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51 citation(s) found for "Tan, Benjamin".

Cabozantinib in high-grade neuroendocrine neoplasms.
Trikalinos, Nikolaos, Firwana, Belal, Reimers, Melissa A., Mehan, Paul, Rohatgi, Anjali , Pressey, Olive, Waldron, Nicholas, Wu, Shuang , Tan, Benjamin , Suresh, Rama , Pedersen, Katrina S. , Firwana, Belal , Reimers, Melissa A. , Liu, Jingxia

Mayo Clinic

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4183-4183

10.1200/jco.2026.44.16_suppl.4183 Get It

4183 Background: High grade neuroendocrine neoplasms (HG-NENs) are treated with platinum doublets mirroring guidelines for small cell lung cancer (SCLC) but recurrences are common and salvage options are limited in efficacy. Cabozantinib (CABO), an inhibitor of VEGFR, MET, and TAM kinases (TYRO3, AXL, and MER) was approved by the FDA for treatment of well differentiated (WD) NENs of both pancreatic and extrapancreatic origins based on the CABINET study (Chan, NEJM 2025). However, its efficacy in the whole spectrum of HG-NEN patients including poorly differentiated disease (PDD) has not been prospectively explored. Methods: This was a single institution, Phase II study of CABO in patients with HG-NENs who had progressed on at least one prior treatment. Key inclusion/exclusion criteria were NENs of any origin except SCLC, high grade by Ki-67 of > 20% or histology consensus, ECOG of < = 1, appropriate hematological parameters and no history of bleeding or active cardiac disease. CABO was given orally starting at 60 mg po daily in 3-week cycles. The primary endpoint of this study was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). A Simon optimal 2-stage design tested the null hypothesis that the true ORR is < = 1% at the type I error rate of 5%, resulting in projected enrollment of up to 32 total patients. Toxicities were graded according to CTCAE v5.0 and response was evaluated according to RECIST v1. Results: All patients have been accrued, with 4/32 patients still on treatment. Median age at diagnosis was 62 years and male to female ratio was 1.46. Origin of tumor was GI in 68.8% of the cases, the rest being thoracic (6.3%), prostate (6.3%) cervical (6.3%) head/neck (3.1%) and unknown (9.4%). Median Ki-67 was 55%, 11 patients had Ki-67 > 70%. Histology was WD-HG in 40% of patients and PDD in 60%. Two patients had mixed PDD/other components (MiNEN). Median PFS in evaluable patients was 4.01 months [95% CI 1.61 to 9.30] and mOS was 9.89 mo [95% CI 6.73 to 18.96]. Three patients so far (9.3%) have had partial response as best response (PDD-colon, WD-pancreas and PDD-cervical) while 19/32 (59.4%) patients have had stable disease as best response so far (disease control rate 68.8%). Five (15.6%) patients have received more than 10 treatment cycles. The three longest treated patients had WD-pancreas (23 and 17 cycles) and PDD-unknown (12 cycles). One patient had eventual resection of a metastatic site and is currently without evidence of disease. Three patients withdrew from the trial because of toxicities (shortness of breath, GI bleeding, thromboembolism). Twenty-six patients have expired. Conclusions: CABO monotherapy showed efficacy in some HG-NEN patients with not just WD but also the very aggressive PDD histology. No new side effects to the ones previously described for this agent were noted. Supported by Exelixis and a Siteman investment program grant. Clinical trial information: NCT04412629 .
Final results of a phase II study of fluorouracil (FU), leucovorin (LV), and nanoliposomal irinotecan (nal-IRI) in previously treated biliary tract cancer (NAPOLI-2).
Tan, Benjamin R., Turk, Anita, Sung, Max W. , Aranha, Olivia, Mukherji, Reetu , Noel, Marcus Smith , Lim, Kian-Huat, Khushman, M., Trikalinos, Nikolaos, Marshall, John, Wang, Hongkun, Weinberg, Benjamin A. , Tan, Benjamin , He, Aiwu Ruth , Aranha, Olivia , Ratner, Lee , Suresh, Rama , Lim, Kian-Huat, Marshall, John L , Pedersen, Katrina S.

