headshot of Quaovi Sodji

Quaovi Sodji, MD, PhD

Assistant Professor

Department of Human Oncology

After completing a Clinical Instructor position in the department of Human Oncology at the University of Wisconsin-Madison in the laboratories of Dr. Morris in the Department of Human Oncology and Dr. Capitini in the Pediatrics Department, I recently transitioned into an Assistant Professor in the Department of Human Oncology. My independent laboratory research focuses on the development of novel cancer therapeutics including immunotherapeutic agents and using radiation delivered by radionuclides to enhance the efficacy and safety of cancer immunotherapy.

At the Georgia Institute of Technology, I focused on learning and understanding the basis of organic chemistry and acquiring technical skills such as column chromatography, NMR spectroscopy etc. under the supervision of Dr. Adegboyega Oyelere and in collaboration with Dr. Mostapha El-Sayed. I focused on structural modifications to tamoxifen for the delivery of chemotherapeutic agents to estrogen receptor positive breast cancer cells. I subsequently enrolled in the University System of Georgia MD/PhD program, which enable me to pursue my graduate career at the Georgia Institute of Technology in the drug discovery field with projects aiming at improving the therapeutic index of histone deacetylase (HDAC) inhibitors, through isoform selectivity and targeted delivery under the supervision of Dr. Adegboyega Oyelere. Multiple HDAC inhibitors were designed in-silico, synthesized and tested, yielding small molecules selective for isoform 6 or 8 inhibition and targeting folate receptors in malignant cells.

At Stanford University, I investigated the mechanisms of natural killer (NK) cell exclusion from the tumor microenvironment (TME) of pancreatic cancer in the research laboratory of Dr. Amato Giaccia. We subsequently found that inhibiting the complement C3a enhances NK cells infiltration in the TME and may represent a novel immunotherapy approach against pancreatic cancer which for optimal results should be used in combination with radiation therapy.

At the University of Wisconsin-Madison, as an instructor, I investigated the use of targeted radionuclide therapy (TRT) to enhance the safety and efficacy of CAR T cell therapy.

Education

Clinical Instructor, University of Wisconsin, Madison, Cancer Biology (2022-2023)

Postdoctoral Fellowship, Stanford University, Radiation Oncology (2022)

Residency, Stanford University Medical Center, Radiation Oncology (2021)

Intern, Medical College of Georgia, Internal Medicine (2017)

MD/PhD, Medical College of Georgia, (2016)

PhD, Georgia Institute of Technology, Medicinal Chemistry (2014)

BS, Georgia Institute of Technology, Biochemistry (2008)

Academic Appointments

Assistant Professor, Human Oncology (2023)

Selected Honors and Awards

Society for Translational Oncology distinguished fellow (2022)

Invited Participant/Speaker - Radiation Oncology Symposium, Radiology and Radiation Oncology Section of the National Medical Association annual meeting, “The Role of Immune Checkpoint Inhibitors in Cancer and Approaches to Combination with Radiotherapy” (2022)

American Society of Clinical Oncology (ASCO) Young Investigator Award (2021)

Roentgen Resident/Fellow Research Award (2021)

NIH/NMA Academic Career Fellow Award (2021)

Stanford Cancer Institute Fellowship Award (2020)

Radiological Society of North America (RSNA) Resident/Fellow Research Grant (2020)

Invited Participant/Speaker - Malcom Bagshaw Visiting Professorship, “Durability of Abscopal Effect in Metastatic Melanoma Patients after the Combination of Radiation Therapy and Ipilimumab” (2019)

American Board of Radiology Holman Research Pathway (2017 - 2021)

Outstanding Student in Radiation Oncology, Medical College of Georgia Class of 2016 (2016)

Invited Speaker - Molecular Oncology and Biomarkers Seminar Series at the Georgia Regents University Cancer Center, “Folate and Pteroic acid for the Targeted Delivery of Histone Deacetylase Inhibitors" (2014)

Invited Speaker - Hematology/Oncology Departmental Seminar at the Medical College of Georgia, “Histone Deacetylase as a Target for Cancer Therapy " (2013)

