Browsing by Subject "radiotherapy"

Now showing 1 - 7 of 7
  • Thumbnail Image
    Item
    Blood-based biomarkers for precision medicine in lung cancer: precision radiation therapy
    (2017-12) De Ruysscher, Dirk; Jin, Jianyue; Lautenschlaeger, Tim; She, Jin-Xiong; Liao, Zhongxing; Kong, Feng-Ming (Spring); Medicine, School of Medicine
    Both tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose. However, the effects of radiation on the tumor and on organs at risk (OARs) are also influenced by the applied dose and volume of irradiated tissues. Combining all these biological, clinical, imaging, and dosimetric parameters in a validated prognostic or predictive model poses a major challenge. Here we aimed to provide an objective review of the potential of blood markers to guide high precision radiation therapy. A combined biological-mathematical approach opens new doors beyond prognostication of patients, as it allows truly precise oncological treatment. Indeed, the core for individualized and precision medicine is not only selection of patients, but even more the optimization of the therapeutic window on an individual basis. A holistic model will allow for determination of an individual dose-response relationship for each organ at risk for each tumor in each individual patient for the complete oncological treatment package. This includes, but is not limited to, radiotherapy alone. Individualized dose-response curves will allow for consideration of different doses of radiation and combinations with other drugs to plan for both optimal toxicity and complete response. Insights into the interactions between a multitude of parameters will lead to the discovery of new pathways and networks that will fuel new biological research on target discovery.
  • Thumbnail Image
    Item
    Circulating Lymphocyte Counts Early During Radiotherapy are Associated with Recurrence in Pediatric Medulloblastoma
    (Elsevier, 2021) Grassberger, Clemens; Shinnick, Daniel; Yeap, Beow Y.; Tracy, Mark; Ellsworth, Susannah; Hess, Clayton B.; Weyman, Elizabeth A.; Gallotto, Sara L.; Lawell, Miranda P.; Bajaj, Benjamin; Ebb, David H.; Ioakeim-Ioannidou, Myrsini; Loeffler, Jay; MacDonald, Shannon; Tarbell, Nancy J.; Yock, Torunn I.; Radiation Oncology, School of Medicine
    Background Decreased peripheral lymphocyte counts are associated with outcome after RT in several solid tumors, though appear late during or after the radiation course and often correlate with other clinical factors. Here we investigate if absolute lymphocyte counts (ALC) are independently associated with recurrence in pediatric medulloblastoma early during RT. Methods We assessed 202 medulloblastoma patients treated between 2000 and 2016 and analyzed ALC throughout therapy, focusing on both early markers (ALC during week 1 – ALC wk1; grade 3+ Lymphopenia during week 2 – Lymphopenia wk2) and late markers (ALC nadir). Uni- and multivariable regressions were used to assess association of clinical and treatment variables with ALC and of ALC with recurrence. Results Thirty-six recurrences were observed, with a median time to recurrence of 1.6 years (Range 0.2-10.3) and 7.1 years median follow-up. ALC during RT was associated with induction chemotherapy (p<0.001), concurrent carboplatin (p=0.009), age (p=0.01) and high-risk status (p=0.05). On univariable analysis, high-risk disease (HR 2.0[1.06–3.9],p=0.03) and M stage≥1 (HR 2.2[1.1–4.4]) were associated with recurrence risk, as was lower ALC early during RT (ALC wk1 HR 0.28[0.12–0.65],p=0.003; Lymphopenia wk2 HR 2.27[1.1-4.6],p=0.02). Neither baseline ALC nor nadir correlated with outcome. These associations persisted when excluding carboplatin and pre-RT chemotherapy patients, and in the multivariable analysis accounting for confounders lymphocyte counts remain significant (ALC wk1 HR 0.23[0.09–0.57],p=0.002; Lymphopenia wk2 HR 2.3[1.1–4.8],p=0.03). Conclusion ALC during weeks 1 and 2 of RT was associated with recurrence and low ALC is an independent prognostic factor in medulloblastoma. Strategies to mitigate the risk of radiation-induced lymphopenia should be considered.
