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1.
J Appl Clin Med Phys ; 24(3): e13829, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36808798

RESUMEN

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines (MPPGs) will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: (1) Must and must not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. (2) Should and should not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee April 28, 2022.


Asunto(s)
Braquiterapia , Oncología por Radiación , Humanos , Estados Unidos , Física Sanitaria/educación , Sociedades
2.
J Neurooncol ; 113(3): 467-77, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23673513

RESUMEN

To determine whether immediate post-operative brachytherapy can be safely applied to newly diagnosed glioblastomas to retard tumor progression prior to initiation of external beam radiation therapy (EBRT) and temozolomide. Between 1996 and 2011, eleven patients underwent implantation of GliaSite (n = 9) or MammoSite (n = 2) at the time of surgical resection. Brachytherapy was carried out on post-operative day 2-3, with 45-60 Gy delivered to a 1 cm margin. All patients underwent subsequent standard radiation/temozolomide treatment 4-5 weeks post-irradiation. There were no wound related complications. Toxicity was observed in two patients (2/11 or 18 %), including one post-operative seizure and one case of cerebral edema that resolved after a course of steroid treatment. Immediate post-operative and pre-irradiation/temozolomide magnetic resonance imaging assessment was available for 9 of the 11 patients. Two of these nine patients (22 %) developed new regions of contrast enhancement prior to irradiation/temozolomide. This compares favorably to historical data where 53 % of patient suffer such tumor progression. While there was a trend toward improved 6 month progression free survival in the brachytherapy/temozolomide/radiation treated patients, the overall survival of these patients were comparable to historical controls. This case series demonstrates the safety of immediate post-operative brachytherapy when applied prior to EBRT and temozolomide in the treatment of newly diagnosed glioblastomas.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Braquiterapia , Neoplasias Encefálicas/terapia , Quimioradioterapia Adyuvante , Dacarbazina/análogos & derivados , Glioblastoma/terapia , Anciano , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Estudios de Casos y Controles , Dacarbazina/uso terapéutico , Femenino , Estudios de Seguimiento , Glioblastoma/diagnóstico , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico , Tasa de Supervivencia , Temozolomida
3.
Nat Commun ; 13(1): 3869, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35790753

RESUMEN

Locally advanced cancers remain therapeutically challenging to eradicate. The most successful treatments continue to combine decades old non-targeted chemotherapies with radiotherapy that unfortunately increase normal tissue damage in the irradiated field and have systemic toxicities precluding further treatment intensification. Therefore, alternative molecularly guided systemic therapies are needed to improve patient outcomes when applied with radiotherapy. In this work, we report a trimodal precision cytotoxic chemo-radio-immunotherapy paradigm using spatially targeted auristatin warheads. Tumor-directed antibodies and peptides conjugated to radiosensitizing monomethyl auristatin E (MMAE) specifically produce CD8 T cell dependent durable tumor control of irradiated tumors and immunologic memory. In combination with ionizing radiation, MMAE sculpts the tumor immune infiltrate to potentiate immune checkpoint inhibition. Here, we report therapeutic synergies of targeted cytotoxic auristatin radiosensitization to stimulate anti-tumor immune responses providing a rationale for clinical translational of auristatin antibody drug conjugates with radio-immunotherapy combinations to improve tumor control.


Asunto(s)
Inmunoconjugados , Neoplasias , Aminobenzoatos , Anticuerpos Antineoplásicos , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Inmunoterapia , Neoplasias/terapia , Oligopéptidos , Péptidos
4.
Brachytherapy ; 19(6): 874-880, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32950407

RESUMEN

Developing any new radiation oncology program requires planning and analysis of the current state of the facility and its capacity to take on another program. Staff must consider a large number of factors to establish a feasible, safe, and sustainable program. We present a simple and generic outline that lays out the process for developing and implementing a new HDR brachytherapy program in any setting, but with particular emphasis on challenges associated with starting the program in a limited resource setting. The sections include feasibility of a program, starting cases, machine and equipment selection, and quality and safety.