Southern Regional Education Board Dissertation Award (2013)

National MD/PhD Student Conference Travel Award (2013)

NOBCChE Advancing Science Award (2013)

Graduate Assistance in Areas of National Need (GAANN) NSF fellowship, Chemistry/Biochemistry Department, Georgia Institute of Technology (2012)

Graduate Assistance in Areas of National Need (GAANN) fellowship, Center for Drug Design, Development and Delivery, Georgia Institute of Technology (2011)

President’s fellowship, Georgia Institute of Technology (2010 - 2014)

W.M. Spicer Scholarship in Chemistry, Georgia Institute of Technology (2008)

Tower Gold Award Georgia Institute of Technology (2008)

Merck Index Award, Georgia Institute of Technology Chemistry (2008)

Merck Undergraduate Research Award, Georgia Institute of Technology (2007)

Faculty Honors, Georgia Institute of Technology (2006 - 2008)

Outstanding Student in Organic Chemistry, Georgia Perimeter College (2006)

Targeted radionuclide therapy (TRT) and chimeric antigen receptor (CAR) T cell therapy are emerging therapies that have revolutionized cancer therapy. However, each of these therapies is confronted by limitations that can potentially be resolved by the other. As such, understanding the mechanisms that govern the interactions between these novel therapies and ways to effectively harness their potential synergism will be crucial for advancing the field of oncology. Following the understanding of the mechanisms of these interactions, I propose the development of modulators including CAR T cell therapy, small molecules, and drug-antibody conjugates capable of effectively harnessing the collaborative effects between TRT and CAR T cells therapy.

  • Comparative Study of the Effect of Radiation Delivered by Lutetium-177 or Actinium-225 on Anti-GD2 Chimeric Antigen Receptor T Cell Viability and Functions Cancers
    Sodji QH, Forsberg MH, Cappabianca D, Kerr CP, Sarko L, Shea A, Adam DP, Eickhoff JC, Ong IM, Hernandez R, Weichert J, Bednarz BP, Saha K, Sondel PM, Capitini CM, Morris ZS
    2023 Dec 30;16(1):191. doi: 10.3390/cancers16010191.
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      Chimeric antigen receptor (CAR) T cells have been relatively ineffective against solid tumors. Low-dose radiation which can be delivered to multiple sites of metastases by targeted radionuclide therapy (TRT) can elicit immunostimulatory effects. However, TRT has never been combined with CAR T cells against solid tumors in a clinical setting. This study investigated the effects of radiation delivered by Lutetium-177 (177Lu) and Actinium-225 (225Ac) on the viability and effector function of CAR T cells in vitro to evaluate the feasibility of such therapeutic combinations. After the irradiation of anti-GD2 CAR T cells with various doses of radiation delivered by 177Lu or 225Ac, their viability and cytotoxic activity against GD2-expressing human CHLA-20 neuroblastoma and melanoma M21 cells were determined by flow cytometry. The expression of the exhaustion marker PD-1, activation marker CD69 and the activating receptor NKG2D was measured on the irradiated anti-GD2 CAR T cells. Both 177Lu and 225Ac displayed a dose-dependent toxicity on anti-GD2 CAR T cells. However, radiation enhanced the cytotoxic activity of these CAR T cells against CHLA-20 and M21 irrespective of the dose tested and the type of radionuclide. No significant changes in the expression of PD-1, CD69 and NKG2D was noted on the CAR T cells following irradiation. Given a lower CAR T cell viability at equal doses and an enhancement of cytotoxic activity irrespective of the radionuclide type, 177Lu-based TRT may be preferred over 225Ac-based TRT when evaluating a potential synergism between these therapies in vivo against solid tumors.

