Portrait Michael Bassetti, PhD

Michael Bassetti, MD, PhD

Associate Professor (CHS)

Department of Human Oncology

I am an associate 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

  • Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions Frontiers in oncology
    Hall WA, Small C, Paulson E, Koay EJ, Crane C, Intven M, Daamen LA, Meijer GJ, Heerkens HD, Bassetti M, Rosenberg SA, Aitken K, Myrehaug S, Dawson LA, Lee P, Gani C, Chuong MD, Parikh PJ, Erickson BA
    2021 May 11;11:628155. doi: 10.3389/fonc.2021.628155. eCollection 2021.
    • More

      INTRODUCTION: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC.

      METHODS: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications.

      RESULTS: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed.

      CONCLUSIONS: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

      PMID:34046339 | PMC:PMC8144850 | DOI:10.3389/fonc.2021.628155


      View details for PubMedID 34046339
  • Combining Stereotactic Body Radiotherapy and Microwave Ablation Appears Safe and Feasible for Renal Cell Carcinoma in an Early Series Clinical genitourinary cancer
    Blitzer GC, Wojcieszynski A, Abel EJ, Best S, Lee FT, Hinshaw JL, Wells S, Ziemlewicz TJ, Lubner MG, Alexander M, Yadav P, Bayouth JE, Floberg J, Cooley G, Harari PM, Bassetti MF
    2021 Apr 20:S1558-7673(21)00095-1. doi: 10.1016/j.clgc.2021.04.010. Online ahead of print.
    • More

      Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement. Seven patients with RCC were treated at our institution with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, 2 with grade 1 hematuria and 1 with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR (estimated glomerular filtration rate) preceding and following SBRT and MW ablation was 69 mL/min/1.73 m2 and 68 mL/min/1.73 m2 (P = .19), respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.

      PMID:34024743 | DOI:10.1016/j.clgc.2021.04.010


      View details for PubMedID 34024743
  • Delta radiomics for rectal cancer response prediction using low field magnetic resonance guided radiotherapy: an external validation Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)
    Cusumano D, Boldrini L, Yadav P, Yu G, Musurunu B, Chiloiro G, Piras A, Lenkowicz J, Placidi L, Romano A, Luca VD, Votta C, Barbaro B, Gambacorta MA, Bassetti MF, Yang Y, Indovina L, Valentini V
    2021 Apr;84:186-191. doi: 10.1016/j.ejmp.2021.03.038. Epub 2021 Apr 23.
    • More

      INTRODUCTION: A recent study performed on 16 locally advanced rectal cancer (LARC) patients treated using magnetic resonance guided radiotherapy (MRgRT) has identified two delta radiomics features as predictors of clinical complete response (cCR) after neoadjuvant radio-chemotherapy (nCRT). This study aims to validate these features (ΔLleast and Δglnu) on an external larger dataset, expanding the analysis also for pathological complete response (pCR) prediction.

      METHODS: A total of 43 LARC patients were enrolled: Gross Tumour Volume (GTV) was delineated on T2/T1* MR images acquired during MRgRT and the two delta features were calculated. Receiver Operating Characteristic (ROC) curve analysis was performed on the 16 cases of the original study and the best cut-off value was identified. The performance of ΔLleast and Δglnu was evaluated at the best cut-off value.

      RESULTS: On the original dataset of 16 patients, ΔLleast reported an AUC of 0.81 for cCR and 0.93 for pCR, while Δglnu 0.72 and 0.54 respectively. The best cut-off values of ΔLleast was 0.73 for both outcomes, while Δglnu reported 0.54 for cCR and 0.93 for pCR. At the external validation, ΔLleast showed an accuracy of 81% for cCR and 79% for pCR, while Δglnu reported 63% for cCR and 40% for pCR.

      CONCLUSION: The accuracy of ΔLleast in predicting cCR and pCR is significantly higher than those obtained considering Δglnu, but inferior if compared with other image-based biomarker, such as the early-regression index. Studies with larger cohorts of patients are recommended to further investigate the role of delta radiomic features in MRgRT.

      PMID:33901863 | DOI:10.1016/j.ejmp.2021.03.038


      View details for PubMedID 33901863
  • Evaluating dose constraints for radiation induced liver damage following magnetic resonance image guided Stereotactic Body radiotherapy Physics and imaging in radiation oncology
    Yadav P, Kuczmarska-Haas A, Musunuru HB, Witt J, Blitzer G, Mahler P, Bassetti MF
    2021 Feb 6;17:91-94. doi: 10.1016/j.phro.2021.01.009. eCollection 2021 Jan.
    • More

      This study reports dose corresponding to visible radiation induced liver damage following Stereotactic Body Radiation Therapy (SBRT) for liver metastasis, and the optimal time for follow up scans using post radiation imaging. Diagnostic magnetic resonance scans of nine patients treated with liver SBRT using a 0.35 T MRI-guided radiotherapy system were analyzed. The dice coefficients between the region of visible liver damage and the delivered dose were calculated. A median dose of 35 Gy correlated most closely with the visible radiation induced liver damage. We compared scans over two to nine months and observed maximal dice coefficients at two to five months post radiation. We have presented a new method for developing treatment planning guidelines for liver SBRT.

