RESUMO
Over the past two decades, it has been established that cancer patients with oligometastases, i.e., only a few detectable metastases confined to one or a few organs, may benefit from an aggressive local treatment approach such as the application of high-precision stereotactic body radiotherapy (SBRT). Specifically, some studies have indicated that achieving long-term local tumor control of oligometastases is associated with prolonged overall survival. This motivates investigations into which factors may modify the dose-response relationship of SBRT by making metastases more or less radioresistant. One such factor relates to the uptake of the positron emission tomography tracer 2-deoxy-2-[18F]fluoro-D-glucose (FDG) which reflects the extent of tumor cell glycolysis or the Warburg effect, respectively. Here we review the biological mechanisms how the Warburg effect drives tumor cell radioresistance and metastasis and draw connections to clinical studies reporting associations between high FDG uptake and worse clinical outcomes after SBRT for oligometastases. We further review the evidence for distinct metabolic phenotypes of metastases preferentially seeding to specific organs and their possible translation into distinct radioresistance. Finally, evidence that obesity and hyperglycemia also affect outcomes after SBRT will be presented. While delivered dose is the main determinant of a high local tumor control probability, there might be clinical scenarios when metabolic targeting could make the difference between achieving local control or not, for example when doses have to be compromised in order to spare neighboring high-risk organs, or when tumors are expected to be highly therapy-resistant due to heavy pretreatment such as chemotherapy and/or radiotherapy.
Assuntos
Neoplasias , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Fluordesoxiglucose F18 , Prognóstico , Neoplasias/patologia , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: To describe the case of successful radiotherapeutic treatment of a woman suffering from Brooke-Spiegler syndrome who had multiple disfiguring cylindromas on the entire scalp and further tumors on the trunk. METHODS: After decades of treatment with conventional therapies including surgery and topically applied salicylic acid, the 73-year-old woman agreed to undergo radiotherapeutic treatment. She received 60â¯Gy to the scalp and 36â¯Gy to painful nodules in the lumbar spine region. RESULTS: Over a follow-up period of 14 and 11 years, respectively, the scalp nodules almost completely regressed, while the lumbar nodules became painless and considerably smaller. Apart from alopecia, no late adverse effects of treatment remain. CONCLUSION: This case should remind us of the potential role that radiotherapy could play in treating Brooke-Spiegler syndrome. The required dose for treatment of such extensive disease is still a matter of debate due to the scarcity of radiotherapeutic experience. This case demonstrates that for scalp tumors, 30â¯× 2â¯Gy can result in long-term tumor control, while other dose prescriptions may be adequate for tumors in other locations.
Assuntos
Carcinoma Adenoide Cístico , Síndromes Neoplásicas Hereditárias , Neoplasias Cutâneas , Feminino , Humanos , Idoso , Neoplasias Cutâneas/patologia , Síndromes Neoplásicas Hereditárias/patologia , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgiaRESUMO
Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.
Assuntos
Adenocarcinoma , Neoplasias das Glândulas Suprarrenais , Neoplasias Pulmonares , Segunda Neoplasia Primária , Radiocirurgia , Adenocarcinoma/radioterapia , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/secundário , Humanos , Neoplasias Pulmonares/patologia , Radiocirurgia/métodos , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
PURPOSE: Patients with head and neck cancer (HNC) are at risk of malnutrition, especially during radiochemotherapy. We aimed to study the impact of a ketogenic diet (KD) versus an unspecified standard diet (SD) on body composition and survival in HNC patients undergoing radio(chemo)therapy. METHODS: As part of a controlled clinical trial, non-metastasized HNC patients were enrolled into either a KD (Nâ¯= 11) or an SD (Nâ¯= 21) group between May 2015 and May 2021. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Overall and progression-free survival was assessed during regular follow-up. RESULTS: A total of 7 KD and 21 SD patients completed the study and were eligible for comparative analysis. Chemotherapy was significantly associated with declines in all body composition parameters, while the KD had opposing, yet nonsignificant effects. In patients receiving chemotherapy, average weekly reductions of body mass (BM) and skeletal muscle mass (SMM) were 0.9â¯kg and 0.31â¯kg in the KD group versus 1.2â¯kg and 0.57â¯kg in the SD group, respectively. Patients in the KD group receiving no chemotherapy achieved an average increase of 0.04â¯kg BM and 0.12â¯kg SMM per week. After a median follow-up of 42 months (range 6.7-78 months) there were no significant differences in progression-free or overall survival between the groups. CONCLUSION: The KD may partially counteract the detrimental effects of radiochemotherapy on body composition in HNC patients. This should encourage further research into KDs in frail cancer patient populations and motivate their implementation as complementary therapy for selected patients.