      PMID:38201618 | PMC:PMC10778389 | DOI:10.3390/cancers16010191


      View details for PubMedID 38201618
  • Time to resolution of iodine-123 metaiodobenzylguanidine (<sup>123</sup> I-MIBG) avidity and local control outcomes for high-risk neuroblastoma following radiation therapy Journal of medical imaging and radiation oncology
    Oh J, Gutkin P, Wang YP, Sandhu N, Majzner RG, Nadel H, Shimada H, Lansinger O, von Eyben R, Donaldson S, Bruzoni M, Sodji QH, Hiniker SM
    2023 Feb;67(1):81-88. doi: 10.1111/1754-9485.13487. Epub 2022 Oct 27.
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      INTRODUCTION: 123 I-MIBG scan is used in neuroblastoma (NB) to monitor treatment response. Time to resolution of 123 I-MIBG avidity after radiation therapy (RT) is unknown. We sought to determine time to resolution of 123 I-MIBG avidity after RT and local failure (LF) rate.

      METHODS: We performed a retrospective review of children with high-risk NB who underwent 123 I-MIBG scans pre- and post-RT from 2003 to 2019. Time from RT to resolution of 123 I-MIBG activity was analysed. LF and cumulative incidence of local progression (CILP) after RT stratified by site, presence of residual disease and use of boost RT were determined.

      RESULTS: Forty-two patients with median age 3.9 years (1.9-4.7 years) were included, with median follow-up time 3.9 years (1.4-6.9). Eighty-six lesions were treated with RT to median dose of 21.6 Gy. Eighteen of 86 lesions were evaluable for time to resolution of MIBG avidity after RT, with median resolution time of 78 days (36-208). No LF occurred among 26 patients who received RT to primary sites after GTR, versus 4/12 (25%) patients treated with residual primary disease. 2-year CILP was 19% (12% primary disease 25% metastatic disease (P = 0.18)). 2-year CILP for non-residual primary, residual primary, non-residual metastatic and residual metastatic lesions was 0%, 42%, 11% and 30% respectively (P = 0.01) and for boosted and non-boosted residual lesions was 29% and 35% (P = 0.44).

      CONCLUSION: Median time to MIBG resolution after RT was 78 days. Primary lesions without residual disease had excellent local control. LF rate was higher after RT for residual disease, with no benefit for boost RT.

      PMID:36300562 | DOI:10.1111/1754-9485.13487


      View details for PubMedID 36300562
  • The Combination of Radiotherapy and Complement C3a Inhibition Potentiates Natural Killer cell Functions Against Pancreatic Cancer Cancer research communications
    Sodji QH, Nambiar DK, Viswanathan V, von Eyben R, Colburg D, Binkley MS, Li CG, Olcina MM, Chang DT, Le Q, Giaccia AJ
    2022 Jul;2(7):725-738. doi: 10.1158/2767-9764.crc-22-0069. Epub 2022 Jul 27.
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      Pancreatic cancer is one of the deadliest cancers, against which current immunotherapy strategies are not effective. Herein, we analyzed the immune cell composition of the tumor microenvironment of pancreatic cancer samples in The Cancer Genome Atlas and found that the presence of intratumoral NK cells correlates with survival. Subsequent analysis also indicated that NK cell exclusion from the microenvironment is found in a high percentage of clinical pancreatic cancers and in preclinical models of pancreatic cancer. Mechanistically, NK cell exclusion is regulated in part by complement C3a and its receptor signaling. Inhibition of the C3a receptor enhances NK cell infiltration in syngeneic mouse models of pancreatic cancer resulting in tumor growth delay. However, tumor growth inhibition mediated by NK cells is not sufficient alone for complete tumor regression, but is potentiated when combined with radiation therapy. Our findings indicate that although C3a inhibition is a promising approach to enhance NK cell-based immunotherapy against pancreatic cancer, its combination with radiation therapy hold greater therapeutic benefit.