  • Thumbnail Image
    Item
    Laser-plasma generated very high energy electrons (VHEEs) in radiotherapy
    (SPIE, 2017-05) Kokurewicz, Karolina; Welsh, G. H.; Brunetti, E.; Wiggins, S. Mark; Boyd, M.; Sorensen, A.; Chalmers, A.; Schettino, G.; Subiel, Anna; DesRosiers, Colleen; Jaroszynski, Dino A.; Radiation Oncology, School of Medicine
    As an alternative modality to conventional radiotherapy, electrons with energies above 50 MeV penetrate deeply into tissue, where the dose can be absorbed within a tumour volume with a relatively small penumbra. We investigate the physical properties of VHEEs and review the state-of-the-art in treatment planning and dosimetry. We discuss the advantages of using a laser wake eld accelerator (LWFA) and present the characteristic features of the electron bunch produced by the LWFA and compare them with that from a conventional linear accelerator.
  • Thumbnail Image
    Item
    Nationally representative trends and geographic variation in treatment of localized prostate cancer: the Urologic Diseases in America project
    (Nature Publishing Group, 2015-06) Cary, K. C.; Punnen, S.; Odisho, A. Y.; Litwin, M. S.; Saigal, C. S.; Cooperberg, M. R.; NIDDK Urologic Diseases in America Project; Department of Urology, IU School of Medicine
    BACKGROUND: Several treatment options for clinically localized prostate cancer currently exist under the established guidelines. We aim to assess nationally representative trends in treatment over time and determine potential geographic variation using two large national claims registries. METHODS: Men with prostate cancer insured by Medicare (1998-2006) or a private insurer (Ingenix database, 2002-2006) were identified using International Classification of Diseases-9 and Current Procedural Terminology-4 codes. Geographic variation and trends in the type of treatment utilized over time were assessed. Geographic data were mapped using the GeoCommons online mapping platform. Predictors of any treatment were determined using a hierarchical generalized linear mixed model using the logit link function. RESULTS: The use of radical prostatectomy increased, 33-48%, in the privately insured i3 database while remaining stable at 12% in the Medicare population. There was a rapid uptake in the use of newer technologies over time in both the Medicare and i3 cohorts. The use of laparoscopic-assisted prostatectomy increased from 1% in 2002 to 41% in 2006 in i3 patients, whereas the incidence increased from 3% in 2002 to 35% in 2006 for Medicare patients. The use of neoadjuvant/adjuvant androgen deprivation therapy was lower in the i3 cohort and has decreased over time in both i3 and Medicare. Physician density had an impact on the type of primary treatment received in the New England region; however, this trend was not seen in the western or southern regions of the United States. CONCLUSIONS: Using two large national claims registries, we have demonstrated trends over time and substantial geographic variation in the type of primary treatment used for localized prostate cancer. Specifically, there has been a large increase in the use of newer technologies (that is, laparoscopic-assisted prostatectomy and intensity-modulated radiation therapy). These results elucidate the need for improved data collection on prostate cancer treatment outcomes to reduce unwarranted variation in care.