      PMID:33898785 | PMC:PMC8058022 | DOI:10.1016/j.phro.2021.01.009


      View details for PubMedID 33898785
  • MR-Guided Radiotherapy for Rectal Cancer: Current Perspective on Organ Preservation Frontiers in oncology
    Boldrini L, Intven M, Bassetti M, Valentini V, Gani C
    2021 Mar 30;11:619852. doi: 10.3389/fonc.2021.619852. eCollection 2021.
    • More

      Online MRI-guided radiotherapy (MRgRT) is one of the most recent technological advances in radiotherapy. MRgRT permits the visualization of tumorous and healthy tissue while the patient is on the treatment table and online daily plan adaptations following the observed anatomical changes. In the context of rectal cancer, online MRgRT is a very promising modality due to the pronounced geographical variability of tumor tissues and the surrounding healthy tissues. This current paper will discuss the possible applications of online MRgRT, in particular, in terms of radiotherapy dose escalation and response prediction in organ preservation approaches for rectal cancer.

      PMID:33859937 | PMC:PMC8042309 | DOI:10.3389/fonc.2021.619852


      View details for PubMedID 33859937
  • Review of MR-Guided Radiotherapy for Esophageal Cancer Frontiers in oncology
    Lee SL, Bassetti M, Meijer GJ, Mook S
    2021 Mar 22;11:628009. doi: 10.3389/fonc.2021.628009. eCollection 2021.
    • More

      In this review, we outline the potential benefits and the future role of MRI and MR-guided radiotherapy (MRgRT) in the management of esophageal cancer. Although not currently used in most clinical practice settings, MRI is a useful non-invasive imaging modality that provides excellent soft tissue contrast and the ability to visualize cancer physiology. Chemoradiation therapy with or without surgery is essential for the management of locally advanced esophageal cancer. MRI can help stage esophageal cancer, delineate the gross tumor volume (GTV), and assess the response to chemoradiotherapy. Integrated MRgRT systems can help overcome the challenge of esophageal motion due to respiratory motion by using real-time imaging and tumor tracking with respiratory gating. With daily on-table MRI, shifts in tumor position and tumor regression can be taken into account for online-adaptation. The combination of accurate GTV visualization, respiratory gating, and online adaptive planning, allows for tighter treatment volumes and improved sparing of the surrounding normal organs. This could lead to a reduction in radiotherapy induced cardiac toxicity, pneumonitis and post-operative complications. Tumor physiology as seen on diffusion weighted imaging or dynamic contrast enhancement can help individualize treatments based on the response to chemoradiotherapy. Patients with a complete response on MRI can be considered for organ preservation while patients with no response can be offered an earlier resection. In patients with a partial response to chemoradiotherapy, areas of residual cancer can be targeted for dose escalation. The tighter and more accurate targeting enabled with MRgRT may enable hypofractionated treatment schedules.

      PMID:33828980 | PMC:PMC8019940 | DOI:10.3389/fonc.2021.628009


      View details for PubMedID 33828980
  • Diagnostic Performance of MRI for Esophageal Carcinoma: A Systematic Review and Meta-Analysis Radiology
    Lee SL, Yadav P, Starekova J, Christensen L, Chandereng T, Chappell R, Reeder SB, Bassetti MF
    2021 Jun;299(3):583-594. doi: 10.1148/radiol.2021202857. Epub 2021 Mar 30.
    • More

      Background Although CT, endoscopic US, and PET are critical in determining the appropriate management of esophageal carcinoma (squamous cell carcinoma and adenocarcinoma), previous reports show that staging accuracy remains low, particularly for nodal involvement sensitivity. Purpose To perform a systematic review and meta-analysis to determine the diagnostic performance of MRI for multiple staging thresholds in patients with biopsy-proven esophageal carcinoma (differentiation of stage T0 disease from stage T1 or higher disease, differentiation of stage T2 or lower disease from stage T3 or higher disease, and differentiation of stage N0 disease from stage N1 or higher disease [where T refers to tumor stage and N refers to nodal stage]). Materials and Methods Studies of the diagnostic performance of MRI in determining the stage of esophageal carcinoma in patients before esophagectomy and pathologic staging between 2000 and 2019 were searched in PubMed, Scopus, Web of Science, and Cochrane Library by a librarian and radiation oncologist. Pooled diagnostic performance of MRI was calculated with a bivariate random effects model. Bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2) tool. Results Twenty studies with a total of 984 patients were included in the analysis. Pooled accuracy for stage T0 versus stage T1 or higher had a sensitivity of 92% (95% CI: 82, 96) and a specificity of 67% (95% CI: 51, 81). Pooled accuracy for stage T2 or lower versus stage T3 or higher had a sensitivity of 86% (95% CI: 76, 92) and a specificity of 86% (95% CI: 75, 93). Pooled accuracy for stage N0 versus stage N1 or higher had a sensitivity of 71% (95% CI: 60, 80) and a specificity of 72% (95% CI: 64, 79). The concern for applicability was low for the patient selection, index test, and reference test domains, except for 10% of studies (two of 20) that had unclear concern for patient selection applicability. Conclusion MRI has high sensitivity but low specificity for the detection of esophageal carcinoma, which shows promise for determining neoadjuvant therapy response and for detecting locally advanced disease for potential trimodality therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Leeflang in this issue.