      PMID:35937458 | PMC:PMC9354534 | DOI:10.1158/2767-9764.crc-22-0069


      View details for PubMedID 35937458
  • Syndrome of inappropriate secretion of antidiuretic hormone following high dose rate brachytherapy for prostate cancer: a case report BMC urology
    Ayoola A, Sodji QH, Chin S, Panousis P, Bagshaw HP, Buyyounouski MK
    2022 Mar 10;22(1):32. doi: 10.1186/s12894-022-00984-y.
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      BACKGROUND: The syndrome of inappropriate secretion of antidiuretic hormone is a disorder characterized by the excess release of antidiuretic hormone and can result in hyponatremia. If managed inappropriately, severe hyponatremia can cause seizures, cerebral edema, and even death. There are various known causes of this inappropriate release of antidiuretic hormone, including malignancy, CNS disorders, and disturbances in the hypothalamic-pituitary-renal axis. However, reports of syndrome of inappropriate secretion of antidiuretic hormone after brachytherapy for prostate cancer are exceedingly rare.

      CASE PRESENTATION: We report a case of symptomatic hyponatremia secondary to the inappropriate secretion of antidiuretic hormone after prostate high-dose rate brachytherapy under general anesthesia in a patient with adenocarcinoma of the prostate.

      CONCLUSIONS: In rare instances, inappropriate secretion of antidiuretic hormone can occur after high-dose rate brachytherapy for prostate cancer. The cause is likely multifactorial, involving pain or discomfort ensuing from the surgical procedure, the general anesthesia or intraoperative drugs administered. However, due to the potential severity of the side effects, timely diagnosis is crucial to ensure prompt, and effective management.

      PMID:35272646 | PMC:PMC8908680 | DOI:10.1186/s12894-022-00984-y


      View details for PubMedID 35272646
  • Detection of Recurrence After Thoracic Stereotactic Ablative Radiotherapy Using FDG-PET-CT Clinical lung cancer
    Sodji QH, Harris JP, Quon A, Modlin LA, Lau B, Jiang A, Trakul N, Maxim PG, Diehn M, Loo BW, Hiniker SM
    2022 May;23(3):282-289. doi: 10.1016/j.cllc.2022.01.006. Epub 2022 Feb 4.
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      INTRODUCTION/BACKGROUND: Differentiating local recurrence (LR) from post-treatment changes following stereotactic ablative radiotherapy (SABR) for thoracic tumors is challenging. We sought to evaluate the performance of FDG-PET-CT in distinguishing recurrence from post-radiation changes in patients with stage I-II non-small cell lung cancer (NSCLC) treated with SABR.

      MATERIALS AND METHODS: We performed a retrospective review of patients with stage I-II NSCLC treated with SABR and subsequently followed with surveillance FDG-PET-CT scans from 2004 to 2014. The radiology reports were coded as 0 or 1 if minimally or substantially concerning for LR, respectively, and correlated with outcome. Prognostic factors for false-positive FDG-PET-CT were assessed using logistic regression models.

      RESULTS: We identified 145 patients meeting inclusion criteria for the retrospective analysis. Amongst the 39 (26.9%) patients with FDG-PET-CT scans concerning for LR 3 to 24 months after treatment, 14 were confirmed to have LR. Thus, the positive predictive value (PPV) of FDG-PET-CT in identifying LR was 36% (14/39). Factors associated with a false-positive scan included concerning FDG-PET-CT at the earliest post-treatment time point (3 months) (odds ratio 0.67, P= .04) and older age (odds ratio 2.3, P= .02).

      CONCLUSION: Our analysis indicates that the PPV of a concerning FDG-PET-CT after SABR for early-stage NSCLC is relatively low, especially at early post-treatment timepoints, but accuracy is improving over time with institutional experience.

      PMID:35246393 | DOI:10.1016/j.cllc.2022.01.006


      View details for PubMedID 35246393
  • Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges Cancers
    Wu B, Sodji QH, Oyelere AK
    2022 Jan 22;14(3):552. doi: 10.3390/cancers14030552.
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      Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chronic inflammatory diseases and cancers. We also recognized the value of the re-evaluation of the disease-specific roles of multiple pathways implicated in the pathophysiology of chronic inflammatory diseases and cancers-as well as the application of data from single-cell RNA sequencing in the success of future drug discovery endeavors.

