University of Wisconsin–Madison
Portrait Michael Bassetti, PhD

Michael Bassetti, MD, PhD

Assistant Professor

Department of Human Oncology

I am an assistant professor in the Department of Human Oncology with a clinical focus on gastrointestinal cancers and research interests in MRI-guided radiation and immunotherapy. I have been developing the use of real-time MRI-guided radiation to reduce toxicity, maximize local control and improve patient outcomes. Additionally, I am involved in combining immunotherapies with anatomically targeted high-dose radiotherapy to improve the antigen specific T cell response.

Cancers of the gastrointestinal tract are in proximity to sensitive normal organs such as intestine, stomach, kidneys and the biliary system. Management of motion during radiation treatment is critical when treating abdominal cancers, which can be heavily influenced by diaphragmatic movement. With the advent of focused, high-dose, stereotactic body radiation therapy (SBRT), tracking the tumor and normal tissues during treatment is critical for the use of hypo-fractionated radiation into the abdomen. MRI guidance has the potential for improved patient alignment and the ability to directly visualize tumor position during radiotherapy treatment. It also allows a much clearer understanding of delivered dose to each organ aiding in our understanding of organ-specific dose tolerance and offering physicians the ability to rapidly alter the radiation treatment plan. I am investigating if this can be used to increase tumor control and decrease associated radiation related toxicity to normal organs. I have been heavily involved in developing clinical trials and protocols for the clinical use for MRI guidance in treatment of GI tumors.

A second research focus is combining stereotactic radiation treatment with immune checkpoint inhibitors. Focused radiation causes a multitude of immunomodulatory effects and there is strong support that this can be synergistic with T cell responses. PD-1 inhibitors that lower the threshold for a T cell response, are being investigated for synergy with radiation to colorectal and pancreatic cancers.

Education

Resident, University of Michigan, Radiation Oncology (2013)

Postdoctoral Fellow, University of Michigan, (2012)

Fellow, University of Michigan, Internal Medicine (2012)

PhD, University of Colorado–Denver, Immunology (2008)

MD, University of Colorado Denver School of Medicine, Medicine (2008)

BS, University of Washington, Biochemistry (1996)

Academic Appointments

Assistant Professor, Human Oncology (2013)

Selected Honors and Awards

Teacher of the Year, American Residents in Radiation Oncology (ARRO) (2015)

Holman Research Pathway Fellowship, American Board of Radiology (2012)

Making a Difference Award (service excellence award), University of Michigan (2010)

Medical Science Research Forum Award, University of Colorado (2003)

Boards, Advisory Committees and Professional Organizations

American Society of Clinical Oncology (ASCO) (2012–pres.)

American Society of Therapeutic Radiation Oncology (ASTRO) Radiation Biology/Cancer Biology Task Force Member (2011–2013)

American Board of Radiology (ABR) Member (2008–pres.)

ASTRO Member (2008–pres.)

Research Focus

MRI-Guided Radiation, Immunotherapy, Combining Stereotactic Radiation Treatment with Immune Checkpoint Inhibitors

  • NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018. J Natl Compr Canc Netw
    Kalemkerian GP, Loo BW, Akerley W, Attia A, Bassetti M, Boumber Y, Decker R, Dobelbower MC, Dowlati A, Downey RJ, Florsheim C, Ganti AKP, Grecula JC, Gubens MA, Hann CL, Hayman JA, Heist RS, Koczywas M, Merritt RE, Mohindra N, Molina J, Moran CA, Morgensztern D, Pokharel S, Portnoy DC, Rhodes D, Rusthoven C, Santana-Davila R, Williams CC, Hoffmann KG, Hughes M
    2018 Oct; 16 (10): 1171-1182
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      The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on "Signs and Symptoms of SCLC" and "Principles of Pathologic Review."

      View details for PubMedID 30323087
  • Investigating a novel split-filter dual-energy CT technique for improving pancreas tumor visibility for radiation therapy. J Appl Clin Med Phys
    Di Maso LD, Huang J, Bassetti MF, DeWerd LA, Miller JR
    2018 Aug 17; :
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      PURPOSE: Tumor delineation using conventional CT images can be a challenge for pancreatic adenocarcinoma where contrast between the tumor and surrounding healthy tissue is low. This work investigates the ability of a split-filter dual-energy CT (DECT) system to improve pancreatic tumor contrast and contrast-to-noise ratio (CNR) for radiation therapy treatment planning.