Assuntos
Dieta Cetogênica , Neoplasias de Cabeça e Pescoço , Humanos , Composição Corporal/fisiologia , Dieta Cetogênica/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Intervalo Livre de ProgressãoRESUMO
BACKGROUND AND PURPOSE: The standard treatment of glioblastoma patients consists of surgery followed by normofractionated radiotherapy (NFRT) with concomitant and adjuvant temozolomide chemotherapy. Whether accelerated hyperfractionated radiotherapy (HFRT) yields comparable results to NFRT in combination with temozolomide has only sparsely been investigated. The objective of this study was to compare NFRT with HFRT in a multicenter analysis. MATERIALS AND METHODS: A total of 484 glioblastoma patients from four centers were retrospectively pooled and analyzed. Three-hundred-ten and 174 patients had been treated with NFRT (30 × 1.8 Gy or 30 × 2 Gy) and HFRT (37 × 1.6 Gy or 30 × 1.8 Gy twice/day), respectively. The primary outcome of interest was overall survival (OS) which was correlated with patient-, tumor- and treatment-related variables via univariable and multivariable Cox frailty models. For multivariable modeling, missing covariates were imputed using multiple imputation by chained equations, and a sensitivity analysis was performed on the complete-cases-only dataset. RESULTS: After a median follow-up of 15.7 months (range 0.8-88.6 months), median OS was 16.9 months (15.0-18.7 months) in the NFRT group and 14.9 months (13.2-17.3 months) in the HFRT group (p = 0.26). In multivariable frailty regression, better performance status, gross-total versus not gross-total resection, MGMT hypermethylation, IDH mutation, smaller planning target volume and salvage therapy were significantly associated with longer OS (all p < 0.01). Treatment differences (HFRT versus NFRT) had no significant effect on OS in either univariable or multivariable analysis. CONCLUSIONS: Since HFRT with temozolomide was not associated with worse OS, we assume HFRT to be a potential option for patients wishing to shorten their treatment time.
Assuntos
Neoplasias Encefálicas , Quimiorradioterapia , Glioblastoma , Temozolomida , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Seguimentos , Fragilidade , Glioblastoma/terapia , Humanos , Estudos Retrospectivos , Análise de Sobrevida , Temozolomida/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: Interest in ketogenic diets (KDs) as complementary nutritional treatments for cancer patients is rising, although some skepticism about their safety exists. We, therefore, studied the effects of KDs on quality of life and blood parameters in rectal cancer patients undergoing radio-chemotherapy. METHODS: EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters were obtained prior to, in the middle of and at the end of radiotherapy within the KETOCOMP study (ClinicalTrials.gov Identifier: NCT02516501). A total of 18 patients consuming a KD were compared to 23 patients consuming their standard diet (SD). Baseline-end differences were measured using Wilcoxon tests, and repeated measures analysis was performed using linear mixed effects models. RESULTS: Eighty-nine percent of patients on the KD reported subjectively feeling good or very good, but roughly half of them rated the daily routine implementation as difficult. Only the SD group experienced significant declines in physical and role functioning, while the KD group improved in role (p = 0.045), emotional (p = 0.018) and social functioning (p = 0.009).Urinary frequency, buttock pain and fatigue significantly increased in the SD group, but to a much lesser extent in the KD group. Several biomarkers of metabolic health (gamma-glutamyl-transpeptidase, triglyceride-glucose index, HDL cholesterol/triglyceride ratio, and free T3) improved in the KD, but not the SD group. CONCLUSIONS: Despite being perceived as difficult to implement by ≈50% of patients, KDs are feasible as complementary therapies alongside radio-chemotherapy and associated with subjective well-being. The hypothesis that they exert beneficial effects on quality of life and metabolic health in rectal cancer patients is supported by our data. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02516501, registered Aug 6th 2015.
