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1.
Z Med Phys ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34373188

RESUMO

PURPOSE: Robotic systems to assist needle placements for low-dose rate brachytherapy enable conformal dose planning only restricted to path planning around risk structures. We report a treatment planning system (TPS) combining multiple direction needle-path planning with inverse dose optimization algorithms. METHODS: We investigated in a path planning algorithm to efficiently locate needle injection points reaching the target volume without puncturing risk structures. A candidate needle domain with all combinations of trajectories is used for the optimization process. We report a modular algorithm for inverse radiation plan optimization. The initial plan with V100>99% is generated by the "greedy optimizer". The "remove-seed algorithm" reduces the number of seeds in the high dose regions. The "depth-optimizer" varies the insertion depth of the needles. The "coverage-optimizer" locates under-dosed areas in the target volume and supports them with an additional amount of seeds. The dose calculation algorithm is benchmarked on an image set of a phantom with a liver metastasis (prescription dose Dpr=100Gy) and is re-planned in a commercial CE-marked TPS to compare the calculated dose grids using a global gamma analysis. The inverse optimizer is benchmarked by calculating 10 plans on the same phantom to investigate the stability and statistical variability of the dose parameters. RESULTS: The path planning algorithm efficiently removes 72.5% of all considered injection points. The candidate needle domain consists of combinations of 1971 tip points and 827 injection points. The global gamma analysis with gamma 1%=2.9Gy, 1mm showed a pass rate of 98.5%. The dose parameters were V100=99.1±0.3%, V150=76.4±2.5%, V200=44.5±5.5% and D90=125.9±3.6Gy and 10.7±1.3 needles with 34.0±0.8 seeds were used. The median of the TPS total running time was 4.4minutes. CONCLUSIONS: The TPS generates treatment plans with acceptable dose coverage in a reasonable amount of time. The gamma analysis shows good accordance to the commercial TPS. The TPS allows taking full advantage of robotic navigation tools to enable a new precise and safe method of minimally invasive low-dose-rate brachytherapy.

2.
Med Phys ; 48(1): 94-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33119944

RESUMO

PURPOSE: To characterize treatment plan (TP) quality, a quantitative quality control (QC) tool is proposed. The tool is validated using volumetric modulated arc therapy (VMAT) plans for treatment of prostate cancer by estimating the achievable organ at risk (OAR) sparing, based on the knowledge learned from prior plans. METHODS: Prostate TP quality was investigated by evaluating the achieved OAR sparing in the rectum and bladder, based on their proximity to target surface. The knowledge base used in this work comprises 450 plans, consisting of 181 homogenous prostate plans and 269 simultaneous integrated boost (SIB) prostate plans. A knowledge-based algorithm was used to relate the absorbed doses of the OARs (rectum and bladder) and their proximity to the planning target volume (PTV). A metric (Mq,r value) was calculated to characterize the OAR sparing based on the weighted differences of the mean doses at binned distances to the PTV surface. The 90% probability ellipse of the normally distributed OARs Mq,r values was considered to define a threshold above which the treatment plan was re-optimized. RESULTS: Following re-optimization, 8/11 of the homogenous plans and 6/13 of the SIB plans outside the 90% probability ellipse could be re-optimized to gain better OAR sparing while achieving the same or better target coverage. However, 3/4 of the homogenous TPs and 1/9 of the SIB TPs between 80% and 90% were improved. Mq,r values of bladder and rectum after re-optimizing the plans in both groups of homogenous and SIB showed lower values compared to the corresponding values before re-optimization, which implies that better OARs sparing was achieved. CONCLUSIONS: This work demonstrates an effective anatomy-specific QC tool for identifying suboptimal plans and determining the achievable OAR sparing for each individual patient anatomy.


Assuntos
Próstata , Neoplasias da Próstata , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Bases de Conhecimento , Masculino , Órgãos em Risco , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica
3.
J Contemp Brachytherapy ; 12(5): 480-486, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33299437

RESUMO

Purpose: Radiotherapy is the mainstay in the treatment of locally inoperable tumors. Interstitial electronic needle-based kilovoltage brachytherapy (EBT) could be an economic alternative to high-dose-rate (HDR) brachytherapy or permanent seed implantation (PSI). In this work, we evaluated if locally inoperable tumors treated with PSI at our institution may be suitable for EBT. Material and methods: A total of 10 post-interventional computed tomography (CT) scans of patients, who received PSI and simulated stepping-source EBT applied with Intrabeam system and needle applicator were used. EBT treatment planning software with 3-dimensional image and projection of applicator were applied for designing trajectories and establishing dwell positions. Dwell position doses were summarized, and doses covering 90% of the target volume (D90) achieved with stepping-source EBT were compared to those of PSI. Additionally, conformality of dose distributions and total irradiation time were assessed using conformation number (CN) or conformal index (COIN). Results: In all patients, D90 of EBT exceeded the prescribed dose or D90 of PSI on average by 4.7% or 21.3% relative to the prescribed dose, respectively. Mean number of trajectories was 5.0 for EBT and 6.9 for PSI. Average CN/COIN for EBT was 0.69, with a mean irradiation time of 27.8 minutes for standardized dose of 13 Gy. Conclusions: Stepping-source EBT allowed for a conformal treatment of inoperable interstitial tumors with similar D90. Fewer trajectories were required for EBT in majority of cases.

