Stephen Rosenberg, Post Grad Trainee

Stephen Rosenberg, MD

Radiation Oncology Resident

Department of Human Oncology

Education

MD, Rutgers Robert Wood Johnson Medical School, (2013)

MS, Rutgers Graduate School of Biomedical Sciences, Clinical and Translational Science (2011)

BS, Brown University, (2008)

Selected Honors and Awards

Outstanding Resident Award, University of Wisconsin School of Medicine and Public Health (2017)

American College of Radiation Oncology (ACRO) Essay Travel Award (2016)

American Society of Clinical Oncology (ASCO) Conquer Cancer Foundation Oncology Trainee Travel Award (2015)

Dr. Suzanne Munson Intern of the Year Award, Memorial Sloan Kettering Cancer Center (2014)

Outstanding Academic Achievement, Rutgers Graduate School of Biomedical Sciences (2011)

Howard Hughes Medical Institute (HHMI) Medical Fellowat Rutgers Robert Wood Johnson Medical School (2010–2011)

Dean’s Scholarship, Rutgers Graduate School of Biomedical Sciences, Full-Tuition Academic Scholarship for Masters of Science in Clinical and Translational Science (2009–2010)

George Smith Endowed Scholarship Trust, Full-Tuition Academic Scholarship to Rutgers Robert Wood Johnson Medical School (2008–2013)

Honors within Biological Sciences (Dissertation), Brown University (2008)

Magna Cum Laude, Brown University (2008)

Sigma Xi, Honor Research Society, Brown University (2008)

Senior Prize in Biology, Brown University (2008)

“For Our Girls” Memorial Award, NJ College Scholarship (2004)

Boards, Advisory Committees and Professional Organizations

Resident Representative, Program Evaluation Committee, University of Wisconsin (2017–pres.)

Committee Member, ARRO Educational Committee (2015–pres.)

European Society for Radiotherapy and Oncology (ESTRO) (2015–pres.)

American College of Radiation Oncology (ACRO) (2014–pres.)

American College of Radiology (ACR) (2014–pres.)

Radiological Society of North America (RSNA) (2014–pres.)

Graduate Medical Education Committee Representative, Memorial Sloan Kettering Cancer Center (2013–2014)

American Society for Radiation Oncology (ASTRO) (2012–pres.)

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

Alumni Interviewer, Brown University Admissions (2011–pres.)

New York Academy of Sciences (NYAS) (2011–pres.)

Medical Student Course Representative, Rutgers Robert Wood Johnson Medical School (2009–2010)

  • Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Cancer Med
    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 Apr 01; :
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      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.

      View details for PubMedID 30932367
  • The Impact of MRI on Radiation Oncology Graduate Medical Education. J Am Coll Radiol
    Singer L, Rosenberg SA
    2019 Feb 05; :
  • A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy. Adv Radiat Oncol
    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
    2019 Jan-Mar; 4 (1): 142-149
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      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.

      View details for PubMedID 30706022
  • Low cardiac and left anterior descending coronary artery dose achieved with left-sided multicatheter interstitial-accelerated partial breast irradiation. Brachytherapy
    Witt JS, Gao RW, Sudmeier LJ, Rosenberg SA, Francis DM, Wallace CR, Das RK, Anderson BM
    2019 Jan - Feb; 18 (1): 50-56
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      PURPOSE: Studies have shown that an additional mean dose of 1 Gy to the heart can increase the relative risk of cardiac events. The purpose of this study was to quantify the dose delivered to the heart and left anterior descending artery (LAD) in a series of patients with left-sided breast cancer (BC) or ductal carcinoma in situ treated with multicatheter-accelerated partial breast irradiation (MC-APBI) at a single institution.

      METHODS AND MATERIALS: Patients with left-sided BC or ductal carcinoma in situ treated consecutively from 2005 to 2011 with MC-APBI were retrospectively identified. Cardiac and LAD contours were generated for each patient. Cardiac dosimetry and distance to the planning target volume were recorded. Patient health records were reviewed and cardiac events were recorded based on Common Terminology Criteria for Adverse Events version 4.0.