      MATERIALS AND METHODS: Multiphasic scans of 20 pancreatic tumors were acquired using a split-filter DECT technique with iodinated contrast medium, OMNIPAQUETM . Analysis was performed on the pancreatic and portal venous phases for several types of DECT images. Pancreatic gross target volume (GTV) contrast and CNR were calculated and analyzed from mixed 120 kVp-equivalent images and virtual monoenergetic images (VMI) at 57 and 40 keV. The role of iterative reconstruction on DECT images was also investigated. Paired t-tests were used to assess the difference in GTV contrast and CNR among the different images.

      RESULTS: The VMIs at 40 keV had a 110% greater image noise compared to the mixed 120 kVp-equivalent images (P < 0.0001). VMIs at 40 keV increased GTV contrast from 15.9 ± 19.9 HU to 93.7 ± 49.6 HU and CNR from 1.37 ± 2.05 to 3.86 ± 2.78 in comparison to the mixed 120 kVp-equivalent images. The iterative reconstruction algorithm investigated decreased noise in the VMIs by about 20% and improved CNR by about 30%.

      CONCLUSIONS: Pancreatic tumor contrast and CNR were significantly improved using VMIs reconstructed from the split-filter DECT technique, and the use of iterative reconstruction further improved CNR. This gain in tumor contrast may lead to more accurate tumor delineation for radiation therapy treatment planning.

      View details for PubMedID 30117641
  • A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies. Cureus
    Mittauer K, Paliwal B, Hill P, Bayouth JE, Geurts MW, Baschnagel AM, Bradley KA, Harari PM, Rosenberg S, Brower JV, Wojcieszynski AP, Hullett C, Bayliss RA, Labby ZE, Bassetti MF
    2018 Apr 04; 10 (4): e2422
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      Magnetic resonance-guided radiation therapy (MRgRT) offers advantages for image guidance for radiotherapy treatments as compared to conventional computed tomography (CT)-based modalities. The superior soft tissue contrast of magnetic resonance (MR) enables an improved visualization of the gross tumor and adjacent normal tissues in the treatment of abdominal and thoracic malignancies. Online adaptive capabilities, coupled with advanced motion management of real-time tracking of the tumor, directly allow for high-precision inter-/intrafraction localization. The primary aim of this case series is to describe MR-based interventions for localizing targets not well-visualized with conventional image-guided technologies. The abdominal and thoracic sites of the lung, kidney, liver, and gastric targets are described to illustrate the technological advancement of MR-guidance in radiotherapy.

      View details for PubMedID 29872602
  • Pancreatic gross tumor volume contouring on computed tomography (CT) compared with magnetic resonance imaging (MRI): Results of an international contouring conference. Pract Radiat Oncol
    Hall WA, Heerkens HD, Paulson ES, Meijer GJ, Kotte AN, Knechtges P, Parikh PJ, Bassetti MF, Lee P, Aitken KL, Palta M, Myrehaug S, Koay EJ, Portelance L, Ben-Josef E, Erickson BA
    2018 Mar - Apr; 8 (2): 107-115
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      PURPOSE: Accurate identification of the gross tumor volume (GTV) in pancreatic adenocarcinoma is challenging. We sought to understand differences in GTV delineation using pancreatic computed tomography (CT) compared with magnetic resonance imaging (MRI).

      METHODS AND MATERIALS: Twelve attending radiation oncologists were convened for an international contouring symposium. All participants had a clinical and research interest in pancreatic adenocarcinoma. CT and MRI scans from 3 pancreatic cases were used for contouring. CT and MRI GTVs were analyzed and compared. Interobserver variability was compared using Dice's similarity coefficient (DSC), Hausdorff distances, and Jaccard indices. Mann-Whitney tests were used to check for significant differences. Consensus contours on CT and MRI scans and constructed count maps were used to visualize the agreement. Agreement regarding the optimal method to determine GTV definition using MRI was reached.

      RESULTS: Six contour sets (3 from CT and 3 from MRI) were obtained and compared for each observer, totaling 72 contour sets. The mean volume of contours on CT was significantly larger at 57.48 mL compared with a mean of 45.76 mL on MRI, P = .011. The standard deviation obtained from the CT contours was significantly larger than the standard deviation from the MRI contours (P = .027). The mean DSC was 0.73 for the CT and 0.72 for the MRI (P = .889). The conformity index measurement was similar for CT and MRI (P = .58). Count maps were created to highlight differences in the contours from CT and MRI.