      PMID:35158821 | PMC:PMC8833582 | DOI:10.3390/cancers14030552


      View details for PubMedID 35158821
  • Acute and Late Esophageal Toxicity After SABR to Thoracic Tumors Near or Abutting the Esophagus International journal of radiation oncology, biology, physics
    Sodji QH, Ko R, von Eyben R, Owen SG, Capaldi PI, Bush K, Binkley MS, Alrowais F, Pickthorn B, Maxim PG, Gensheimer MF, Diehn M, Loo BW
    2022 Apr 1;112(5):1144-1153. doi: 10.1016/j.ijrobp.2021.12.008. Epub 2021 Dec 20.
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      PURPOSE: Our purpose was to evaluate the incidence of acute and late esophageal toxicity in patients with thoracic tumors near or abutting the esophagus treated with SABR.

      METHODS AND MATERIALS: Among patients with thoracic tumors treated with SABR, we identified those with tumors near or abutting the esophagus. Using the linear-quadratic model with an α/ß ratio of 10, we determined the correlation between dosimetric parameters and esophageal toxicity graded using the Common Terminology Criteria for Adverse Events, version 5.0.

      RESULTS: Out of 2200 patients treated with thoracic SABR, 767 patients were analyzable for esophageal dosimetry. We identified 55 patients with tumors near the esophagus (52 evaluable for esophagitis grade) and 28 with planning target volume (PTV) overlapping the esophagus. Dose gradients across the esophagus were consistently sharp. Median follow-up and overall survival were 16 and 23 months, respectively. Thirteen patients (25%) developed temporary grade 2 acute esophageal toxicity, 11 (85%) of whom had PTV overlapping the esophagus. Symptoms resolved within 1 to 3 months in 12 patients and 6 months in all patients. No grade 3 to 5 toxicity was observed. Only 3 patients (6%) developed late or persistent grade 2 dysphagia or dyspepsia of uncertain relationship to SABR. The cumulative incidence of acute esophagitis was 15% and 25% at 14 and 60 days, respectively. Acute toxicity correlated on univariate analysis with esophageal Dmax, D1cc, D2cc, Dmax/Dprescription, and whether the PTV was overlapping the esophagus. Esophageal Dmax (BED10) <62 Gy, D1cc (BED10) <48 Gy, D2cc (BED10) <43 Gy, and Dmax/Dprescription <85% were associated with <20% risk of grade 2 acute esophagitis. Only 2 local recurrences occurred.

      CONCLUSIONS: Although 25% of patients with tumors near the esophagus developed acute esophagitis (39% of those with PTV overlapping the esophagus), these toxicities were all grade 2 and all temporary. This suggests the safety and efficacy of thoracic SABR for tumors near or abutting the esophagus when treating with high conformity and sharp dose gradients.

      PMID:34942312 | DOI:10.1016/j.ijrobp.2021.12.008


      View details for PubMedID 34942312
  • C3aR Signaling Inhibits NK-cell Infiltration into the Tumor Microenvironment in Mouse Models Cancer immunology research
    Nandagopal S, Li CG, Xu Y, Sodji QH, Graves EE, Giaccia AJ
    2022 Feb;10(2):245-258. doi: 10.1158/2326-6066.CIR-21-0435. Epub 2021 Nov 24.
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      Many solid tumors have low levels of cytotoxic CD56dim natural killer (NK) cells, suggesting that CD56dim NK-cell exclusion from the tumor microenvironment (TME) contributes to the decreased response rate of immunotherapy. Complement component 3a (C3a) is known for its tumor-promoting and immunosuppressive roles in solid tumors. Previous reports have implicated the involvement of the C3a receptor (C3aR) in immune cell trafficking into the TME. C3aR is predominantly expressed on the surface of activated cytotoxic NK cells, but a specific role for C3aR in NK-cell biology has not been investigated. Because solid tumors generate elevated C3a and have decreased NK-cell infiltration, we hypothesized that C3aR might play a role in cytotoxic NK-cell recruitment into the TME. Our results indicate that blocking C3aR signaling in NK cells increased NK-cell infiltration into the TME in mouse models and led to tumor regression. Because the critical lymphocyte trafficking integrin LFA-1 orchestrates the migration of activated NK cells, we wanted to gain insight into the interaction between C3aR signaling and LFA-1. Our results demonstrated that direct interaction between C3aR and LFA-1, which led to a high-affinity LFA-1 conformation, decreased NK-cell infiltration into the TME. We propose that approaches to enhance cytotoxic NK-cell infiltration into the TME, through either disrupting C3a and C3aR interaction or inhibiting the formation of high-affinity LFA-1, represent a new strategy to improve the efficiency of immunotherapy for cancer treatment.