4.
Brachytherapy ; 19(5): 635-641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32651094

RESUMO

PURPOSE: The purpose of the study was to report the outcomes of a single-center adjuvant electronic brachytherapy (e-BT) experience for patients with endometrial carcinoma. METHODS AND MATERIALS: Patients were retrospectively assessed. Intracavitary e-BT was applied through a cylindrical applicator (diameters 2.5-3.5 cm). e-BT single doses ranged between 4 and 7 Gy (EQD2 ∼ 6-12, α/ß of 10 Gy and an relative biological effectiveness of 1.3) at 5-mm depth. Adverse events are reported at first week, 1-3 months, 3-12 months, 12-24 months, and >24 months. The overall survival, disease-free survival, distant disease control rate, and local control rate were estimated using the Kaplan-Meier method. RESULTS: Twenty-nine patients were assessed. The median age was 68 [48-86] years. External beam radiotherapy was added in n = 8 (27.6%) patients. Staging was 13.8% for T1a, 51.7% for T1b, 24.1% for T2, 6.9% for T3a, and 3.4% for T3b. Grading was G3 in 51.7% (n = 15), G2 in 20.7% (n = 6), and G1 in 27.6% (n = 8). Median followup was 47 months [5-88]. Overall Grade 1, 2, and 3 toxicity was 89.7% (n = 26), 17.2% (n = 5), and 6.9% (n = 2), respectively. No Grade 3 cystitis or proctitis or any Grade 4 or 5 toxicity occurred during followup. No local recurrences were detected. Estimated distant disease control rate was 92.1% (n = 2, distant metastasis at 7 and 11 months). Estimated 4-year overall survival was 84.8% (n = 4 events, two unrelated to disease) and disease-free survival was 84.6%. CONCLUSIONS: Our data suggest that e-BT resembles a very-low-toxicity profile and a high local control rate in the adjuvant scenario for patients with endometrial carcinoma.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias do Endométrio/radioterapia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Cistite/epidemiologia , Intervalo Livre de Doença , Eletrônica , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Dor Pélvica/epidemiologia , Proctite/epidemiologia , Lesões por Radiação/epidemiologia , Radioterapia , Estudos Retrospectivos , Taxa de Sobrevida , Doenças Vaginais/epidemiologia
5.
Asian Pac J Cancer Prev ; 21(5): 1399-1407, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32458648

RESUMO

PURPOSE: Concurrent chemo-radiotherapy (CCRT) is the primary treatment modality for locally advanced head and neck squamous cell cancer patients (LAHNSCC). Intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) and concurrent chemotherapy is not broadly implicated in our region mainly because of the lack of experience. This study aims at evaluating the response and compliance of this approach in our patients. METHODS: Forty patients with LAHNSCC were included and 50% received induction chemotherapy. All the patients were treated with IMRT-SIB radiotherapy for 70Gy over 33 daily fractions. Weekly cisplatin (40mg/m2) was administered during the radiation course. RESULTS: With median follow-up of 1.5 years, LC was achieved in 82.5% of cases and distant control rate was 90%. More than 5 interrupted radiation sessions and GTV volume > 50 cc significantly affected LRC (P= 0.02 and 0.001 respectively). Eighty percent of cases experienced grade 3 or 4 toxicities. Induction chemotherapy and PTV-70 volume >150 cc significantly affected the degree of toxicities (P=0.018 and 0.0001 respectively).The 2 years disease free survival (DFS) was 77%. ECOG PS, large GTV volume (> 50 cc) and RT interruption (>5 sessions) had negative impact on DFS (P= 0.041, 0.002 and 0.001 respectively). The 2 years overall survival (OS) was 87%. Radiation interruption (> 5 sessions) was the only factor which had significant detrimental effect on OS (P= 0.001). CONCLUSION: Induction chemotherapy seems to have a negative impact on patient's compliance to CCRT. Bulky tumors and prolonged radiation interruptions were associated with significantly lower LRC, DFS and OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Neoplasias de Cabeça e Pescoço/mortalidade , Cooperação do Paciente/estatística & dados numéricos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto , Idoso , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Taxa de Sobrevida , Adulto Jovem
6.
Radiat Oncol ; 15(1): 110, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410696