      CONCLUSIONS: Using MRI as a primary image set to define a pancreatic adenocarcinoma GTV resulted in smaller contours compared with CT. No differences in DSC or the conformity index were seen between MRI and CT. A stepwise method is recommended as an approach to contour a pancreatic GTV using MRI.

      View details for PubMedID 29426692
  • Dosimetric Comparison of Real-Time MRI-Guided Tri-Cobalt-60 Versus Linear Accelerator-Based Stereotactic Body Radiation Therapy Lung Cancer Plans. Technol Cancer Res Treat
    Wojcieszynski AP, Hill PM, Rosenberg SA, Hullett CR, Labby ZE, Paliwal B, Geurts MW, Bayliss RA, Bayouth JE, Harari PM, Bassetti MF, Baschnagel AM
    2017 Jun; 16 (3): 366-372
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      PURPOSE: Magnetic resonance imaging-guided radiation therapy has entered clinical practice at several major treatment centers. Treatment of early-stage non-small cell lung cancer with stereotactic body radiation therapy is one potential application of this modality, as some form of respiratory motion management is important to address. We hypothesize that magnetic resonance imaging-guided tri-cobalt-60 radiation therapy can be used to generate clinically acceptable stereotactic body radiation therapy treatment plans. Here, we report on a dosimetric comparison between magnetic resonance imaging-guided radiation therapy plans and internal target volume-based plans utilizing volumetric-modulated arc therapy.

      MATERIALS AND METHODS: Ten patients with early-stage non-small cell lung cancer who underwent radiation therapy planning and treatment were studied. Following 4-dimensional computed tomography, patient images were used to generate clinically deliverable plans. For volumetric-modulated arc therapy plans, the planning tumor volume was defined as an internal target volume + 0.5 cm. For magnetic resonance imaging-guided plans, a single mid-inspiratory cycle was used to define a gross tumor volume, then expanded 0.3 cm to the planning tumor volume. Treatment plan parameters were compared.

      RESULTS: Planning tumor volumes trended larger for volumetric-modulated arc therapy-based plans, with a mean planning tumor volume of 47.4 mL versus 24.8 mL for magnetic resonance imaging-guided plans ( P = .08). Clinically acceptable plans were achievable via both methods, with bilateral lung V20, 3.9% versus 4.8% ( P = .62). The volume of chest wall receiving greater than 30 Gy was also similar, 22.1 versus 19.8 mL ( P = .78), as were all other parameters commonly used for lung stereotactic body radiation therapy. The ratio of the 50% isodose volume to planning tumor volume was lower in volumetric-modulated arc therapy plans, 4.19 versus 10.0 ( P < .001). Heterogeneity index was comparable between plans, 1.25 versus 1.25 ( P = .98).

      CONCLUSION: Magnetic resonance imaging-guided tri-cobalt-60 radiation therapy is capable of delivering lung high-quality stereotactic body radiation therapy plans that are clinically acceptable as compared to volumetric-modulated arc therapy-based plans. Real-time magnetic resonance imaging provides the unique capacity to directly observe tumor motion during treatment for purposes of motion management.

      View details for PubMedID 28168936
  • Minimally Invasive Esophagectomy in a Patient With Tetralogy of Fallot and Right-Sided Aortic Arch. Ann Thorac Surg
    Thomas MJ, Bartlett HL, Bassetti MF, Lubner SJ, Kirvassilis G, Anagnostopoulos PV, Maloney JD, Macke RA
    2017 Jan; 103 (1): e77-e79
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      Improvements in surgical technique and perioperative care have resulted in increased long-term survival for patients with congenital heart disease. As these patients begin to reach their later years, clinicians are challenged with determining optimal management of noncardiac diseases in this complex patient population, including surgically treatable malignancies. We present a case of esophageal cancer in a patient with previously repaired tetralogy of Fallot and right-sided aortic arch, treated with neoadjuvant therapy followed by laparoscopic and left thoracoscopic esophagectomy.

