Publications by authors named "Ryan J Brisson"

10 Publications

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The role of chemotherapy in the management of olfactory neuroblastoma: A 40-year surveillance, epidemiology, and end results registry study.

Health Sci Rep 2021 Jun 2;4(2):e257. Epub 2021 May 2.

Department of Radiation Oncology Beaumont Health Royal Oak Michigan.

Background: In this retrospective surveillance, epidemiology, and end results (SEER) registry analysis, we investigated the role of chemotherapy (CT) in the treatment of olfactory neuroblastoma (ON), an exceedingly rare sino-nasal tumor typically treated with surgery and/or radiation therapy (RT).

Methods: We analyzed all patients in the SEER registry diagnosed with a single primary malignancy of ON, a primary tumor site within the nasal cavity or surrounding sinuses, sufficient staging information to derive Kadish staging, and >0 days of survival, ensuring follow-up data. Receipt of CT in the SEER registry was documented as either Yes or No/Unknown.

Results: Six hundred and thirty-six patients were identified. One hundred and ninety-five patients received CT as part of their treatment for ON. Following propensity score matching and inverse probability of treatment weighting, there was inferior overall survival (OS) (HR 1.7, 95% CI: 1.3-2.2, = .001) and cancer-specific survival (CSS) (HR 1.8, 95% CI: 1.3-2.4,  < .001) for patients who received CT compared to those who were not treated with CT or had unknown CT status. On subgroup analysis, the only patient population that derived benefit from CT were patients who did not receive surgery and were treated with CT and/or RT (HR 0.3, 95% CI: 0.14-0.61,  < .001).

Conclusions: Based on this retrospective SEER registry analysis, the use of CT in the management of ON is associated with decreased OS. Our analysis suggests that patients who are considered nonsurgical candidates may benefit from the addition of CT.
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http://dx.doi.org/10.1002/hsr2.257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088587PMC
June 2021

A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab-resistant head and neck cancer: The MAESTRO study.

Cancer 2020 07 4;126(14):3237-3243. Epub 2020 May 4.

Comprehensive Cancer Center, University of Chicago Medicine, Chicago, Illinois, USA.

Background: Patients with cetuximab-resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) have poor outcomes. This study hypothesized that dual blockade of mammalian target of rapamycin and epidermal growth factor receptor (EGFR) would overcome cetuximab resistance on the basis of the role of phosphoinositide 3-kinase signaling in preclinical models of EGFR resistance.

Methods: In this multicenter, randomized clinical study, patients with recurrent/metastatic HNSCC with documented progression on cetuximab (in any line in the recurrent/metastatic setting) received 25 mg of temsirolimus weekly plus cetuximab at 400/250 mg/m weekly (TC) or single-agent temsirolimus (T). The primary outcome was progression-free survival (PFS) in the TC arm versus the T arm. Response rates, overall survival, and toxicity were secondary outcomes.

Results: Eighty patients were randomized to therapy with TC or T alone. There was no difference for the primary outcome of median PFS (TC arm, 3.5 months; T arm, 3.5 months). The response rate was 12.5% in the TC arm (5 responses, including 1 complete response [2.5%]) and 2.5% in the T arm (1 partial response; P = .10). Responses were clinically meaningful in the TC arm (range, 3.6-9.1 months) but not in the T-alone arm (1.9 months). Fatigue, electrolyte abnormalities, and leukopenia were the most common grade 3 or higher adverse events and occurred in less than 20% of patients in both arms.

Conclusions: The study did not meet its primary endpoint of improvement in PFS. However, TC induced responses in cetuximab-refractory patients with good tolerability. The post hoc observation of activity in patients with acquired resistance (after prior benefit from cetuximab monotherapy) may warrant further investigation.
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http://dx.doi.org/10.1002/cncr.32929DOI Listing
July 2020

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes.

Int J Radiat Oncol Biol Phys 2020 07 18;107(4):662-671. Epub 2020 Apr 18.

Department of Radiation and Cellular Oncology, University of Chicago Medicine, Chicago, Illinois. Electronic address:

Purpose: To report functional outcomes for patients with human papillomavirus-positive oropharyngeal cancer treated on a phase 2 protocol of risk- and induction chemotherapy response-adapted dose and volume de-escalated radiation therapy (RT)/chemoradiation (CRT).

Methods And Materials: Patients were stratified as low risk (LR) or high risk (HR) according to T/N-stage and smoking history. Induction chemotherapy was followed by radiographic response assessment. LR patients with ≥50% response received 50 Gy RT (RT50), whereas LR patients with 30% to 50% response or HR patients with ≥50% response received 45 Gy CRT (CRT45). All other patients received 75 Gy CRT (CRT75) with RT limited to the first echelon of uninvolved nodes. Pre- and post-RT/CRT modified barium swallow studies were performed. Percutaneous endoscopic gastrostomy (PEG) tube placement, body mass index (BMI), and narcotic use were recorded. Statistical comparisons used linear or logistic regression, the Mann-Whitney U test, the χ test, or Fisher's exact test as appropriate.