RESUMO

BACKGROUND: Soft tissue sarcomas (STS) treatment remains a therapeutic challenge. Intraoperative radiotherapy (IORT) resembles a safe and efficient for STS treatment. The first data on electronic-IORT (eIORT) using low-energy photons is herein presented. METHODS: Thirty-one patients with newly and recurrent STS were retrospectively assessed. EIORT was applied with low-energy photons during surgery. The dose was either prescribed to the applicator surface (spherical applicators) or 5 mm depth (flat applicators). Overall progression-free survival (O-PFS), local progression-free survival (L-PFS), overall survival (OS) and adverse events were evaluated. RESULTS: Median follow-up was 4.88 (1.0-8.95) years. Twenty-five patients (80.6%) had recurrent STS with prior treatment. The resection status was R1 in 25.8% and R2 in 6.5%. The distribution was 51.7% for extremities, 35.5% for abdomen and pelvis, 9.7% for thorax and 3.2% for head and neck tumors. The median O-PFS was 11.0 months, with 42.6% 5-year estimated O-PFS. The only local recurrence in the primary setting occurred after 22 months. Median L-PFS in recurrent STS was 12.5 months, with 65.5% 5-year estimated L-PFS. The 5-year OS estimated rate was 94.7% (3 events after 7 years). No G3 toxicity related to eIORT was observed. Two patients exhibited G2 acute neuropathic pain. Late neuropathic pain was seen in 6 patients being 3 graded as G1 and 3 as G2. No wound-related toxicity was found. CONCLUSION: Electronic IORT with low-energy photons is a safe treatment option for STS, yielding similar outcomes as historical series reporting IORT with electrons or HDR brachytherapy.


Assuntos
Recidiva Local de Neoplasia/radioterapia , Fótons/uso terapêutico , Radiocirurgia/métodos , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
Strahlenther Onkol ; 196(4): 349-355, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31641788

RESUMO

PURPOSE: To investigate long-term oncological outcome and incidence of chronic side effects in patients with breast cancer and intraoperative radiotherapy given as an upfront boost (IORT boost). METHODS: Retrospective analysis of 400 patients with an IORT boost with low-energy X­rays (20 Gy), subsequent whole-breast irradiation (46-50 Gy), and annual oncological follow-up. Side effects were prospectively evaluated (LENT-SOMA scales) over a period of up to 15 years. Side effects scored ≥grade 2 at least three times during follow-up were judged to be chronic. RESULTS: The median age was 63 years (30-85) and the median follow-up was 78 months (2-180) after IORT boost. In 15 patients a local recurrence occurred, resulting in a local recurrence rate at 5, 10, and 15 years of 2.0%, 6.6%, and 10.1%, respectively. The overall survival rates at 5, 10, and 15 years were 92.1%, 81.8%, and 80.7%, respectively. The most common high-grade side effects were fibrosis (21%) and pain (8.6%). The majority of side effects occurred within the first 3 years. The actuarial rates of chronic fibrosis were 19.1% and 21.1% at 5 and ≥8 years, of chronic pain 8.6% at ≥4 years, of chronic edema of the breast 2.4% at ≥2 years, of chronic lymphedema 0.0% at 5 and 10 years, and of chronic hyperpigmentation 0.5% at ≥2 years. Side effects were similar or less than expected from an external beam boost. CONCLUSION: IORT boost appears to be a highly efficient and safe method for upfront delivery of the tumor bed boost in high-risk breast cancer patients.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Radioterapia Adjuvante , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Doença Crônica , Terapia Combinada , Feminino , Seguimentos , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
8.
Radiother Oncol ; 142: 162-167, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629553

RESUMO

PURPOSE: To report the results of the first international pooled analysis of patients with glioblastoma treated with intraoperative radiotherapy (IORT) in addition to standard of care therapy. METHODS: Data from 51 patients treated at five centers in Germany, China and Peru were analyzed. All patients underwent tumor resection followed by a single application of IORT (10-40 Gy, prescribed to the applicator surface) with low-energy X-rays. Thereafter, standard adjuvant radiochemotherapy and maintenance chemotherapy were applied. Factors of interest were overall survival (OS), progression-free survival (PFS), local PFS (L-PFS; defined as appearance of new lesions ≤1 cm to the cavity border) and distant PFS (D-PFS; lesions >1 cm). The same endpoints were estimated at 1-, 2- and 3-years using the Kaplan-Meier method. Additionally, rates and severity (as per Common Terminology Criteria for Adverse Events Version 5.0) of radionecrosis (RN) were analyzed. RESULTS: The median age was 55 years (range: 16-75) and the median Karnofsky Performance Status was 80 (20-100). At a median follow-up of 18.0 months (2-42.4), the median OS, PFS, L-PFS and D-PFS were 18.0 months (95% CI: 14.7-21.3), 11.4 months (95%CI: 7.58-15.22), 16 months (95%CI: 10.21-21.8) and 30.0 months (95%CI: 18.59 - 41.41), respectively. The estimated 1-, 2- and 3-year OS, PFS, L-PFS and D-PFS were 79.5%, 38.7% and 25.6%; 46.2%, 29.4%, and 5.9%; 60.9, 37.9%, and 12.6%; and 76.7%, 65.0%, and 39.0% respectively. First progression occurred locally in only 35.3% of cases. Grade 1 RN was detected in 7.8% and grade 3 in 17.6% of the patients. No grade 4 toxicity was reported and no treatment-related deaths occurred. CONCLUSION: Compared to historical data, this pooled analysis suggests improved efficacy and safety of IORT with low-energy X-rays for newly diagnosed glioblastoma. Prospective data is warranted to confirm these findings.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Glioblastoma/radioterapia , Glioblastoma/cirurgia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/patologia , China , Intervalo Livre de Doença , Feminino , Alemanha , Glioblastoma/patologia , Humanos , Cuidados Intraoperatórios/métodos , Avaliação de Estado de Karnofsky , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Peru , Intervalo Livre de Progressão , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Adulto Jovem
9.
BMC Cancer ; 19(1): 430, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072314