      PMID:33787334 | DOI:10.1148/radiol.2021202857


      View details for PubMedID 33787334
  • Delta Radiomics Analysis for Local Control Prediction in Pancreatic Cancer Patients Treated Using Magnetic Resonance Guided Radiotherapy Diagnostics (Basel, Switzerland)
    Cusumano D, Boldrini L, Yadav P, Casà C, Lee SL, Romano A, Piras A, Chiloiro G, Placidi L, Catucci F, Votta C, Mattiucci GC, Indovina L, Gambacorta MA, Bassetti M, Valentini V
    2021 Jan 5;11(1):72. doi: 10.3390/diagnostics11010072.
    • More

      The aim of this study is to investigate the role of Delta Radiomics analysis in the prediction of one-year local control (1yLC) in patients affected by locally advanced pancreatic cancer (LAPC) and treated using Magnetic Resonance guided Radiotherapy (MRgRT). A total of 35 patients from two institutions were enrolled: A 0.35 Tesla T2*/T1 MR image was acquired for each case during simulation and on each treatment fraction. Physical dose was converted in biologically effective dose (BED) to compensate for different radiotherapy schemes. Delta Radiomics analysis was performed considering the gross tumour volume (GTV) delineated on MR images acquired at BED of 20, 40, and 60 Gy. The performance of the delta features in predicting 1yLC was investigated in terms of Wilcoxon Mann-Whitney test and area under receiver operating characteristic (ROC) curve (AUC). The most significant feature in predicting 1yLC was the variation of cluster shade calculated at BED = 40 Gy, with a p-value of 0.005 and an AUC of 0.78 (0.61-0.94). Delta Radiomics analysis on low-field MR images might play a promising role in 1yLC prediction for LAPC patients: further studies including an external validation dataset and a larger cohort of patients are recommended to confirm the validity of this preliminary experience.

      PMID:33466307 | PMC:PMC7824764 | DOI:10.3390/diagnostics11010072


      View details for PubMedID 33466307
  • Reduction of cardiac dose using respiratory-gated MR-linac plans for gastro-esophageal junction cancer Medical dosimetry : official journal of the American Association of Medical Dosimetrists
    Lee SL, Mahler P, Olson S, Witt JS, Musunuru HB, Rajamanickam V, Bassetti MF, Yadav P
    2021 Summer;46(2):152-156. doi: 10.1016/j.meddos.2020.10.002. Epub 2020 Oct 21.
    • More

      Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

      PMID:33097372 | DOI:10.1016/j.meddos.2020.10.002


      View details for PubMedID 33097372
  • A Phase 1 Dose Escalation Study of Neoadjuvant SBRT Plus Elective Nodal Radiation with Concurrent Capecitabine for Resectable Pancreatic Cancer International journal of radiation oncology, biology, physics
    Witt JS, Kuczmarska-Haas A, Lubner M, Reeder SB, Cho SY, Minter R, Weber S, Ronnekleiv-Kelly S, Abbott D, LoConte N, Mulkerin DL, Lubner SJ, Uboha NV, Deming D, Ritter MA, Mohindra P, Bassetti MF
    2021 Feb 1;109(2):458-463. doi: 10.1016/j.ijrobp.2020.09.010. Epub 2020 Sep 14.
    • More

      PURPOSE: The role of neoadjuvant radiation for resectable pancreatic adenocarcinoma is controversial. We performed a prospective dose-escalation study of neoadjuvant stereotactic body radiation therapy (SBRT) with concurrent capecitabine and elective nodal irradiation (ENI) followed by surgical resection to explore the toxicity and feasibility of this approach.

      METHODS AND MATERIALS: Patients with biopsy proven, resectable cancers of the pancreatic head were enrolled. A 4 + 4 dose-escalation design was employed delivering 5 fractions of 5 to 7 Gy to primary tumor with concurrent capecitabine. The maximum tolerated dose level was expanded for an additional 4 patients. Patients at all dose levels were treated with ENI delivering 25 Gy in 5 fractions. Dose-limiting toxicity was defined as any grade ≥3 nonhematologic toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0) attributable to chemoradiation occurring within 90 days of SBRT.

      RESULTS: A total of 17 patients were enrolled with 16 patients evaluable and 13 patients ultimately proceeding to surgery. The most common toxicity was nausea (56%). There were no dose-limiting toxicities, and SBRT was maximally dose escalated to 35 Gy in 5 fractions for 8 patients. All patients completing surgery had R0 resections. Seven patients (54%) had moderate treatment effect identified in pathologic specimens. Three patients (23%) developed locoregional recurrences, with 2 (15%) partially included within the treated volume.

      CONCLUSIONS: SBRT was safely dose escalated to 35 Gy in 5 fractions along with concurrent capecitabine and ENI. This regimen will be used in a future expansion cohort.

      PMID:32942002 | DOI:10.1016/j.ijrobp.2020.09.010


      View details for PubMedID 32942002
  • External Validation of Early Regression Index (ERI<sub>TCP</sub>) as Predictor of Pathologic Complete Response in Rectal Cancer Using Magnetic Resonance-Guided Radiation Therapy International journal of radiation oncology, biology, physics
    Cusumano D, Boldrini L, Yadav P, Yu G, Musurunu B, Chiloiro G, Piras A, Lenkowicz J, Placidi L, Broggi S, Romano A, Mori M, Barbaro B, Azario L, Gambacorta MA, Spirito MD, Bassetti MF, Yang Y, Fiorino C, Valentini V
    2020 Dec 1;108(5):1347-1356. doi: 10.1016/j.ijrobp.2020.07.2323. Epub 2020 Aug 3.
    • More

      PURPOSE: Tumor control probability (TCP)-based early regression index (ERITCP) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERITCP in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels.

      METHODS AND MATERIALS: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERITCP was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERITCP with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index.

      RESULTS: Fourteen patients showed pCR. ERITCP correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERITCP results are robust with respect to interobserver variability (intraclass correlation index = 0.99).

      CONCLUSIONS: This study confirmed the validity and the robustness of ERITCP as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions.