Mayo Clinic

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4122-4122

10.1200/jco.2026.44.16_suppl.4122 Get It

4122 Background: BTCs are rare and aggressive malignancies. The first-line standard of care regimen for advanced BTC (aBTC) is gemcitabine (GEM), cisplatin, and an immune checkpoint inhibitor. Although FOLFOX is a preferred second-line treatment, it is limited by neuropathy. Nal-IRI contains IRI free base in liposome nanoparticles, which shelter IRI from conversion to its active metabolite (SN-38) and increase intratumoral SN-38 compared with IRI alone. The NAPOLI-1 trial of FU/LV/nal-IRI vs. FU/LV in second-line advanced pancreatic adenocarcinoma showed an overall survival (OS) benefit. The NIFTY trial (South Korea) demonstrated median OS (mOS) benefit of FU/LV/nal-IRI over FU/LV in a second-line aBTC population (8.6 vs. 5.3 months [mo], HR 0.68, 95% CI 0.48-0.95); however, the NALIRICC trial (Germany) did not (6.9 vs. 8.2 mo, HR 1.08, 95% CI 0.68-1.72). We sought to characterize second-line FU/LV/nal-IRI efficacy in US patients (pts) with second-line aBTC. Methods: This was a single-arm, open-label, multicenter phase II study of pts with aBTC previously treated with GEM/platinum chemotherapy. Pts received nal-IRI 70 mg/m 2 IV over 90 minutes, LV 400 mg/m 2 IV over 30 minutes every 14 days, and FU 2400 mg/m 2 IV over 46 hours every 14 days. The primary objective was to determine progression-free survival rate at 4 mo (PFS 4mo ) using RECIST v. 1.1 criteria. Median PFS reported for pts receiving second-line 5-FU doublet chemotherapy was 3 mo with a PFS of 30%. FU/LV/nal-IRI was of interest if it could increase the PFS 4mo to 50% or higher. Using a one-sided α of 0.05 and 80% power, 17 of 39 evaluable pts had to be progression-free at 4 mo to detect a difference in PFS 4mo between 30% and 50%. Results: Forty-eight pts were enrolled: median age 64.5 years; 69% women; 27% gallbladder primary; 54% intra- and 19% extrahepatic. Ten pts came off study due to toxicity without disease progression before 4 mo on study and were replaced to evaluate the PFS 4mo endpoint. Of 38 evaluable pts, 18 pts (PFS 4mo 47%) were alive and progression-free at 4 mo, meeting the primary endpoint. With a median follow-up of 7.1 mo, median time to disease progression or study discontinuation due to toxicity for all pts was 2.3 mo (95% CI 1.8-4.6, PFS 4mo 38%), and for pts evaluable for the primary endpoint, median PFS was 3.5 mo (95% CI 1.8-5.5). Five pts (10%) had PFS beyond 12 mo. mOS for all pts was 7.9 mo (95% CI 5.7-11.7). Of 41 evaluable pts, the response rate was 2% (1 PR), and the disease control rate was 54%. Adverse events (AEs) were consistent with known toxicities from the FU/LV/nal-IRI regimen. Conclusions: FU/LV/nal-IRI is an effective second-line regimen for aBTC in US pts. There was significant early toxicity as 21% of pts came off study due to AEs before 4 mo. Correlative studies, including longitudinal analyses of circulating tumor DNA using banked blood specimens, are planned (NCT04005339). Clinical trial information: NCT04005339 .
Physical activity and molecular residual disease (MRD) in stage III colon cancer: Findings from CALGB (Alliance)/SWOG 80702.
Ma, Chao, Shi, Qian, Nowak, Jonathan Andrew, Pederson, Levi , Twombly, Tyler S., Zhao, Melissa , Shergill, Ardaman , Kumar, Pankaj, Couture, Félix , Kuebler, J. Philip , Krishnamurthi, Smitha S., Tan, Benjamin, Ogino, Shuji, Brown, Justin, Jurdi, Adham A., Af, Shields, Meyerhardt, J., Zhang, George Q. , Shi, Qian , Nowak, Jonathan A. , Väyrynen, Juha P. , Takashima, Yasutoshi , Kumar, Pankaj , Krishnamurthi, Smitha , Ogino, Shuji , Jurdi, Adham Adel

Mayo Clinic

Journal of Clinical Oncology | January 12, 2026 | Volume: 44 | Issue: 2_suppl | Pages: 163-163