Asunto(s)
Braquiterapia , Desarrollo de Programa/métodos , Oncología por Radiación/organización & administración , Braquiterapia/efectos adversos , Braquiterapia/instrumentación , Braquiterapia/métodos , Braquiterapia/normas , Humanos , Garantía de la Calidad de Atención de Salud , Oncología por Radiación/educación , Dosificación Radioterapéutica , Administración de la Seguridad
5.
Mol Cancer Ther ; 19(1): 157-167, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31597712

RESUMEN

The most successful therapeutic strategies for locally advanced cancers continue to combine decades-old classical radiosensitizing chemotherapies with radiotherapy. Molecular targeted radiosensitizers offer the potential to improve the therapeutic ratio by increasing tumor-specific kill while minimizing drug delivery and toxicity to surrounding normal tissue. Auristatins are a potent class of anti-tubulins that sensitize cells to ionizing radiation damage and are chemically amenable to antibody conjugation. To achieve tumor-selective radiosensitization, we synthesized and tested anti-HER2 antibody-drug conjugates of two auristatin derivatives with ionizing radiation. Monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) were attached to the anti-HER2 antibodies trastuzumab and pertuzumab through a cleavable linker. While MMAE is cell permeable, MMAF has limited cell permeability as free drug resulting in diminished cytotoxicity and radiosensitization. However, when attached to trastuzumab or pertuzumab, MMAF was as efficacious as MMAE in blocking HER2-expressing tumor cells in G2-M. Moreover, MMAF anti-HER2 conjugates selectively killed and radiosensitized HER2-rich tumor cells. Importantly, when conjugated to targeting antibody, MMAF had the advantage of decreased bystander and off-target effects compared with MMAE. In murine xenograft models, MMAF anti-HER2 antibody conjugates had less drug accumulated in the normal tissue surrounding tumors compared with MMAE. Therapeutically, systemically injected MMAF anti-HER2 conjugates combined with focal ionizing radiation increased tumor control and improved survival of mice with HER2-rich tumor xenografts. In summary, our results demonstrate the potential of cell-impermeable radiosensitizing warheads to improve the therapeutic ratio of radiotherapy by leveraging antibody-drug conjugate technology.


Asunto(s)
Aminobenzoatos/uso terapéutico , Quimioradioterapia/métodos , Oligopéptidos/uso terapéutico , Receptor ErbB-2/metabolismo , Aminobenzoatos/farmacología , Animales , Femenino , Humanos , Ratones , Ratones Desnudos , Oligopéptidos/farmacología , Permeabilidad , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Radiother Oncol ; 90(1): 36-42, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18952310

RESUMEN

PURPOSE: To present the clinical implementation of a new HDR device for partial breast irradiation, the Strut-Adjusted Volume Implant (SAVI), at the University of California, San Diego. METHODS AND MATERIALS: The SAVI device has multiple peripheral struts that can be differentially loaded with the HDR source. Planning criteria used for evaluation of the treatment plans included the following dose volume histogram (DVH) criteria: V90 >90%, V150 <50cc and V200 <20cc. RESULTS: SAVI has been used on 20 patients to date at UC San Diego. In each case, the dose was modulated according to patient-specific anatomy to cover the tumor bed, while sparing normal tissues. The dosimetric data show that we can achieve greater than 90% coverage with respect to V90 (median of 95.3%) and also keep a low V150 and V200 dose at 24.5 and 11.2cc, respectively. Complete treatment can be done within a 30-min time slot, which includes implant verification, setup, and irradiation time as well as wound dressing. CONCLUSION: SAVI has been implemented at UC San Diego for accelerated partial breast irradiation with excellent tumor bed conformance and minimal normal tissue exposure. Patient positioning is the key to identifying any inter-fraction device motion. Device asymmetry or tissue conformance has been shown to resolve itself 24h after the device implantation. The device can be implemented into an existing HDR program with minimal effort.


Asunto(s)
Braquiterapia/instrumentación , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Diseño de Equipo , Femenino , Humanos , Radiografía Intervencional , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
7.
Brachytherapy ; 8(2): 207-209, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19230788