      PMID:32758641 | DOI:10.1016/j.ijrobp.2020.07.2323


      View details for PubMedID 32758641
  • Investigating split-filter dual-energy CT for improving liver tumor visibility for radiation therapy Journal of applied clinical medical physics
    DiMaso LD, Miller JR, Lawless MJ, Bassetti MF, DeWerd LA, Huang J
    2020 Aug;21(8):249-255. doi: 10.1002/acm2.12904. Epub 2020 May 15.
    • More

      PURPOSE: Accurate liver tumor delineation is crucial for radiation therapy, but liver tumor volumes are difficult to visualize with conventional single-energy CT. This work investigates the use of split-filter dual-energy CT (DECT) for liver tumor visibility by quantifying contrast and contrast-to-noise ratio (CNR).

      METHODS: Split-filter DECT contrast-enhanced scans of 20 liver tumors including cholangiocarcinomas, hepatocellular carcinomas, and liver metastases were acquired. Analysis was performed on the arterial and venous phases of mixed 120 kVp-equivalent images and VMIs at 57 keV and 40 keV gross target volume (GTV) contrast and CNR were calculated.

      RESULTS: For the arterial phase, liver GTV contrast was 12.1 ± 10.0 HU and 43.1 ± 32.3 HU (P < 0.001) for the mixed images and 40 keV VMIs. Image noise increased on average by 116% for the 40 keV VMIs compared to the mixed images. The average CNR did not change significantly (1.6 ± 1.5, 1.7 ± 1.4, 2.4 ± 1.7 for the mixed, 57 keV and 40 keV VMIs (P > 0.141)). For individual cases, however, CNR increases of up to 607% were measured for the 40 keV VMIs compared to the mixed image. Venous phase 40 keV VMIs demonstrated an average increase of 35.4 HU in GTV contrast and 121% increase in image noise. Average CNR values were also not statistically different, but for individual cases CNR increases of up to 554% were measured for the 40 keV VMIs compared to the mixed image.

      CONCLUSIONS: Liver tumor contrast was significantly improved using split-filter DECT 40 keV VMIs compared to mixed images. On average, there was no statistical difference in CNR between the mixed images and VMIs, but for individual cases, CNR was greatly increased for the 57 keV and 40 keV VMIs. Therefore, although not universally successful for our patient cohort, split-filter DECT VMIs may provide substantial gains in tumor visibility of certain liver cases for radiation therapy treatment planning.

      PMID:32410336 | PMC:PMC7484851 | DOI:10.1002/acm2.12904


      View details for PubMedID 32410336
  • Validation of an MR-guided online adaptive radiotherapy (MRgoART) program: Deformation accuracy in a heterogeneous, deformable, anthropomorphic phantom Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
    Mittauer KE, Hill PM, Bassetti MF, Bayouth JE
    2020 May;146:97-109. doi: 10.1016/j.radonc.2020.02.012. Epub 2020 Mar 6.
    • More

      BACKGROUND AND PURPOSE: To investigate deformable image registration (DIR) and multi-fractional dose accumulation accuracy of a clinical MR-guided online adaptive radiotherapy (MRgoART) program, utilizing clinically-based magnitudes of abdominal deformation vector fields (DVFs).

      MATERIALS AND METHODS: A heterogeneous anthropomorphic multi-modality abdominal deformable phantom was comprised of MR and CT anatomically-relevant materials. Thermoluminescent dosimeters (TLDs) were affixed within regions of interest (ROIs). CT and MR simulation scans were acquired. CT was deformed to MR for dose calculations. MRgoART was executed on a MR-linac (MRIdian) for 5 Gy/5 fractions. Before each fraction, a deformation was applied. Ground truth was known for ROI volume, TLD position, and TLD dose measured by an accredited dosimetry calibration laboratory. To validate the range of applied deformations, phantom DVFs were compared to DVFs of clinical abdominal MRgoART fractions. MR-MR deformation accuracy was quantified through dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and as mean-absolute-error (MAE) for CT-MR-MR deformation. Arithmetic-summation of calculated dose at respective TLD positions and deform-accumulated dose (MIM) was compared to TLD measured dose, respectively. MR-MR deformation statistics were quantified for MRIdian and MIM.

      RESULTS: Mean phantom DVFs were 5.0 ± 2.9 mm compared to mean DVF of clinical abdominal patients at 5.2 ± 3.0 mm. Respective mean DSC, HD, MDA was 0.93 ± 0.03, 0.74 ± 0.80 cm, 0.08 ± 0.03 cm for MRIdian and 0.93 ± 0.03, 0.54 ± 0.27 cm, 0.08 ± 0.03 cm for MIM (N = 80 ROIs). Mean MAE was 20.5 HU. Respective mean and median dose differences were 0.3%, -0.3% for arithmetic-summation and 4.1%, 0.6% for deformed-accumulation. Maximum differences were 0.21 Gy (arithmetic-summation), 0.31 Gy (deformed-accumulation).

      CONCLUSIONS: MRgoART deformation and dosimetric accuracy has been benchmarked for mean fractional DVFs of 5 mm in a multiple-rigid-body deformable phantom. Deformation accuracy was within TG132 criteria and clinically acceptable end-to-end MRgoART dosimetric agreement was observed for this phantom. Further efforts are needed in validation of deform-accumulated dose.