      PMID:34819308 | PMC:PMC9351714 | DOI:10.1158/2326-6066.CIR-21-0435


      View details for PubMedID 34819308
  • Multidisciplinary management of newly diagnosed pediatric large cell neuroendocrine carcinoma of the lung causing hemoptysis Pediatric blood & cancer
    Marquez CP, Violari EG, Sodji Q, Jiang AL, Donaldson SS, Josephs S, Hiniker SM
    2021 Oct;68(10):e29182. doi: 10.1002/pbc.29182. Epub 2021 Jun 14.
  • Radiation Therapy for Primary Cutaneous Gamma Delta Lymphoma Prior to Stem Cell Transplantation Cancer investigation
    Wu YF, Skinner L, Lewis J, Khodadoust MS, Kim YH, Kwong BY, Weng W, Hoppe RT, Sodji Q, Hui C, Kastelowitz N, Fernandez-Pol S, Hiniker SM
    2023 Jan 31:1-8. doi: 10.1080/07357907.2021.1919696. Online ahead of print.
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      We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34 Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the four extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5 months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

      PMID:33899635 | DOI:10.1080/07357907.2021.1919696


      View details for PubMedID 33899635
  • Predicting per-lesion local recurrence in locally advanced non-small cell lung cancer following definitive radiation therapy using pre- and mid-treatment metabolic tumor volume Radiation oncology (London, England)
    Binkley MS, Koenig JL, Kashyap M, Xiang M, Liu Y, Sodji Q, Maxim PG, Diehn M, Loo BW, Gensheimer MF
    2020 May 19;15(1):114. doi: 10.1186/s13014-020-01546-y.
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      BACKGROUND: We evaluated whether pre- and mid-treatment metabolic tumor volume (MTV) predicts per lesion local recurrence (LR) in patients treated with definitive radiation therapy (RT, dose≥60 Gy) for locally advanced non-small cell lung cancer (NSCLC).

      METHODS: We retrospectively reviewed records of patients with stage III NSCLC treated from 2006 to 2018 with pre- and mid-RT PET-CT. We measured the MTV of treated lesions on the pre-RT (MTVpre) and mid-RT (MTVmid) PET-CT. LR was defined per lesion as recurrence within the planning target volume. Receiver operating characteristic (ROC) curves, cumulative incidence rates, and uni- and multivariable (MVA) competing risk regressions were used to evaluate the association between MTV and LR.

      RESULTS: We identified 111 patients with 387 lesions (112 lung tumors and 275 lymph nodes). Median age was 68 years, 69.4% were male, 46.8% had adenocarcinoma, 39.6% had squamous cell carcinoma, and 95.5% received concurrent chemotherapy. Median follow-up was 38.7 months. 3-year overall survival was 42.3%. 3-year cumulative incidence of LR was 26.8% per patient and 11.9% per lesion. Both MTVpre and MTVmid were predictive of LR by ROC (AUC = 0.71 and 0.76, respectively) and were significantly associated with LR on MVA (P = 0.004 and P = 7.1e-5, respectively). Among lesions at lower risk of LR based on MTVpre, higher MTVmid was associated with LR (P = 0.001).

      CONCLUSION: Per-lesion, larger MTVpre and MTVmid predicted for increased risk of LR. MTVmid was more highly predictive of LR than MTVpre and if validated may allow for further discrimination of high-risk lesions at mid-RT informing dose painting strategies.

