQoL scores over time were determined, and differences between the post-treatment and follow-up assessments were calculated up to 18 months for neurocognition and 60 months for HRQoL. RESULTS: 28/30 patients were analyzed. The three preselected HRQoL scales (role, social and cognitive functioning) showed improved scores, to a clinically relevant extent (≥ 10 points), compared to post-treatment levels up to 30 months, but decreased afterwards. Z-scores for verbal working memory were worse during follow-up compared to post-treatment scores and remained impaired during 18 months follow-up (i.e. z-score below - 1 standard deviation). Attention was impaired post-treatment, and remained impaired to a clinically relevant extent during follow-up. Coordination/processing speed and lexical verbal fluency improved compared to post-treatment scores, and remained within the normal range thereafter. Other tests of verbal fluency were stable over time, with z-scores within the normal range. CONCLUSIONS: This long-term follow-up study showed that the NOA-07 treatment regimen was not associated with a deterioration in HRQoL in the post-treatment period. Verbal working memory deteriorated, while other neurocognitive domains did not seem to be impacted negatively by the treatment.

5.
Strahlenther Onkol ; 195(2): 103-112, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30191285

RESUMO

PURPOSE: To compare relative and absolute dose-volume parameters (DV) of the rectum and their clinical correlation with acute and late radiation proctitis (RP) after radiotherapy (RT) for prostate cancer (PCa). PATIENTS AND METHODS: 366 patients received RT for PCa. In total, 49.2% received definitive RT, 20.2% received postoperative RT and 30.6% received salvage RT for biochemical recurrence. In 77.9% of patients, RT was delivered to the prostate or prostate bed, and additional whole pelvic RT was performed in 22.1%. 33.9% received 3D-RT, and 66.1% received IMRT. The median follow-up was 59.5 months (18.0-84.0 months). The relative (in %) and absolute (in ccm) rectal doses from 20-75 Gy including the receiver operating characteristics curves (rAUC) from 30-65 Gy (in % and ccm) and several other clinical parameters were analyzed in univariate and multivariate analyses. We performed the statistical analyses separately for the entire cohort (n = 366), patients with (n = 81) and without (n = 285) pelvic RT, comparing RP vs. RP ≥ grade I. RESULTS: With the exception of the V50Gyccm (p = 0.02) in the univariate analyses for acute RP in the entire patient cohort, no absolute DV parameter (in ccm) was statistically significant associated with either acute or late RP. In the multivariate analyses, 3D-RT (p < 0.008) and rAUCV30-50 Gy% (p = 0.006) were significant parameters for acute RP for the entire cohort, and the V50Gy% (p = 0.01) was the significant parameter for patients with pelvic RT. The rAUCV40-50 Gy% (p = 0.004) was significant for RT to the prostate/prostate bed. Regarding the statistical analysis for late RP, the rAUCV30-65 Gy% (p = 0.001) was significant for the entire cohort, and rAUCV30-50 Gy% (p = 0.001) was significant for RT of the prostate/prostate bed. No parameter was significant in patients with pelvic RT. CONCLUSION: Absolute DV parameters in ccm are not required for RT in PCa patients.


Assuntos
Proctite/etiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Correlação de Dados , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/cirurgia , Doses de Radiação , Radioterapia Adjuvante , Estudos Retrospectivos , Terapia de Salvação
6.
Am J Hum Genet ; 104(1): 21-34, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30554720

RESUMO

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.


Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/genética , Predisposição Genética para Doença , Herança Multifatorial/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Anamnese , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Receptores Estrogênicos/metabolismo , Reprodutibilidade dos Testes , Medição de Risco
7.
Radiat Oncol ; 13(1): 213, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390700

RESUMO

PURPOSE: To determine the prognostic impact of comorbidity and age in medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) using the age-adjusted Charlson Comorbidity Index (aCCI). PATIENTS AND METHODS: Between November 2008 and January 2015, 196 consecutive patients with medically inoperable NSCLC were treated with SBRT at a single institution. The prescribed isocenter dose was either 60.0 Gray (Gy) in six fractions for central lung cancer or 56.25 Gy in three fractions for peripheral lung cancer. Baseline comorbidities were retrospectively retrieved according to available outclinic medical records as well as the hospital information system. The aCCI was scored for each patient and subjected according to outcome and toxicity as well as all of the single items of the aCCI and other clinical parameters using univariate and multivariate analysis. RESULTS: Thirty-one point 6 % (62/196) of patients were deceased, of whom 17.3% (34/196) died due to lung cancer and 14.3% (28/196) due to comorbidities. The median overall survival (OS) was 15.0 months (95% CI [11.9-18.1]), whereas the median cancer-specific survival (CSS) was not reached. An aCCI ≥7 compared with an aCCI ≤6 was significantly associated with an increased risk of death (HR 1.79, 95% CI [1.02-2.80], p = 0.04) and cancer-specific death (HR 9.26, 95% CI [4.83-24.39], p < 0.001), respectively. Neither OS nor CCS were significantly associated with age, sex, side (left vs. right), lobe, localization (central vs. peripheral), packyears, TNM, or any item of the aCCI. Considering the 14.3% (28/196) of deceased patients who died due to comorbidities, aCCI ≥9 was significantly associated with non-cancer-related death (HR 3.12, 95% CI [1.22-8.33], p = 0.02). The observed cumulative rate of radiation pneumonitis (RP) ≥2 was 12.7% (25/196). The aCCI had no statistical association with RP. CONCLUSION: Advanced age and numerous comorbidities characterizing this patient population were successfully assessed using the aCCI in terms of survival. Therefore, we recommend that age and comorbidity be indexed using the aCCI as a simple scoring system for all patients treated with SBRT for lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/radioterapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radiocirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
Neuro Oncol ; 20(3): 400-410, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29016837

RESUMO

Background: Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy. Methods: The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy. Results: Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock. Conclusions: Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/terapia , Quimiorradioterapia , Radiação Cranioespinal , Meduloblastoma/terapia , Adulto , Neoplasias Cerebelares/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Lomustina/administração & dosagem , Masculino , Meduloblastoma/patologia , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Vincristina/administração & dosagem , Adulto Jovem
9.
Radiat Oncol ; 12(1): 165, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29096667

RESUMO

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is the most common subacute side effect after concurrent chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer. Several clinical and dose-volume (DV) parameters are associated with a distinct risk of symptomatic RP. The aim of this study was to assess the spatial dose distribution of the RP volume from first occurence to maximum volume expansion of RP. MATERIAL AND METHODS: Between 2007 and 2015, 732 patients with lung cancer were treated in an institution. Thirty-three patients met the following inclusion criteria: an RP grade II after CRT and a radiation dose ≥60 Gy and no prior medical history of cardiopulmonary comorbidities. The images of the first chest computed tomography (CT) confirming the diagnosis of RP and the CT images showing the maximum expansion of RP were merged with the treatment plan. The RP volume was delineated within the treatment plan, and a DV analysis was performed to evaluate the lung dose volume areas in which the RP manifested over time and whether dose volume changes within the RP volume occurred. RESULTS: A change from clinical diagnosis to maximum expansion of RP was observed as the RP at clinical appearance mainly manifested in the lower dose areas of the lung, whereas the RP volume at maximum expansion manifested in the higher dose areas, resulting in a significant shift of the assessed relative mean dose volume proportions within the RP volume. The mean relative dose volume proportion 0- ≤ 20 Gy decreased from 30.2% (range, 0-100) to 21.9% (range, 0-100; p = 0.04) at the expense of the dose volume > 40 Gy which increased from 39.2% (range, 0-100) to 49.8% (range, 0-100; p = 0.02), whereas the dose relative volume proportion > 20- ≤ 40 Gy showed no relevant change and slightly decreased from 30.6% (range, 0-85.7) to 28.3%, (range, 0-85.7; p = 0.34). CONCLUSION: We observed a considerable increase in the relative dose proportions within the RP volume from diagnosis to maximum volume extent from low dose zones below 20 Gy to zones above 40 Gy. Although the clinical impact on RP remains unknown, a reduction of healthy healthy lung tissue receiving >40 Gy (V40) might be an additional parameter for irradiation planning in lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/etiologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Pneumonite por Radiação/patologia , Radioterapia Conformacional/efeitos adversos
10.
In Vivo ; 31(5): 949-955, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28882964