RESUMO

BACKGROUND: The spine is the most frequent location of bone metastases. Local treatment aims at palliation of pain and, given the increased likelihood of long-term cancer survival, at local control. Kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provided instantaneous pain relief in 70% of patients at the first day after the intervention and resulted in local control rates of > 93% at 1 year in a recently conducted phase I/II trial. To assess its clinical value, we designed a phase III trial which tests Kypho-IORT against the most widespread standard-of-care, external beam radiotherapy (EBRT), in patients with painful vertebral metastases. METHODS: This phase III study includes patients ≥50 years of age with up to 4 vertebral metastases and a pain score of at least 3/10 points on the visual/numeric analogy scale (VAS). Patients randomized into the experimental arm (A) will undergo Kypho-IORT (Kyphoplasty plus IORT with 8 Gy prescribed to 13 mm depth). Patients randomized into the control arm (B) will receive EBRT with either 30 Gy in 10 fractions or 8 Gy as a single dose. The primary end point is pain reduction defined as at least - 3 points on the VAS compared to baseline at day 1. Assuming that 40% of patients in the Kypho-IORT arm and 5% of patients in the control arm will achieve this reduction and 20% will drop out, a total of 54 patients will have to be included to reach a power of 0.817 with a two-sided alpha of 0.05. Secondary endpoints are evaluation of the percentage of patients with a pain reduction of at least 3 points at 2 and 6 weeks, local tumor control, frequency of re-intervention, secondary fractures/sintering, complication rates, skin toxicity/wound healing, progression-free survival (PFS), overall survival (OS) and quality of life. DISCUSSION: This trial will generate level 1 evidence on the clinical value of a one-stop procedure which may provide instantaneous pain relief, long-term control and shortened intervals to further adjuvant (systemic) therapies in patients with spinal metastases. TRIAL REGISTRATION: Registered with ClinicalTrials.gov, number: NCT02773966 (Registration date: 05/16/2016).


Assuntos
Dor do Câncer/terapia , Cuidados Intraoperatórios/métodos , Cifoplastia/métodos , Manejo da Dor/métodos , Neoplasias da Coluna Vertebral/terapia , Dor do Câncer/diagnóstico , Dor do Câncer/etiologia , Ensaios Clínicos Fase III como Assunto , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Humanos , Pessoa de Meia-Idade , Medição da Dor , Intervalo Livre de Progressão , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/secundário , Coluna Vertebral/efeitos da radiação , Coluna Vertebral/cirurgia
10.
Radiother Oncol ; 135: 78-85, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015174

RESUMO

PURPOSE: Lung tumors treated with hypo-fractionated deep-inspiration breath-hold stereotactic body radiotherapy benefit from fast imaging and treatment. Single breath-hold cone-beam-CT (CBCT) could reduce motion artifacts and improve treatment precision. Thus, gantry speed was accelerated to 18°/s, limiting acquisition time to 10-20 s. Image quality, dosimetry and registration accuracy were compared with standard-CBCT (3°/s). METHODS AND MATERIALS: For proof-of-concept, image quality was analyzed following customer acceptance tests, CT-dose index measured, and registration accuracy determined with an off-centered ball-bearing-phantom. A lung-tumor patient was simulated with differently shaped tumor-mimicking inlays in a thorax-phantom. Signal-to-noise-ratio, contrast-to-noise-ratio and geometry of the inlays quantified image quality. Dose was measured in representative positions. Registration accuracy was determined with inlays scanned in pre-defined positions. Manual, automatic (clinical software) and objective-automatic (in-house-developed) registration was performed on planning-CT, offsets between results and applied shifts were compared. RESULTS: Image quality of ultrafast-CBCT was adequate for high-contrast areas, despite contrast-reduction of ∼80% due to undersampling. Dose-output was considerably reduced by 60-83% in presented setup; variations are due to gantry-braking characteristics. Registration accuracy was maintained better than 1 mm, mean displacement errors were 0.0 ±â€¯0.2 mm with objective-automatic registration. Ultrafast-CBCT showed no significant registration differences to standard-CBCT. CONCLUSIONS: This study of first tests with faster gantry rotation of 18°/s showed promising results for ultrafast high-contrast lung tumor CBCT imaging within single breath-hold of 10-20 s. Such fast imaging times, in combination with fast treatment delivery, could pave the way for intra-fractional combined imaging and treatment within one breath-hold phase, and thus mitigate residual motion and increase treatment accuracy and patient comfort. Even generally speaking, faster gantry rotation could set a benchmark with immense clinical impact where time matters most: palliative patient care, general reduction in uncertainty, and increase in patient throughput especially important for emerging markets with high patient numbers.