RESUMEN

INTRODUCTION: With the publication of several trials demonstrating equivalence between partial breast irradiation and whole breast irradiation, the popularity of partial breast radiation has increased. Methods of delivery include interstitial brachytherapy, intracavitary brachytherapy, and 3D conformal irradiation, although the least amount of data exists on 3D conformal. Despite the relative paucity of data on 3D conformal, it is the most common method delivered on the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 trial. To date, minimal toxicities and good cosmetic results have been associated with accelerated partial breast irradiation. METHODS AND MATERIAL: In this case study, we present a 64-year-old female patient, diagnosed with Grade 1 tubular carcinoma, who developed both expected and unexpected toxicities after 3D conformal accelerated partial breast irradiation. DISCUSSION/RESULTS/CONCLUSION: Along with chest wall pain, she developed hyperpigmentation of the skin as well as fibrosis of the skin, pectoralis minor, and pectoralis major. The fibrosis she developed limited her comfortable range of motion in the ipsilateral arm. She also developed symptomatic fractures of the fourth and fifth ribs in the anterior axillary line. Upon fusing the treatment-planning CT with a diagnostic CT, it was evident that the rib fractures fell within the 100% isodose line of the 3D conformal plan.


Asunto(s)
Adenocarcinoma/radioterapia , Neoplasias de la Mama/radioterapia , Hiperpigmentación/etiología , Radiodermatitis/complicaciones , Radioterapia Conformacional/efectos adversos , Piel/efectos de la radiación , Adenocarcinoma/diagnóstico , Biopsia , Mama , Neoplasias de la Mama/diagnóstico , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Humanos , Hiperpigmentación/patología , Mamografía , Persona de Mediana Edad , Radiodermatitis/patología , Piel/patología , Tomografía Computarizada por Rayos X
8.
Brachytherapy ; 18(4): 429-436, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30979631

RESUMEN

PURPOSE: The purpose of this study was to report a list of accepted fractionation schemes for high-dose-rate (HDR) brachytherapy for gynecological cancers in a definitive, neoadjuvant, or adjuvant setting. METHODS AND MATERIALS: Members of the American Brachytherapy Society (ABS) Task Force with expertise in gynecological brachytherapy reviewed the literature and existing ABS guidelines regarding various dose-fractionation schedules for HDR brachytherapy to create this compendium. Other resources include current guidelines published by medical societies, clinical trials, the published medical literature, and the clinical experience of the ABS Task Force members. The ABS consensus statements for HDR brachytherapy practice were reviewed for these fractionation schemes and form the major source for this report. Specific recommendations for therapy and recommendations for further investigations were made when there was agreement. RESULTS: A variety of dose-fractionation schedules for HDR brachytherapy alone or integrating brachytherapy with external-beam radiation exist. The choice of a given fractionation schedule may be appropriate depending on the practice situation for the patient and the resources available. While there is no single optimal dose-fractionation scheme for any disease site or clinical situation, higher doses per fraction with fewer fractions per regimen have been known to increase toxicity. The corresponding 2-Gray (Gy) per fraction radiobiologic equivalent doses have been provided (normalized therapy dose) to compare the various regimens where indicated and can be used to estimate isoeffective schedules. CONCLUSIONS: This compendium of HDR brachytherapy fractionation schedules provides various options to the gynecologic brachytherapist and a ready reference for clinical use in the management of gynecological cancer treatments.


Asunto(s)
Braquiterapia/métodos , Fraccionamiento de la Dosis de Radiación , Neoplasias de los Genitales Femeninos/radioterapia , Femenino , Humanos , Terapia Neoadyuvante , Guías de Práctica Clínica como Asunto , Radiobiología , Radioterapia Adyuvante , Sociedades Médicas , Estados Unidos
9.
Brachytherapy ; 15(5): 570-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27364873

RESUMEN

PURPOSE: There is a lack of prescriptive, practical information for those doing the work of commissioning high-dose-rate (HDR) gynecologic (GYN) treatment equipment. The purpose of this work is to develop a vendor-neutral, consensus-based, commissioning template to improve standardization of the commissioning process. METHODS AND MATERIALS: A series of commissioning procedures and tests specific to HDR GYN treatments were compiled within one institution. The list of procedures and tests was then sent to five external reviewers at clinics engaged in HDR GYN treatments. External reviewers were asked to (1) suggest deletions, additions, and improvements/modifications to descriptions, (2) link the procedures and tests to common, severe failure modes based on their effectiveness at mitigating those failure modes, and (3) rank the procedures and tests based on perceived level of importance. RESULTS: External reviewers suggested the addition of 14 procedures and tests. The final template consists of 67 procedures and tests. "Treatment process" and "staff training" sections were identified as mitigating the highest number of commonly reported failure modes. The mean perceived importance for all procedures and tests was 4.4 of 5, and the mean for each section ranged from 3.6 to 4.8. Sections of the template that were identified as mitigating the highest number of commonly reported failure modes were not assigned the highest perceived importance. CONCLUSION: The commissioning template developed here provides a standardized approach to process and equipment commissioning. The discord between perceived importance and mitigation of the highest number of failure modes suggests that increased focus should be placed on procedures and tests in "treatment process" and "staff training" sections.