      PMID:32146260 | DOI:10.1016/j.radonc.2020.02.012


      View details for PubMedID 32146260
  • MRI-guided adaptive radiotherapy for liver tumours: visualising the future The Lancet. Oncology
    Witt JS, Rosenberg SA, Bassetti MF
    2020 Feb;21(2):e74-e82. doi: 10.1016/S1470-2045(20)30034-6.
    • More

      MRI-guided radiotherapy is a novel and rapidly evolving technology that might enhance the risk-benefit ratio. Through direct visualisation of the tumour and the nearby healthy tissues, the radiation oncologist can deliver highly accurate treatment even to mobile targets. Each individual treatment can be customised to changing anatomy, potentially reducing the risk of radiation-related toxicities while simultaneously increasing the dose delivered to the tumour. MRI-guided radiotherapy offers a new tool for the radiation oncologist, and creates an opportunity to achieve durable local control of liver tumours that might not otherwise be possible. Future work will allow us to expand the population eligible for curative-intent radiotherapy, optimise and customise radiation doses to specific tumours, and hopefully create opportunities for improving outcomes through machine learning and radiomics-based approaches. This Review outlines the current and future applications for MRI-guided radiotherapy with respect to metastatic and primary liver cancers.

      PMID:32007208 | DOI:10.1016/S1470-2045(20)30034-6


      View details for PubMedID 32007208
  • STAT-ART: The Promise and Practice of a Rapid Palliative Single Session of MR-Guided Online Adaptive Radiotherapy (ART) Frontiers in oncology
    Mittauer KE, Hill PM, Geurts MW, Costa AD, Kimple RJ, Bassetti MF, Bayouth JE
    2019 Oct 22;9:1013. doi: 10.3389/fonc.2019.01013. eCollection 2019.
    • More

      This work describes a novel application of MR-guided online adaptive radiotherapy (MRgoART) in the management of patients whom urgent palliative care is indicated using statum-adaptive radiotherapy (STAT-ART). The implementation of STAT-ART, as performed at our institution, is presented including a discussion of the advantages and limitations compared to the standard of care for palliative radiotherapy on conventional c-arm linacs. MR-based treatment planning techniques of STAT-ART for density overrides and deformable image registration (DIR) of diagnostic CT to the treatment MR are also addressed.

      PMID:31696053 | PMC:PMC6817496 | DOI:10.3389/fonc.2019.01013


      View details for PubMedID 31696053
  • The transformation of radiation oncology using real-time magnetic resonance guidance: A review European journal of cancer (Oxford, England : 1990)
    Hall WA, Paulson ES, Heide vd, Fuller CD, Raaymakers BW, Lagendijk JW, Li XA, Jaffray DA, Dawson LA, Erickson B, Verheij M, Harrington KJ, Sahgal A, Lee P, Parikh PJ, Bassetti MF, Robinson CG, Minsky BD, Choudhury A, Tersteeg HA, Schultz CJ, Consortium CR
    2019 Nov;122:42-52. doi: 10.1016/j.ejca.2019.07.021. Epub 2019 Oct 12.
    • More

      Radiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment. These impacts extend beyond improved imaging and dose deposition. Real-time MRI-guided RT is actively transforming the work flows and capabilities of virtually every aspect of RT. It has the opportunity to change entirely the delivery methods and response assessments of numerous malignancies. This review intends to approach the topic of MRI-based RT guidance from a vendor neutral and international perspective. It also aims to provide an introduction to this topic targeted towards oncologists without a speciality focus in RT. Speciality implications, areas for physician education and research opportunities are identified as they are associated with MRI-guided RT. The uniquely disruptive implications of MRI-guided RT are discussed and placed in context. We further aim to describe and outline important future changes to the speciality of radiation oncology that will occur with MRI-guided RT. The impacts on RT caused by MRI guidance include target identification, RT planning, quality assurance, treatment delivery, training, clinical workflow, tumour response assessment and treatment scheduling. In addition, entirely novel research areas that may be enabled by MRI guidance are identified for future investigation.

      PMID:31614288 | DOI:10.1016/j.ejca.2019.07.021


      View details for PubMedID 31614288
  • Impact of adjuvant fractionated stereotactic radiotherapy dose on local control of brain metastases Journal of neuro-oncology
    Musunuru HB, Witt JS, Yadav P, Francis DM, Kuczmarska-Haas A, Labby ZE, Bassetti MF, Howard SP, Baschnagel AM
    2019 Nov;145(2):385-390. doi: 10.1007/s11060-019-03308-7. Epub 2019 Oct 12.
    • More

      PURPOSE: The aim of this study was to determine whether a higher biological effective dose (BED) would result in improved local control in patients treated with fractionated stereotactic radiotherapy (FSRT) for their resected brain metastases.

      METHODS: Patients with newly diagnosed brain metastases without previous brain radiotherapy were retrospectively reviewed. Patients underwent surgical resection of at least one brain metastasis and were treated with adjuvant FSRT, delivering 25-36 Gy in 5-6 fractions. Outcomes were computed using Kaplan-Meier survival analysis and univariate analysis.

      RESULTS: Fifty-four patients with 63 post-operative cavities were included. Median follow-up was 16 months (3-60). Median metastasis size at diagnosis was 2.9 cm (0.6-8.1) and median planning target volume was 19.7 cm3 (6.3-68.1). Two-year local control (LC) was 83%. When stratified by dose, 2 years LC rate was 95.1% in those treated with 30-36 Gy in 5-6 fractions (BED10 of 48-57.6 Gy10) versus 59.1% lesions treated with 25 Gy in 5 fractions (BED10 of 37.5 Gy10) (p < 0.001). LC was not associated with resection cavity size. One year overall survival was 68.7%, and was independent of BED10. Symptomatic radiation necrosis occurred in 7.9% of patients and was not associated with dose.