      PMID:32429982 | PMC:PMC7238662 | DOI:10.1186/s13014-020-01546-y


      View details for PubMedID 32429982
  • Durability of response in metastatic melanoma patients after combined treatment with radiation therapy and ipilimumab Melanoma management
    Sodji QH, Gutkin PM, Swetter SM, Reddy SA, Hiniker SM, Knox SJ
    2020 Feb 12;7(1):MMT36. doi: 10.2217/mmt-2019-0020.
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      AIM: We previously reported a prospective trial evaluating the safety and efficacy of combining ipilimumab and radiation therapy in patients with metastatic melanoma. Herein, we provide a long-term update on patients with complete response (CR) or partial response (PR).

      PATIENTS & METHODS: We continued to follow these patients with serial imaging including computed tomography, PET or MRI.

      RESULTS: Two of the three patients with CR are still alive and without evidence of melanoma but with chronic treatment-induced hypophysitis. The third patient died of hepatocellular carcinoma, but with no evidence of melanoma. Among the three patients with PR, two achieved CR after pembrolizumab monotherapy.

      CONCLUSION: This long-term follow up reveals the striking durability of the CRs, which appears to correlate with a grade 2-3 hypophysitis.

      PMID:32399174 | PMC:PMC7212514 | DOI:10.2217/mmt-2019-0020


      View details for PubMedID 32399174
  • FLT-PET-CT for the Detection of Disease Recurrence After Stereotactic Ablative Radiotherapy or Hyperfractionation for Thoracic Malignancy: A Prospective Pilot Study Frontiers in oncology
    Hiniker SM, Sodji Q, Quon A, Gutkin PM, Arksey N, Graves EE, Chin FT, Maxim PG, Diehn M, Loo BW
    2019 May 31;9:467. doi: 10.3389/fonc.2019.00467. eCollection 2019.
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      Differentiating local recurrence from post-treatment changes on PET scans following stereotactic ablative radiotherapy (SABR) or hyperfractionation for lung tumors is challenging. We performed a prospective pilot study of 3-deoxy-3-[18F]-fluorothymidine (FLT)-PET-CT in patients with equivocal post-radiation FDG-PET-CT to assess disease recurrence. Methods: We prospectively enrolled 10 patients, 9 treated with SABR and 1 with hyperfractionated external beam radiotherapy for thoracic malignancy with subsequent equivocal follow-up FDG-PET-CT, to undergo FLT-PET-CT prior to biopsy or serial imaging. FLT-PET scans were interpreted by a radiologist with experience in reading FLT-PET-CT and blinded to the results of any subsequent biopsy or imaging. Results: Of the 10 patients enrolled, 8 were evaluable after FLT-PET-CT. Based on the FLT-PET-CT, a blinded radiologist accurately predicted disease recurrence vs. inflammatory changes in 7 patients (87.5%). The combination of higher lesion SUVmax and higher ratio of lesion SUVmax to SUVmax of mediastinal blood pool was indicative of recurrence. Qualitative assessment of increased degree of focality of the lesion also appears to be indicative of disease recurrence. Conclusion: Adjunctive FLT-PET-CT imaging can complement FDG-PET-CT scan in distinguishing post-treatment radiation changes from disease recurrence in thoracic malignancies. These findings support the investigation of FLT-PET-CT in a larger prospective study.

      PMID:31214507 | PMC:PMC6555304 | DOI:10.3389/fonc.2019.00467


      View details for PubMedID 31214507
  • Management of Metastatic Spinal Cord Compression Southern medical journal
    Sodji Q, Kaminski J, Willey C, Kim N, Mourad W, Vender J, Dasher B
    2017 Sep;110(9):586-593. doi: 10.14423/SMJ.0000000000000700.
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      Cancer metastasis is a key event in tumor progression associated not only with mortality but also significant morbidity. Metastatic disease can promote end-organ dysfunction and even failure through mass effect compression of various vital organs including the spinal cord. In such cases, prompt medical attention is needed to restore neurological function, relieve pain, and prevent permanent damage. The three therapeutic approaches to managing metastatic spinal cord compression include corticosteroids, surgery, and radiation therapy. Although each may improve patients' symptoms, their combination has yielded the best outcome. In cancer patients with clinical suspicion of spinal cord compression, dexamethasone should be initiated followed by surgical decompression, when possible, and radiation. The latter becomes the preferred treatment in patients with inoperable disease.