Assuntos
Suspensão da Respiração , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Pulmonares/radioterapia , Radioterapia Guiada por Imagem/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Aceleradores de Partículas , Imagens de Fantasmas , Dosagem Radioterapêutica , Rotação
11.
Strahlenther Onkol ; 195(7): 640-647, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30796496

RESUMO

PURPOSE: Partial breast irradiation using intraoperative radiotherapy (IORT) after breast-conserving surgery could be sufficient for a selected group of breast cancer patients. We report the results of a cohort of patients from a single center treated as part of the randomized phase-3 TARGIT-A trial. METHODS: Patients (≥50 years) with cT1 cN0 cM0 and invasive ductal histology on biopsy were randomized between IORT with 20 Gy (arm-A) or postoperative whole-breast RT (WBRT) up to 56 Gy in 2 Gy fractions (arm-B). Postoperatively, patients in arm-A with multifocality, lymphovascular invasion, nodal invasion, extensive intraductal component, invasive lobular carcinoma, or resection margins <1 cm received additional postoperative WBRT. RESULTS: Between 2002 and 2012, 184 patients were randomized, of whom 90 in arm-A and 90 in arm-B were evaluated. Median follow-up was 8.5 years. The 5­year overall survival was 94.4% in arm-A and 93.3% in arm-B (p = 0.73). Two local recurrences were observed: one at 70.3 months in an arm-A patient who received IORT + WBRT and another at 4.5 months in an arm-B patient who refused all forms of adjuvant treatment, thus resulting in a 5-year local recurrence of 0% in arm-A and 1.1% in arm-B. The 5­year in-breast recurrence (outside of the index quadrant) was 0% in arm-A and 1.2% in arm-B. Salvage mastectomy was performed successfully in all patients with relapse. CONCLUSION: Long-term follow-up of this single-center cohort consolidates the earlier reports of low local recurrence rates after single-dose IORT. Our results are in line with non-inferiority of risk-adapted IORT for selected patients with early breast cancer.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Mastectomia Segmentar , Terapia Neoadjuvante , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Estudos de Coortes , Terapia Combinada , Seguimentos , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Taxa de Sobrevida
12.
Neurosurgery ; 84(1): 41-49, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29528443

RESUMO

BACKGROUND: The median time to recurrence of glioblastoma (GB) following multimodal treatment is ∼7 mo. Nearly all cancers recur locally, suggesting that augmenting local treatments may improve outcomes. OBJECTIVE: To investigate whether intraoperative radiotherapy (IORT) to the resection cavity is safe and effective. METHODS: INTRAGO was a phase I/II trial to evaluate the safety and tolerability of IORT with 20 to 40 Gy of low-energy photons in addition to standard radiochemotherapy (ClinicalTrials.gov ID, NCT02685605). The primary endpoint was safety as per occurrence of dose-limiting toxicities. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also performed an exploratory analysis of the local PFS (L-PFS), defined as recurrence within 1 cm of the treated margin. RESULTS: Fifteen patients were treated at 3 dose levels. Of these, 13 underwent incomplete resection, 6 had unresected satellites, and 3 did not receive per-protocol treatment (PPT). The MGMT promoter was unmethylated in 10 patients. The median follow-up was 13.8 mo. The majority of grade 3 to 5 adverse events were deemed unrelated to IORT. Five cases of radionecrosis were observed, 2 were classified as grade 3 events. Other grade 3 events judged related to radiotherapy (external-beam radiotherapy and/or IORT) were wound dehiscence (n = 1), CSF leakage (n = 1), cyst formation (n = 1). No IORT-related deaths occurred. The median PFS was 11.2 mo (95% confidence interval [CI]: 5.4-17.0) for all patients and 11.3 mo (95% CI: 10.9-11.6) for those receiving PPT. The median L-PFS was 14.3 mo (95% CI: 8.4-20.2) for all patients and 17.8 mo (95% CI: 9.7-25.9) for those receiving PPT. The median OS was 16.2 mo (95% CI: 11.1-21.4) for all patients and 17.8 mo (95% CI: 13.9-21.7) for those receiving PPT. CONCLUSION: These data suggest that IORT is associated with manageable toxicity. Considering the limitations of a 15-patient phase I/II trial, further studies aimed at assessing an outcome benefit are warranted.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Cuidados Intraoperatórios , Radioterapia/métodos , Idoso , Quimiorradioterapia , Terapia Combinada , Relação Dose-Resposta à Radiação , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radioterapia/efeitos adversos , Resultado do Tratamento
13.
Radiat Oncol ; 11: 16, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26830843