Asunto(s)
Braquiterapia/normas , Consenso , Neoplasias de los Genitales Femeninos/radioterapia , Braquiterapia/instrumentación , Braquiterapia/métodos , Femenino , Personal de Salud/educación , Humanos
10.
Int J Radiat Oncol Biol Phys ; 96(2): 440-448, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27598809

RESUMEN

PURPOSE: To perform a comprehensive comparative planning study evaluating the utility of the proposed direction modulated brachytherapy (DMBT) tandem applicator against standard applicators, in the setting of image guided adaptive brachytherapy of cervical cancer. METHODS AND MATERIALS: A detailed conceptual article was published in 2014. The proposed DMBT tandem applicator has 6 peripheral grooves of 1.3-mm width, along a 5.4-mm-thick nonmagnetic tungsten alloy rod of density 18.0 g/cm(3), capable of generating directional dose profiles. We performed a comparative planning study with 45 cervical cancer patients enrolled consecutively in the prospective observational EMBRACE study. In all patients, MRI-based planning was performed while utilizing various tandem-ring (27 patients) and tandem-ring-needles (18 patients) applicators, in accordance with the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology recommendations. For unbiased comparisons, all cases were replanned with an in-house-developed inverse optimization code while enforcing a uniform set of constraints that are reflective of the clinical practice. All plans were normalized to the same high-risk clinical target volume D90 values achieved in the original clinical plans. RESULTS: In general, if the standard tandem was replaced with the DMBT tandem while maintaining all other planning conditions the same, there was consistent improvement in the plan quality. For example, among the 18 tandem-ring-needles cases, the average D2cm(3) reductions achieved were -2.48% ± 11.03%, -4.45% ± 5.24%, and -5.66% ± 6.43% for the bladder, rectum, and sigmoid, respectively. An opportunity may also exist in avoiding use of needles altogether for when the total number of needles required is small (approximately 2 to 3 needles or less), if DMBT tandem is used. CONCLUSIONS: Integrating the novel DMBT tandem onto both intracavitary and intracavitary-interstitial applicator assembly enabled consistent improvement in the sparing of the OARs, over a standard "single-channel" tandem, though individual variations in benefit were considerable. Although at an early stage of development, the DMBT concept design is demonstrated to be useful and pragmatic for potential clinical translation.


Asunto(s)
Braquiterapia/instrumentación , Implantación de Prótesis/instrumentación , Radioisótopos/administración & dosificación , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/radioterapia , Braquiterapia/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Persona de Mediana Edad , Implantación de Prótesis/métodos , Dosificación Radioterapéutica
11.
Int J Radiat Oncol Biol Phys ; 93(1): 150-7, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26130230

RESUMEN

PURPOSE/OBJECTIVES: A report of clinical outcomes of a computed tomography (CT)-based image guided brachytherapy (IGBT) technique for treatment of cervical cancer. METHODS AND MATERIALS: Seventy-six women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma diagnosed between 2007 and 2014 were treated with definitive external beam radiation therapy (EBRT) with or without concurrent chemotherapy followed by high-dose-rate (HDR) IGBT. All patients underwent planning CT simulation at each implantation. A high-risk clinical target volume (HRCTV) encompassing any visible tumor and the entire cervix was contoured on the simulation CT. When available, magnetic resonance imaging (MRI) was performed at implantation to assist with tumor delineation. The prescription dose was prescribed to the HRCTV. RESULTS: The median follow-up time was 17 months. Thirteen patients (17%) had an MRI done before brachytherapy, and 16 patients (21%) were treated without MRI guidance. The mean EBRT/IGBT sum 2-Gy equivalent dose (EQD2) delivered to the 90% volume of the HRCTV was 86.3 Gy. The mean maximum EQD2s delivered to 2 cm(3) of the rectum, sigmoid, and bladder were 67.5 Gy, 66.2 Gy, and 75.3 Gy, respectively. The 2-year cumulative incidences of local, locoregional, and distant failure were 5.8% (95% confidence interval [CI]: 1.4%-14.8%), 15.1% (95% CI: 5.4%-29.4%), and 24.3% (95% CI: 12.1%-38.9%), respectively. The 2-year overall and disease-free survival rates were 75% (95% CI, 61%-91%) and 73% (95% CI, 60%-90%), respectively. Twenty-nine patients (38%) experienced grade ≥ 2 acute toxicity, with 5 cases of acute grade 3 toxicity and no grade ≥ 4 toxicities. One patient experienced grade 3 gastrointestinal toxicity. No other late grade ≥ 3 events were observed. CONCLUSIONS: This is the largest report to date of CT/MRI-based IGBT for the treatment of cervical cancer. The results are promising, with excellent local control and acceptable toxicity. Further investigation is needed to assess the long-term safety and efficacy of this treatment.