10.1200/jco.2026.44.2_suppl.163 Get It

163 Background: Being physically inactive is an independent predictor of poor outcomes in patients with stage III colon cancer. Whether physical activity can mitigate the oncologic risk of postoperative MRD is unknown. Methods: We concluded a post hoc analysis of a phase III trial evaluating celecoxib vs. placebo and 3 vs. 6 months of adjuvant chemotherapy in patients with resected stage III colon cancer. Self-reported physical activity was assessed in standardized measures of metabolic equivalent hours per week (MET-h/wk) at 2 timepoints: 1) midway through and 2) 6 months after completing adjuvant chemotherapy, modeled as a time-weighted average. MRD was determined via a clinically validated, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera, Natera, Inc.). Disease-free survival (DFS) and overall survival (OS) were estimated using flexible parametric survival models. Results: Among 763 patients (median follow-up 6.0 years), 24% were highly active (≥18 MET-h/wk) and 32% were inactive (<3 MET-h/wk); 18% were ctDNA positive. Adjusting for covariates, DFS improved in patients who were ctDNA negative and moderately active (Ref: inactive; 3-17.9 MET-h/wk; HR=0.62, 95% CI [0.40-0.97]) or highly active (HR = 0.53 [0.30-0.94]). No benefit was seen among patients who were ctDNA positive (Ref: inactive; moderately active: HR = 1.20 [0.75-1.92]; highly active: HR=0.83 [0.45-1.54]). The interaction was not significant (Pint=0.269). Physical activity did not impact OS regardless of ctDNA status. The interaction of physical activity and adjuvant celecoxib use is shown in Table. Conclusions: Among patients who were ctDNA negative, physical activity was associated with improved DFS, and may demonstrate increased survival benefit alongside adjuvant celecoxib. The additive effects of both interventions were inconclusive among those who were ctDNA positive. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org; Natera, Pfizer; NCT01150045. Disease-free survival by physical activity level and celecoxib use, stratified by ctDNA status. 3-yr event # at risk Adjusted HR (95% CI) P-value Pint ctDNA Negative 0.258 Inactive + placebo 23 182 Ref Active + placebo 17 132 0.74 (0.43-1.28) 0.283 Inactive + celecoxib 23 167 0.92 (0.57-1.48) 0.720 Active + celecoxib 10 146 0.40 (0.22-0.79) 0.007 ctDNA Positive 0.221 Inactive + placebo 26 33 Ref Active + placebo 15 20 0.96 (0.50-1.84) 0.903 Inactive + celecoxib 34 54 0.62 (0.37-1.05) 0.076 Active + celecoxib 14 29 0.34 (0.18-0.64) 0.001 ctDNA, circulating tumor DNA; HR, hazard ratio; CI, confidence interval. Active = ≥9 MET-h/week, inactive = <9 MET-h/week. Celecoxib use defined by assignment in CALGB/SWOG 80702. Models adjusted by T and N stage, age, sex, race, assigned cycles of fluorouracil, leucovorin, and oxaliplatin, KRAS and BRAF status, BMI, and Western diet.
Neoadjuvant epacadostat (INCB024360) combined with short course radiotherapy in patients with locally advanced rectal cancer: Efficacy and safety from a phase 2 trial.
Khushman, M., Park, Haeseong , Huang, K, Parikh, Parag J., Lim, Kian-Huat, Tan, Benjamin, Andreatos, Nikolaos , Mutch, Matthew, Chapman, William, Hunt, Steven, Silviera, Matthew L., Cowan, Michelle L., Wise, Paul E, Kim, Hyun, Ciorba, Matthew A. , Pedersen, Katrina S. , Brown, Amberly , Lim, Kian-Huat, Suresh, Rama , Mutch, Matthew G. , Hunt, Steven R., Mo, Allen , Shetty, Anup S.

Mayo Clinic

Journal of Clinical Oncology | January 12, 2026 | Volume: 44 | Issue: 2_suppl | Pages: 162-162

10.1200/jco.2026.44.2_suppl.162 Get It

162 Background: In preclinical studies, the tryptophan-metabolizing enzyme, Indoleamine 2, 3-dioxygenase 1 (IDO1), promotes resistance to radiation in colorectal cancer, and IDO1 inhibition with epacadostat improves tumor radiosensitivity. In a phase 1 trial, patients (pts) with locally advanced rectal cancer (LARC, n=17) were treated with epacadostat in combination with short course radiotherapy (SCRT) and CAPOX which was well-tolerated, and the recommended phase 2 dose (RP2D) of epacadostat was 400mg BID. Here we report efficacy and safety from the NCI-supported phase 2 (NCT03516708) multicenter, open-label trial (treatment cohort). Methods: Pts were treated with standard of care (SOC) SCRT, then SOC neoadjuvant chemotherapy (NAC) followed by SOC surgical resection or non-operative management (NOM). Epacadostat (400 mg BID) started with SCRT and continued until starting NAC (a minimum of 21 days). Eight pts were enrolled prior to discontinuation of epacadostat by Incyte in February/March 2025. The primary endpoint is Neoadjuvant Rectal (NAR) score. In patients who underwent NOM, we calculated MRI-based tumor regression grade (MR-TRG). Secondary endpoints are pathologic complete response (pCR) rate, complete clinical response (cCR) rate, and progression free survival (PFS). Results: Table 1 summarizes baseline characteristics and endpoints (primary and secondary). NOM was pursued in 7/8 (87.5%) pts, surgical resection was performed on 1/8 (12.5%). At median follow-up of 12 months, local tumor regrowth occurred in 1 pt initially treated with NOM (after tumor regrowth, he underwent salvage surgery and is currently on surveillance). Treatment with epacadostat was interrupted in 2/8 (25%) patients due to grade 3 maculopapular skin rash. Most frequent treatment-emergent adverse events (TEAEs) regardless of causality (all grades (G)/G3-4) were bloating (75%/0%), increased ALT (62.5%/0%), increased AST (50%/0%), nausea (50%/0%), and constipation (50%/0%). Grade 3 diarrhea and grade 3 non-cardiac chest pain occurred in 1 patient each (both unrelated to epacadostat). Conclusions: Epacadostat demonstrates promising efficacy and manageable safety in patients with LARC. The biomarker cohort and correlative studies are ongoing. Clinical trial information: NCT03516708 . Baseline characteristics and endpoints. Patient Age Sex Ethnicity Stage Surgery/NOM NAR MR-TRG cCR/pCR Recurrence 1 52 M Caucasian T3N1 NOM NA 2 Y/NA No 2 45 M Caucasian T3N1 NOM NA 3 Y/NA Local tumor regrowth 3 48 M Caucasian T3N2 NOM NA 3 Y/NA No 4 61 M Caucasian T4N2 NOM NA 3 Y/NA No 5 57 M Caucasian T3N0 NOM NA 1 Y/NA No 6 60 F Caucasian T3N1 Surgery 15 3 N/ypT3N0 No 7 67 M Caucasian T4N0 NOM NA 3 Y/NA No 8 51 M Caucasian T4N2 NOM NA P NA No
Predictive Role of Circulating Tumor DNA in Stage III Colon Cancer Treated With Celecoxib
Meyerhardt, Jeffrey A. , Twombly, Tyler S., Pederson, Levi , Väyrynen, Juha P. , Zhao, Melissa , Shergill, Ardaman , Kumar, Pankaj , Couture, Felix, Kuebler, Philip , Krishnamurthi, Smitha , Giannakis, Marios , Ogino, Shuji, Sharma, Shruti, Aleshin, Alexey , Shields, Anthony F. , Kuebler, J. Philip , Meyerhardt, Jeffrey A , Väyrynen, Juha , Zhang, George Q. , Shi, Qian , Ma, Chao , Takashima, Yasutoshi , Couture, Felix, Tan, Benjamin, O’Reilly, Eileen M. , Ogino, Shuji , Jurdi, Adham Adel , Sharma, Shruti , Nowak, Jonathan A.

