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1.
Int J Gynecol Cancer ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32193219

RESUMO

Therapeutic strategies combining radiation therapy with novel agents have become an area of intense research focus in oncology and are actively being investigated for a wide range of solid tumors. The mechanism of action of these systemic agents can be stratified into three general categories: (1) enhancement or alteration of the immune system; (2) disruption of DNA damage response mechanisms; and (3) impediment of cellular signaling pathways involving growth, angiogenesis, and hypoxia. Pre-clinical data suggest that radiation therapy has immunogenic qualities and may optimize response to immuno-oncology therapies by priming the immune system, whereas other novel systemic agents can enhance radiosensitivity through augmentation of genomic instability and alteration of central signaling pathways related to growth and survival. Gynecologic cancers in particular have the potential for synergistic response to combination approaches incorporating radiation therapy and novel systemic therapies. Several clinical trials have been proposed to elucidate the efficacy and safety of such approaches. Here we discuss the mechanisms of novel therapies and the rationale for these combination strategies, reviewing the relevant pre-clinical and clinical data. We explore their optimal use with respect to indications, interactions, and potential synergy in combination with radiation therapy and review ongoing trials and active areas of investigation.

2.
J Natl Cancer Inst ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32219419

RESUMO

Cervical cancer is the fourth most common cancer in women worldwide, and prognosis is poor for those who experience recurrence or develop metastatic disease, in part due to the lack of active therapeutic directions. The National Cancer Institute convened a Cervical Cancer Clinical Trials Planning Meeting (CTPM) in October 2018 to facilitate the design of hypothesis-driven clinical trials focusing on locally advanced, metastatic and recurrent cervical cancer around the theme of enhancing susceptibility to DNA repair inhibition and DNA damage. Prior to the meeting, a group of experts in the field summarized available preclinical and clinical data to identify potentially active inducers and inhibitors of DNA. The goals of the CTPM focused on identification of novel experimental strategies capitalizing on DNA damage and repair (DDR) regulators and cell cycle aberrations, optimization of radiotherapy as a DDR agent, and design of clinical trials incorporating DDR regulation into the primary and recurrent/metastatic therapies for cervical carcinoma. Meeting deliverables were novel clinical trial concepts to move into the National Clinical Trials Network. This report provides an overview for the rationale of this meeting and the state of the science related to DDR regulation in cervical cancer.

4.
Cancer ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125711

RESUMO

BACKGROUND: Advances in radiotherapy (RT) have led to improved oncologic outcomes for women with gynecologic cancers; however, the long-term effects and survivorship implications need further evaluation. The purpose of this study was to determine the incidence of pelvic fractures and changes in bone mineral density (BMD) after pelvic RT. METHODS: Two hundred thirty-nine women who had pelvic RT for cervical, endometrial, or vaginal cancer between 2008 and 2015 were prospectively studied. BMD scans and biomarkers of bone turnover were obtained at the baseline and 3 months, 1 year, and 2 years after RT. Imaging studies were assessed for pelvic fractures for up to 5 years. Patients with osteopenia, osteoporosis, or pelvic fractures at any point were referred to the endocrinology service for evaluation and treatment. RESULTS: The median age at diagnosis was 51 years; 132 patients (56%) were menopausal. The primary diagnoses were cervical (63.6%), endometrial (30.5%), and vaginal cancer (5.9%). Sixteen patients (7.8%; 95% confidence interval, 4.5%-12.4%) had pelvic fractures with actuarial rates of 3.6%, 12.7%, and 15.7% at 1, 2, and 3 years, respectively. Fractures were associated with baseline osteoporosis (P < .001), higher baseline bone-specific alkaline phosphatase (P < .001), and older age (P = .007). The proportion of patients with osteopenia/osteoporosis increased from 50% at the baseline to 58%, 59%, and 70% at 3 months, 1 year, and 2 years, respectively. CONCLUSIONS: A high proportion of women had significant decreases in BMD after pelvic RT, with 7.8% diagnosed with a pelvic fracture. BMD screening and pharmacologic intervention should be strongly considered for these high-risk women.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31987960