Asunto(s)
Braquiterapia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagen por Resonancia Magnética Intervencional/métodos , Persona de Mediana Edad , Dosificación Radioterapéutica , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Adulto Joven
12.
Cancer Res ; 75(7): 1376-1387, 2015 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-25681274

RESUMEN

Intrinsic tumor resistance to radiotherapy limits the efficacy of ionizing radiation (IR). Sensitizing cancer cells specifically to IR would improve tumor control and decrease normal tissue toxicity. The development of tumor-targeting technologies allows for developing potent radiosensitizing drugs. We hypothesized that the anti-tubulin agent monomethyl auristatin E (MMAE), a component of a clinically approved antibody-directed conjugate, could function as a potent radiosensitizer and be selectively delivered to tumors using an activatable cell-penetrating peptide targeting matrix metalloproteinases and RGD-binding integrins (ACPP-cRGD-MMAE). We evaluated the ability of MMAE to radiosensitize both established cancer cells and a low-passage cultured human pancreatic tumor cell line using clonogenic and DNA damage assays. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule- and dose-dependent manner, correlating with mitotic arrest. Radiosensitization was evidenced by decreased clonogenic survival and increased DNA double-strand breaks in irradiated cells treated with MMAE. MMAE in combination with IR resulted in increased DNA damage signaling and activation of CHK1. To test a therapeutic strategy of MMAE and IR, PANC-1 or HCT-116 murine tumor xenografts were treated with nontargeted free MMAE or tumor-targeted MMAE (ACPP-cRGD-MMAE). While free MMAE in combination with IR resulted in tumor growth delay, tumor-targeted ACPP-cRGD-MMAE with IR produced a more robust and significantly prolonged tumor regression in xenograft models. Our studies identify MMAE as a potent radiosensitizer. Importantly, MMAE radiosensitization can be localized to tumors by targeted activatable cell-penetrating peptides.


Asunto(s)
Oligopéptidos/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Animales , Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Péptidos de Penetración Celular/administración & dosificación , Quimioradioterapia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Roturas del ADN de Doble Cadena , Sistemas de Liberación de Medicamentos , Femenino , Células HCT116 , Humanos , Ratones , Ratones Desnudos , Oligopéptidos/administración & dosificación , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Tolerancia a Radiación , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Int J Radiat Oncol Biol Phys ; 89(3): 666-73, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24751413