Assuntos
Dieta Cetogênica , Neoplasias Retais , Composição Corporal , Humanos , Qualidade de Vida , Neoplasias Retais/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Obesity and low muscle mass are associated with worse outcomes of breast cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in breast cancer patients undergoing radiotherapy. METHODS: Patients with non-metastasized breast cancer were allocated to either the KD (N = 32) or the SD (N = 31) during radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters and quality of life were assessed before, during, and at the end of radiotherapy. RESULTS: A total of 29 KD and 30 SD patients completed the study. During radiotherapy, mean and median fasting BHB concentrations in the KD group were 0.72 and 0.49 mmol/l (range 0.06-4.9) which was significantly higher than those in the SD group (p < 2.2 × 10-16). There was a very small and insignificant increase in body weight and fat mass in the SD group, as well as a decrease of fat free mass. In contrast, patients in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses. The KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p < 0.0001). The KD significantly decreased free T3 levels by 0.06 pg/ml/week (p = 6.3 × 10-5). Global quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20). CONCLUSIONS: In breast cancer patients undergoing curative radiotherapy, a KD based on natural foods is feasible. After initial water losses, the KD tends to reduce body weight and fat mass while preserving fat free and skeletal muscle mass. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02516501 , registered on August 06, 2015.
Assuntos
Composição Corporal , Peso Corporal , Neoplasias da Mama/dietoterapia , Dieta Cetogênica/métodos , Qualidade de Vida , Adulto , Idoso , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: To report the development of an ultimately fatal occurrence of Fournier's gangrene in a rectal cancer patient undergoing neoadjuvant radiotherapy without chemotherapy. METHODS: A 53-year-old male patient with G2 cT3 cN1a cM0 stage IIIB adenocarcinoma of the lower rectum and several comorbidities including ulcerative colitis was treated with 56â¯Gy to the primary tumor in 28 fractions because he declined the recommended simultaneous chemotherapy. He was also enrolled in the ketogenic diet arm of our KETOCOMP study, so that prospective measurements of blood parameters, quality of life, and body composition were made. RESULTS: The patient died 6 days after completion of radiotherapy due to septic shock associated with Fournier's gangrene reaching from the right buttock into the gluteal muscles and descending into the scrotum. In retrospect, there were several signs probably indicating the development of the gangrene: (i) a decline in bioelectrical phase angle; (ii) an accelerated weight and fat-free mass loss starting in the third week of radiotherapy; (iii) an increase in C-reactive protein (CRP) and concurrent drop in high-density lipoprotein (HDL) cholesterol and insulin-like growth factor(IGF)-1 concentrations; and (iv) the occurrence of a sharp pain in the perianal region reported in the fifth week of radiotherapy. Notably, his self-reported quality of life score was the same at the end of as before radiotherapy. CONCLUSIONS: This case highlights the occurrence of Fournier's gangrene as an extremely rare but life-threatening complication during neoadjuvant radiotherapy for rectal cancer which should be refreshed in the awareness of radiation oncologists and radiologists.
Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Gangrena de Fournier/mortalidade , Terapia Neoadjuvante/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Neoplasias Retais/mortalidade , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Causas de Morte , Comorbidade , Fracionamento da Dose de Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Fatores de RiscoRESUMO
BACKGROUND: The objective of this study was to prospectively evaluate dose-intensified hypofractionated stereotactic body radiation therapy (SBRT) in patients with painful spinal metastases in a multicenter, single-arm, phase 2 study. METHODS: Patients with 2 or fewer distinct, noncontiguous, painful, mechanically stable, unirradiated spinal metastases from a solid tumor with a Karnofsky performance status ≥ 60 were eligible. Patients with a long (Mizumoto score ≤ 4) or intermediate overall survival expectancy (Mizumoto score = 5-9) received 48.5 Gy in 10 fractions or 35 Gy in 5 fractions, respectively, with SBRT. The primary outcome was the overall (complete and partial) pain response as measured with international consensus guidelines 3 months after SBRT. RESULTS: There were 57 patients enrolled between 2012 and 2015, and 54 of these patients with 60 painful vertebral metastases were analyzed. The 3-month pain response was evaluated in 42 patients (47 lesions). An overall pain response was observed in 41 lesions (87%), and the pain response remained stable for at least 12 months. The mean maximum pain scores on a visual analogue scale significantly improved from the baseline of 6.1 (standard deviation, 2.5) to 2.0 (standard deviation, 2.3) 3 months after treatment (P < .001). The 5-level EuroQol 5-Dimension Questionnaire quality-of-life (QOL) dimensions (self-reported mobility, usual activities, and pain/discomfort) significantly improved from the baseline to 3 months after treatment. The 12-month overall survival and local control rates were 61.4% (95% confidence interval [CI], 48%-74.8%) and 85.9% (95% CI, 76.7%-95%), respectively. Grade 3 toxicity was limited to acute pain in 1 patient (2%). No patient experienced radiation-induced myelopathy. Six patients (11%) developed progressive vertebral compression fractures (VCFs), and 8 patients (15%) developed new VCFs. CONCLUSIONS: Dose-intensified SBRT achieved durable local metastasis control and resulted in pronounced and long-term pain responses and improved QOL. Cancer 2018;124:2001-9. © 2018 American Cancer Society.