      RESULTS: Twenty consecutive patients with left-sided BC treated with MC-APBI were retrospectively identified. Median followup was 41.4 months. Mean equivalent dose in 2 Gy fractions delivered to the heart and LAD were 1.3 (standard deviation: 0.7, range: 0.2-2.9) and 3.8 (standard deviation: 3.0, range: 0.4-11.3) Gy, respectively. There was an inverse linear relationship (R2 = 0.52) between heart-to-lumpectomy cavity distance and mean heart equivalent dose in 2 Gy fractions. One patient (5%) experienced symptomatic cardiac toxicity.

      CONCLUSIONS: MC-APBI consistently delivers average doses to the heart and LAD that are similar to those achieved in most series with deep inspiration breath-hold and lower than free-breathing radiotherapy techniques. Distance from the heart to the lumpectomy cavity and the availability of other heart-sparing technologies should be considered to minimize the risk of cardiac toxicity.

      View details for PubMedID 30262411
  • In Reply to Lin and Golden. Int J Radiat Oncol Biol Phys
    Jang S, Rosenberg SA, Bradley KA, Kimple RJ
    2018 Nov 01; 102 (3): 672
  • Results From 10 Years of a Free Oral Cancer Screening Clinic at a Major Academic Health Center. Int J Radiat Oncol Biol Phys
    Blitzer GC, Rosenberg SA, Anderson BM, McCulloch TM, Wieland AM, Hartig GK, Bruce JY, Witek ME, Kimple RJ, Harari PM
    2018 09 01; 102 (1): 146-148
  • Beyond 'charting outcomes' in the radiation oncology match: analysis of self-reported applicant data. Med Educ Online
    Jang S, Rosenberg SA, Hullett C, Bradley KA, Kimple RJ
    2018 Dec; 23 (1): 1489691
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      The Charting Outcomes resource is useful in gauging an applicant's competiveness for a given specialty. However, many variables are not reported in Charting Outcomes that may influence an applicant's ability to match. A significant proportion of applicants record their experiences in an anonymous, self-reported applicant spreadsheet. We analyzed factors associated with a successful match using this dataset to test the hypothesis that research productivity and high academic performance correlates with success rates. A retrospective analysis of "RadOnc Interview Spreadsheet" for the 2015, 2016, and 2017 radiation oncology match was performed. Data were accessed via studentdoctor.net. Board scores, research characteristics, Sub-I participation, and interview invitation rates were available. Mann-Whitney U, Kruskal-Wallis, and chi-square tests were used for statistical analysis. When possible, results were compared to those reported in the National Residency Match Program's "Charting Outcomes" report. A total of 158 applicants were examined for the applicant characteristics. Applicants applied to a median of 61 programs and received a median of 14 interviews. The mean step 1 score was 248 (range: 198 to 272) and most were in the highest grade point average quartile (68.3%). 21.7% participated in additional research year(s), and 19% obtained a PhD. The majority of applicants took three radiation oncology electives (48.7%). On multivariate analysis, alpha-omega-alpha (AOA) honors society status (p=0.033), participating in a research year (p=0.001) and number of journal publications (p=0.047) significantly correlated with higher interview invitation rates. In summary, this study identifies important considerations for radiation oncology applicants that have not been previously reported, such as induction into AOA and number of journal publications.

      View details for PubMedID 29943670
  • In Reply to Hamstra. Int J Radiat Oncol Biol Phys
    Rosenberg SA, Bradley KA, Kimple RJ
    2018 Apr 01; 100 (5): 1293-1294
  • Bone marrow suppression as a complication of total skin helical tomotherapy in the treatment of mycosis fungoides. Radiat Oncol
    Schaff EM, Rosenberg SA, Olson SJ, Howard SP, Bradley KA
    2018 Apr 13; 13 (1): 67
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      BACKGROUND: Total skin electron beam therapy (TSEBT) is an effective treatment in mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to TSEBT and may offer several dosimetric and treatment advantages. There are currently very few published treatment results using TSHT in place of TSEBT for treatment of mycosis fungoides.