RESUMEN

PURPOSE: To demonstrate that utilization of the direction-modulated brachytherapy (DMBT) concept can significantly improve treatment plan quality in the setting of high-dose-rate (HDR) brachytherapy for cervical cancer. METHODS AND MATERIALS: The new, MRI-compatible, tandem design has 6 peripheral holes of 1.3-mm diameter, grooved along a nonmagnetic tungsten-alloy rod (ρ = 18.0 g/cm(3)), enclosed in Delrin tubing (polyoxymethylene, ρ = 1.41 g/cm(3)), with a total thickness of 6.4 mm. The Monte Carlo N-Particle code was used to calculate the anisotropic (192)Ir dose distributions. An in-house-developed inverse planning platform, geared with simulated annealing and constrained-gradient optimization algorithms, was used to replan 15 patient cases (total 75 plans) treated with a conventional tandem and ovoids (T&O) applicator. Prescription dose was 6 Gy. For replanning, we replaced the conventional tandem with that of the new DMBT tandem for optimization but left the ovoids in place and kept the dwell positions as originally planned. All DMBT plans were normalized to match the high-risk clinical target volume V100 coverage of the T&O plans. RESULTS: In general there were marked improvements in plan quality for the DMBT plans. On average, D2cc for the bladder, rectum, and sigmoid were reduced by 0.59 ± 0.87 Gy (8.5% ± 28.7%), 0.48 ± 0.55 Gy (21.1% ± 27.2%), and 0.10 ± 0.38 Gy (40.6% ± 214.9%) among the 75 plans, with best single-plan reductions of 3.20 Gy (40.8%), 2.38 Gy (40.07%), and 1.26 Gy (27.5%), respectively. The high-risk clinical target volume D90 was similar, with 6.55 ± 0.96 Gy and 6.59 ± 1.06 Gy for T&O and DMBT, respectively. CONCLUSIONS: Application of the DMBT concept to cervical cancer allowed for improved organ at risk sparing while achieving similar target coverage on a sizeable patient population, as intended, by maximally utilizing the anatomic information contained in 3-dimensional imaging. A series of mechanical and clinical validations are to be followed.


Asunto(s)
Braquiterapia/métodos , Imagen por Resonancia Magnética , Órganos en Riesgo/efectos de la radiación , Traumatismos por Radiación/prevención & control , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias del Cuello Uterino/radioterapia , Adulto , Algoritmos , Braquiterapia/instrumentación , Colon Sigmoide/efectos de la radiación , Diseño de Equipo , Femenino , Humanos , Radioisótopos de Iridio/uso terapéutico , Persona de Mediana Edad , Método de Montecarlo , Dosificación Radioterapéutica , Recto/efectos de la radiación , Tungsteno , Vejiga Urinaria/efectos de la radiación , Adulto Joven
14.
Med Dosim ; 37(1): 9-14, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-21458981

RESUMEN

The SAVI and Contura breast brachytherapy applicators represent 2 recent advancements in brachytherapy technology that have expanded the number of women eligible for accelerated partial breast irradiation in the treatment of early-stage breast cancer. Early clinical experience with these 2 single-entry, multichannel high-dose-rate brachytherapy devices confirms their ease of use and dosimetric versatility. However, current clinical guidelines for SAVI and Contura brachytherapy may result in a smaller or less optimal volume of treated tissue compared with traditional interstitial brachytherapy. This study evaluates the feasibility of using the SAVI and Contura to irradiate larger and irregularly shaped target volumes, approaching what is treatable with the interstitial technique. To investigate whether additional tissue can be treated, 17 patients treated with the SAVI and 3 with the Contura were selected. For each patient, the planning target volume (PTV) was modified to extend 1.1 cm, 1.3 cm, and 1.5 cm beyond the tumor bed cavity. To evaluate dose conformance to an irregularly shaped target volume, 9 patients treated with the SAVI and 3 with the Contura were selected from the original 20 patients. The following asymmetric PTV margin combinations were assessed for each patient: 1.5/0.3, 1.3/0.3, and 1.1/0.3 cm. For all patients, treatment planning was performed, adopting the National Surgical Adjuvant Breast and Bowel Project guidelines, and dosimetric comparisons were made. The 6-1 and 8-1 SAVI devices can theoretically treat a maximal tissue margin of 1.5 cm and an asymmetric PTV with margins ranging from 0.3 to 1.5 cm. The 10-1 SAVI and Contura can treat a maximal margin of 1.3 cm and 1.1 cm, respectively, and asymmetric PTV with margins ranging from 0.3-1.3 cm. Compared with the Contura, the SAVI demonstrated greater dosimetric flexibility. Risk of developing excessive hot spots increased with the size of the SAVI device. Both the SAVI and Contura appear capable of treating >1.0-cm margins and irregularly shaped PTVs. The 6-1 SAVI device demonstrated the greatest versatility in targeting PTVs approaching what is treatable using the interstitial technique.