Assuntos
Dor do Câncer/radioterapia , Hipofracionamento da Dose de Radiação , Radiocirurgia/métodos , Neoplasias da Coluna Vertebral/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor do Câncer/diagnóstico , Dor do Câncer/etiologia , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Qualidade de Vida , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Planejamento da Radioterapia Assistida por Computador , Medula Espinal/efeitos da radiação , Doenças da Medula Espinal/epidemiologia , Doenças da Medula Espinal/etiologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/secundário , Resultado do TratamentoRESUMO
PURPOSE: To investigate whether the tumour uptake of radionuclide in peptide receptor radionuclide therapy (PRRT) of meningioma can be predicted by a PET scan with (68)Ga-labelled somatostatin analogue. METHODS: In this pilot trial, 11 meningioma patients with a PET scan indicating somatostatin receptor expression received PRRT with 7.4 GBq (177)Lu-DOTATOC or (177)Lu-DOTATATE, followed by external beam radiotherapy. A second PET scan was scheduled for 3 months after therapy. During PRRT, multiple whole-body scans and a SPECT/CT scan of the head and neck region were acquired and used to determine the kinetics and dose in the voxel with the highest radionuclide uptake within the tumour. Maximum voxel dose and retention of activity 1 h after administration in PRRT were compared to the maximum standardized uptake values (SUV(max)) in the meningiomas from the PET scans before and after therapy. RESULTS: The median SUV(max) in the meningiomas was 13.7 (range 4.3 to 68.7), and the maximum fractional radionuclide uptake in voxels of size 0.11 cm³ was a median of 23.4 × 10(-6) (range 0.4 × 10(-6) to 68.3 × 10(-6)). A strong correlation was observed between SUV(max) and the PRRT radionuclide tumour retention in the voxels with the highest uptake (Spearman's rank test, P < 0.01). Excluding one patient who showed large differences in biokinetics between PET and PRRT and another patient with incomplete data, linear regression analysis indicated significant correlations between SUV(max) and the therapeutic uptake (r = 0.95) and between SUV(max) and the maximum voxel dose from PRRT (r = 0.76). Observed absolute deviations from the values expected from regression were a median of 5.6 × 10(-6) (maximum 9.3 × 10(-6)) for the voxel fractional radionuclide uptake and 0.40 Gy per GBq (maximum 0.85 Gy per GBq) (177)Lu for the voxel dose from PRRT. CONCLUSION: PET with (68)Ga-labelled somatostatin analogues allows the pretherapeutic assessment of tumour radionuclide uptake in PRRT of meningioma and an estimate of the achievable dose.
Assuntos
Meningioma/diagnóstico por imagem , Meningioma/terapia , Terapia de Alvo Molecular , Tomografia por Emissão de Pósitrons , Receptores de Somatostatina/metabolismo , Adulto , Idoso , Transporte Biológico , Feminino , Radioisótopos de Gálio/metabolismo , Humanos , Masculino , Meningioma/metabolismo , Pessoa de Meia-Idade , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Compostos Organometálicos/uso terapêutico , Somatostatina/análogos & derivados , Somatostatina/metabolismoRESUMO
BACKGROUND: One third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70% of these patients. Conventional radiotherapy with of 1-10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3-6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology - intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery - have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1) A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3) Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept. METHODS / DESIGN: It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥ 2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this two-centre phase II trial. CONCLUSIONS: Results of this study will refine the methods of patient selection, target volume definition, treatment planning and delivery as well as quality assurance for radiosurgery. It is the intention of this study to form the basis for a future randomized controlled trial comparing conventional radiotherapy with fractionated radiosurgery for palliation of painful vertebral metastases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01594892.