      PMID:28863223 | DOI:10.14423/SMJ.0000000000000700


      View details for PubMedID 28863223
  • Predictive role of PD-L1 expression in the response of renal Medullary carcinoma to PD-1 inhibition Journal for immunotherapy of cancer
    Sodji Q, Klein K, Sravan K, Parikh J
    2017 Aug 15;5(1):62. doi: 10.1186/s40425-017-0267-9.
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      BACKGROUND: Renal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response.

      CASE PRESENTATION: Two African-American patients (male and female) with sickle cell trait who presented to our center with hematuria and flank pain were diagnosed with metastatic renal medullary carcinoma. PD-L1 was expressed at rate of 25% and 60% in patient 1 and 2 respectively. Following nephrectomy, they were started on nivolumab. Patient 1 initially responded to the treatment with regression of metastatic lesions. However, following this early response, patient 1 who has been receiving nivolumab for more than 15 months, was noted to have a disease progression. Patient 2 had disease progression after 3 months of nivolumab therapy.

      CONCLUSIONS: Although PD-L1 is expressed in these patients with renal medullary carcinoma, response to nivolumab was only observed in patient 1 whose tumor has the lowest rate of PD-L1 expression. This may suggest that in RMC, response to PD-L1 inhibition therapy may not correlate with the rate of PD-L1 expression.

      PMID:28807004 | PMC:PMC5557570 | DOI:10.1186/s40425-017-0267-9


      View details for PubMedID 28807004
  • Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids European journal of medicinal chemistry
    Sodji QH, Kornacki JR, McDonald JF, Mrksich M, Oyelere AK
    2015;96:340-59. doi: 10.1016/j.ejmech.2015.04.014. Epub 2015 Apr 8.
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      Histone deacetylase (HDAC) inhibition has recently emerged as a novel therapeutic approach for the treatment of various pathological conditions including cancer. Currently, two HDAC inhibitors (HDACi) – Vorinostat and Romidepsin – have been approved for the treatment of cutaneous T-cell lymphoma. However, HDACi remain ineffective against solid tumors and are associated with adverse events including cardiotoxicity. Targeted delivery may enhance the therapeutic indices of HDACi and enable them to be efficacious against solid tumors. We showed herein that morphing of folic and pteroic acids into the surface recognition group of HDACi results in hydroxamate and benzamide HDACi which derived tumor homing by targeting folate receptor (FR), a receptor commonly overexpressed in solid tumors. We observed a correlation between the potency of HDAC1 inhibition and cytotoxicity as only the potent pteroate hydroxamates, 11d and 11e, displayed antiproliferative activity against two representative FR-expression cancer cells. Our observation further supports the previous results which suggest that for a drug to be successfully targeted using the FR, it must be extremely potent against its primary target as the FR has a low delivery efficiency.

      PMID:25899338 | PMC:PMC4433810 | DOI:10.1016/j.ejmech.2015.04.014


      View details for PubMedID 25899338
  • The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors Bioorganic & medicinal chemistry letters
    Sodji Q, Patil V, Jain S, Kornacki JR, Mrksich M, Tekwani BL, Oyelere AK
    2014 Oct 15;24(20):4826-30. doi: 10.1016/j.bmcl.2014.08.060. Epub 2014 Sep 4.
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      Histone deacetylase inhibitors (HDACi) pleiotropy is largely due to their nonselective inhibition of various cellular HDAC isoforms. Connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting HDACi pleiotropy. The contribution of classes I and II HDACs to the antileishmanial activity of HDACi was investigated using the amastigote and promastigote forms of Leishmania donovani. We observed that the antileishmanial activities of HDACi are largely due to the inhibition of HDAC6-like activity. This observation could facilitate the development of HDACi as antileishmanial agents.

      PMID:25240614 | PMC:PMC4225773 | DOI:10.1016/j.bmcl.2014.08.060


      View details for PubMedID 25240614

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Quaovi H. Sodji, MD, PhD

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