      CASE PRESENTATION: Two patients with mycosis fungoides were treated at our institution using TSHT. The first patient was a 69-year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated to a dose of 12 Gy in 8 fractions, with a bone marrow mean dose of 1.66 Gy and V10 = 0.41%. Two weeks after ending treatment the patient developed myelosuppression including grade 4 thrombocytopenia and required blood and platelet transfusions. The second patient was a 29-year-old Caucasian female with stage I (T2 N0 M0 B0) disease. This patient previously had been treated for mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a localized region and experienced mild thrombocytopenia at that time. The patient then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6 fractions with a mean bone marrow dose of 2.3 Gy and V10 = 4.28%. This patient once again experienced myelosuppression that included grade 4 thrombocytopenia. She also required blood and platelet transfusions.

      CONCLUSIONS: Both patients treated with TSHT experienced severe bone marrow suppression including grade 4 thrombocytopenia. This was more severe than expected considering the relatively low overall prescription dose and despite a planning constraint placed on the bone marrow of a mean dose of < 2 Gy. These outcomes suggest that patients treated using TSHT should be closely monitored for myelosuppression and caution used even when treating to a dose of 12 Gy.

      View details for PubMedID 29653544
  • Value of Elective Radiation Oncology Rotations: How Many Is Too Many? Int J Radiat Oncol Biol Phys
    Jang S, Rosenberg SA, Hullet C, Bradley KA, Kimple RJ
    2018 03 01; 100 (3): 558-559
  • Primary intracranial leiomyosarcoma in an immunocompetent patient: Case report and review of the literature. Clin Neurol Neurosurg
    Gallagher SJ, Rosenberg SA, Francis D, Salamat S, Howard SP, Kimple RJ
    2018 02; 165: 76-80
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      Primary leiomyosarcoma is a rare tumor in the CNS, with few reported cases. Here, we describe a case of a primary intracranial leiomyosarcoma of the tentorium cerebelli. A 43-year-old woman presented with headache, acute vision loss, and difficulty speaking. MRI revealed a large heterogeneous-enhancing occipital mass, which was subsequently resected and diagnosed as a primary intracranial leiomyosarcoma. The patient went onto adjuvant radiotherapy delivering 60 Gy in 30 fractions. These tumors are exceedingly rare in immunocompetent individuals. We reviewed the 16 cases that have been reported in the literature. Surgical resection was the most common treatment (92%) with 53% receiving adjuvant radiation. There currently is no standard treatment regimen for intracranial leiomyosarcomas. Additional case reports that include descriptive treatment approaches with patient outcomes may help ascertain the best approach to treating these malignancies.

      View details for PubMedID 29324399
  • Familial Trigeminal Neuralgia Treated with Stereotactic Radiosurgery: A Case Report and Literature Review. J Radiat Oncol
    Denu RA, Rosenberg SA, Howard SP
    2017 Jun; 6 (2): 149-152
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      Background: Trigeminal neuralgia (TN) is a chronic pain condition characterized by brief episodes of lancinating pain in one or more distributions of the trigeminal nerve. Episodes of pain secondary to TN are triggered by certain stimuli, such as chewing, shaving, or touching the face. Although a common cause of TN is compression of the trigeminal nerve root entry zone by an artery or vein, many cases of TN are idiopathic. However, there have been limited reports in the literature of familial TN.