RESUMO

AIM: To evaluate treatment-related factors such as overall treatment time (OTT) and radiation treatment time (RTT) in head-and-neck cancer. PATIENTS AND METHODS: A total of 216 patients with locoregionally advanced inoperable head and neck cancer were treated with definitive radio(chemo)therapy. Mean follow-up was 37 months. RESULTS: Median time from diagnosis to start of radiotherapy (total waiting time) was 34 days, and comprised of referral waiting time and time for preparatory work. Median RTT was 40 days, and median OTT was 91 days. At 6, 12 and 24 months local recurrence-free survival (LRFS) was 75%, 65% and 60%; metastasis-free survival (MFS) was 84%, 77% and 70%; overall survival (OS) was 72%, 58% and 40%. Tumor stage, boost and chemotherapy were significant for OS, waiting time for preparatory work and RTT were significant for MFS, and referral waiting time and total radiotherapy dose for LRFS. CONCLUSION: RTT ≤40 days was a prognostic factor for better MFS. Prolonged waiting time had a converse effect for radiotherapy with better outcome on MFS and LRFS.


Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante , Recidiva , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
11.
Strahlenther Onkol ; 192(1): 8-16, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26416291

RESUMO

BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.


Assuntos
Neoplasias da Mama/terapia , Mama/efeitos da radiação , Estética , Mamoplastia , Mastectomia Segmentar , Dor Pós-Operatória/etiologia , Lesões por Radiação/etiologia , Radioterapia Conformacional , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente
12.
Strahlenther Onkol ; 191(11): 845-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26307627

RESUMO

BACKGROUND: Chemoradiation (CRT) is the standard of care in patients with node-positive (cN+) and node-negative (cN0) anal cancer. Depending on the tumor size (T-stage), total doses of 50-60 Gray (Gy) in daily fractions of 1.8-2.0 Gy are usually applied to the tumor site. Inguinal and iliac lymph nodes usually receive a dose of ≥ 45 Gy. Since 2010, our policy has been to apply a reduced total dose of 39.6 Gy to uninvolved nodal regions. This paper provides preliminary results of the efficacy and safety of this protocol. PATIENTS AND METHODS: Overall, 30 patients with histologically confirmed and node-negative anal cancer were treated in our department from 2009-2014 with definitive CRT. Histology all cases showed squamous cell carcinoma. A total dose of 39.6 Gy [single dose (SD) 1.8 Gy] was delivered to the iliac/inguinal lymph nodes. The area of the primary tumor received 50-59.4 Gy, depending on the T-stage. In parallel with the irradiation, 5-fluorouracil (5-FU) at a dose of 1000 mg/m(2) was administered by continuous intravenous infusion over 24 h on days 1-4 and 29-32, and mitomycin C (MMC) at a dose of 10 mg/m(2) (maximum absolute dose 14 mg) was administered on days 1 and 29. The distribution of the tumor stages was as follows: T1, n = 8; T2, n = 17; T3 n = 3. Overall survival (OS), local control (LC) of the lymph nodes, colostomy-free survival (CFS), and acute and chronic toxicities were assessed. RESULTS: The median follow-up was 27.3 months (range 2.7-57.4 months). Three patients (10.0 %) died, 2 of cardiopulmonary diseases and one of liver failure, yielding a 3-year OS of 90.0 %. Two patients (6.7 %) relapsed early and received salvage colostomies, yielding a 3-year CFS of 93.3 %. No lymph node relapses were observed, giving a lymph node LC of 100 %. According to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE V. 4.0), there were no grade IV gastrointestinal or genitourinary acute toxicities. Seven patients showed acute grade III perineal skin toxicity. Acute grade III groin skin toxicity was not observed. CONCLUSION: Reducing the total irradiation dose to uninvolved nodal regions to 39.6 Gy in chemoradiation protocols for anal carcinoma was safe and effective, and a prospective evaluation in future clinical trials is warranted.