  • Thumbnail Image
    Item
    Radiation Induced Cerebral Microbleeds in Pediatric Patients with Brain Tumors Treated with Proton Radiotherapy
    (Elsevier, 2018) Kralik, Stephen F.; Mereniuk, Todd R.; Grignon, Laurent; Shih, Chie-Schin; Ho, Chang Y.; Finke, Whitney; Coleman, Peter W.; Watson, Gordon A.; Buchsbaum, Jeffrey; Radiology and Imaging Sciences, School of Medicine
    Purpose Proton beam radiotherapy (PBT) has been increasingly utilized to treat pediatric brain tumors, however, limited information exists regarding radiation induced cerebral microbleeds (CMBs) among these patients. The purpose was to evaluate the incidence, risk factors, and imaging appearance of CMBs in pediatric patients with brain tumors treated with PBT. Methods A retrospective study was performed on 100 pediatric patients with primary brain tumors treated with PBT. CMBs were diagnosed by examining serial MRIs including susceptibility-weighted imaging. Radiation therapy plans were analyzed to determine doses to individual CMBs. Clinical records were used to determine risk factors associated with the development of CMBs in these patients. Results The mean age at time of PBT was 8.1 years. The median follow-up duration was 57 months. The median time to development of CMBs was 8 months (mean 11 months; range 3-28 months). The percentage of patients with CMBs was 43%, 66%, 80%, 81%, 83%, and 81% at 1-year, 2-years, 3-years, 4-year, 5-years, and greater than 5 years from completion of proton radiotherapy. The majority (87%) of CMBs were found in areas of brain exposed to ≥ 30 Gy. Risk factors included maximum radiotherapy dose (P=0.001), percentage and volume of brain exposed to ≥ 30 Gy (P=0.0004; P=0.0005), and patient age at time of PBT (P=0.0004). Chemotherapy was not a significant risk factor (P=0.35). No CMBs required surgical intervention. Conclusion CMBs develop in a high percentage of pediatric patients with brain tumors treated with proton radiotherapy within the first few years following treatment. Significant risk factors for development of CMBs include younger age at time of PBT, higher maximum radiotherapy dose, and higher percentage and volume of brain exposed to ≥ 30 Gy. These findings demonstrate similarities with CMBs that develop in pediatric brain tumor patients treated with photon radiotherapy.
  • Thumbnail Image
    Item
    Radioluminescent nanoparticles for radiation-controlled release of drugs
    (Elsevier, 2019-06) Misra, Rahul; Sarkar, Kaustabh; Lee, Jaewon; Pizzuti, Vincenzo J.; Lee, Deborah S.; Currie, Melanie P.; Torregrosa-Allen, Sandra E.; Long, David E.; Durm, Gregory A.; Langer, Mark P.; Elzey, Bennett D.; Won, You-Yeon; Radiation Oncology, School of Medicine
    The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO4 (CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30–40 fractions of 2–3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle (“PEG-PLA/CWO/PTX”) formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1 month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1 month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO4, or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols.
  • Thumbnail Image
    Item
    Workshop Report for Cancer Research: Defining the Shades of Gy: Utilizing the Biological Consequences of Radiotherapy in the Development of New Treatment Approaches—Meeting Viewpoint
    (AACR, 2018-05) Ahmed, Mansoor M.; Coleman, C. Norman; Mendonca, Marc; Bentzen, Soren; Vikram, Bhadrasain; Seltzer, Stephen M.; Goodhead, Dudley; Obcemea, Ceferino; Mohan, Radhe; Prise, Kevin M.; Capala, Jacek; Citrin, Deborah; Kao, Gary; Aryankalayil, Molykutty; Eke, Iris; Buchsbaum, Jeffrey C.; Prasanna, Pataje G. S.; Liu, Fei-Fei; Le, Quynh-Thu; Teicher, Beverly; Kirsch, David G.; Smart, DeeDee; Tepper, Joel; Formenti, Silvia; Haas-Kogan, Daphne; Raben, David; Mitchell, James; Radiation Oncology, School of Medicine
    The ability to physically target radiotherapy using image-guidance is continually improving with photons and particle therapy that include protons and heavier ions such as carbon. The unit of dose deposited is the gray (Gy); however, particle therapies produce different patterns of ionizations, and there is evidence that the biological effects of radiation depend on dose size, schedule, and type of radiation. This National Cancer Institute (NCI)–sponsored workshop addressed the potential of using radiation-induced biological perturbations in addition to physical dose, Gy, as a transformational approach to quantifying radiation.