      CONCLUSION: In the post-operative setting, high-dose FSRT (BED10 > 37.5 Gy10) were associated with a significantly higher rate of LC compared to lower BED regimens. Overall, 25 Gy in 5 fractions is not an adequate dose to control microscopic disease. If selecting a 5-fraction regimen, 30 Gy in five fractions appears to provide excellent tumor bed control.

      PMID:31606876 | DOI:10.1007/s11060-019-03308-7


      View details for PubMedID 31606876
  • Dosimetric study for spine stereotactic body radiation therapy: magnetic resonance guided linear accelerator versus volumetric modulated arc therapy Radiology and oncology
    Yadav P, Musunuru HB, Witt JS, Bassetti M, Bayouth J, Baschnagel AM
    2019 Sep 24;53(3):362-368. doi: 10.2478/raon-2019-0042.
    • More

      Background Stereotactic body radiation therapy (SBRT) given in 1-5 fractions is an effective treatment for vertebral metastases. Real-time magnetic resonance-guided radiotherapy (MRgRT) improves soft tissue contrast, which translates into accurate delivery of spine SBRT. Here we report on clinical implementation of MRgRT for spine SBRT, the quality of MRgRT plans compared to TrueBeam based volumetric modulated arc therapy (VMAT) plans in the treatment of spine metastases and benefits of MRgRT MR scan. Patients and methods Ten metastatic lesions were included in this study for plan comparison. Lesions were spread across thoracic spine and lumbosacral spine. Three fraction spine SBRT plans: 27Gy to planning target volume (PTV) and 30Gy to gross tumor volume (GTV) were generated on the ViewRay MRIdian Linac system and compared to TrueBeamTM STx based VMAT plans. Plans were compared using metrics such as minimum dose, maximum dose, mean dose, ratio of the dose to 50% of the volume (R50), conformity index, homogeneity index and dose to the spinal cord. Results MRIdian plans achieved equivalent target coverage and spinal cord dose compared to VMAT plans. The maximum and minimum PTV doses and homogeneity index were equivalent for both planning systems. R50 was lower for MRIdian plans compared to VMAT plans, indicating a lower spread of intermediate doses with MRIdian system (5.16 vs. 6.11, p = 0.03). Conclusions MRgRT can deliver high-quality spine SBRT plans comparable to TrueBeam volumetric modulated arc therapy (VMAT) plans.

      PMID:31553704 | PMC:PMC6765155 | DOI:10.2478/raon-2019-0042


      View details for PubMedID 31553704
  • Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation American journal of clinical oncology
    Witt JS, Jagodinsky JC, Liu Y, Yadav P, Kuczmarska-Haas A, Yu M, Maloney JD, Ritter MA, Bassetti MF, Baschnagel AM
    2019 Aug;42(8):662-667. doi: 10.1097/COC.0000000000000573.
    • More

      PURPOSE: The purpose of this study was to evaluate predictors of cardiac events in esophageal cancer patients treated with neoadjuvant chemoradiotherapy (NA CRT) followed by surgery compared with surgery alone.

      MATERIALS AND METHODS: We retrospectively identified patients treated for esophageal cancer between 2006 and 2016. A total of 123 patients were identified; 70 were treated with surgery alone, and 53 were treated with NA CRT. Cardiac events were scored based on Common Terminology Criteria for Adverse Events (version 4.03), and dosimetric data was compiled for all patients who received radiation. Univariate analysis and multivariable analysis (MVA) were performed to identify predictors of cardiac events. Competing risk of death regression was performed to a model the cumulative incidence of cardiac events.

      RESULTS: The overall rates of grade ≥3 cardiac events were 24.5% in the NA CRT group versus 10% in the surgery group (P=0.04). On MVA, use of NA CRT (P<0.01, hazard ratio [HR]: 3.45, 95% confidence interval [CI]: 1.35-9.09) predicted for grade ≥3 cardiac events, though no dosimetric variable predicted for grade ≥3 cardiac events or overall survival. On MVA, NA CRT predicted for pericardial effusions of any grade (P<0.01, HR: 3.70, 95% CI: 1.67-8.33). The V45 Gy was the most significant predictor of pericardial effusions (P=0.012, HR: 1.03, 95% CI: 1.01-1.06) CONCLUSIONS:: NA CRT significantly increased the rate of grade ≥3 cardiac events compared with patients treated with surgery alone. Although no dosimetric parameter predicted for grade ≥3 cardiac events or survival, the V45 Gy predicted for pericardial effusions.

      PMID:31313677 | PMC:PMC6828548 | DOI:10.1097/COC.0000000000000573


      View details for PubMedID 31313677
  • Patient-Derived Cancer Organoid Cultures to Predict Sensitivity to Chemotherapy and Radiation Clinical cancer research : an official journal of the American Association for Cancer Research
    Pasch CA, Favreau PF, Yueh AE, Babiarz CP, Gillette AA, Sharick JT, Karim MR, Nickel KP, DeZeeuw AK, Sprackling CM, Emmerich PB, DeStefanis RA, Pitera RT, Payne SN, Korkos DP, Clipson L, Walsh CM, Miller D, Carchman EH, Burkard ME, Lemmon KK, Matkowskyj KA, Newton MA, Ong IM, Bassetti MF, Kimple RJ, Skala MC, Deming DA
    2019 Sep 1;25(17):5376-5387. doi: 10.1158/1078-0432.CCR-18-3590. Epub 2019 Jun 7.
    • More

      PURPOSE: Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts treatment sensitivity for individual patients is needed.