Results: Twenty-eight LR and 34 HR patients were enrolled; 49 completed RT50/CRT45 and 11 completed CRT75. PEG-tube dependency at the end of RT/CRT and 3 months post-RT/CRT significantly differed according to risk and treatment groups (all P < .05). Treatment intensity was independently associated with 3-month PEG status while adjusting for risk group (P = .002). The CRT75 group had a median -8.42% change from baseline BMI at 1 year post-RT/CRT versus -2.54% for the RT50/CRT45 group (P = .01). At the end of RT/CRT, CRT75 patients were less likely to tolerate a normal diet, more likely to have swallowing performance status scale scores ≥4, more likely to have Rosenbek's penetration-aspiration scores ≥7, more likely to have developed trismus, and more likely to require narcotics >2 months (all P < .05).

Conclusions: Induction chemotherapy followed by risk- and response-adapted dose and volume de-escalated RT/CRT is associated with clinically meaningful functional outcomes including (1) improved swallowing function, (2) higher BMI, and (3) shorter narcotic use for patients receiving de-escalation.
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http://dx.doi.org/10.1016/j.ijrobp.2020.04.014DOI Listing
July 2020

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma.

Cancer 2020 05 19;126(10):2146-2152. Epub 2020 Feb 19.

Kimmel Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland.

Background: MET signaling is a well described mechanism of resistance to anti-EGFR therapy, and MET overexpression is common in head and neck squamous cell carcinomas (HNSCCs). In the current trial, the authors compared the oral MET inhibitor tivantinib (ARQ197) in combination with cetuximab (the TC arm) versus a control arm that received cetuximab monotherapy (C) in patients with recurrent/metastatic HNSCC.

Methods: In total, 78 evaluable patients with cetuximab-naive, platinum-refractory HNSCC were enrolled, including 40 on the TC arm and 38 on the C arm (stratified by human papillomavirus [HPV] status). Patients received oral tivantinib 360 mg twice daily and intravenous cetuximab 500 mg/m once every 2 weeks. The primary outcome was the response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), and secondary outcomes included progression-free and overall survival. After patients progressed on the C arm, tivantinib monotherapy was optional.

Results: The response rate was 7.5% in the TC arm (N = 3; 1 complete response) and 7.9% in the C arm (N = 3; not significantly different [NS]). The median progression-free survival in both arms was 4 months (NS), and the median overall survival was 8 months (NS). Both treatments were well tolerated, with a trend toward increased hematologic toxicities in the TC arm (12.5% had grade 3 leukopenia). The response rate in 31 HPV-positive/p16-positive patients was 0% in both arms, whereas the response rate in HPV-negative patients was 12.7% (12.5% in the TC arm and 13% in the C arm). Fifteen patients received tivantinib monotherapy, and no responses were observed.

Conclusions: Combined tivantinib plus cetuximab does not significantly improve the response rate or survival compared with cetuximab alone but does increase toxicity in an unselected HNSCC population. Cetuximab responses appear to be limited to patients who have HPV-negative HNSCC. MET-aberration-focused trials for HNSCC and the use of higher potency, selective MET inhibitors remain of interest.
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http://dx.doi.org/10.1002/cncr.32762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011819PMC
May 2020

A pilot study of the pan-class I PI3K inhibitor buparlisib in combination with cetuximab in patients with recurrent or metastatic head and neck cancer.

Head Neck 2019 11 4;41(11):3842-3849. Epub 2019 Sep 4.

Department of Medicine, The University of Chicago Medicine, Chicago, Illinois.

Background: This study assessed the maximum tolerated dose (MTD) of the PI3K inhibitor buparlisib given concurrently with cetuximab in recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Methods: Twelve patients with R/M HNSCC were enrolled. Patients were given oral buparlisib starting day 7 and daily thereafter. The dose of buparlisib was escalated in a 3 + 3 design followed by a dose expansion cohort of 6 patients. The MTD of buparlisib per protocol was 100 mg daily with cetuximab given intravenously every 14 days starting day 0.

Results: Ten patients had ≥2 previous treatment regimens (11 with prior cetuximab). There were no dose limiting toxicities observed during dose escalation. One patient achieved a partial response and 4 achieved stable disease.

Conclusion: Based on this pilot study, buparlisib at 100 mg daily plus cetuximab proved to be well-tolerated. Patients previously treated with cetuximab monotherapy showed benefit from this combination.
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http://dx.doi.org/10.1002/hed.25910DOI Listing
November 2019

The time course of semantic and relational processing during verbal analogical reasoning.

Brain Cogn 2019 02 1;129:25-34. Epub 2018 Dec 1.

Loyola University Chicago, Department of Psychology, 1032 W Sheridan Rd., Chicago, IL 60660, United States.