Mayo Clinic

JAMA Oncology | December 4, 2025 | Volume: 12 | Issue: 2 | Pages: 149

10.1001/jamaoncol.2025.5144 | PMID 41343176 Get It

Importance Observational studies have associated use of aspirin and selective cyclooxygenase inhibitors with decreased recurrence and improved survival in patients with colon cancer. While randomized clinical trials have not shown benefit across all patients, these findings suggest that select subgroups may benefit from their use. Despite the well-established prognostic value of circulating tumor DNA (ctDNA), its role in guiding treatment remains unclear. Objective To investigate the predictive value of postoperative ctDNA for survival outcomes with adjuvant celecoxib alongside conventional chemotherapy in patients with stage III colon cancer. Design, Setting, and Participants This was a post hoc analysis of the phase 3 Cancer and Leukemia Group B (now Alliance)/Southwest Oncology Group 80702 randomized clinical trial (2010-2015) assessing adjuvant celecoxib vs placebo and 3 vs 6 months of adjuvant 5-fluorouracil, leucovorin, and oxaliplatin for stage III colon cancer. Patients consented to biospecimen collection and had ctDNA analysis performed. Data analysis was performed from September 2024 to June 2025. Exposures Postoperative ctDNA positivity was determined using a clinically validated, tumor-informed 16-plex-polymerase chain reaction-next-generation sequencing assay (Signatera; Natera Inc) performed between surgery and initiation of adjuvant therapy. Main Outcomes and Measures Disease-free survival (DFS) and overall survival (OS). Survival by ctDNA status and adjuvant celecoxib use were assessed as part of a post hoc companion study with prespecified statistical analysis plan. Results Among 940 patients (mean [SD] age, 60.9 [10.8] years; 426 female [45.3%] and 515 male [54.7%] individuals; 222 [23.6%] with prior low-dose aspirin use; and median follow-up of 6.0 [95% CI, 6.0-6.0] years), 767 (81.6%) were ctDNA negative and 173 (18.4%) were ctDNA positive. ctDNA positivity was highly prognostic of worse DFS (reference, ctDNA negativity; adjusted hazard ratio [aHR], 6.12; 95% CI, 4.66-8.03) and OS (aHR, 5.86; 95% CI, 4.19-8.19). In patients with ctDNA positivity, celecoxib was associated with improved DFS (aHR, 0.61; 95% CI, 0.42-0.89) and OS (aHR, 0.62; 95% CI, 0.40-0.96) compared to placebo. Among patients with ctDNA negativity, celecoxib did not provide survival benefit (DFS: aHR, 0.76; 95% CI, 0.53-1.09; OS: aHR, 0.85; 95% CI, 0.54-1.36), although the interaction was not significant ( P for interaction, .41 and .33 for DFS and OS, respectively). These findings persisted when stratifying patients by microsatellite instability status and PIK3CA mutational status. Conclusion and Relevance The findings of this post hoc analysis suggest that ctDNA status has the potential to inform clinical decision-making among patients with stage III colon cancer who should consider adjuvant celecoxib in addition to conventional chemotherapy. Trial Registration ClinicalTrials.gov Identifier: NCT01150045
Sex differences in chemotherapy completion, toxicities, and survival in colon cancer: an analysis of 2201 patients from CALGB/SWOG 80702 (Alliance)
Cheng, En , Shi, Qian , Shields, Anthony F. , Xue, Xiaonan , Rohan, Thomas E. , Kuang, Chaoyuan , Shergill, Ardaman , Ma, Chao , Couture, Felix, Kuebler, J. Philip , Kumar, Pankaj , Krishnamurthi, Smitha , Ng, Kimmie , Meyerhardt, Jeffrey A. , Krishnamurthi, Smitha , Ng, Kimmie , O'Reilly, Eileen M , Brown, Justin C , Meyerhardt, Jeffrey A , Shi, Qian , Couture, Felix, Kumar, Pankaj , Tan, Benjamin, O’Reilly, Eileen M. , Brown, Justin C. , Cheng, En

Mayo Clinic

JNCI: Journal of the National Cancer Institute | September 20, 2025 | Volume: 117 | Issue: 12 | Pages: 2643-2652