      Case Presentation: A 31-year-old male presented with classic TN symptoms in the right V1/V2 distribution that recently progressed to the V3 distribution a case of familial TN. His father an brother both have TN. Carbamazepine, oxcarbazepine, and rhizotomy did not improve his symptoms. He was treated with stereotactic radiosurgery (SRS) with a dose of 85 Gy delivered to the proximal trigeminal root with improvement in his pain. We also review and summarize the over 160 cases of familial TN found in the literature.

      Conclusions: This is the first reported case of familial TN treated with SRS. Patients with familial TN are more likely to have bilateral disease, to present with earlier onset, and to become refractory to medical therapy and may require more aggressive approaches. We propose that SRS is a good treatment approach for these patients.

      View details for PubMedID 29201285
  • The Second Stain: A Viral Whodunnit. Int J Radiat Oncol Biol Phys
    Rosenberg SA, Kimple RJ
    2017 12 01; 99 (5): 1061
  • 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
  • Strategies for Translating Evidence-Based Medicine in Lung Cancer into Community Practice. Curr Oncol Rep
    Rosenberg SA, Baschnagel AM, Bagley SJ, Housri N
    2017 Jan; 19 (1): 5
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      The landscape of non-small cell lung cancer (NSCLC) treatment has rapidly evolved over the past decade. This is exemplified by the use of molecular targeted agents, immunotherapies, and newer technologies such as stereotactic body radiotherapy (SBRT). As the translation of preclinical discoveries into clinical practice continues, the effective dissemination and implementation of evidence-based treatment of NSCLC will remain a foremost challenge for oncologists. To further extend evidence-based medicine into the community setting, community oncologists are being engaged on multiple fronts including leadership and participation in national clinical trials and utilization of internet-based resources.

      View details for PubMedID 28168606
  • 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
  • Management of leptomeningeal metastases: Prognostic factors and associated outcomes. J Clin Neurosci
    Brower JV, Saha S, Rosenberg SA, Hullett CR, Ian Robins H
    2016 May; 27: 130-7
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      Limited data are currently available to direct treatment recommendations in the management of leptomeningeal metastases (LM). Here we review treatment modalities clinicians should understand in order to manage patients with LM. We first describe our institution's experience with the treatment of LM and use this dataset to frame the discussion of LM management. Between 1999 and 2014, 1361 patients with central nervous system metastases were reviewed, 124 (9.1%) had radiographic evidence of LM, and these patients form the cohort for this analysis. Mean age at diagnosis of LM was 52years. Median survival for the entire cohort was 2.3months. The most common primary malignancies were non-small cell lung cancer (25.8%), breast cancer (17.7%), small cell lung cancer (16.9%) and melanoma (8.9%). Univariate analyses demonstrated that greater Karnofsky Performance Status (KPS) (p=0.001) and administration of systemic chemotherapy (p<0.001) resulted in improved median survival. Multivariate Cox analyses revealed that receipt of chemotherapy and a complete course of whole brain radiotherapy (WBRT) (median dose 30Gy in 10 fractions, range 24-40Gy) were predictive of longer survival, (p=0.013 and 0.019, respectively). These data suggest that there is a group of patients with good KPS who may experience significantly longer median survival than expected. Multivariate analysis from this single institution retrospective study demonstrated a benefit for WBRT and chemotherapy in individuals with good KPS. These findings provide contemporary data from a large cohort of LM patients, which may be utilized to guide treatment recommendations, assist in patient counseling and direct future investigations into optimization of treatment regimens.

      View details for PubMedID 26778048
  • Long-term patterns of relapse and survival following definitive intensity-modulated radiotherapy for non-endemic nasopharyngeal carcinoma. Oral Oncol
    Setton J, Han J, Kannarunimit D, Wuu YR, Rosenberg SA, DeSelm C, Wolden SL, Jillian Tsai C, McBride SM, Riaz N, Lee NY
    2016 Feb; 53: 67-73
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      BACKGROUND: We report treatment outcomes for a large non-endemic cohort of patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and chemotherapy.