      EXPERIMENTAL DESIGN: Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, and response to chemotherapy and radiation were assessed using bright-field and optical metabolic imaging on spheroid and single-cell levels, respectively.

      RESULTS: We demonstrate that patient-derived cancer organoids represent the cancers from which they were derived, including key histologic and molecular features. These cultures were generated from numerous cancers, various biopsy sample types, and in different clinical settings. Next-generation sequencing reveals the presence of subclonal populations within the organoid cultures. These cultures allow for the detection of clonal heterogeneity with a greater sensitivity than bulk tumor sequencing. Optical metabolic imaging of these organoids provides cell-level quantification of treatment response and tumor heterogeneity allowing for resolution of therapeutic differences between patient samples. Using this technology, we prospectively predict treatment response for a patient with metastatic colorectal cancer.

      CONCLUSIONS: These studies add to the literature demonstrating feasibility to grow clinical patient-derived organotypic cultures for treatment effectiveness testing. Together, these culture methods and response assessment techniques hold great promise to predict treatment sensitivity for patients with cancer undergoing chemotherapy and/or radiation.

      PMID:31175091 | PMC:PMC6726566 | DOI:10.1158/1078-0432.CCR-18-3590


      View details for PubMedID 31175091
  • Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer Cancer medicine
    Rudra S, Jiang N, Rosenberg SA, Olsen JR, Roach MC, Wan L, Portelance L, Mellon EA, Bruynzeel A, Lagerwaard F, Bassetti MF, Parikh PJ, Lee PP
    2019 May;8(5):2123-2132. doi: 10.1002/cam4.2100. Epub 2019 Apr 1.
    • More

      BACKGROUND: Adaptive magnetic resonance imaging-guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation.

      METHODS: We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high-dose (biologically effective dose [BED10 ] >70) and standard-dose groups (BED10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan-Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT.

      RESULTS: Median follow-up was 17 months. High-dose patients (n = 24, 55%) had statistically significant improvement in 2-year OS (49% vs 30%, P = 0.03) and trended towards significance for 2-year FFLF (77% vs 57%, P = 0.15) compared to standard-dose patients (n = 20, 45%). FFDF at 18 months in high-dose vs standard-dose groups was 24% vs 48%, respectively (P = 0.92). High-dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21-0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72-0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard-dose group and did not occur in the high-dose group.

      CONCLUSIONS: Patients treated with dose-escalated MRgRT demonstrated improved OS. Prospective evaluation of high-dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted.

      PMID:30932367 | PMC:PMC6536981 | DOI:10.1002/cam4.2100


      View details for PubMedID 30932367
  • A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy Advances in radiation oncology
    Rosenberg SA, Henke LE, Shaverdian N, Mittauer K, Wojcieszynski AP, Hullett CR, Kamrava M, Lamb J, Cao M, Green OL, Kashani R, Paliwal B, Bayouth J, Harari PM, Olsen JR, Lee P, Parikh PJ, Bassetti M
    2018 Aug 23;4(1):142-149. doi: 10.1016/j.adro.2018.08.005. eCollection 2019 Jan-Mar.
    • More

      PURPOSE: Daily magnetic resonance (MR)-guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment.

      METHODS AND MATERIALS: Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test.

      RESULTS: The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively.

      CONCLUSIONS: This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

      PMID:30706022 | PMC:PMC6349638 | DOI:10.1016/j.adro.2018.08.005


      View details for PubMedID 30706022
  • NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018 Journal of the National Comprehensive Cancer Network : JNCCN
    Kalemkerian GP, Loo BW, Akerley W, Attia A, Bassetti M, Boumber Y, Decker R, Dobelbower MC, Dowlati A, Downey RJ, Florsheim C, Ganti KP, 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, Sands J, Santana-Davila R, Williams CC, Hoffmann KG, Hughes M
    2018 Oct;16(10):1171-1182. doi: 10.6004/jnccn.2018.0079.
    • More

      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."

      PMID:30323087 | DOI:10.6004/jnccn.2018.0079


      View details for PubMedID 30323087
  • Investigating a novel split-filter dual-energy CT technique for improving pancreas tumor visibility for radiation therapy Journal of applied clinical medical physics
    Maso DD, Huang J, Bassetti MF, DeWerd LA, Miller JR
    2018 Sep;19(5):676-683. doi: 10.1002/acm2.12435. Epub 2018 Aug 17.
    • More

      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.

      PMID:30117641 | PMC:PMC6123148 | DOI:10.1002/acm2.12435


      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 4;10(4):e2422. doi: 10.7759/cureus.2422.
    • More

      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.

      PMID:29872602 | PMC:PMC5985918 | DOI:10.7759/cureus.2422


      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 Practical radiation oncology
    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. doi: 10.1016/j.prro.2017.11.005. Epub 2017 Nov 29.
    • More

      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.

      PMID:29426692 | DOI:10.1016/j.prro.2017.11.005


      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 Technology in cancer research & treatment
    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. doi: 10.1177/1533034617691407. Epub 2017 Feb 7.
    • More

      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.

      PMID:28168936 | PMC:PMC5616053 | DOI:10.1177/1533034617691407


      View details for PubMedID 28168936
  • Minimally Invasive Esophagectomy in a Patient With Tetralogy of Fallot and Right-Sided Aortic Arch The Annals of thoracic surgery
    Thomas MJ, Bartlett HL, Bassetti MF, Lubner SJ, Kirvassilis G, Anagnostopoulos PV, Maloney JD, Macke RA
    2017 Jan;103(1):e77-e79. doi: 10.1016/j.athoracsur.2016.06.092.
    • More

      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.