10.1093/jnci/djaf281 | PMID 40996326 Get It

Abstract Background Completing adjuvant chemotherapy and reducing toxicities are critical for maximizing survival after a colon cancer diagnosis. Sex, as a biological variable, may affect colon cancer chemotherapy completion, toxicities, and survival differently. Methods From a National Cancer Institute–sponsored trial conducted among patients with stage III colon cancer (Cancer and Leukemia Group B (Alliance)/Southwest Oncology Group 80702), we included 2201 patients receiving the standard adjuvant chemotherapy regimen of fluorouracil, leucovorin, and oxaliplatin. We calculated relative dose intensity to indicate chemotherapy completion and considered reduced relative dose intensity (values &lt;85%) as a clinically significant deviation from standard fluorouracil, leucovorin, and oxaliplatin. Using National Cancer Institute’s Common Terminology Criteria for Adverse Events, we defined severe adverse events (grade ≥3) as the occurrence of any following event, including neutrophil count decrease, nausea, platelet count decrease, hypertension, peripheral neuropathy, diarrhea, fatigue, gastritis, creatinine level increase, gastric ulcer, myocardial ischemia, and cerebral ischemia. The primary survival outcome was disease-free survival (time from enrollment to colon cancer recurrence or death from any cause), and secondary survival outcomes were recurrence-free and overall survival. Results Compared with men, women were at statistically significantly higher risks of experiencing reduced relative dose intensity (adjusted odds ratio = 1.59, 95% CI = 1.29 to 1.96; P &lt; .001) and severe advance events (adjusted odds ratio = 1.72, 95% CI = 1.41 to 2.11; P &lt; .001). Yet, women had statistically significantly better disease-free survival (adjusted hazard ratio = 0.72, 95% CI = 0.59 to 0.87; P &lt; .001) as well as better recurrence-free and overall survival. Conclusions Our findings suggested that women with colon cancer are more likely to have worse chemotherapy completion rates and more severe adverse events, but they have better survival. Sex as a biological variable warrants further consideration in chemotherapy administration and survivorship management after colon cancer diagnosis.
Factors associated with early neurological deterioration in minor distal medium vessel acute ischemic stroke: A multinational multicenter study
Lakhani, Dhairya A. , Salim, Hamza , Yedavalli, Vivek , Milhem, Fathi , Adeeb, Nimer , Faizy, Tobias D. , Naamani, Kareem El, Henninger, Nils , Sundararajan, Sri Hari , Khalife, Jane, Ghozy, Sherief, Tan, Benjamin Yong‐Qiang , Regenhardt, Robert W. , Heit, Jeremy J. , Rouchaud, Aymeric, Fiehler, Jens, Puri, Ajit S., Dyzmann, Christian , Colasurdo, Marco, Filipe, João Pedro , Abdalkader, Mohamad , Marrota, Thomas, Spears, Julian , Biswas, Arundhati , Clarençon, Frédéric , Varela, Ricardo , Baker, Amanda , Altschul, David , Gonzalez, Nestor R. , Möhlenbruch, Markus , Costalat, Vincent, Gory, Benjamin, Stracke, Christian Paul , Hecker, Constantin, Shaikh, Hamza , Griessenaur, Christoph, Liebeskind, David S. , Alexandre, Andrea , Tancredi, Illario, Kalsoum, Erwah , Lubicz, Boris , Patel, Aman B. , Guenego, Adrien , Investigators, for the MAD MT, Salim, Hamza , Faizy, Tobias D , Henninger, Nils , Tan, Benjamin Yq , Cancelliere, Nicole M , Alexandru Radu, Răzvan , Ota, Takahiro , Jabbour, Pascal , Clarençon, Frédéric , Siegler, James E , Nguyen, Thanh N , Essibayi, Muhammed Amir , Gonzalez, Nestor R , Marnat, Gaultier , Pedicelli, Alessandro , Alexandre, Andrea M , Guenego, Adrien , Dmytriw, Adam A , Liebeskind, David S. , Heit, Jeremy J , Altschul, David J , Regenhardt, Robert W , Lakhani, Dhairya , Yedavalli, Vivek S , Varela, Ricardo , Musmar, Basel , Daraghma, Motaz , Naamani, Kareem El , Kühn, Anna Luisa , Khalife, Jane , Ghozy, Sherief , Scarcia, Luca , Yeo, Leonard Ll , Cancelliere, Nicole M , Rouchaud, Aymeric , Sheth, Sunil A , Puri, Ajit S , Colasurdo, Marco , Renieri, Leonardo , Harker, Pablo , Radu, Răzvan Alexandru , Klein, Piers , Marotta, Thomas R. , Mowla, Ashkan , Jabbour, Pascal , Siegler, James E. , Nguyen, Thanh N. , Essibayi, Muhammed Amir , Costalat, Vincent , Gory, Benjamin , Hecker, Constantin , Griessenauer, Christoph J. , Tancredi, Illario , Mendes Pereira, Vitor , Wintermark, Max , Dmytriw, Adam A. , Investigators, for the MAD MT

Mayo Clinic

International Journal of Stroke | September 16, 2025 | Volume: 21 | Issue: 3 | Pages: 343-352