      METHODS: We identified 177 consecutive patients with newly diagnosed, non-metastatic nasopharyngeal cancer treated with definitive IMRT between 1998 and 2011. Endpoints included local, regional, distant control, and overall survival.

      RESULTS: Median follow-up was 52months. The 3-/5-year actuarial rates of local control, regional control, distant control, and overall survival were 92%/83%, 93%/91%, 86%/83%, and 87%/74%, respectively. The median time to local recurrence was 30months; the annual hazard of local recurrence did not diminish until the 6th year of follow-up.

      CONCLUSIONS: Overall, we observed excellent rates of disease control and survival consistent with initially reported results from our institution. Attaining locoregional control in patients with extensive primary tumors remains a significant clinical challenge. With mature follow-up we observed that more than half of observed local relapses occurred after 2years, a pattern distinct from that of carcinomas arising from other head and neck sites. These findings raise the possibility that patients with NPC may benefit from close follow-up during post-treatment years 3-5.

      View details for PubMedID 26675283
  • 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
  • Targeting Glutamatergic Signaling and the PI3 Kinase Pathway to Halt Melanoma Progression. Transl Oncol
    Rosenberg SA, Niglio SA, Salehomoum N, Chan JL, Jeong BS, Wen Y, Li J, Fukui J, Chen S, Shin SS, Goydos JS
    2015 Feb; 8 (1): 1-9
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      Our group has previously reported that the majority of human melanomas (>60%) express the metabotropic glutamate receptor 1 (GRM1) and that the glutamate release inhibitor riluzole, a drug currently used to treat amyotrophic lateral sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group previously reported that in vitro riluzole treatment reduces cell growth in three-dimensional (3D) soft agar colony assays by 80% in cells with wildtype phosphoinositide 3-kinase (PI3K) pathway activation. However, melanoma cell lines harboring constitutive activating mutations of the PI3K pathway (PTEN and NRAS mutations) showed only a 35% to 40% decrease in colony formation in soft agar in the presence of riluzole. In this study, we have continued our preclinical studies of riluzole and its effect on melanoma cells alone and in combination with inhibitors of the PI3 kinase pathway: the AKT inhibitor, API-2, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. We modeled these combinatorial therapies on various melanoma cell lines in 3D and 2D systems and in vivo. Riluzole combined with mTOR inhibition is more effective at halting melanoma anchorage-independent growth and xenograft tumor progression than either agent alone. PI3K signaling changes associated with this combinatorial treatment shows that 3D (nanoculture) modeling of cell signaling more closely resembles in vivo signaling than monolayer models. Riluzole combined with mTOR inhibition is effective at halting tumor cell progression independent of BRAF mutational status. This makes this combinatorial therapy a potentially viable alternative for metastatic melanoma patients who are BRAF WT and are therefore ineligible for vemurafenib therapy.

      View details for PubMedID 25749171
  • Interdigitating dendritic cell sarcoma presenting in the skin: diagnosis and the role of surgical resection, chemotherapy and radiotherapy in management. Rare Tumors
    Rosenberg SA, Niglio SA, Jo VY, Goydos JS
    2014 Oct 27; 6 (4): 5573
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      We report the case of an interdigitating dendritic cell sarcoma (IDCS) presenting in the skin. A 41-year old woman had a slowly enlarging mass on her right scapula that was excised multiple times under a presumptive diagnosis of a recurrent sebaceous cyst. However, the lesion was refractory to standard therapies. History and physical exam was unrevealing for any systemic signs or symptoms of disease. The patient's metastatic work-up was negative. The lesion was resected with wide margins and was found to be consistent with IDCS. Patients that present with IDCS on the skin may present concurrently with metastatic disease and may have increased risk of secondary malignancies. The use of adjuvant chemoradiation after primary resection is controversial. However, the use of chemoradiation likely has benefit for local regional control for primary tumors that are unamendable to complete primary resection.