Asunto(s)
Braquiterapia/instrumentación , Neoplasias de la Mama/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Adulto , Anciano , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Persona de Mediana Edad , Dosificación Radioterapéutica , Resultado del Tratamiento
15.
Clin Cancer Res ; 18(9): 2579-90, 2012 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-22379115

RESUMEN

PURPOSE: Radiotherapy is part of the standard of care in high-grade gliomas but its outcomes remain poor. Integrating oncolytic viruses with standard anticancer therapies is an area of active investigation. The aim of this study was to determine how tumor-targeted ionizing radiation (IR) could be combined with systemically delivered oncolytic vaccinia virus. EXPERIMENTAL DESIGN: U-87 glioma xenografts were grown subcutaneously or orthotopically. Oncolytic vaccinia viruses GLV-1h68 and LIVP 1.1.1 were injected systemically and IR was given focally to glioma xenografts. In a bilateral tumor model, glioma xenografts were grown in both flanks, oncolytic vaccinia was injected systemically and radiation was delivered specifically to the right flank tumor, whereas the left flank tumor was shielded. Viral replication and tumor regression, after systemic injection, was analyzed and compared in irradiated and nonirradiated glioma xenografts. RESULTS: Systemically administered oncolytic vaccinia virus replicated to higher titers in preirradiated U-87 xenografts than in nonirradiated glioma xenografts. This increased oncolytic viral replication correlated with increased tumor xenograft regression and mouse survival in subcutaneous and orthotopic U-87 glioma models compared with monotherapies. The ability of focal IR to mediate selective replication of oncolytic vaccinia was shown in a bilateral glioma model in which systemically administered oncolytic vaccinia replicated preferentially in the irradiated tumor compared with the nonirradiated tumor in the same mouse. CONCLUSION: These findings show a potential clinical role of focal IR in sensitizing irradiated tumor sites for preferential vaccinia virus-mediated oncolysis.


Asunto(s)
Neoplasias Encefálicas/terapia , Glioma/terapia , Viroterapia Oncolítica , Radiación Ionizante , Vaccinia/terapia , Replicación Viral , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Células Cultivadas , Chlorocebus aethiops , Terapia Combinada , Fibroblastos/citología , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Glioma/genética , Glioma/mortalidad , Riñón/citología , Riñón/metabolismo , Riñón/efectos de la radiación , Masculino , Ratones , Ratones Desnudos , Tasa de Supervivencia , Vaccinia/genética , Vaccinia/mortalidad , Virus Vaccinia/genética , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Med Dosim ; 36(4): 344-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21144735

RESUMEN

A popular choice for treatment of recurrent gliomas was cranial brachytherapy using the GliaSite Radiation Therapy System. However, this device was taken off the market in late 2008, thus leaving a treatment void. This case study presents our experience treating a cranial lesion for the first time using a Contura multilumen, high-dose-rate (HDR) brachytherapy balloon applicator. The patient was a 47-year-old male who was diagnosed with a recurrent right frontal anaplastic oligodendroglioma. Previous radiosurgery made him a good candidate for brachytherapy. An intracavitary HDR balloon brachytherapy device (Contura) was placed in the resection cavity and treated with a single fraction of 20 Gy. The implant, treatment, and removal of the device were all completed without incident. Dosimetry of the device was excellent because the dose conformed very well to the target. V90, V100, V150, and V200 were 98.9%, 95.7%, 27.2, and 8.8 cc, respectively. This patient was treated successfully using the Contura multilumen balloon. Contura was originally designed for deployment in a postlumpectomy breast for treatment by accelerated partial breast irradiation. Being an intracavitary balloon device, its similarity to the GliaSite system makes it a viable replacement candidate. Multiple lumens in the device also make it possible to shape the dose delivered to the target, something not possible before with the GliaSite applicator.


Asunto(s)
Braquiterapia/instrumentación , Neoplasias Encefálicas/radioterapia , Oligodendroglioma/radioterapia , Neoplasias Encefálicas/cirugía , Terapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Oligodendroglioma/cirugía , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Tomografía Computarizada por Rayos X
17.
J Contemp Brachytherapy ; 3(3): 131-3, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23346122

RESUMEN

Melanoma of the iris is a rare condition compared to posterior ocular tumors and in this case report we present a 51-year-old female patient with diffuse iris melanoma. Traditional COMS (Collaborative Ocular Melanoma Study) plaques are used at our institution for radiation therapy, so a novel modification of the traditional plaque was required to allow better conformance with placement on the cornea. The usual silastic insert was machined to dimensions in compliance with the cornea, placed without incident, and treatment delivered with excellent patient tolerance of the modified plaque.

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