10.1177/17474930251381946 | PMID 40954523 Get It

Background: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases. Methods: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END. Results: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12–5.02, p = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26–0.81, p = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69–3.98, p = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END. Conclusion: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.
Baseline predictors of poor clinical outcome despite recanalization of distal middle cerebral artery occlusions
Chafai, Imene , Salim, Hamza , Musmar, Basel , Adeeb, Nimer , Yedavalli, Vivek , Tjoumakaris, Stavropoula , Henninger, Nils , Nedelcu, Simona , Sundararajan, Sri Hari , Kühn, Anna Luisa , Khalife, Jane , Tan, Benjamin Yong‐Qiang , Heit, Jeremy J. , Regenhardt, Robert W. , Puri, Ajit S , Dyzmann, Christian , Filipe, João Pedro , Marotta, Thomas R. , Spears, Julian , Biswas, Arundhati , Clarençon, Frédéric , Varela, Ricardo , Baker, Amanda , Altschul, David , Gonzalez, Nestor R. , Möhlenbruch, Markus , Costalat, Vincent , Stracke, Christian Paul , Shaikh, Hamza , Liebeskind, David S. , Alexandre, Andrea , Tancredi, Illario , Faizy, Tobias D. , Kalsoum, Erwah , Patel, Aman B. , Wang, Maud , Lubicz, Boris , Guenego, Adrien , ##, On behalf of the MAD MT Investigators, Tjoumakaris, Stavropoula , Ghozy, Sherief , Scarcia, Luca , Tan, Benjamin Yq , Heit, Jeremy J , Regenhardt, Robert W , Cancelliere, Nicole M , Bernstock, Joshua D , Rouchaud, Aymeric , Fiehler, Jens , Sheth, Sunil A , Essibayi, Muhammed Amir , Colasurdo, Marco , Marnat, Gaultier , Renieri, Leonardo , Filipe, João Pedro , Harker, Pablo , Alexandru Radu, Răzvan , Marotta, Thomas R , Spears, Julian , Ota, Takahiro , Mowla, Ashkan , Jabbour, Pascal , Clarençon, Frédéric , Nguyen, Thanh N , Varela, Ricardo , Altschul, David J , Gonzalez, Nestor R , Möhlenbruch, Markus A , Gory, Benjamin , Stracke, Paul , Hecker, Constantin , Shaikh, Hamza A , Liebeskind, David S. , Pedicelli, Alessandro , Alexandre, Andrea M , Tancredi, Illario , Faizy, Tobias D , Kalsoum, Erwah , Fahed, Robert , Wang, Maud , Mendes Pereira, Vitor , Lubicz, Boris , Dmytriw, Adam A , Guenego, Adrien , Kühn, Anna Luisa , Musmar, Basel , Salim, Hamza , Yedavalli, Vivek S , Henninger, Nils , Nedelcu, Simona , Ghozy, Sherief , Cancelliere, Nicole M , Bernstock, Joshua D. , Rouchaud, Aymeric , Fiehler, Jens , Essibayi, Muhammed Amir , Colasurdo, Marco , Renieri, Leonardo , Harker, Pablo , Radu, Răzvan Alexandru , Mowla, Ashkan , Jabbour, Pascal , Nguyen, Thanh N. , Baker, Amanda, Aziz‐Sultan, Mohammad Ali , Hecker, Constantin , Fahed, Robert , Dmytriw, Adam A. , ##, On behalf of the MAD MT Investigators

Mayo Clinic

Interventional Neuroradiology | July 16, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1177/15910199251342841 | PMID 40665742 Get It