RESUMO

PURPOSE: Patients receiving pelvic radiation for cervical cancer experience high rates of acute gastrointestinal (GI) toxicity. The association of changes in the gut microbiome with bowel toxicity from radiation is not well characterized. METHODS AND MATERIALS: Thirty-five patients undergoing definitive chemoradiation therapy (CRT) underwent longitudinal sampling (baseline and weeks 1, 3, and 5) of the gut microbiome and prospective assessment of patient-reported GI toxicity. DNA was isolated from stool obtained at rectal examination and analyzed with 16S rRNA sequencing. GI toxicity was assessed with the Expanded Prostate Cancer Index Composite instrument to evaluate frequency, urgency, and discomfort associated with bowel function. Shannon diversity index was used to characterize alpha (within sample) diversity. Weighted UniFrac principle coordinates analysis was used to compare beta (between sample) diversity between samples using permutational multivariate analysis of variance. Linear discriminant analysis effect size highlighted microbial features that best distinguish categorized patient samples. RESULTS: Gut microbiome diversity continuously decreased over the course of CRT, with the largest decrease at week 5. Expanded Prostate Cancer Index Composite bowel function scores also declined over the course of treatment, reflecting increased symptom burden. At all individual time points, higher diversity of the gut microbiome was linearly correlated with better patient-reported GI function, but baseline diversity was not predictive of eventual outcome. Patients with high toxicity demonstrated different compositional changes during CRT in addition to compositional differences in Clostridia species. CONCLUSIONS: Over time, increased radiation toxicity is associated with decreased gut microbiome diversity. Baseline diversity is not predictive of end-of-treatment bowel toxicity, but composition may identify patients at risk for developing high toxicity.

6.
Int J Radiat Oncol Biol Phys ; 106(3): 475-484, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580930

RESUMO

PURPOSE: To estimate the overall rate, symptomatic proportion, and most common sites of pelvic insufficiency fracture (PIF) after external beam radiation therapy for gynecologic cancers based on posttreatment computed tomography, magnetic resonance imaging, positron emission tomography, or bone scintigraphy. METHODS AND MATERIALS: A systematic search of databases (PubMed and EMBASE) was performed (CRD42019125679). The pooled summary of overall PIF and the proportion of symptomatic cases were calculated using the random-effects model weighted by the inverse variance. A multivariate meta-regression was performed to evaluate potential sources of heterogeneity regarding PIF fractures. RESULTS: Twenty-one studies met the inclusion criteria (total 3929 patients). Five hundred four patients developed PIF, translating to an overall rate of 14% (95% confidence interval, 10%-18%, based on 21 studies). Among these cases with PIF, the proportion of symptomatic patients was 61% (95% confidence interval, 52%-69%, based on 14 studies). The total number of PIFs was 704 (mean, 1.72 PIFs per each patient to develop PIF, based on 14 studies). More recent series (P = .0074) and the use of intensity modulated radiation therapy (P = .0299) were associated with lower fracture rates. The most common fracture sites were sacroiliac joint (39.7%), body of the sacrum (33.9%), pubis (13%), lumbar vertebra (7%), iliac bone (2.8%), acetabulum (2.1%), and femoral head/neck (1.5%). The median time to fracture was 7.1 to 19 months after radiation therapy. CONCLUSIONS: The incidence of PIF after radiation therapy for gynecologic cancers is high (14%), with the majority affecting the sacral bone or joint (73.6%), although this risk appears to be lower with intensity modulated radiation therapy. Posttreatment bone surveillance is warranted in this population because nearly 40% of patients were asymptomatic at the time of PIF diagnosis.


Assuntos
Fraturas Ósseas/epidemiologia , Fraturas Espontâneas/epidemiologia , Neoplasias dos Genitais Femininos/radioterapia , Ossos Pélvicos/lesões , Intervalos de Confiança , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/etiologia , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Humanos , Ossos Pélvicos/efeitos da radiação , Radioterapia de Intensidade Modulada , Análise de Regressão
7.
Brachytherapy ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31786169