RESUMO

PURPOSE: A method is presented to radiobiologically compare sequential (SEQ) and simultaneously integrated boost (SIB) breast radiotherapy. METHODS: The method is based on identically prescribed biologically effective dose (iso-BED) which was achieved by different prescribed doses due to different fractionation schemes. It is performed by converting the calculated three-dimensional dose distribution to the corresponding BED distribution taking into consideration the different number of fractions for generic α/ß ratios. A cumulative BED volume histogram (BEDVH) is then derived from the BED distribution and is compared for the two delivery schemes. Ten breast cancer patients (4 right-sided and 6 left-sided) were investigated. Two tangential intensity modulated whole breast beams with two other oblique (with different gantry angles) beams for the boost volume were used. The boost and the breast target volumes with either α/ß = 10 or 3 Gy, and ipsi-lateral and contra-lateral lungs, heart, and contra-lateral breast as organs at risk (OARs) with α/ß = 3 Gy were compared. RESULTS: Based on the BEDVH comparisons, the use of SIB reduced the biological breast mean dose by about 3 %, the ipsi-lateral lung and heart by about 10 %, and contra-lateral breast and lung by about 7 %. CONCLUSION: BED based comparisons should always be used in comparing plans that have different fraction sizes. SIB schemes are dosimetrically more advantageous than SEQ in breast target volume and OARs for equal prescribed BEDs for breast and boost.


Assuntos
Neoplasias da Mama/radioterapia , Dosagem Radioterapêutica , Radioterapia/métodos , Fracionamento da Dose de Radiação , Feminino , Humanos , Imageamento Tridimensional , Modelos Estatísticos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Eficiência Biológica Relativa , Estudos Retrospectivos , Risco , Software , Tomografia Computadorizada por Raios X
14.
Radiat Oncol ; 10: 139, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-26156086

RESUMO

PURPOSE: To dosimetrically evaluate different breast SIB techniques with respect to target coverage and organs at risk (OARs) doses. METHODS: Four IMRT techniques were compared in 12 patients. Three techniques employ tangential whole breast irradiation with either two coplanar fields (T-2F), or four non-coplanar fields (T-NC), or one Volumetric Modulated Arc Therapy (T-VMAT) for the boost volume. The fourth technique is a fully-modulated VMAT technique (f-VMAT). Dosimetric parameters were compared for the boost and breast target volumes as well as OARs. Delivery efficiency was analysed based on number of monitor units (MUs) and estimated delivery time. RESULTS: T-VMAT and f-VMAT ranked highest with respect to integral assessment of boost and breast treatment quality measures. T-VMAT significantly outperformed f-VMAT with respect to ipsi-lateral lung and left-sided patients' heart volumes ≥ 5 Gy (35 % ± 5 % vs. 52 % ± 6 % and 11 % ± 5 % vs. 22 % ± 6 %, respectively). f-VMAT significantly outperformed T-VMAT with respect to ipsi-lateral lung volume ≥ 20 Gy (13 % ± 2 % vs. 15 % ± 3 %) and heart volume ≥ 30 Gy in left breast cancer (0 % ± 0 % vs. 1 % ± 1 %). T-VMAT and f-VMAT needed 442 ± 58 and 1016 ± 152 MUs, respectively. CONCLUSIONS: The hybrid T-VMAT is considered the technique of choice due to its balance of quality, efficiency and dose to OARs.


Assuntos
Neoplasias da Mama/radioterapia , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Adulto , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Amostragem , Tomografia Computadorizada por Raios X , Carga Tumoral
15.
BMC Cancer ; 14: 992, 2014 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-25535398