Objective Mechanical thrombectomy (MT) is well-established for the treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO), with growing data supporting the expansion to distal and medium vessel occlusions (DMVO). Despite successful recanalization in DMVO, certain patients still experience poor long-term clinical outcomes, prompting our study to comprehensively explore pre-MT factors influencing outcome despite excellent recanalization (final modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2c). Methods We retrospectively examined data from patients who consecutively underwent MT for a primary middle cerebral artery (MCA) DMVO across 37 centers in North America, Asia, and Europe. We identified baseline clinical and imaging factors associated with poor clinical outcome (defined as a modified Rankin Scale [mRS] score of 3–6) at 3 months, despite excellent recanalization using a multivariable model. Results Between September 2017 and July 2021, 623 patients achieved mTICI > 2b and they were included in our study. Among them, 198 (32%) experienced a poor clinical outcome (mRS 3–6). Predictors of poor clinical outcome included higher age (OR 1.05 [1.03–1.07], p < 0.001), higher NIHSS at admission (OR 1.12 [1.08–1.15], p < 0.001), higher baseline mRS (OR 1.77 [0.96–3.26], p = 0.067), and diabetes (OR 1.59 [1.01–2.48], p = 0.044). Higher ASPECTS was associated with a decreased risk of poor clinical outcome (OR 0.82 [0.71–0.94], p = 0.006). Conclusion Older age, diabetes, higher baseline mRS, and NIHSS were associated with poor clinical outcome in MCA DMVO despite excellent recanalization. Conversely, a higher ASPECTS decreased the probability of such an outcome.
Petechial hemorrhage in mechanical thrombectomy for distal and medium-vessel occlusions: technical considerations and outcomes
Baker, Amanda , Adeeb, Nimer , Henninger, Nils , Sundararajan, Sri Hari , Khalife, Jane, Tan, Benjamin Yong‐Qiang , Regenhardt, Robert W. , Heit, Jeremy J. , Cancelliere, Nicole M., Fiehler, Jens, Puri, Ajit S., Dyzmann, Christian , Colasurdo, Marco, Filipe, João Pedro , Harker, Pablo, Abdalkader, Mohamad , Marotta, Thomas R. , Spears, Julian , Jabbour, Pascal , Biswas, Arundhati , Clarençon, Frédéric , Varela, Ricardo , Gonzalez, Nestor R. , Möhlenbruch, Markus , Costalat, Vincent , Gory, Benjamin , Yedavalli, Vivek , Stracke, Christian Paul , Shaikh, Hamza, Liebeskind, David S., Alexandre, Andrea , Faizy, Tobias D., Tancredi, Illario , Kalsoum, Erwah , Lubicz, Boris , Patel, Aman B. , Guenego, Adrien , Altschul, David , _, _, Amllay, Abdelaziz, Gopinathan, Anil, Dusart, Anne , Capirossi, Carolina , Mounayer, Charbel, Hsieh, Cheng-Yang, Stapleton, Christopher J. , Bellante, Flavio, Shaikh, Hamza , Cuellar-Saenz, Hugo H., Rabinov, James D. , Berge, Jérôme , Martinez-Gutierrez, Juan Carlos, Premat, Kévin , Chervak, Lina , Elhorany, Mahmoud, Quintero‐Consuegra, Miguel , Kan, Peter , Khandelwal, Priyank , Kadirvel, Ramanathan , Dofuku, Shogo , Nedelcu, Simona, Tjoumakaris, Stavropoula I, Barreau, Xavier, Liebeskind, David S. , Liebeskind, David S. , Heit, Jeremy J , Altschul, David J , Gonzalez, Nestor R , Regenhardt, Robert W , Yedavalli, Vivek S , Henninger, Nils , Tan, Benjamin Yq , Alexandre, Andrea M , Varela, Ricardo , Essibayi, Muhammed Amir , Salim, Hamza , Fazzari, Melissa J. , Khatri, Deepak , Baker, Amanda, Musmar, Basel , Kühn, Anna Luisa , Khalife, Jane , Ghozy, Sherief , Scarcia, Luca , Yeo, Leonard Ll , Cancelliere, Nicole M , Rouchaud, Aymeric , Sheth, Sunil A , Puri, Ajit S , Colasurdo, Marco , Renieri, Leonardo , Harker, Pablo , Aziz, Yasmin , Radu, Răzvan Alexandru , Klein, Piers , Ota, Takahiro , Mowla, Ashkan , Naamani, Kareem El , Jabbour, Pascal , Siegler, James E. , Nguyen, Thanh N. , Gory, Benjamin , Hecker, Constantin , Marnat, Gaultier , Griessenauer, Christoph J. , Pedicelli, Alessandro , Faizy, Tobias D. , Mendes Pereira, Vitor , Dmytriw, Adam A. , _, _, Amllay, Abdelaziz , Vagal, Achala , Schiphorst, Adrien ter , Thomas, Ajith J , Mounayer, Charbel , Weyland, Charlotte S. , Hsieh, Cheng‐Yang , Forestier, Géraud , Cuellar, Hugo , Valente, Iacopo , Sibon, Igor , Jesser, Jessica , Martinez-Gutierrez, Juan Carlos , Meyer, Lukas , Elhorany, Mahmoud , Aziz‐Sultan, Mohammad Ali , Killer-Oberpfalzer, Monika , Khandelwal, Priyank , Fahed, Robert , Salazar‐Marioni, Sergio , Nedelcu, Simona , Tjoumakaris, Stavropoula , Saleme, Suzana , Barreau, Xavier

Mayo Clinic

Journal of Neurosurgery | July 4, 2025 | Volume: 143 | Issue: 6 | Pages: 1501-1513