RESUMO

PURPOSE: We integrated a brachytherapy procedural workflow within an existing diagnostic 3.0-T (3T) MRI suite. This setup facilitates intraoperative MRI guidance for optimal applicator positioning, particularly for interstitial needle placements in gynecologic cases with extensive parametrial involvement. METHODS AND MATERIALS: Here we summarize the multidisciplinary collaboration, equipment, and supplies necessary to implement an intraoperative MRI-guided brachytherapy program; outline the operational workflow via process maps; and address safety precautions. We evaluate internal resource utilization associated with this progressive approach via time-driven activity-based costing methodology, comparing institutional costs to that of a traditional workflow (within a CT suite, followed by separate postprocedure MRI) over a single brachytherapy procedural episode. RESULTS: Resource utilization was only 15% higher for the intraoperative MRI-based workflow, attributable to use of the MRI suite and increased radiologist effort. Personnel expenses were the greatest cost drivers for either workflow, accounting for 76-77% of total resource utilization. However, use of the MRI suite allows for potential cost-shifting opportunities from other resources, such as CT, during the procedural episode. Improvements in process speed can also decrease costs: for each 10% decrease in case duration from baseline procedure time, total costs could decrease by roughly 8%. CONCLUSIONS: This analysis supports the feasibility of an intraoperative MRI-guided brachytherapy program within a diagnostic MRI suite and defines many of the resources required for this procedural workflow. Longer followup will define the full utility of this approach in optimizing the therapeutic ratio for gynecologic cancers, which may translate into lower costs and higher value with time, over a full cycle of care.

8.
Gynecol Oncol ; 155(2): 237-244, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31500892

RESUMO

OBJECTIVES: The aim of this study was to characterize variation in the gut microbiome of women with locally advanced cervical cancer and compare it to healthy controls. METHODS: We characterized the 16S rDNA fecal microbiome in 42 cervical cancer patients and 46 healthy female controls. Shannon diversity index (SDI) was used to evaluate alpha (within sample) diversity. Beta (between sample) diversity was examined using principle coordinate analysis (PCoA) of unweighted Unifrac distances. Relative abundance of microbial taxa was compared between samples using Linear Discriminant Analysis Effect Size (LEfSe). RESULTS: Within cervical cancer patients, bacterial alpha diversity was positively correlated with age (p = 0.22) but exhibited an inverse relationship in control subjects (p < 0.01). Alpha diversity was significantly higher in cervical cancer patients as compared to controls (p < 0.05), though stratification by age suggested this relationship was restricted to older women (>50 years; p < 0.01). Beta diversity (unweighted Unifrac; p < 0.01) also significantly differed between cervical cancer patients and controls. Based on age- and race-adjusted LEfSe analysis, multiple taxa significantly differed between cervical cancer patients and controls. Prevotella, Porphyromonas, and Dialister were significantly enriched in cervical cancer patients, while Bacteroides, Alistipes and members of the Lachnospiracea family were significantly enriched in healthy subjects. CONCLUSION: Our study suggests differences in gut microbiota diversity and composition between cervical cancer patients and controls. Associations within the gut microbiome by age may reflect etiologic/clinical differences. These findings provide rationale for further study of the gut microbiome in cervical cancer.


Assuntos
Microbioma Gastrointestinal/genética , Neoplasias do Colo do Útero/microbiologia , Idoso , Fezes/microbiologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
9.
Pract Radiat Oncol ; 9(6): 479-491, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31302301

RESUMO

PURPOSE: Guidelines for the care of women undergoing pelvic radiation therapy (RT) recommend vaginal dilator therapy (VDT) to prevent radiation-induced vaginal stenosis (VS); however, no standard protocol exists. This review seeks to update our current state of knowledge concerning VS and VDT in radiation oncology. METHODS AND MATERIALS: A comprehensive literature review (1972-2017) was conducted using search terms "vaginal stenosis," "radiation," and "vaginal dilator." Information was organized by key concepts including VS definition, time course, pathophysiology, risk factors, and interventions. RESULTS: VS is a well-described consequence of pelvic RT, with early manifestations and late changes evolving over several years. Strong risk factors for VS include RT dose and volume of vagina irradiated. Resultant vaginal changes can interfere with sexual function and correlational studies support the use of preventive VDT. The complexity of factors that drive noncompliance with VDT is well recognized. There are no prospective data to guide optimal duration of VDT, and the consistency with which radiation oncologists monitor VS and manage its consequences is unknown. CONCLUSIONS: This review provides information concerning VS definition, pathophysiology, and risk factors and identifies domains of VDT practice that are understudied. Prospective efforts to monitor and measure outcomes of patients who are prescribed VDT are needed to guide practice.