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent primary malignant brain tumor in adults. Despite multimodal therapies, almost all GBM recur within a narrow margin around the initial resected lesion. Thus, novel therapeutic intensification strategies must target both, the population of dispersed tumor cells around the cavity and the postoperative microenvironment. Intraoperative radiotherapy (IORT) is a pragmatic and effective approach to sterilize the margins from persistent tumor cells, abrogate post-injury proliferative stimuli and to bridge the therapeutic gap between surgery and radiochemotherapy. Therefore, we have set up INTRAGO, a phase I/II dose-escalation study to evaluate the safety and tolerability of IORT added to standard therapy in newly diagnosed GBM. In contrast to previous approaches, the study involves the application of isotropic low-energy (kV) x-rays delivered by spherical applicators, providing optimal irradiation properties to the resection cavity. METHODS/DESIGN: INTRAGO includes patients aged 50 years or older with a Karnofsky performance status of at least 50% and a histologically confirmed (frozen sections) supratentorial GBM. Safety and tolerability (i.e., the maximum tolerated dose, MTD) will be assessed using a classical 3 + 3 dose-escalation design. Dose-limiting toxicities (DLT) are wound healing deficits or infections requiring surgical intervention, IORT-related cerebral bleeding or ischemia, symptomatic brain necrosis requiring surgical intervention and early termination of external beam radiotherapy (before the envisaged dose of 60 Gy) due to radiotoxicity. Secondary end points are progression-free and overall survival. TRIAL REGISTRATION: The study is registered with clinicaltrials.gov, number: NCT02104882 (Registration Date: 03/26/2014).


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Protocolos Clínicos , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Cuidados Intraoperatórios , Terapia Combinada , Humanos , Radiografia , Dosagem Radioterapêutica
16.
Strahlenther Onkol ; 190(10): 864-6, 868-71, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25209551

RESUMO

PURPOSE: Hodgkin lymphoma (HL) is a highly curable disease. Reducing late complications and second malignancies has become increasingly important. Radiotherapy target paradigms are currently changing and radiotherapy techniques are evolving rapidly. DESIGN: This overview reports to what extent target volume reduction in involved-node (IN) and advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy-compared with involved-field (IF) and 3D radiotherapy (3D-RT)- can reduce high doses to organs at risk (OAR) and examines the issues that still remain open. RESULTS: Although no comparison of all available techniques on identical patient datasets exists, clear patterns emerge. Advanced dose-calculation algorithms (e.g., convolution-superposition/Monte Carlo) should be used in mediastinal HL. INRT consistently reduces treated volumes when compared with IFRT with the exact amount depending on the INRT definition. The number of patients that might significantly benefit from highly conformal techniques such as IMRT over 3D-RT regarding high-dose exposure to organs at risk (OAR) is smaller with INRT. The impact of larger volumes treated with low doses in advanced techniques is unclear. The type of IMRT used (static/rotational) is of minor importance. All advanced photon techniques result in similar potential benefits and disadvantages, therefore only the degree-of-modulation should be chosen based on individual treatment goals. Treatment in deep inspiration breath hold is being evaluated. Protons theoretically provide both excellent high-dose conformality and reduced integral dose. CONCLUSION: Further reduction of treated volumes most effectively reduces OAR dose, most likely without disadvantages if the excellent control rates achieved currently are maintained. For both IFRT and INRT, the benefits of advanced radiotherapy techniques depend on the individual patient/target geometry. Their use should therefore be decided case by case with comparative treatment planning.


Assuntos
Doença de Hodgkin/radioterapia , Linfonodos/efeitos da radiação , Neoplasias do Mediastino/radioterapia , Oncologia/normas , Guias de Prática Clínica como Assunto , Radioterapia Conformacional/métodos , Radioterapia Conformacional/normas , Medicina Baseada em Evidências , Alemanha , Humanos , Resultado do Tratamento
17.
J Appl Clin Med Phys ; 15(1): 4502, 2014 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-24423847

RESUMO

The use of IORT as a treatment modality for patients with close or positive margins has increased over the past decade. For situations where a flat area (up to 6 cm in diameter) has to be treated intraoperatively, new applicators for superficial treatment with a miniature X-ray source (INTRABEAM system) were developed. Here we report our evaluation of the dosimetric characteristics of these new applicators and their first clinical use. Each of these flat and surface applicators consists of a radiation protective metal tube and a flattening filter, which converts the spherical dose distribution of the X-ray source into a flat one. The homogeneity of each dose distribution and depth-dose measurements were evaluated using film dosimetry in a solid water phantom and a soft X-ray ionization chamber in a water tank. The first patient was treated with 5 Gy delivered in 5 mm using a 4 cm FLAT applicator over 21 minutes. The flat applicators show the maximum homogeneity, with a uniformity ratio of 1.02-1.08 in certain depths. In 1 mm depth surface applicators show a uniformity ratio of 1.15-1.28. They also show a higher dose rate and a steeper dose gradient compared to the flat applicators. The results of this investigation demonstrated that the flat and surface applicators have unique dosimetric characteristics that need to be considered during the treatment planning stages. This work also showed that it is possible to perform a superficial localized IORT which provides new application possibilities for use of the INTRABEAM system.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Mastectomia , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Terapia Combinada , Feminino , Humanos , Período Intraoperatório , Imageamento por Ressonância Magnética , Prognóstico , Dosagem Radioterapêutica , Raios X
18.
Radiother Oncol ; 110(3): 471-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24444525