10.3171/2025.3.jns243030 | PMID 40614268 Get It

OBJECTIVE Mechanical thrombectomy (MT) is well established for large-vessel occlusion (LVO) strokes, but its safety in distal and medium-vessel occlusions (DMVOs) requires further investigation. This study analyzed the relationship between procedural approaches, petechial hemorrhage (PetH), and clinical outcomes in DMVO thrombectomy, with particular attention to technical considerations and the complex interplay between tissue injury and hemorrhagic complications. METHODS A retrospective cohort study was conducted on DMVO stroke patients treated with MT at 37 stroke centers worldwide from 2016 to 2024. Patients were categorized based on follow-up imaging into those with or without PetH. Four logistic regression models analyzed the association of PetH with favorable functional outcomes (modified Rankin Scale score ≤ 2) at 90 days, early neurological improvement (≥ 4-point National Institutes of Health Stroke Scale score decrease at 24 hours), all-cause mortality, and independent determinants of PetH. Adjusted odds ratios (aORs), 95% confidence intervals, and p values were reported. RESULTS Of 1428 patients, 439 (30.7%) developed PetH. Factors independently associated with PetH were multiple thrombectomy passes (aOR 1.58, 95% CI 1.21–2.06; p = 0.001), IV thrombolysis (aOR 1.31, 95% CI 1.01–1.69; p = 0.04), and the combined use of a stent retriever with aspiration as the first-line method compared with aspiration alone (aOR 1.66, 95% CI 1.15–2.38; p = 0.007). Conversely, general anesthesia (aOR 0.55, 95% CI 0.40–0.77; p < 0.001), higher Alberta Stroke Program Early CT Scores (aOR 0.76, 95% CI 0.69–0.83; p < 0.001), and successful recanalization (aOR 0.56, 95% CI 0.39–0.80; p = 0.002) were significantly associated with a lower odds of PetH. PetH was associated with a decreased odds of favorable functional outcomes (aOR 0.51, 95% CI 0.36–0.73; p < 0.001), reduced early neurological improvement (aOR 0.59, 95% CI 0.44–0.79; p < 0.001), and increased all-cause mortality (aOR 1.84, 95% CI 1.23–2.76; p < 0.001). CONCLUSIONS PetH is a frequent sequela following MT in DMVO strokes and is associated with poorer outcomes, likely reflecting underlying ischemic injury rather than direct causation. Procedural factors influence PetH risk, suggesting medical treatment as first-line therapy for DMVOs, with MT reserved for refractory cases using less aggressive approaches.
Association between empirical dietary inflammatory pattern (EDIP) and survival in patients with stage III colon cancer: Findings from CALGB/SWOG 80702 (Alliance).
Char, Sara K., Kumthekar, Priya , Guthrie, Katherine A. , Couture, Félix , Kuebler, J. Phillip, Kumar, Pankaj , Tan, Benjamin , Krishnamurthi, Smitha , Wolpin, Brian M. , Geoffroy, Francois J., Shields, Anthony F. , Ng, Kimmie , Char, Sara K., Shi, Qian , Zemla, Tyler , Ma, Chao , Cheng, En , Tabung, Fred K. , O’Reilly, Eileen M. , Meyerhardt, Jeffrey A. , Yuan, Chen

Mayo Clinic

Journal of Clinical Oncology | June 4, 2025 | Volume: 43 | Issue: 17_suppl | Pages: No page available

10.1200/jco.2025.43.17_suppl.lba3509 Get It

LBA3509 Background: Systemic inflammation has been implicated in colon cancer progression. We examined whether intake of a proinflammatory diet is associated with survival among patients (pts) with stage III colon cancer. Methods: This prospective cohort study was nested within a randomized phase III trial of adjuvant therapy in pts with stage III colon cancer who had undergone curative-intent resection. EDIP score – a validated tool to classify the inflammatory nature of diets – was derived as a cumulative exposure using data from food-frequency questionnaires completed within 6 weeks of randomization and 14-16 months (mo) after randomization. Cox proportional hazards regression was used to assess the associations of EDIP with disease-free survival (DFS) and overall survival (OS). Results: Of 1625 included pts, the mean (SD) age was 60.9 (10.5) years (yrs). Compared to pts in the lowest EDIP quintile, pts in the highest quintile (a more inflammatory diet) were younger (58.7 ± 10.8 vs 61.3 ± 9.5 yrs old) and more likely to be female (64.0% vs 48.9%) and have worse performance status (ECOG 1-2: 35.7% vs 19.4%). Pts in the highest quintile were less likely to be White (76.6% vs 92.0 %) and more likely to be Black (15.4% vs 3.7%). Baseline aspirin use, assigned chemotherapy (3 mo vs 6 mo), and assigned pharmacotherapy (celecoxib vs placebo) were not significantly different across EDIP quintiles. Compared with pts in the lowest EDIP quintile, pts in the highest quintile had significantly worse OS (multivariable hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.77, P trend =0.01), but not DFS (HR 1.36, 95% CI 0.99-1.86, P trend =0.22). Diet and physical activity jointly influenced OS. Those with lower EDIP scores (quintiles 1-4, 80% of the study population) and higher physical activity (≥9 MET-h/wk) had the best OS (HR 0.37, 95% CI 0.25-0.53) compared with pts in the highest EDIP quintile (20% of the study population) and lower physical activity (<9 MET-h/wk) ( P interaction <0.001). The association between higher EDIP and OS was consistent when analyzed by celecoxib and placebo treatment arms ( P interaction 0.54). The relationship between EDIP and OS did not differ significantly according to aspirin use, with HR 1.60 (95% CI 0.71-3.60) among aspirin users and HR 2.01 (95% CI 1.27-3.16) among aspirin non-users ( P interaction 0.06). Conclusions: Our findings suggest that greater intake of a proinflammatory dietary pattern is associated with worse OS in pts with stage III colon cancer. Regular physical activity may attenuate the association, and further investigation of diet and physical activity intervention is warranted. Support: U10CA180821, U10CA180882, U24CA196171, U10CA180863, CCS 707213, UG1CA233234, U10CA180820, U10CA180868, U10CA180888; https://acknowledgments.alliancefound.org. Pfizer; ClinicalTrials.gov Identifier: NCT01150045.