Assuntos
Medição da Dor/métodos , Radiocirurgia/métodos , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia , Idoso , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Dor/etiologia , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , TempoRESUMO
BACKGROUND: The goal of this study was to evaluate accelerated radiotherapy with and without temozolomide (TMZ) for glioblastoma multiforme (GBM). METHODS: This retrospective analysis evaluated 86 patients with histologically proven GBM who were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was 90. A total of 41 patients received radiotherapy only from 2002-2005 and 45 patients were treated with TMZ concomitantly and after radiotherapy from 2005-2007. RESULTS: Median overall survival (OS) was 12.5 months and 2-year OS was 15.4%. Patient characteristics were well balanced between the two groups except for better performance status (p = 0.05) and higher frequency of retreatment for the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and treatment with TMZ (HR 0.60) were correlated with OS in the multivariate analysis: treatment with and without TMZ resulted in median OS of 16 months and 11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45 patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant TMZ. CONCLUSION: TMZ added to accelerated radiotherapy for GBM resulted in prolonged overall survival with low rates of severe hematological toxicity.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Dacarbazina/análogos & derivados , Fracionamento da Dose de Radiação , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/mortalidade , Quimioterapia Adjuvante , Terapia Combinada , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Feminino , Seguimentos , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Temozolomida , Adulto JovemRESUMO
BACKGROUND & AIMS: Ketogenic diets (KDs) have been proposed as complementary nutritional treatments for cancer patients. Because it is important to gain knowledge about the safety of KDs adopted during cancer therapy, we studied the effects of KDs on quality of life and blood parameters in women with early-stage breast cancer undergoing radiotherapy. METHODS: A total of 29 patients consuming a KD were compared to 30 patients consuming their standard diet (SD) with respect to EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters that were obtained prior to, in the middle of and at the end of radiotherapy. Baseline-to-end differences were assessed using Wilcoxon tests, and longitudinal changes were analyzed using linear mixed effects models. RESULTS: Compared to the SD, women consuming a KD experienced significant improvements in emotional functioning, social functioning, sleep quality, future perspectives and systemic therapy side effects (all p-values <0.01). While breast symptoms increased significantly in both groups, the increase was less pronounced in the KD group. There was no hint of a detrimental effect of the KDs on either liver or kidney function; in contrast, biomarkers of metabolic health (gamma-glutamyl-transpeptidase, creatinine, triglycerides, IGF-1, free T3) significantly improved in the KD, but not the SD group. CONCLUSIONS: These data support the hypothesis that consuming a KD during radiotherapy is safe for women with breast cancer and has the potential to improve quality of life and metabolic health. CLINICALTRIALS. GOV IDENTIFIER: NCT02516501.
Assuntos
Neoplasias da Mama/psicologia , Neoplasias da Mama/radioterapia , Dieta Cetogênica/psicologia , Qualidade de Vida , Lesões por Radiação/prevenção & controle , Adulto , Biomarcadores/sangue , Neoplasias da Mama/sangue , Feminino , Humanos , Lesões por Radiação/etiologia , Qualidade do Sono , Resultado do TratamentoRESUMO
BACKGROUND: Vitamin D has been shown to be associated with reduced risk and severity of COVID-19 and exerts regulating effects on all hallmarks of cancer. The goal of this study was to analyze the vitamin D status of a cancer patient cohort from our clinic in the Franconian region, Germany. METHODS: 25-hydroxyvitamin D concentrations were available for 116 patients included in prospective trials in our clinic. Associations of vitamin D with anthropometric and blood parameters were investigated using Kendall's τ correlation coefficients and linear regression. RESULTS: A total of 57 patients (49.1%) were vitamin D deficient (<20 ng/mL), and 92.2% did not meet the recommended vitamin D level of 40 ng/mL. There was a strong negative association between vitamin D and leukocyte count (τ = -0.173, p = 0.007) and C-reactive protein concentration (τ = -0.172, p = 0.007). In linear regression, the most important variables for predicting vitamin D levels were (in order of decreasing importance) season, fat mass index, platelet, and leukocyte count. CONCLUSIONS: Despite appeals towards medical societies to target widespread vitamin D deficiency in Germany more than 10 years ago, our data indicate that these have been without avail. Low vitamin D levels in cancer patients should be corrected using reasonable sun exposure and supplements.