10.
Gynecol Oncol ; 154(2): 328-332, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31221496

RESUMO

OBJECTIVE: To evaluate clinicopathologic factors and adjuvant treatment effects on recurrence free (RFS) and overall survival (OS) in early stage uterine clear cell carcinoma (UCCC). METHODS: Our retrospective review included central pathology confirmed stage I or II UCCC treated and/or followed between 2000 and 2016. Cases with pure or mixed histology with >50% UCCC were included. Data were analyzed using Kaplan-Meier method and Cox proportional hazards regressions. RESULTS: 112 women were identified. Median age was 65.5 years (range 34-94). Most patients had mixed UCCC (61%), while 39% had pure UCCC. The majority of patients had stage IA UCCC (66%) versus stage IB (15%) or stage II (18%) disease. Adjuvant treatment included chemotherapy + radiation (26%), brachytherapy (27%), whole pelvic radiation (15%), chemotherapy alone (8%), and observation (24%). Thirty-eight (34%) women had recurrent disease. Median RFS was 4.32 years (95% CI 2.77-5.78). On multivariate analysis, age ≥70 (HR 2.48, 95% 1.28-4.81) and positive LVSI (HR 2.19, 95% CI 1.15-4.18) were associated with shorter RFS. Median OS was 9.8 years (95% CI 7.46-15.93). On multivariate analyses, age ≥70 (HR 3.57, 95% CI 1.64-7.74) and positive LVSI (HR 2.46, 95% CI 1.12-5.37) were associated with shorter OS. In this retrospective descriptive uncontrolled patient series, adjuvant treatment type did not impact RFS or OS. CONCLUSIONS: OS approaches 10 years for early stage UCCC patients. Women ≥70 years have worse PFS and OS regardless of treatment modality, encouraging consideration of quality of life implications when electing for adjuvant therapy.


Assuntos
Adenocarcinoma de Células Claras/terapia , Neoplasias Uterinas/terapia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Conduta Expectante
11.
Brachytherapy ; 18(5): 620-626, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31160198

RESUMO

PURPOSE: Postinsertion computed tomography (CT) can identify air gaps (AGs) around the cylinder in vaginal cuff brachytherapy (VCB). This study investigates the incidence and location of AGs. METHODS AND MATERIALS: Planning CTs of 22 prospectively recruited patients (NCT02091050) treated with 2.6 cm (n = 8) and 3.0 cm (n = 14) cylinders were evaluated. In addition, a systematic literature review and meta-analysis was performed (PubMed and EMBASE). The pooled incidence of AGs was calculated by using the random-effects model weighted by inverse variance. RESULTS: In 18 cases (82%), a total of 45 AGs were found: 26 within the 2 cm cranial length and 19 between 2 and 4 cm of the cylinder. The mean AG diameter was 3.7 mm (range: 1.3-11.8). Cylinder diameter, primary tumor site, and use of external beam radiotherapy were not associated with AG incidence. Systematic literature review revealed nine additional relevant studies, totaling 657 patients. The pooled incidence of patients with ≥1 AG was 67% (95% confidence interval: 50-83). AGs were located at the apex in 43.4%-94.4% of cases. In patients with ≥1 AG (n = 244), the pooled mean number of AGs was 2.18 per patient. The mean dose reduction varied from 9.6% to 29.3%. CONCLUSION: More than two-thirds of VCB cases present with AGs, which are most commonly at the apex and can potentially reduce mucosal dose. By identifying AGs, postinsertion CT can facilitate selection of optimal cylinder size in VCB.


Assuntos
Braquiterapia/métodos , Neoplasias do Endométrio/radioterapia , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/radioterapia , Vagina/diagnóstico por imagem , Feminino , Humanos , Membrana Mucosa , Estudos Prospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
13.
Gynecol Oncol ; 154(1): 22-28, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31109659

RESUMO

OBJECTIVE: To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer. METHODS: We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT + RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT ±â€¯CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001). CONCLUSIONS: Combined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/terapia , Cisplatino/uso terapêutico , Neoplasias do Endométrio/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Endometrioide/patologia , Quimiorradioterapia Adjuvante , Neoplasias do Endométrio/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
14.
Int J Gynecol Cancer ; 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126968

RESUMO

OBJECTIVES: Knowledge of the detailed pattern of failure can be useful background knowledge in clinical decision making and potentially drive the development of new treatment strategies by increasing radiotherapy dose prescription to high-risk sub-regions of the target. Here, we analyze patterns of recurrence in patients with vulvar cancer treated with radiotherapy according to original planning target volumes and radiation dose delivered. METHODS: We analyzed dose-planning and post-treatment recurrence scans from patients with vulvar cancer treated at two institutions from January 2009 through October 2014. We delineated the recurrences and merged the dose-planning and recurrence scans for each patient by using deformable co-registration. We estimated the center of each recurrence on the merged scans with the goal of relating them to the original dose plan. RESULTS: We evaluated 157 patients who received radiotherapy for vulvar cancer. Median age was 68 years (range 29-91). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVB were included. Twenty-nine patients had recurrent disease; 156 patients had squamous cell carcinoma and one patient had adenosquamous carcinoma of the vulva. Among the 157 patients, 37 patients with recurrent disease had recurrence scans available for review, for a total of 80 recurrence sites; 53% of the recurrences were located in the region to which the highest dose (60-70 Gy) had been prescribed. Patients who received definitive radiotherapy developed failure primarily in the high-dose region (80.5%), whereas patients who received adjuvant radiotherapy had a more scattered failure pattern (p<0.0001). Among the latter group, 29.5% failed in the high-dose region. CONCLUSIONS: Patients who received definitive versus adjuvant radiotherapy had different failure patterns, indicating that separate approaches are needed to improve both adjuvant and definitive radiotherapy for vulvar cancer.

15.
Med Phys ; 46(9): 3767-3775, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31077593

RESUMO

PURPOSE: Breast cancer is the most common cancer in women globally and radiation therapy is a cornerstone of its treatment. However, there is an enormous shortage of radiotherapy staff, especially in low- and middle-income countries. This shortage could be ameliorated through increased automation in the radiation treatment planning process, which may reduce the workload on radiotherapy staff and improve efficiency in preparing radiotherapy treatments for patients. To this end, we sought to create an automated treatment planning tool for postmastectomy radiotherapy (PMRT). METHODS: Algorithms to automate every step of PMRT planning were developed and integrated into a commercial treatment planning system. The only required inputs for automated PMRT planning are a planning computed tomography scan, a plan directive, and selection of the inferior border of the tangential fields. With no other human input, the planning tool automatically creates a treatment plan and presents it for review. The major automated steps are (a) segmentation of relevant structures (targets, normal tissues, and other planning structures), (b) setup of the beams (tangential fields matched with a supraclavicular field), and (c) optimization of the dose distribution by using a mix of high- and low-energy photon beams and field-in-field modulation for the tangential fields. This automated PMRT planning tool was tested with ten computed tomography scans of patients with breast cancer who had received irradiation of the left chest wall. These plans were assessed quantitatively using their dose distributions and were reviewed by two physicians who rated them on a three-tiered scale: use as is, minor changes, or major changes. The accuracy of the automated segmentation of the heart and ipsilateral lung was also assessed. Finally, a plan quality verification tool was tested to alert the user to any possible deviations in the quality of the automatically created treatment plans. RESULTS: The automatically created PMRT plans met the acceptable dose objectives, including target coverage, maximum plan dose, and dose to organs at risk, for all but one patient for whom the heart objectives were exceeded. Physicians accepted 50% of the treatment plans as is and required only minor changes for the remaining 50%, which included the one patient whose plan had a high heart dose. Furthermore, the automatically segmented contours of the heart and ipsilateral lung agreed well with manually edited contours. Finally, the automated plan quality verification tool detected 92% of the changes requested by physicians in this review. CONCLUSIONS: We developed a new tool for automatically planning PMRT for breast cancer, including irradiation of the chest wall and ipsilateral lymph nodes (supraclavicular and level III axillary). In this initial testing, we found that the plans created by this tool are clinically viable, and the tool can alert the user to possible deviations in plan quality. The next step is to subject this tool to prospective testing, in which automatically planned treatments will be compared with manually planned treatments.


Assuntos
Mastectomia , Planejamento da Radioterapia Assistida por Computador/métodos , Automação , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Dosagem Radioterapêutica
16.
Radiother Oncol ; 135: 58-64, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015171

RESUMO

OBJECTIVE: To determine the utility of volumetric diffusion weighted imaging (DWI) compared to other clinical factors for predicting recurrence and survival in cervical cancer patients treated with definitive chemoradiation. METHODS AND MATERIALS: We retrospectively studied cervical cancer patients treated with definitive chemoradiation between 2009-2013 at a single institution with a baseline MRI with DWI and 18F-FDG positron emission tomography/computed tomography (FDG-PET) scan. To identify clinical and imaging metrics correlated with survival and recurrence endpoints, variable importance values were calculated from random forest models. To provide clinically relevant threshold values, recursive partitioning analysis dichotomized patients into potential risk groups based on selected metrics. Cox's proportional hazard models assessed the effect of clinical and imaging factors on survival endpoints. RESULTS: Ninety-three patients were included in the analysis (median age 50 years). At a median follow-up of 35.6 months, 32 patients (34%) had disease recurrence. In the best multivariate model including clinical and imaging parameters, 90th percentile ADC < 1.917 was the only significantly associated factor with worse progression free survival (PFS). Overall survival, PFS, and distant metastasis free survival (DMFS) were significantly different between patient groups divided on 90th percentile ADC with threshold of 1.917 × 10-3 mm2/s and MRI volume with threshold of 18.9 cc (P = 0.037, P = 0.0002, P = 0.001). High MRI volume and low ADC were associated with worse clinical outcomes. CONCLUSIONS: Volumetric 90th percentile ADC value of the primary tumor on pretreatment MRI was a significant predictor of PFS and DMFS in cervical cancer patients, independent of established clinical factors and SUV on FDG-PET.

17.
Brachytherapy ; 18(4): 445-452, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30992185

RESUMO

PURPOSE: The purpose of this study was to quantify the cost of resources required to deliver adjuvant radiation therapy (RT) for high- to intermediate-risk endometrial cancer using time-driven activity-based costing (TDABC). METHODS AND MATERIALS: Comparisons were made for three and five fractions of vaginal cuff brachytherapy (VCB), 28 fractions of intensity-modulated radiation therapy (IMRT), and combined modality RT (25-fraction IMRT followed by 2-fraction VCB). Process maps were developed representing each phase of care. Salary and equipment costs were obtained to derive capacity cost rates, which were multiplied by process times and summed to calculate total costs. Costs were compared with 2018 Medicare physician fee schedule reimbursement. RESULTS: Full cycle costs for 5-fraction VCB, IMRT, and combined modality RT were 42%, 61%, and 93% higher, respectively, than for 3-fraction VCB. Differences were attributable to course duration and number of fractions/visits. Accumulation of cost throughout the cycle was steeper for VCB, rising rapidly within a shorter time frame. Personnel cost was the greatest driver for all modalities, constituting 76% and 71% of costs for IMRT and VCB, respectively, with VCB requiring 74% more physicist time. Total reimbursement for 5-fraction VCB was 40% higher than for 3-fractions. Professional reimbursement for IMRT was 31% higher than for 5-fraction VCB, vs. IMRT requiring 43% more physician TDABC than 5-fraction VCB. CONCLUSIONS: TDABC is a feasible methodology to quantify the cost of resources required for delivery of adjuvant IMRT and brachytherapy and produces directionally accurate costing data as compared with reimbursement calculations. Such data can inform institution-specific financial analyses, resource allocation, and operational workflows.


Assuntos
Braquiterapia/economia , Neoplasias do Endométrio/radioterapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Instalações de Saúde/economia , Recursos em Saúde/economia , Radioterapia de Intensidade Modulada/economia , Braquiterapia/métodos , Braquiterapia/estatística & dados numéricos , Fracionamento da Dose de Radiação , Equipamentos e Provisões/economia , Feminino , Recursos em Saúde/estatística & dados numéricos , Humanos , Reembolso de Seguro de Saúde/estatística & dados numéricos , Medicare/economia , Radioterapia Adjuvante/economia , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/estatística & dados numéricos , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/estatística & dados numéricos , Salários e Benefícios/economia , Estados Unidos
18.
Med Phys ; 46(6): 2567-2574, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31002389

RESUMO

PURPOSE: To assess the risk of failure of a recently developed automated treatment planning tool, the radiation planning assistant (RPA), and to determine the reduction in these risks with implementation of a quality assurance (QA) program specifically designed for the RPA. METHODS: We used failure mode and effects analysis (FMEA) to assess the risk of the RPA. The steps involved in the workflow of planning a four-field box treatment of cervical cancer with the RPA were identified. Then, the potential failure modes at each step and their causes were identified and scored according to their likelihood of occurrence, severity, and likelihood of going undetected. Additionally, the impact of the components of the QA program on the detectability of the failure modes was assessed. The QA program was designed to supplement a clinic's standard QA processes and consisted of three components: (a) automatic, independent verification of the results of automated planning; (b) automatic comparison of treatment parameters to expected values; and (c) guided manual checks of the treatment plan. A risk priority number (RPN) was calculated for each potential failure mode with and without use of the QA program. RESULTS: In the RPA automated treatment planning workflow, we identified 68 potential failure modes with 113 causes. The average RPN was 91 without the QA program and 68 with the QA program (maximum RPNs were 504 and 315, respectively). The reduction in RPN was due to an improvement in the likelihood of detecting failures, resulting in lower detectability scores. The top-ranked failure modes included incorrect identification of the marked isocenter, inappropriate beam aperture definition, incorrect entry of the prescription into the RPA plan directive, and lack of a comprehensive plan review by the physician. CONCLUSIONS: Using FMEA, we assessed the risks in the clinical deployment of an automated treatment planning workflow and showed that a specialized QA program for the RPA, which included automatic QA techniques, improved the detectability of failures, reducing this risk. However, some residual risks persisted, which were similar to those found in manual treatment planning, and human error remained a major cause of potential failures. Through the risk analysis process, we identified three key aspects of safe deployment of automated planning: (a) user training on potential failure modes; (b) comprehensive manual plan review by physicians and physicists; and (c) automated QA of the treatment plan.


Assuntos
Análise do Modo e do Efeito de Falhas na Assistência à Saúde , Planejamento da Radioterapia Assistida por Computador , Automação , Humanos , Controle de Qualidade
19.
J Glob Oncol ; 5: 1-9, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30629457

RESUMO

PURPOSE: The purpose of this study was to validate a fully automatic treatment planning system for conventional radiotherapy of cervical cancer. This system was developed to mitigate staff shortages in low-resource clinics. METHODS: In collaboration with hospitals in South Africa and the United States, we have developed the Radiation Planning Assistant (RPA), which includes algorithms for automating every step of planning: delineating the body contour, detecting the marked isocenter, designing the treatment-beam apertures, and optimizing the beam weights to minimize dose heterogeneity. First, we validated the RPA retrospectively on 150 planning computed tomography (CT) scans. We then tested it remotely on 14 planning CT scans at two South African hospitals. Finally, automatically planned treatment beams were clinically deployed at our institution. RESULTS: The automatically and manually delineated body contours agreed well (median mean surface distance, 0.6 mm; range, 0.4 to 1.9 mm). The automatically and manually detected marked isocenters agreed well (mean difference, 1.1 mm; range, 0.1 to 2.9 mm). In validating the automatically designed beam apertures, two physicians, one from our institution and one from a South African partner institution, rated 91% and 88% of plans acceptable for treatment, respectively. The use of automatically optimized beam weights reduced the maximum dose significantly (median, -1.9%; P < .001). Of the 14 plans from South Africa, 100% were rated clinically acceptable. Automatically planned treatment beams have been used for 24 patients with cervical cancer by physicians at our institution, with edits as needed, and its use is ongoing. CONCLUSION: We found that fully automatic treatment planning is effective for cervical cancer radiotherapy and may provide a reliable option for low-resource clinics. Prospective studies are ongoing in the United States and are planned with partner clinics.

20.
Gynecol Oncol ; 152(1): 101-105, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30396690

RESUMO

OBJECTIVES: To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI). METHODS: A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information. Variables were compared between patients with PNI to those without PNI. RESULTS: Of the 421 patients included in the study, 32 (7.6%) had tumors with PNI. There were no significant differences in age, race/ethnicity, smoking history, histologic subtype, or grade between the group of patients with PNI and the group without PNI. The group with PNI was more likely to have lichen sclerosus (25.0% vs. 15.4%, p = 0.024), stage III/IV disease (59.4% vs. 36.0%, p = 0.007), lymph node involvement (50.0% vs. 21.6%, p = 0.002), and lymphovascular space invasion (LVSI) (53.1% vs. 15.9%, p < 0.001). A higher proportion of patients in the PNI group underwent primary or adjuvant radiation therapy (68.8% vs. 45.0%, p = 0.016). The median follow-up was 67.1 months (range < 1.0 to 284.3). Patients with PNI had significantly shorter overall survival (OS), median 25.5 vs. 94.3 months (p < 0.001), and progression-free survival (PFS), median 17.5 vs. 29.0 months (p = 0.004). After adjusting for stage, patients with PNI had a greater risk for death and progression (OS: hazard ratio, 2.71; p < 0.001; PFS: hazard ratio, 1.64; p-value = 0.020). CONCLUSION: PNI should be considered an independent poor prognostic factor for patients with vulvar carcinoma, and should be included as part of the pathologic analysis.


Assuntos
Períneo/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Neoplasias Vulvares/mortalidade
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