RESUMO

PURPOSE: Second cancer risk after breast conserving therapy is becoming more important due to improved long term survival rates. In this study, we estimate the risks for developing a solid second cancer after radiotherapy of breast cancer using the concept of organ equivalent dose (OED). MATERIALS AND METHODS: Computer-tomography scans of 10 representative breast cancer patients were selected for this study. Three-dimensional conformal radiotherapy (3D-CRT), tangential intensity modulated radiotherapy (t-IMRT), multibeam intensity modulated radiotherapy (m-IMRT), and volumetric modulated arc therapy (VMAT) were planned to deliver a total dose of 50 Gy in 2 Gy fractions. Differential dose volume histograms (dDVHs) were created and the OEDs calculated. Second cancer risks of ipsilateral, contralateral lung and contralateral breast cancer were estimated using linear, linear-exponential and plateau models for second cancer risk. RESULTS: Compared to 3D-CRT, cumulative excess absolute risks (EAR) for t-IMRT, m-IMRT and VMAT were increased by 2 ± 15%, 131 ± 85%, 123 ± 66% for the linear-exponential risk model, 9 ± 22%, 82 ± 96%, 71 ± 82% for the linear and 3 ± 14%, 123 ± 78%, 113 ± 61% for the plateau model, respectively. CONCLUSION: Second cancer risk after 3D-CRT or t-IMRT is lower than for m-IMRT or VMAT by about 34% for the linear model and 50% for the linear-exponential and plateau models, respectively.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias Induzidas por Radiação , Segunda Neoplasia Primária/etiologia , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Risco
19.
Radiat Oncol ; 8: 276, 2013 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-24279376

RESUMO

PURPOSE: Evaluation of dose escalated salvage radiotherapy (SRT) in patients after radical prostatectomy (RP) who had never received antihormonal therapy. To investigate prognostic factors of the outcome of SRT and to analyze which patient subsets benefit most from dose escalation. MATERIALS AND METHODS: Between 2002 and 2008, 76 patients were treated in three different dose-groups: an earlier cohort treated with 66 Gy irrespective of pre-RT-characteristics and two later cohorts treated with 70 Gy or 75 Gy depending on pre-RT-characteristics. Biochemical-relapse-free-survival (bRFS), clinical-relapse-free-survival (cRFS) and late toxicity were evaluated. RESULTS: Four-year bRFS and cRFS were 62.5% and 85%. Gleason score <8, positive surgical resection margin (PSRM) and low PSA (≤0.5 ng/ml) before SRT resulted in higher bRFS. Analysis of the whole group showed no clear dose-outcome relationship. Patients with PSRM, however, had improved bRFS when escalating >66 Gy. While > 70 Gy did not improve the overall results, 4-year bRFS for patients with manifest local recurrence in the high-dose group was still comparable to those without manifest local recurrences. No grade 4 and minimal grade 3 gastrointestinal and urinary toxicity were observed. CONCLUSIONS: Dose-escalated SRT achieves high biochemical control. The data strongly support the application of at least 70 Gy rather than 66 Gy. They do not prove positive effects of doses >70 Gy but do not disprove them as these doses were only applied to an unfavorable patients selection.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia/métodos , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Dosagem Radioterapêutica , Recidiva , Terapia de Salvação/métodos , Resultado do Tratamento
20.
Radiother Oncol ; 109(1): 152-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24100152

RESUMO

PURPOSE: To estimate the risk of undertreatment in hippocampal-sparing whole brain radiotherapy (HS-WBRT). METHODS: Eight hundred and fifty six metastases were contoured together with the hippocampi in cranial MRIs of 100 patients. For each metastasis, the distance to the closest hippocampus was calculated. Treatment plans for 10 patients were calculated and linear dose profiles were established. For SCLC and NSCLC, dose-response curves were created based on data from studies on prophylactic cranial irradiation, allowing estimating the risk for intracranial failure. RESULTS: Only 0.4% of metastases were located inside a hippocampus in 3% of all patients. SCLC showed a relatively high rate of hippocampal metastasis (18.2% of all SCLC patients) and HS-WBRT in a commonly applied fractionation scheme would increase the risk for brain relapse by ∼4% compared to conventional WBRT. NSCLC showed a lower rate of brain metastasis in the hippocampi (2.8%) and HS-WBRT would account for a slightly increased absolute risk of 0.2%. CONCLUSIONS: Prophylactic or therapeutic HS-WBRT is expected to be associated with a low risk of undertreatment. For SCLC, it bears a minimally elevated risk of failure compared to standard WBRT. In NSCLC, HS-WBRT is most likely not associated with a clinically relevant increase in risk of failure.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana , Hipocampo/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Relação Dose-Resposta à Radiação , Feminino , Hipocampo/patologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Risco
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