Assuntos
COVID-19/complicações , Neoplasias/radioterapia , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Adulto , Idoso , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/mortalidade , COVID-19/virologia , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Estudos Prospectivos , SARS-CoV-2 , Vitamina D/análogos & derivados , Deficiência de Vitamina D/sangueRESUMO
BACKGROUND & AIMS: Obesity and low muscle mass are associated with worse outcomes of colorectal cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in rectal cancer patients undergoing radiotherapy. METHODS: Patients with non-metastasized rectal cancer were allocated to either the KD (N = 24) or the SD (N = 25) group during radiotherapy. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Pathologic response in patients undergoing neoadjuvant treatment was evaluated at the time of surgery. RESULTS: A total of 18 KD and 23 SD patients completed the study and were eligible for analysis. The SD group experienced no noteworthy changes in any body composition parameter. In contrast, patients in the KD group lost significant amounts of body weight and fat mass, averaging 0.5 and 0.65 kg/week (p < 0.0001). There was a rapid loss of intracellular water consistent with initial intramuscular glycogen and water depletion, but skeletal muscle tissue was conserved. Pathological tumor responses were somewhat greater in the KD group, with a larger mean Dworak regression grade (p = 0.072) and larger percentage of near-complete (yT0N0 or yT1N1) responses (43 versus 15%, p = 0.116) that almost reached statistical significance in intention-to-treat analysis (50% versus 14%, p = 0.018). CONCLUSIONS: In rectal cancer patients undergoing curative radiotherapy, a KD significantly reduced body weight and fat mass while preserving skeletal muscle mass. We could demonstrate a trend for KDs contributing synergistically to pathological tumor response, a finding in line with preclinical data that warrants future confirmation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.
Assuntos
Composição Corporal , Dieta Cetogênica/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Adulto , Idoso , Peso Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Radioterapia Adjuvante , Neoplasias Retais/fisiopatologia , Resultado do TratamentoRESUMO
PURPOSE: To report long-term outcome of fractionated stereotactic body radiation therapy (SBRT) for painful spinal metastases. METHODS AND MATERIALS: This prospective, single-arm, multicenter phase 2 clinical trial enrolled 57 patients with 63 painful, unirradiated spinal metastases between March 2012 and July 2015. Patients were treated with 48.5 Gy in 10 SBRT fractions (long life expectancy [Mizumoto score ≤4]) or 35 Gy in 5 SBRT fractions (intermediate life expectancy [Mizumoto score 5-9]). Pain response was defined as pain improvement of a minimum of 2 points on a visual analog scale, and net pain relief was defined as the sum of time with pain response (complete and partial) divided by the overall follow-up time. RESULTS: All 57 patients received treatment per protocol; 32 and 25 patients were treated with 10- and 5-fraction SBRT, respectively. The median follow-up of living patients was 60 months (range, 33-74 months). Of evaluable patients, 82% had complete or partial pain response (responders) at 3 months' follow-up (primary endpoint), and pain response remained stable over 5 years. Net pain relief was 74% (95% CI, 65%-80%). Overall survival rates of 1, 3, and 5 years were 59.6% (95% CI, 47%-72%), 33.3% (95% CI, 21%-46%), and 21% (95% CI, 10%-32%), respectively. Freedom from local spinal-metastasis progression was 82% at the last imaging follow-up. Late grade-3 toxicity was limited to pain in 2 patients (nonresponders). There were no cases of myelopathy. SBRT resulted in long-term improvements of all dimensions of the 5-level EuroQol 5-Dimension Questionnaire except anxiety/depression. CONCLUSIONS: Fractionated SBRT achieved durable pain response and improved quality of life at minimum late toxicity.