Assuntos
Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/secundário , Linfonodos/efeitos da radiação , Radioterapia Conformacional/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Projetos Piloto , Proteção Radiológica , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento
13.
Radiat Oncol ; 10: 90, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25889036

RESUMO

BACKGROUND: It is currently not possible to get an approval of our ethics committee for a randomized trial cmparing 5x4 Gy and 10x3 Gy for MSCC that includes patients with favorable survival prognoses. Therefore, this matched-pair study following strict matching criteria was perfomed instead. METHODS: In this study, 142 receiving 5x4 Gy were retrospectively matched (1:1) to 142 patients receiving 10x3 Gy with respect to ten characteristics. These characteristics included age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MSCC, pre-RT ambulatory status, and time developing motor deficits. RESULTS: On multivariate analysis, post-RT motor function was associated with performance status (p<0.001), tumor type (p < 0.001), and time developing motor deficits (p<0.001). RT was successful in 76% of patients receiving 5x4 Gy and 69% receiving 10x3 Gy (p=0.14). Pre.RT ambulatory status showed a strong trend with respect to local control (LC) of MSCC in the multivariate analysis (p=0.058). 1-year LC rates were 87% after 5x4 Gy and 93% after 10x3 Gy (p=0.16). On multivariate analysis, survival (OS) was associated with performance score (p<0.001), visceral metastases (p<0.001), and pre-RT ambulatory status (p=0.004). 1-year OS rates were 68% after 5x4 Gy and 73% after 10x3 Gy (p = 0.64). CONCLUSIONS: In patients irradiated for MSCC who had favorable survival prognoses, post-RT motor function, LC and OS were not significantly different after 5x4 Gy and after 10x3 Gy.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias/mortalidade , Compressão da Medula Espinal/mortalidade , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Feminino , Seguimentos , Raios gama , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Neoplasias/radioterapia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Taxa de Sobrevida
14.
BMC Cancer ; 14: 731, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25266325

RESUMO

BACKGROUND: Many patients with cancer suffer from distress, anxiety and depression. However, studies on patients with brain metastases are lacking. In this exploratory study we prospectively assessed distress, anxiety and depression in patients with brain metastases from different solid primary tumour treated with radiotherapy to the brain. METHODS: Patients were recruited between May 2008 and December 2010. Distress, anxiety and depression were subjectively evaluated before radiotherapy, 6 weeks, 3 months and 6 months after radiotherapy using the validated National Comprehensive Cancer Network Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). The treatment group consisted of adult patients (n = 67) with brain metastases who were treated with whole-brain radiotherapy (n = 40) or hypofractionated stereotactic radiotherapy (n = 27). The control group comprised of patients (n = 32) diagnosed with breast cancer without cranial involvement who received adjuvant whole breast radiotherapy. Forty-six patients (24 in the treatment group) completed the study after six months. RESULTS: Before radiotherapy, the treatment group experienced higher distress than the control group (p = 0.029). Using a cut-off ≥ 5, 70% of the treatment group were suffering from significant distress (66% of the control group). No significant time-by-group interaction on distress, anxiety and depression was observed. At all time points, a high proportion of patients reported psychological stress which featured more prominently than most of the somatic problems. Global distress correlated strongly with the Hospital Anxiety score before radiotherapy, but only moderately or weakly with both HADS scores after radiotherapy with the weakest association 6 months after radiotherapy. CONCLUSION: In conclusion, the course of distress, anxiety and depression does not differ significantly between patients with brain metastases and breast cancer patients without cranial involvement. This finding suggests that both groups need similar psychological support during their treatment. Both screening instruments should be used as they cover different facets of distress.