      View details for PubMedID 28007281
  • Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012. Int J Radiat Oncol Biol Phys
    Brower JV, Chen S, Bassetti MF, Yu M, Harari PM, Ritter MA, Baschnagel AM
    2016 Dec 01; 96 (5): 985-993
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      PURPOSE: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy.

      METHODS AND MATERIALS: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching.

      RESULTS: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses).

      CONCLUSIONS: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.

      View details for PubMedID 27869098
  • Online patient information from radiation oncology departments is too complex for the general population. Pract Radiat Oncol
    Rosenberg SA, Francis DM, Hullet CR, Morris ZS, Brower JV, Anderson BM, Bradley KA, Bassetti MF, Kimple RJ
    2017 Jan - Feb; 7 (1): 57-62
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      PURPOSE: Nearly two-thirds of cancer patients seek information about their diagnosis online. We assessed the readability of online patient education materials found on academic radiation oncology department Web sites to determine whether they adhered to guidelines suggesting that information be presented at a sixth-grade reading level.

      METHODS AND MATERIALS: The Association of American Medical Colleges Web site was used to identify all academic radiation oncology departments in the United States. One-third of these department Web sites were selected for analysis using a random number generator. Both general information on radiation therapy and specific information regarding various radiation modalities were collected. To test the hypothesis that the readability of these online educational materials was written at the recommended grade level, a panel of 10 common readability tests was used. A composite grade level of readability was constructed using the 8 readability measures that provide a single grade-level output.

      RESULTS: A mean of 5605 words (range, 2058-12,837) from 30 department Web sites was collected. Using the composite grade level score, the overall mean readability level was determined to be 13.36 (12.83-13.89), corresponding to a collegiate reading level. This was significantly higher than the target sixth-grade reading level (middle school, t (29) = 27.41, P < .001).

      CONCLUSIONS: Online patient educational materials from academic radiation oncology Web sites are significantly more complex than recommended by the National Institutes of Health and the Department of Health and Human Services. To improve patients' comprehension of radiation therapy and its role in their treatment, our analysis suggests that the language used in online patient information should be simplified to communicate the information at a more appropriate level.

      View details for PubMedID 27663932
  • Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites. J Natl Compr Canc Netw
    Rosenberg SA, Francis D, Hullett CR, Morris ZS, Fisher MM, Brower JV, Bradley KA, Anderson BM, Bassetti MF, Kimple RJ
    2016 Jun; 14 (6): 735-40
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      BACKGROUND: The NIH and Department of Health & Human Services recommend online patient information (OPI) be written at a sixth grade level. We used a panel of readability analyses to assess OPI from NCI-Designated Cancer Center (NCIDCC) Web sites.

      METHODS: Cancer.gov was used to identify 68 NCIDCC Web sites from which we collected both general OPI and OPI specific to breast, prostate, lung, and colon cancers. This text was analyzed by 10 commonly used readability tests: the New Dale-Chall Readability Formula, Flesch Reading Ease scale, Flesch-Kinaid Grade Level, FORCAST scale, Fry Readability Graph, Simple Measure of Gobbledygook test, Gunning Frequency of Gobbledygook index, New Fog Count, Raygor Readability Estimate Graph, and Coleman-Liau Index. We tested the hypothesis that the readability of NCIDCC OPI was written at the sixth grade level. Secondary analyses were performed to compare readability of OPI between comprehensive and noncomprehensive centers, by region, and to OPI produced by the American Cancer Society (ACS).

      RESULTS: A mean of 30,507 words from 40 comprehensive and 18 noncomprehensive NCIDCCs was analyzed (7 nonclinical and 3 without appropriate OPI were excluded). Using a composite grade level score, the mean readability score of 12.46 (ie, college level: 95% CI, 12.13-12.79) was significantly greater than the target grade level of 6 (middle-school: P<.001). No difference between comprehensive and noncomprehensive centers was identified. Regional differences were identified in 4 of the 10 readability metrics (P<.05). ACS OPI provides easier language, at the seventh to ninth grade level, across all tests (P<.01).

      CONCLUSIONS: OPI from NCIDCC Web sites is more complex than recommended for the average patient.