Assuntos
Dor do Câncer/radioterapia , Radiocirurgia/métodos , Neoplasias da Coluna Vertebral/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor do Câncer/mortalidade , Intervalos de Confiança , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Radiocirurgia/efeitos adversos , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/secundário , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: :To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. PATIENTS AND METHODS: 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). RESULTS: Treatment was completed as planned by all patients. Acute GI and GU toxicity grade ≥ 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade ≥ 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade ≥ 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). CONCLUSION: High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising.
Assuntos
Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Gastroenteropatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Planejamento de Assistência ao Paciente , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
Preclinical data provide evidence for synergism between ketogenic diets (KDs) and other oncological therapies. The aim of this systematic review was to summarize data from clinical studies that have tested KDs along with other treatments used within medical oncology. The PubMed database was searched using the key words "ketogenic" AND ("cancer" OR "glioblastoma"). A secondary search was conducted by screening the reference lists of relevant articles on this topic. Relevant studies for this review were defined as studies in which KDs were used complementary to surgery, radio-, chemo-, or targeted therapy and at least one of the following four outcomes were reported: (i) Overall survival (OS); (ii) progression-free survival (PFS); (iii) local control rate; (iv) body composition changes. Twelve papers reporting on 13 clinical studies were identified. Nine studies were prospective and six had a control group, but only two were randomized. KD prescription varied widely between studies and was described only rudimentarily in most papers. Adverse events attributed to the diet were rare and only minor (grade 1-2) except for one possibly diet-related grade 4 event. Studies reporting body composition changes found beneficial effects of KDs in both overweight and frail patient populations. Beneficial effects of KDs on OS and/or PFS were found in four studies including one randomized controlled trial. Studies in high-grade glioma patients were not sufficiently powered to prove efficacy. Evidence for beneficial effects of KDs during cancer therapy is accumulating, but more high-quality studies are needed to assess the overall strength of evidence.
Assuntos
Dieta Cetogênica , Neoplasias/terapia , Composição Corporal , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Glioblastoma/mortalidade , Glioblastoma/terapia , Glioma/mortalidade , Glioma/terapia , Humanos , Masculino , Oncologia , Neoplasias/dietoterapia , Neoplasias/mortalidade , Intervalo Livre de Progressão , Taxa de SobrevidaRESUMO
We here express our concern about a general decree to let patients wear face masks in radiation oncology clinics. We believe that potential risks associated with wearing masks, such as the risk of confounding patients, outweigh any benefits of such a policy for which evidence of protection from COVID-19 is generally weak. For asymptomatic patients, wearing masks in addition to hygiene standards will not provide additional protection of others and should be cautioned against.
Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Medicina Baseada em Evidências , Máscaras/estatística & dados numéricos , Máscaras/normas , Pneumonia Viral/epidemiologia , Radioterapia (Especialidade)/normas , Erros de Configuração em Radioterapia/prevenção & controle , COVID-19 , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , SARS-CoV-2RESUMO
BACKGROUND AND AIM: Ketogenic diets (KDs) have gained interest as a complementary treatment for cancer patients. Here we present first results of our ongoing KETOCOMP study (NCT02516501) concerning body composition changes among rectal, breast and head & neck cancer (HNC) patients who consumed a KD during curative radiotherapy (RT). EXPERIMENTAL PROCEDURE: Sixty-one patients eating a non-ketogenic diet were compared to 20 patients on a KD supplemented with 10â¯g essential amino acids on RT days. Body composition was measured prior to and weekly during RT using 8-electrode bioimpedance analysis. Longitudinal body composition data were analyzed using linear mixed effects models. RESULTS AND CONCLUSION: Patients on the KD exhibited nutritional ketosis, defined as serum ß-hydroxybutyrate levels ≥0.5â¯mmol/l, in a median of 69.0% of blood measurements (range 0-100%) performed in our clinic. In rectal and breast cancer patients, KD was significantly associated with a loss of 0.5 and 0.4â¯kg fat mass per week (pâ¯=â¯0.00089 and 8.49â¯×â¯10-5, respectively), with no significant changes in fat free and skeletal muscle mass. In HNC patients, concurrent chemotherapy was the strongest predictor of body weight, fat free and skeletal muscle mass loss during RT, while consuming a KD was significantly associated with a gain in these measures. These preliminary results confirm prior reports indicating that KDs are safe to consume during standard-of-care therapy. They also provide an important first indication that KDs with ample amino acid intake could improve body composition during RT in curative cancer patients.