      View details for PubMedID 25568750
  • Psychosocial correlates of sun protection behaviors among U.S. Hispanic adults. J Behav Med
    Coups EJ, Stapleton JL, Manne SL, Hudson SV, Medina-Forrester A, Rosenberg SA, Gordon M, Tatum KS, Robinson JK, Natale-Pereira A, Goydos JS
    2014 Dec; 37 (6): 1082-90
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      The incidence of skin cancer among U.S. Hispanics increased 1.3% annually from 1992 to 2008. However, little research has focused on skin cancer prevention among the rapidly growing Hispanic population. In this study, we examined theory-driven, psychosocial correlates of sun protection behaviors in a population-based sample of 787 Hispanic adults (49.6% female, mean age = 41.0 years) residing in five southern or western U.S. states. Participants completed an English- or Spanish-language online survey in September 2011. The outcomes of focus were sunscreen use, shade seeking, and use of sun protective clothing. The correlates included suntan benefits, sun protection benefits and barriers, skin color preference, perceived natural skin protection, photo-aging concerns, perceived skin cancer risk, skin cancer worry, skin cancer fatalism, and sun protection descriptive norms. Results of multiple linear regression analyses revealed the following: sun protection barriers were negatively associated with each outcome; descriptive norms were positively associated with each outcome; perceived natural skin protection was inversely associated with sunscreen use; skin cancer worry was positively associated with shade seeking and use of sun protective clothing; skin cancer fatalism was negatively associated with shade seeking; and skin color preference was negatively associated with use of sun protective clothing. A number of additional statistically significant associations were identified in bivariate correlation analyses. This study informs the potential content of interventions to promote engagement in sun protection behaviors among U.S. Hispanics.

      View details for PubMedID 24532153
  • Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. Cell Rep
    He CH, Lee CG, Dela Cruz CS, Lee CM, Zhou Y, Ahangari F, Ma B, Herzog EL, Rosenberg SA, Li Y, Nour AM, Parikh CR, Schmidt I, Modis Y, Cantley L, Elias JA
    2013 Aug 29; 4 (4): 830-41
    • More

      Members of the 18 glycosyl hydrolase (GH 18) gene family have been conserved over species and time and are dysregulated in inflammatory, infectious, remodeling, and neoplastic disorders. This is particularly striking for the prototypic chitinase-like protein chitinase 3-like 1 (Chi3l1), which plays a critical role in antipathogen responses where it augments bacterial killing while stimulating disease tolerance by controlling cell death, inflammation, and remodeling. However, receptors that mediate the effects of GH 18 moieties have not been defined. Here, we demonstrate that Chi3l1 binds to interleukin-13 receptor α2 (IL-13Rα2) and that Chi3l1, IL-13Rα2, and IL-13 are in a multimeric complex. We also demonstrate that Chi3l1 activates macrophage mitogen-activated protein kinase, protein kinase B/AKT, and Wnt/β-catenin signaling and regulates oxidant injury, apoptosis, pyroptosis, inflammasome activation, antibacterial responses, melanoma metastasis, and TGF-β1 production via IL-13Rα2-dependent mechanisms. Thus, IL-13Rα2 is a GH 18 receptor that plays a critical role in Chi3l1 effector responses.

      View details for PubMedID 23972995
  • Linguistic acculturation and skin cancer-related behaviors among Hispanics in the southern and western United States. JAMA Dermatol
    Coups EJ, Stapleton JL, Hudson SV, Medina-Forrester A, Rosenberg SA, Gordon MA, Natale-Pereira A, Goydos JS
    2013 Jun; 149 (6): 679-86
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      OBJECTIVE: To examine the association between linguistic acculturation (assessed using the Language Use and Linguistic Preference subscales from the Bidimensional Acculturation Scale for Hispanics) and skin cancer-related behaviors among US Hispanic adults to determine whether, compared with Hispanics denoted as Spanish-acculturated, English-acculturated Hispanics would report less frequent shade seeking and use of sun protective clothing and higher rates of sunscreen use, sunbathing, and indoor tanning.