Assuntos
Ansiedade/diagnóstico , Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/radioterapia , Depressão/diagnóstico , Psicometria/métodos , Adulto , Idoso , Ansiedade/etiologia , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/secundário , Neoplasias da Mama/psicologia , Neoplasias da Mama/radioterapia , Depressão/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo
15.
Int J Radiat Oncol Biol Phys ; 89(4): 863-71, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24969797

RESUMO

PURPOSE: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. METHODS AND MATERIALS: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine). RESULTS: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (± standard error [SE]) were each 58% (± 10%) for the entire cohort: CNS-PNET was 53% (± 13); pinealoblastoma was 64% (± 15%; P=.524 and P=.627, respectively). CONCLUSIONS: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Quimioterapia de Manutenção/métodos , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/radioterapia , Glândula Pineal , Pinealoma/tratamento farmacológico , Pinealoma/radioterapia , Adolescente , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Protocolos Clínicos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Memória de Curto Prazo , Processos Mentais , Recidiva Local de Neoplasia , Neoplasia Residual , Tumores Neuroectodérmicos Primitivos/mortalidade , Tumores Neuroectodérmicos Primitivos/cirurgia , Testes Neuropsicológicos , Pinealoma/mortalidade , Pinealoma/cirurgia , Estudos Prospectivos , Análise de Regressão , Taxa de Sobrevida , Adulto Jovem
16.
Radiat Oncol ; 9: 86, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24673965

RESUMO

BACKGROUND: To show effectiveness of low-dose splenic irradiation in symptomatic congestive splenomegaly. METHODS: Five patients were referred to our department for symptomatic congestive splenomegaly within three years. Primary diseases were autoimmune hepatitis with liver cirrhosis (n=2), cystic fibrosis (n=1), granulomatous liver disease (n=1) and Werlhof disease with liver cirrhosis (n=1). Mean age was 54 years (range: 36-67). Patients received splenic irradiation with a total dose of 3 Gy (single dose: 0.5 Gy). One patient was re-irradiated after long-term failure with the same treatment schedule. RESULTS: In four patients long term relief of splenic pain could be observed during the follow-up time of median 20 (range: 2-36) months. Four patients showed haematological response after irradiation with an increase of erythrocytes, leucocytes and/or platelets. A slightly decrease in spleen size was found in two patients. CONCLUSIONS: Low-dose splenic irradiation in symptomatic congestive splenomegaly is feasible and perhaps as effective as in lympho-and myeloproliferative malignancies regarding pain relief and haematological response.


Assuntos
Hipertensão Portal/radioterapia , Cirrose Hepática/radioterapia , Pancitopenia/radioterapia , Esplenomegalia/radioterapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/radioterapia , Pancitopenia/complicações , Dosagem Radioterapêutica , Baço/patologia , Esplenomegalia/complicações , Resultado do Tratamento
17.
Otol Neurotol ; 35(1): 171-81, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24335935