      View details for PubMedID 27283166
  • Dosimetric differences in flattened and flattening filter-free beam treatment plans. J Med Phys
    Yan Y, Yadav P, Bassetti M, Du K, Saenz D, Harari P, Paliwal BR
    2016 Apr-Jun; 41 (2): 92-9
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      This study investigated the dosimetric differences in treatment plans from flattened and flattening filter-free (FFF) beams from the TrueBeam System. A total of 104 treatment plans with static (sliding window) intensity-modulated radiotherapy beams and volumetric-modulated arc therapy (VMAT) beams were generated for 15 patients involving three cancer sites. In general, the FFF beam provides similar target coverage as the flattened beam with improved dose sparing to organ-at-risk (OAR). Among all three cancer sites, the head and neck showed more important differences between the flattened beam and FFF beam. The maximum reduction of the FFF beam in the mean dose reached up to 2.82 Gy for larynx in head and neck case. Compared to the 6 MV flattened beam, the 10 MV FFF beam provided improved dose sparing to certain OARs, especially for VMAT cases. Thus, 10 MV FFF beam could be used to improve the treatment plan.

      View details for PubMedID 27217620
  • Gadoxetate for direct tumor therapy and tracking with real-time MRI-guided stereotactic body radiation therapy of the liver. Radiother Oncol
    Wojcieszynski AP, Rosenberg SA, Brower JV, Hullett CR, Geurts MW, Labby ZE, Hill PM, Bayliss RA, Paliwal B, Bayouth JE, Harari PM, Bassetti MF
    2016 Feb; 118 (2): 416-8
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      SBRT is increasingly utilized in liver tumor treatment. MRI-guided RT allows for real-time MRI tracking during therapy. Liver tumors are often poorly visualized and most contrast agents are transient. Gadoxetate may allow for sustained tumor visualization. Here, we report on the first use of gadoxetate during real-time MRI-guided SBRT.

      View details for PubMedID 26627702
  • Adjuvant Chemotherapy for Stage II Rectal Cancer. Semin Oncol
    Deming D, Uboha N, Zafar SY, Rosenberg S, Bassetti M, Glasgow S, Borden EC, Lubner S
    2015 Dec; 42 (6): e99-107
  • Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation. Nat Commun
    Wang L, Liu R, Ye P, Wong C, Chen GY, Zhou P, Sakabe K, Zheng X, Wu W, Zhang P, Jiang T, Bassetti MF, Jube S, Sun Y, Zhang Y, Zheng P, Liu Y
    2015 Jan 20; 6: 5909
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      CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the functional interaction between CD24 and p53, in silico analyses reveal that TP53 mutates at a higher rate among glioma and prostate cancer samples with higher CD24 mRNA levels. These data provide a general mechanism for functional inactivation of ARF and reveal an important cellular context for genetic and viral inactivation of TP53.

      View details for PubMedID 25600590
  • Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med
    Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD
    2013 Dec; 2 (6): 899-906
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      Ipilimumab, an antibody that enhances T-cell activation, may augment immunogenicity of tumor cells that are injured by radiation therapy. We hypothesized that patients with melanoma brain metastasis treated with both ipilimumab and radiotherapy would have improved overall survival, and that the sequence of treatments may affect disease control in the brain. We analyzed the clinical and radiographic records of melanoma patients with brain metastases who were treated with whole brain radiation therapy or stereotactic radiosurgery between 2005 and 2012. The hazard ratios for survival were estimated to assess outcomes as a function of ipilimumab use and radiation type. Seventy patients were identified, 33 of whom received ipilimumab and 37 who did not. The patients who received ipilimumab had a censored median survival of 18.3 months (95% confidence interval 8.1-25.5), compared with 5.3 months (95% confidence interval 4.0-7.6) for patients who did not receive ipilimumab. Ipilimumab and stereotactic radiosurgery were each significant predictors of improved overall survival (hazard ratio = 0.43 and 0.45, with P = 0.005 and 0.008, respectively). Four of 10 evaluable patients (40.0%) who received ipilimumab prior to radiotherapy demonstrated a partial response to radiotherapy, compared with two of 22 evaluable patients (9.1%) who did not receive ipilimumab. Ipilimumab is associated with a significantly reduced risk of death in patients with melanoma brain metastases who underwent radiotherapy, and this finding supports the need for multimodality therapy to optimize patient outcomes. Prospective studies are needed and are underway.