      DESIGN: Online survey study conducted in September 2011.

      SETTING: Five southern and western US states.

      PARTICIPANTS: A population-based sample of 788 Hispanic adults drawn from a nationally representative web panel.

      MAIN OUTCOME MEASURES: Self-reported sunscreen use, shade seeking, use of sun protective clothing, sunbathing, and indoor tanning.

      RESULTS: Multivariate regression analyses were conducted to examine predictors of the skin cancer-related behaviors. As hypothesized, English-acculturated Hispanics had lower rates of shade seeking and use of sun protective clothing and reported higher rates of sunbathing and indoor tanning than Spanish-acculturated Hispanics. English-acculturated Hispanics and bicultural Hispanics (ie, those with high Spanish and high English acculturation) reported comparably high rates of sunbathing and indoor tanning. Results suggested that bicultural Hispanics seek shade and wear sun protective clothing less often than Spanish-acculturated Hispanics but more often than English-acculturated Hispanics. Acculturation was not associated with sunscreen use.

      CONCLUSIONS: Hispanic adults do not routinely engage in behaviors that reduce their risk of skin cancer. Bicultural and English-acculturated Hispanics are particularly in need of skin cancer prevention interventions.

      View details for PubMedID 23752366
  • Skin cancer surveillance behaviors among US Hispanic adults. J Am Acad Dermatol
    Coups EJ, Stapleton JL, Hudson SV, Medina-Forrester A, Rosenberg SA, Gordon M, Natale-Pereira A, Goydos JS
    2013 Apr; 68 (4): 576-84
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      BACKGROUND: Little skin cancer prevention research has focused on the US Hispanic population.

      OBJECTIVE: This study examined the prevalence and correlates of skin cancer surveillance behaviors among Hispanic adults.

      METHODS: A population-based sample of 788 Hispanic adults residing in 5 southern and western states completed an online survey in English or Spanish in September 2011. The outcomes were ever having conducted a skin self-examination (SSE) and having received a total cutaneous examination (TCE) from a health professional. The correlates included sociodemographic, skin cancer-related, and psychosocial factors.

      RESULTS: The rates of ever conducting a SSE or having a TCE were 17.6% and 9.2%, respectively. Based on the results of multivariable logistic regressions, factors associated with ever conducting a SSE included older age, English linguistic acculturation, a greater number of melanoma risk factors, more frequent sunscreen use, sunbathing, job-related sun exposure, higher perceived skin cancer risk, physician recommendation, more SSE benefits, and fewer SSE barriers. Factors associated with ever having a TCE were older age, English linguistic acculturation, a greater number of melanoma risk factors, ever having tanned indoors, greater skin cancer knowledge, higher perceived skin cancer severity, lower skin cancer worry, physician recommendation, more TCE benefits, and fewer SSE barriers.

      LIMITATIONS: The cross-sectional design limits conclusions regarding the causal nature of observed associations.

      CONCLUSIONS: Few Hispanic adults engage in skin cancer surveillance behaviors. The study highlights Hispanic subpopulations that are least likely to engage in skin cancer surveillance behaviors and informs the development of culturally appropriate interventions to promote these behaviors.

      View details for PubMedID 23182066
  • Role of Raf Kinase Inhibitor Protein in Hepatocellular Carcinoma. For Immunopathol Dis Therap
    Walker EJ, Rosenberg SA, Wands JR, Kim M
    2011; 2 (2): 195-204
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      Hepatocellular carcinoma (HCC) accounts for 80-90% of primary liver tumors and is one of the most common and devastating malignant diseases worldwide. The MAPK signaling pathway is activated in over 90% of HCCs, and RKIP has been identified as an inhibitor of the MAPK pathway. It has been observed that downregulation of RKIP expression in HCC tumors contributes to constitutive activation of the ERK/MAPK pathway and promotes proliferation and migration of HCC cells. More important, activation of IGF-I/ERK/MAPK pathways can be blocked by restoration of RKIP levels. The protein levels of RKIP are significantly reduced in HCC, whereas mRNA levels only decreased in 41% of HCC samples studied, suggesting that the downregulation of RKIP in HCC may be influenced through multiple mechanisms both at the mRNA and protein levels. In this context, mTOR inhibitor, insulin, and proteasome inhibitors were found to modulate RKIP expression in FOCUS HCC cells. A better understating of mechanisms by which RKIP expression is downregulated in HCC may be critical to develop a possible target for therapeutic intervention of HCC.