Analogy is an important ability that allows humans to discover relationships between information domains that often vary in surface and relational characteristics. Cognitive neuroscience studies of analogy have demonstrated the importance of the prefrontal cortex during relational comparisons, but little is known about how semantic and relational similarity interact throughout its time course. We used scalp electroencephalography (EEG) analyzed with event-related potentials (ERPs) to examine the neural time course of analogical reasoning while 16 participants solved four-term verbal analogies. Semantic similarity was manipulated by increasing the semantic distance between source and target analogs creating semantically near and far analogies. Relational similarity was manipulated by creating relationally valid and invalid analogies. Only valid analogies were impacted by semantic distance such that far analogies were solved slower and less accurately than near analogies. Correctly solving near analogies elicited more positive waveforms at the N400 and during later relational processing. However, valid analogies elicited more positive signals during only later relational processing and not during the N400. These results suggest that semantic information impacts both early semantic and late relational comparison stages, while relational properties exert more influence in later stages of analogical reasoning. The degree of semantic similarity shared between knowledge domains demonstrated a potent effect throughout the time course of analogy that affected not only semantic access, but also the mapping of relational structures.
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http://dx.doi.org/10.1016/j.bandc.2018.11.012DOI Listing
February 2019

Definitive chemoradiation for locally-advanced oral cavity cancer: A 20-year experience.

Oral Oncol 2018 05 16;80:16-22. Epub 2018 Mar 16.

Department of Radiation and Cellular Oncology, University of Chicago, 5758 S. Maryland Avenue, M/C 9006, Chicago, IL 60637, USA. Electronic address:

Objectives: Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC.

Materials And Methods: Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70-75 Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test.

Results: 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7 years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (P = 0.90), DC (P = 0.24), PFS (P = 0.38), OS (P = 0.10), or ORN (P = 0.38) were not significant across treatment decades.

Conclusion: Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC.
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http://dx.doi.org/10.1016/j.oraloncology.2018.03.008DOI Listing
May 2018

Three-Dimensional Computed Tomography Reconstruction for Revision Parathyroidectomy.

Cureus 2017 Sep 26;9(9):e1715. Epub 2017 Sep 26.

Department of Otolaryngology, Beaumont Health.

A 57-year-old man presented with persistent hyperparathyroidism following primary parathyroidectomy. A four-dimensional computed tomography scan with three-dimensional reconstruction showed two parathyroid glands (one right and one left) and anatomic variation from previous surgery. Revision surgery was performed revealing the parathyroid glands as expected from the preoperative three-dimensional reconstruction. After surgery, the patient recovered well, and preoperative symptoms resolved. The use of three-dimensional computed tomography reconstruction provided accurate localization of the parathyroid glands and surrounding anatomic structures. This resulted in decreased preoperative planning cost, operative time, and estimated blood loss typical for patients who have multiple preoperative imaging studies.
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http://dx.doi.org/10.7759/cureus.1715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703584PMC
September 2017

Pilot Study of 99mTc-labeled Ethylene Dicysteine Deoxyglucose SPECT-CT Imaging in Treatment Response Evaluation in Patients with Locally Advanced Head and Neck Cancer.

Cureus 2017 Apr 11;9(4):e1152. Epub 2017 Apr 11.

Medicine, The University of Chicago Medicine.

Background: The purpose of this study is to describe the preliminary findings of 99mTc-labeled ethylene dicysteine deoxyglucose (99mTc-EC-DG) performed four weeks after chemoradiotherapy in patients with locally advanced head and neck squamous cell carcinoma.

Methods: Review of nine patients with locally advanced head and neck squamous cell carcinomas imaged with 99mTc-EC-DG single photon emission computed tomography-computed tomography (SPECT-CT) at baseline before treatment and at four weeks after treatment completion was performed.

Results: At four weeks post-treatment, five patients had either decreased activity or no significant activity on 99mTc-EC-DG SPECT-CT and were considered to have responded to treatment, whereas four patients did not have significantly decreased uptake on 99mTc-EC-DG SPECT-CT and were considered to have not adequately responded to treatment. Among the five patients considered to have treatment response at four weeks, all were free of disease (true-negative). Among the four patients considered to have stable activity on 99mTc-EC-DG SPECT-CT at four weeks, two were designated as having no response or incomplete response (true-positive), and two were designated as having complete response (false-positive) on subsequent composite assessment.

Conclusions: The pilot data is promising but warrants further investigation of 99mTc-EC-DG SPECT-CT for the assessment of locoregional treatment response at four weeks in patients with locally advanced head and neck squamous cell carcinomas.
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http://dx.doi.org/10.7759/cureus.1152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426824PMC
April 2017

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer.

Int J Radiat Oncol Biol Phys 2016 09 7;96(1):21-9. Epub 2016 May 7.

Departments of Medicine, University of Chicago, Chicago, Illinois.

Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation.

Methods And Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%.

Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients.

Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.
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http://dx.doi.org/10.1016/j.ijrobp.2016.04.030DOI Listing
September 2016