RESUMO

OBJECTIVE: The purpose of this study is to compare the outcomes in patients who underwent microsurgical resection for recurrent vestibular schwannoma after microsurgical resection and previous radiation therapy. STUDY DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Fifteen patients, who underwent microsurgical resection for recurrent vestibular schwannoma after previous surgery (group A), and 5 patients, who underwent microsurgical resection after previous radiation therapy (group B) were included. INTERVENTION: Surgical resection after radiation therapy or previous surgical resection. MAIN OUTCOME MEASURES: Intraoperative findings and postoperative facial nerve function were investigated in groups A and B. RESULTS: Mean tumor volumes were 18.4 ± 2.44 cm3 in group A and 19.0 ± 1.53 cm3 in group B. Total resection was achieved in 10 patients (67%) of group A and in 3 patients (60.0%) of group B. The tumor was more difficult to resect because of severe adhesions to the facial nerve. Anatomic facial nerve preservation could be achieved in 19 patients. Mean follow-up time was 80 months for group A and 28 months for group B. At last follow-up, 7 patients (53.8%) of group A had a good facial nerve function. In 3 patients (75.0%) of group B, the preoperative facial nerve function was preserved postoperatively. Preexistent facial paresis, large tumor with extrameatal growth and brainstem compression correlated with poor postoperative facial nerve function. CONCLUSION: Surgical outcome of recurrent vestibular schwannoma is more unsatisfactory than after primary surgery. It remains to be clarified whether previous surgery may implicate a higher risk for postoperative facial nerve function than previous radiation therapy upon surgery for tumor recurrence.


Assuntos
Microcirurgia , Neuroma Acústico/cirurgia , Radiocirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/radioterapia , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Fam Cancer ; 13(2): 137-42, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24061862

RESUMO

Inherited mutations in PALB2 are known to be associated with increased breast cancer risk. We aimed to investigate the prevalence and risk association of a recurrent PALB2 mutation, c.509_510delGA, among 3,924 unselected breast cancer patients from Belarus, Russia or Germany. High-resolution melting analyses and direct sequencing identified the c.509_510delGA allele in 3/1,008 (0.3 %) German breast cancer patients, 2/994 (0.2 %) Russian breast cancer patients and 5/1,922 (0.3 %) Byelorussian breast cancer patients. Breast tumours were mainly estrogen receptor positive and included both ductal and lobular histology. Only one of the ten patients had a first-degree family history of breast cancer. The mutation was not detected in 2,827 healthy females from the same populations, confirming the association of PALB2*c.509_510delGA with breast cancer risk (p = 0.007). These data indicate that the PALB2*c.509_510delGA mutation is prevalent in about 1 in 400 breast cancer patients from Central and Eastern Europe, and the low occurrence of familial clustering is consistent with a moderate penetrance of this mutation.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Grupo com Ancestrais do Continente Europeu/genética , Proteínas Nucleares/genética , Deleção de Sequência , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Sequência de Bases , Estudos de Casos e Controles , Análise Mutacional de DNA , Proteína do Grupo de Complementação N da Anemia de Fanconi , Feminino , Predisposição Genética para Doença/genética , Alemanha , Humanos , Pessoa de Meia-Idade , Penetrância , República de Belarus , Federação Russa
19.
Int J Radiat Oncol Biol Phys ; 87(4): 705-12, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24064320

RESUMO

PURPOSE: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. METHODS AND MATERIALS: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). RESULTS: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. CONCLUSION: Self-reported attention declined in patients with brain metastases after RT to the brain, whereas it remained relatively stable in breast cancer patients.


Assuntos
Atenção/efeitos da radiação , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Transtornos Cognitivos/etiologia , Cognição/efeitos da radiação , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Idoso , Atenção/fisiologia , Neoplasias Encefálicas/psicologia , Neoplasias da Mama/psicologia , Neoplasias da Mama/radioterapia , Cognição/fisiologia , Transtornos Cognitivos/fisiopatologia , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Memória/fisiologia , Memória/efeitos da radiação , Processos Mentais/fisiologia , Processos Mentais/efeitos da radiação , Pessoa de Meia-Idade , Motivação/fisiologia , Motivação/efeitos da radiação , Estudos Prospectivos , Psicometria , Autorrelato , Fatores de Tempo
20.
Urol Oncol ; 31(1): 74-81, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21396839

RESUMO

BACKGROUND AND OBJECTIVES: Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis. METHODS AND MATERIALS: Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancer patients and 490 healthy males from Northern Germany were genotyped for these polymorphisms. RESULTS: SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02). CONCLUSIONS: These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Apoptose/genética , Biomarcadores Tumorais/genética , Braquiterapia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Seguimentos , Alemanha , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/radioterapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA