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"Trifiletti, Daniel M."
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Fatal heart disease among cancer patients
by
Stoltzfus, Kelsey C.
,
Trifiletti, Daniel M.
,
Zaorsky, Nicholas G.
in
631/67/2324
,
Adult
,
Age Factors
2020
As the overlap between heart disease and cancer patients increases as cancer-specific mortality is decreasing and the surviving population is aging, it is necessary to identify cancer patients who are at an increased risk of death from heart disease. The purpose of this study is to identify cancer patients at highest risk of fatal heart disease compared to the general population and other cancer patients at risk of death during the study time period. Here we report that 394,849 of the 7,529,481 cancer patients studied died of heart disease. The heart disease-specific mortality rate is 10.61/10,000-person years, and the standardized mortality ratio (SMR) of fatal heart disease is 2.24 (95% CI: 2.23–2.25). Compared to other cancer patients, patients who are older, male, African American, and unmarried are at a greatest risk of fatal heart disease. For almost all cancer survivors, the risk of fatal heart disease increases with time.
As the overlap between heart disease and cancer patients increases as cancer-specific mortality is decreasing, identifying cancer patients who are at an increased risk of death from heart disease is important. Here the authors report on risk of death from heart diseases among more than 7.5 million cancer patients.
Journal Article
Progress Toward Long-Term Survivors of Glioblastoma
2019
To identify the frequency and characteristics of long-term survivors of glioblastoma.
Using all cases of glioblastoma with histopathological confirmation in the National Cancer Database from January 1, 2004, through December 31, 2009, clinical, institutional, and treatment-related factors were evaluated with multivariable logistic regression models so as to elucidate factors independently associated with higher than 5-year overall survival after diagnosis.
A total of 48,652 patients met the inclusion criteria, with 2249 (4.6%) achieving 5-year survival. Factors associated with odds of improved 5-year overall survival in multivariable analysis were younger age, female sex, less medical comorbidities, nonwhite race, highest median income quartile, left-sided tumors and tumors outside the brainstem, and treatment with radiotherapy (P<.05 for all). The percentage of patients surviving 5 years remained relatively unchanged over the 6-year study period (P=.97).
Despite improvements in median and short-term overall survival shown in recent large clinical trials for glioblastoma, the percentage of patients with glioblastoma achieving 5-year overall survival remains low. This observation calls for the development of practice-redefining therapies and justifies the increased application of radical novel and experimental treatment paradigms for all patients with glioblastoma.
Journal Article
Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial
by
Brown, Desmond A.
,
Trifiletti, Daniel M.
,
Yan, Elizabeth
in
Adjuvant radiation therapy
,
Biomedical and Life Sciences
,
Biomedicine
2024
Background and Objectives
Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS.
Methods
This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS.
Expected outcomes
If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline.
Discussion
Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease.
Trial registration number
NCT03750227 (Registration date: 21/11/2018).
Journal Article
Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer
by
Bush, Aaron F.
,
Trifiletti, Daniel M.
,
Advani, Pooja
in
Amino acids
,
Atoms & subatomic particles
,
Boron
2022
BNCT is a high LET radiation therapy modality that allows for biologically targeted radiation delivery to tumors while reducing normal tissue impacts. Although the clinical use of BNCT has largely been limited to phase I/II trials and has primarily focused on difficult-to-treat malignancies such as recurrent head and neck cancer and recurrent gliomas, recently there has been a renewed interest in expanding the use of BNCT to other disease sites, including breast cancer. Given its high LET characteristics, its biologically targeted and tumor specific nature, as well as its potential for use in complex treatment settings including reirradiation and widespread metastatic disease, BNCT offers several unique advantages over traditional external beam radiation therapy. The two main boron compounds investigated to date in BNCT clinical trials are BSH and BPA. Of these, BPA in particular shows promise in breast cancer given that is taken up by the LAT-1 amino acid transporter that is highly overexpressed in breast cancer cells. As the efficacy of BNCT is directly dependent on the extent of boron accumulation in tumors, extensive preclinical efforts to develop novel boron delivery agents have been undertaken in recent years. Preclinical studies have shown promise in antibody linked boron compounds targeting ER/HER2 receptors, boron encapsulating liposomes, and nanoparticle-based boron delivery systems. This review aims to summarize the physical and biological basis of BNCT, the preclinical and limited clinical data available to date, and discuss its potential to be utilized for the successful treatment of various breast cancer disease states.
Journal Article
Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of Brain Metastases
by
Ruiz-Garcia, Henry
,
Trifiletti, Daniel M.
,
McGee, Heather M.
in
Antibodies, Monoclonal - pharmacology
,
Antibodies, Monoclonal - therapeutic use
,
Antineoplastic Agents, Immunological - pharmacology
2018
Brain metastases traditionally carried a poor prognosis with an overall survival of weeks to months in the absence of treatment. Radiation therapy modalities include whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). WBRT delivers a relatively low dose of radiation, has neurocognitive sequelae, and has not been investigated for its immunostimulatory effects. Furthermore, WBRT exposes the entire intracranial tumor immune microenvironment to radiation. SRS delivers a high dose of conformal radiation with image guidance to minimize dose to surrounding normal brain tissue, and appears to promote anti-tumor immunity. In parallel with many of these discoveries, immune checkpoint inhibitors (ICIs) have demonstrated a survival advantage in multiple malignancies commonly associated with brain metastases (e.g., melanoma). Combination SRS and ICI are theorized to be synergistic in anti-tumor immunity directed to brain metastases. The purpose of this review is to explore the synergy of SRS and ICIs, including pre-clinical data, existing clinical data, and ongoing prospective trials.
Journal Article
Carbon ion radiation therapy in breast cancer: a new frontier
by
Mahajan, Anita
,
Mutter, Robert W.
,
Trifiletti, Daniel M.
in
Breast cancer
,
Breast Neoplasms - pathology
,
Breast Neoplasms - radiotherapy
2020
Purpose
Breast cancer is the most commonly diagnosed cancer in women, with many efforts aimed at reducing acute and late toxicity given the generally favorable clinical outcomes with the current standard of care. Carbon ion radiation therapy is an emerging technique that may reduce dose to adjacent organs at risk while allowing dose escalation to the target. Given the efficacy of the standard treatments for breast cancer, there have been few prospective studies to date investigating carbon ion radiation therapy in breast cancer.
Methods
PubMed/Medline, Ebsco, Cochrane, and Scopus were systematically reviewed using the search terms “carbon ion” and “breast” in November 2019. Out of the 76 articles screened, 26 articles were included.
Results
This comprehensive review describes the physical and biological properties of carbon ion radiation therapy, with an emphasis on how these properties can be applied in the setting of breast cancer. Studies investigating the role of carbon ion radiation therapy in early stage breast cancers are reviewed. Additionally, the use of carbon ion radiation therapy in locally advanced disease, recurrent disease, and radiation-induced angiosarcoma are discussed.
Conclusion
Although the data is limited, the early clinical results are promising. Further clinical trials are needed, especially in the setting of locally advanced and recurrent disease, to fully define the potential role of carbon ion radiation therapy in the treatment of breast cancer.
Journal Article
The Epidemiology of Lung Metastases
2021
Introduction: Lung metastasis is usually associated with poor outcomes in cancer patients. This study was performed to characterize and analyze the population of patients with de novo (synchronous) lung metastases using the Surveillance, Epidemiology and End Results (SEER) database. Materials and Methods: Baseline characteristics of lung metastasis patients were obtained from SEER case listings. Incidence rates and counts of synchronous lung metastasis were also obtained using the SEER * Stat software. Survival outcomes were analyzed using univariate and multivariable Cox regressions, controlling for confounders. An alpha threshold of 0.05 was used for statistical significance and p -values were subject to correction for multiple comparisons. Results: The age-adjusted incidence rate of synchronous lung metastasis was 17.92 per 100,000 between 2010 and 2015. Synchronous lung metastases most commonly arose from primary lung cancers, colorectal cancers, kidney cancers, pancreatic cancers and breast cancers. During this time period, 4% of all cancer cases presented with synchronous lung metastasis. The percentage of patients presenting with synchronous lung metastasis ranged from 0.5% of all prostate cancers to 13% of all primary lung cancers. The percentage of all cancer cases presenting with synchronous lung metastasis increased over time. De novo metastatic patients with lung metastases had worse overall survival [hazard ratio = 1.22 (1.21–1.23), p < 0.001] compared to those with only extrapulmonary metastases, controlling for potential confounders. Conclusions: Synchronous lung metastasis occurs frequently and is an independent predictors of poor patient outcomes. As treatment for lung metastases becomes more complicated, patients with synchronous lung metastasis represent a high-risk population.
Journal Article
Outcomes of large vestibular schwannomas following subtotal resection: early post-operative volume regression and facial nerve function
2019
Introduction
Subtotal resection (STR) of vestibular schwannoma (VS) tumors remains controversial and little is known regarding post-operative volume changes.
Methods
Authors retrospective reviewed the medical records from January 1st 2002 to January 1st 2018, for all patients who had undergone primary STR of large VS at a single tertiary academic institution.
Results
Our series consists of 34 patients with a mean age of 53.9 (median 53; range 21–87) years that had STR of their VS tumor. The mean pre-operative tumor diameter and volume was 3.9 cm (median 3.0 cm; range 1.6–6.0 cm) and 11.7 cm
3
(median 9.6 cm
3
; range 2.8–44.3 cm
3
), respectively, with a mean extent of resection of 86% (median 90%; range 53–99%). The mean radiographic and clinical follow-up was 40 months (range 6–120 months) and 51 months (range 7–141 months), respectively. 85% of patients had optimal House–Brackmann (HB) scores (Grade 1 & 2) immediately post-operatively, and 91% at 1 year; 94% of patients had normal (HB 1) at last follow-up. There was significant regression of residual tumor volume at 1 year (p = 0.006) and 2 years (p = 0.02), but not at 3 years (p = 0.08), when compared to the prior year. There was significant regression of size over time, with a mean slope estimate of − 0.70 units per year (p < 0.001).
Conclusion
Excellent clinical facial nerve outcomes can be obtained with STR of large VS tumors. Maximal reduction in tumor size occurs at 2-year post-operatively. Thus, in patients undergoing surgery for large VS, STR and a “watch and wait” strategy is a reasonable treatment option that may optimize facial nerve outcomes.
Journal Article
Carbon Ion Radiotherapy: An Evidence-Based Review and Summary Recommendations of Clinical Outcomes for Skull-Base Chordomas and Chondrosarcomas
2023
Skull-base chordoma and chondrosarcoma are rare radioresistant tumors treated with surgical resection and/or radiotherapy. Because of the established dosimetric and biological benefits of heavy particle therapy, we performed a systematic and evidence-based review of the clinical outcomes of patients with skull-base chordoma and chondrosarcoma treated with carbon ion radiotherapy (CIRT). A literature review was performed using a MEDLINE search of all articles to date. We identified 227 studies as appropriate for review, and 24 were ultimately included. The published data illustrate that CIRT provides benchmark disease control outcomes for skull-base chordoma and chondrosarcoma, respectively, with acceptable toxicity. CIRT is an advanced treatment technique that may provide not only dosimetric benefits over conventional photon therapy but also biologic intensification to overcome mechanisms of radioresistance. Ongoing research is needed to define the magnitude of benefit, patient selection, and cost-effectiveness of CIRT compared to other forms of radiotherapy.
Journal Article