      View details for PubMedID 21984963
  • Identification of T-cell factor-4 isoforms that contribute to the malignant phenotype of hepatocellular carcinoma cells. Exp Cell Res
    Tsedensodnom O, Koga H, Rosenberg SA, Nambotin SB, Carroll JJ, Wands JR, Kim M
    2011 Apr 15; 317 (7): 920-31
    • More

      The Wnt/β-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). Downstream signaling events involving the Wnt/β-catenin cascade occur through T-cell factor (TCF) proteins. The human TCF-4 gene is composed of 17 exons with multiple alternative splicing sites. However, the role of different TCF-4 isoforms in the pathogenesis of HCC is unknown. The purpose of this study was to identify and characterize TCF-4 isoforms in HCC. We identified 14 novel TCF-4 isoforms from four HCC cell lines. Functional analysis following transfection and expression in HCC cells revealed distinct effects on the phenotype. The TCF-4J isoform expression produced striking features of malignant transformation characterized by high cell proliferation rate, migration and colony formation even though its transcriptional activity was low. In contrast, the TCF-4K isoform displayed low TCF transcriptional activity; cell proliferation rate and colony formation were reduced as well. Interestingly, TCF-4J and TCF-4K differed by only five amino acids (the SxxSS motif). Thus, these studies suggest that conserved splicing motifs may have a major influence on the transcriptional activity and functional properties of TCF-4 isoforms and alter the characteristics of the malignant phenotype.

      View details for PubMedID 21256126
  • The glutamate release inhibitor Riluzole decreases migration, invasion, and proliferation of melanoma cells. J Invest Dermatol
    Le MN, Chan JL, Rosenberg SA, Nabatian AS, Merrigan KT, Cohen-Solal KA, Goydos JS
    2010 Sep; 130 (9): 2240-9
    • More

      The goal of this study was to examine the effects of metabotropic glutamate receptor-1 (GRM1) blockade on melanoma anchorage-independent growth and invasion. We performed colony and invasion assays using GRM1-expressing melanoma lines and the GRM1-negative UACC930 line. Using the glutamate-release inhibitor Riluzole or the non-competitive GRM1 antagonist BAY 36-7620 we were able to induce considerable inhibition of colony formation and invasion in GRM1-expressing melanoma lines. Neither pharmacological agent induced significant reduction in colony formation or invasion in the GRM1-negative melanoma line, UACC930. Additionally we assessed the efficacy of these inhibitors to inhibit the growth of fresh melanoma tumor samples cultured on a 74-mum nylon mesh. Both Riluzole and BAY 36-7620 significantly inhibited tumor cell growth into the interstitial spaces of the mesh. When repeated with normal mole samples both inhibitors were much less effective in preventing the outgrowth of cells. These experiments show that a specific antagonist of GRM1 (BAY 36-7620) or an inhibitor of glutamate release (Riluzole) can significantly suppress melanoma migration, invasion and colony formation as well as inhibit the proliferation of fresh melanoma cells. These findings, added to our previous work, strengthen the case that GRM1 is a valid therapeutic target in patients with melanoma.

      View details for PubMedID 20505744

Contact Information

Stephen A. Rosenberg, MD

600 Highland Avenue Madison,
Madison, WI 53792
Email