      View details for PubMedID 24403263
  • Current status and recommendations for the future of research, teaching, and testing in the biological sciences of radiation oncology: report of the American Society for Radiation Oncology Cancer Biology/Radiation Biology Task Force, executive summary. Int J Radiat Oncol Biol Phys
    Wallner PE, Anscher MS, Barker CA, Bassetti M, Bristow RG, Cha YI, Dicker AP, Formenti SC, Graves EE, Hahn SM, Hei TK, Kimmelman AC, Kirsch DG, Kozak KR, Lawrence TS, Marples B, McBride WH, Mikkelsen RB, Park CC, Weidhaas JB, Zietman AL, Steinberg M
    2014 Jan 01; 88 (1): 11-7
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      In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective of relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences. The TF was further charged with making suggestions as to critical areas of biological basic research investigation that might be most likely to maintain and build further the scientific foundation and vitality of radiation oncology as an independent and vibrant medical specialty. It was not within the scope of service of the TF to consider the quality of ongoing research efforts within the broader radiation oncology space, to presume to consider their future potential, or to discourage in any way the investigators committed to areas of interest other than those targeted. The TF charge specifically precluded consideration of research issues related to technology, physics, or clinical investigations. This document represents an Executive Summary of the Task Force report.

      View details for PubMedID 24246724
  • Tristetraprolin mediates radiation-induced TNF-α production in lung macrophages. PLoS One
    Ray D, Shukla S, Allam US, Helman A, Ramanand SG, Tran L, Bassetti M, Krishnamurthy PM, Rumschlag M, Paulsen M, Sun L, Shanley TP, Ljungman M, Nyati MK, Zhang M, Lawrence TS
    2013; 8 (2): e57290
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      The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by macrophages. For in vitro studies we irradiated (4 Gy) either a mouse lung macrophage cell line, MH-S or macrophages isolated from TTP knockout mice, and studied the effects of radiation on TTP and TNF-α levels. To study the in vivo relevance, mouse lungs were irradiated with a single dose (15 Gy) and assessed at varying times for TTP alterations. Irradiation of MH-S cells caused TTP to undergo an inhibitory phosphorylation at Ser-178 and proteasome-mediated degradation, which resulted in increased TNF-α mRNA stabilization and secretion. Similarly, MH-S cells treated with TTP siRNA or macrophages isolated from ttp (-/-) mice had higher basal levels of TNF-α, which was increased minimally after irradiation. Conversely, cells overexpressing TTP mutants defective in undergoing phosphorylation released significantly lower levels of TNF-α. Inhibition of p38, a known kinase for TTP, by either siRNA or a small molecule inhibitor abrogated radiation-induced TNF-α release by MH-S cells. Lung irradiation induced TTP(Ser178) phosphorylation and protein degradation and a simultaneous increase in TNF-α production in C57BL/6 mice starting 24 h post-radiation. In conclusion, irradiation of lung macrophages causes TTP inactivation via p38-mediated phosphorylation and proteasome-mediated degradation, leading to TNF-α production. These findings suggest that agents capable of blocking TTP phosphorylation or stabilizing TTP after irradiation could decrease RILT.

      View details for PubMedID 23468959
  • Transgenic Bcl-3 slows T cell proliferation. Int Immunol
    Bassetti MF, White J, Kappler JW, Marrack P
    2009 Apr; 21 (4): 339-48
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      Immunological adjuvants, such as bacterial LPS, increase the mRNA levels of the IkB-related NF-kappaB transcriptional transactivator, Bcl-3, in activated T cells. Adjuvants also increase the life expectancy of activated T cells, as does over-expression of Bcl-3, suggesting that Bcl-3 is part of the pathway whereby adjuvants affect T cell lifespans. However, previous reports, confirmed here, show that adjuvants also increase the life expectancies of Bcl-3-deficient T cells, making Bcl-3's role and effects in adjuvant-induced survival uncertain. To investigate the functions of Bcl-3 further, here we confirm the adjuvant-induced expression of Bcl-3 mRNA and show Bcl-3 induction at the protein level. Bcl-3 was expressed in mice via a transgene driven by the human CD2 promoter. Like other protective events, over-expression of Bcl-3 slows T cell activation very early in T cell responses to antigen, both in vitro and in vivo. This property was intrinsic to the T cells over-expressing the Bcl-3 and did not require Bcl-3 expression by other cells such as antigen-presenting cells.