      PMID:28007281 | DOI:10.1016/j.athoracsur.2016.06.092


      View details for PubMedID 28007281
  • Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012 International journal of radiation oncology, biology, physics
    Brower JV, Chen S, Bassetti MF, Yu M, Harari PM, Ritter MA, Baschnagel AM
    2016 Dec 1;96(5):985-993. doi: 10.1016/j.ijrobp.2016.08.016. Epub 2016 Aug 23.
    • More

      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.

      PMID:27869098 | DOI:10.1016/j.ijrobp.2016.08.016


      View details for PubMedID 27869098
  • Online patient information from radiation oncology departments is too complex for the general population Practical radiation oncology
    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. doi: 10.1016/j.prro.2016.07.008. Epub 2016 Aug 1.
    • More

      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.

      PMID:27663932 | PMC:PMC5219938 | DOI:10.1016/j.prro.2016.07.008


      View details for PubMedID 27663932
  • Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites Journal of the National Comprehensive Cancer Network : JNCCN
    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. doi: 10.6004/jnccn.2016.0075.
    • More

      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.

      PMID:27283166 | PMC:PMC7236813 | DOI:10.6004/jnccn.2016.0075


      View details for PubMedID 27283166
  • Dosimetric differences in flattened and flattening filter-free beam treatment plans Journal of medical physics
    Yan Y, Yadav P, Bassetti M, Du K, Saenz D, Harari P, Paliwal BR
    2016 Apr-Jun;41(2):92-9. doi: 10.4103/0971-6203.181636.
    • More

      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.

      PMID:27217620 | PMC:PMC4871009 | DOI:10.4103/0971-6203.181636


      View details for PubMedID 27217620
  • Gadoxetate for direct tumor therapy and tracking with real-time MRI-guided stereotactic body radiation therapy of the liver Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
    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. doi: 10.1016/j.radonc.2015.10.024. Epub 2015 Nov 25.
    • More

      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.

      PMID:26627702 | DOI:10.1016/j.radonc.2015.10.024


      View details for PubMedID 26627702
  • Adjuvant Chemotherapy for Stage II Rectal Cancer Seminars in oncology
    Deming D, Uboha N, Zafar SY, Rosenberg S, Bassetti M, Glasgow S, Borden EC, Lubner S
    2015 Dec;42(6):e99-107. doi: 10.1053/j.seminoncol.2015.09.033. Epub 2015 Sep 21.
  • Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation Nature communications
    Wang L, Liu R, Ye P, Wong C, Chen G, 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. doi: 10.1038/ncomms6909.
    • More

      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.

      PMID:25600590 | PMC:PMC4300525 | DOI:10.1038/ncomms6909


      View details for PubMedID 25600590
  • Ipilimumab and radiation therapy for melanoma brain metastases Cancer medicine
    Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD
    2013 Dec;2(6):899-906. doi: 10.1002/cam4.140. Epub 2013 Oct 10.
    • More

      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.

      PMID:24403263 | PMC:PMC3892394 | DOI:10.1002/cam4.140


      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 International journal of radiation oncology, biology, physics
    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 1;88(1):11-7. doi: 10.1016/j.ijrobp.2013.09.040. Epub 2013 Nov 15.
    • More

      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.

      PMID:24246724 | DOI:10.1016/j.ijrobp.2013.09.040


      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. doi: 10.1371/journal.pone.0057290. Epub 2013 Feb 28.
    • More

      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.

      PMID:23468959 | PMC:PMC3585360 | DOI:10.1371/journal.pone.0057290


      View details for PubMedID 23468959
  • Transgenic Bcl-3 slows T cell proliferation International immunology
    Bassetti FJ, White J, Kappler JW, Marrack P
    2009 Apr;21(4):339-48. doi: 10.1093/intimm/dxp002. Epub 2009 Feb 10.
    • More

      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.

      PMID:19208752 | PMC:PMC2660861 | DOI:10.1093/intimm/dxp002


      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 International journal of radiation oncology, biology, physics
    Ballonoff A, Rusthoven KE, Schwer A, McCammon R, Kavanagh B, Bassetti M, Newman F, Rabinovitch R
    2008 Dec 1;72(5):1465-71. doi: 10.1016/j.ijrobp.2008.02.068. Epub 2008 May 19.
    • More

      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.

      PMID:18495371 | DOI:10.1016/j.ijrobp.2008.02.068


      View details for PubMedID 18495371
  • Outcomes of patients with n3 neck nodes treated with chemoradiation The Laryngoscope
    Ballonoff A, Raben D, Rusthoven KE, Bassetti M, Kane M, Song JI, Chen C
    2008 Jun;118(6):995-8. doi: 10.1097/MLG.0b013e31816a7120.
    • More

      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.

      PMID:18364595 | DOI:10.1097/MLG.0b013e31816a7120


      View details for PubMedID 18364595
  • A scalable method for multiplex LED-controlled synthesis of DNA in capillaries Nucleic acids research
    Blair S, Richmond K, Rodesch M, Bassetti M, Cerrina F
    2006;34(16):e110. doi: 10.1093/nar/gkl641. Epub 2006 Sep 8.
    • More

      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.

      PMID:16963493 | PMC:PMC1636377 | DOI:10.1093/nar/gkl641


      View details for PubMedID 16963493

Contact Information

Michael Bassetti, MD, PhD

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