      View details for PubMedID 19208752
  • Outcomes and effect of radiotherapy in patients with stage I or II diffuse large B-cell lymphoma: a surveillance, epidemiology, and end results analysis. Int J Radiat Oncol Biol Phys
    Ballonoff A, Rusthoven KE, Schwer A, McCammon R, Kavanagh B, Bassetti M, Newman F, Rabinovitch R
    2008 Dec 01; 72 (5): 1465-71
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      PURPOSE: To assess disease-specific survival (DSS), overall survival (OS), and the effect of radiotherapy (RT) in patients with localized diffuse large B-cell lymphoma (DLBCL).

      PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with Stage I, IE, II, or IIE DLBCL between 1988 and 2004. The analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. Patients who had died or were lost to follow-up within 6 months of diagnosis were excluded.

      RESULTS: A total of 13,420 patients met the search criteria. Of these, 5,547 (41%) had received RT and 7,873 (59%) had not. RT was associated with a significant DSS (hazard ratio, 0.82, p <0.0001) and OS benefit that persisted during the 15 years of follow-up. Elderly patients, defined either as those >60 or >70 years old, had significantly improved DSS and OS associated with RT. On multivariate analysis, RT was significantly associated with increased DSS and OS. The 5-year DSS outcomes were highly variable among patient subsets, defined by age, stage, and extranodal disease (range for RT-treated patients, 70% for Stage II, age >60 years to 87% for Stage I, age </=60 years).

      CONCLUSION: This analysis presents the largest detailed data set of Stage I-II DLBCL patients. The results of our study have demonstrated that RT is associated with a survival advantage in patients with localized DLBCL, a benefit that extends to elderly patients. Outcomes for discrete patient subsets varied greatly. The development of tailored therapy according to the relapse risk is warranted, rather than uniform treatment of all early-stage DLBCL.

      View details for PubMedID 18495371
  • Outcomes of patients with n3 neck nodes treated with chemoradiation. Laryngoscope
    Ballonoff A, Raben D, Rusthoven KE, Bassetti M, Kane M, Song JI, Chen C
    2008 Jun; 118 (6): 995-8
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      OBJECTIVE: To evaluate the outcomes of patients with locally advanced head and neck squamous cell carcinoma with N3 neck nodes treated with definitive chemoradiation.

      STUDY DESIGN: Retrospective review.

      METHODS: Thirty-two patients with nonmetastatic locally advanced head and neck squamous cell carcinoma and N3 neck disease treated with concurrent chemoradiation therapy were evaluated. Overall survival, disease- free survival, locoregional control, and distant control were recorded.

      RESULTS: Median follow-up for surviving patients was 25 (range, 3-93) months. Seventeen of 32 (53%) patients failed, 13 in distant sites only, 2 in the neck only, 1 in the neck and a distant site, and 1 in the neck and primary site. The absolute rates of locoregional control and distant control were 88% and 56%, respectively. Actuarial overall survival and disease-free survival at 2 years were 51% and 29%, respectively.

      CONCLUSION: Patients with N3 neck disease treated with chemoradiation experience a very high rate of distant failure. Future studies investigating the role of additional systemic therapy in these patients are warranted.

      View details for PubMedID 18364595
  • A scalable method for multiplex LED-controlled synthesis of DNA in capillaries. Nucleic Acids Res
    Blair S, Richmond K, Rodesch M, Bassetti M, Cerrina F
    2006; 34 (16): e110
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      As research in synthetic biology and genomic sciences becomes more widespread, the need for diverse oligonucleotide populations has increased. To limit reagent cost, it would be advantageous to obtain high quality populations in minute amounts. Towards that end, synthesis of DNA strands in capillaries utilizing photolabile 3-nitrophenylpropyloxycarbonyl (NPPOC) chemistry and ultraviolet-light emitting diodes (UV-LEDs) was examined. Multiple oligonucleotides were made in single capillaries and were characterized by hybridization, sequencing and gene synthesis. DNA synthesized in capillaries was capable of being hybridized and signal intensities correlated with microarray data. Sequencing demonstrated that the oligonucleotides were of high quality (up to 44% perfect sequences). Oligonucleotides were combined and used successfully for gene synthesis. This system offers a novel, scalable method to synthesize high quality oligonucleotides for biological applications.

      View details for PubMedID 16963493

Contact Information

Michael Bassetti, MD, PhD

600 Highland Avenue Madison,
K4/100
Madison, WI 53792