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Article ; Online: First-line Immunotherapy for Metastatic Merkel Cell Carcinoma: Analysis of Real-world Survival Data and Practice Patterns.

Kakish, Hanna / Sun, James / Ammori, John B / Hoehn, Richard S / Rothermel, Luke D

2024

Abstract: Background: Immune checkpoint inhibitors are a promising new therapy for advanced Merkel Cell Carcinoma (MCC). We investigated real-world utilization and survival outcomes of first-line immunotherapies in a contemporary cohort.: Methods: Using the ... ...

Abstract	Background: Immune checkpoint inhibitors are a promising new therapy for advanced Merkel Cell Carcinoma (MCC). We investigated real-world utilization and survival outcomes of first-line immunotherapies in a contemporary cohort. Methods: Using the National Cancer Database (NCDB), we identified 759 patients with MCC between 2015 and 2020 with stage IV disease and known status of first-line systemic therapy. Univariable and multivariable analyses were used to determine predictors of immunotherapy usage. Overall survival (OS) was compared for patients receiving immunotherapy, chemotherapy, or no systemic therapies. Results: We identified 759 patients meeting our inclusion criteria: 329 patients received immunotherapy, 161 received chemotherapy, and 269 received no systemic therapy. Adjusting for demographic, clinical, and facility factors, high facility volume significantly predicted first-line immunotherapy use (OR 1.99; P=0.017). Median OS was 16.2, 12.3, and 8.7 months, among patients who received immunotherapy, chemotherapy, or no systemic therapy, respectively (P<0.001). On Cox multivariable survival analysis, first-line immunotherapy treatment (HR=0.79, P=0.041) and treatment at high-volume centers (HR=0.58, P=0.004) were associated with improved OS. Conclusions: Consistent with clinical trial results, first-line immunotherapy associated with improvement in median overall survival for patients with stage IV MCC, significantly outperforming chemotherapy in this real-world cohort. Treatment at high-volume centers associated with first-line immunotherapy utilization suggesting that familiarity with this rare disease is important to achieving optimal outcomes for metastatic MCC.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	604536-4
ISSN	1537-453X ; 0277-3732
ISSN (online)	1537-453X
ISSN	0277-3732
DOI	10.1097/COC.0000000000001098
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Zs.A 1557: Show issues

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Article ; Online: Providing context for the HIPECT4 results.

Hoehn, Richard S / Ammori, John B / Rothermel, Luke D / Winter, Jordan M / Charles, Ron / Chakrabarti, Sakti

Cancer

2024 Volume 130, Issue 10, Page(s) 1727–1729

MeSH term(s)	Humans ; Colorectal Neoplasms/pathology ; Pancreatic Neoplasms/pathology
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Editorial ; Journal Article
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35201
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Uh III Zs.146: Show issues

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Article ; Online: Central Hepatectomy: How I Do It.

Rothermel, Luke D / Denbo, Jason / Anaya, Daniel A

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

2022 Volume 26, Issue 9, Page(s) 2024–2028

MeSH term(s)	Carcinoma, Hepatocellular/surgery ; Hepatectomy ; Humans ; Liver Neoplasms/surgery
Language	English
Publishing date	2022-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2012365-6
ISSN	1873-4626 ; 1934-3213 ; 1091-255X
ISSN (online)	1873-4626 ; 1934-3213
ISSN	1091-255X
DOI	10.1007/s11605-022-05363-4
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Zs.A 5207: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Targeting wild-type IDH1 enhances chemosensitivity in pancreatic cancer.

Zarei, Mehrdad / Hajihassani, Omid / Hue, Jonathan J / Graor, Hallie J / Rothermel, Luke D / Winter, Jordan M

bioRxiv : the preprint server for biology

2023

Abstract: Pancreatic cancer (PC) is one of the most aggressive types of cancer, with a five-year overall survival rate of 11% among all-comers. Current systemic therapeutic options are limited to cytotoxic chemotherapies which have limited clinical efficacy and ... ...

Abstract	Pancreatic cancer (PC) is one of the most aggressive types of cancer, with a five-year overall survival rate of 11% among all-comers. Current systemic therapeutic options are limited to cytotoxic chemotherapies which have limited clinical efficacy and are often associated with development of drug resistance. Analysis of The Cancer Genome Atlas showed that wild-type isocitrate dehydrogenase (wtIDH1) is overexpressed in pancreatic tumors. In this study, we focus on the potential roles of wtIDH1 in pancreatic cancer chemoresistance. We found that treatment of pancreatic cancer cells with chemotherapy induced expression of wtIDH1, and this serves as a key resistance factor. The enzyme is protective to cancer cells under chemotherapy-induced oxidative stress by producing NADPH and alpha-ketoglutarate to maintain redox balance and mitochondrial function. An FDA-approved mutant IDH1 inhibitor, ivosidenib (AG-120), is actually a potent wtDH1 inhibitor under a nutrient-deprived microenvironment, reflective of the pancreatic cancer microenvironment. Suppression of wtIDH1 impairs redox balance, results in increased ROS levels, and enhances chemotherapy induced apoptosis in pancreatic cancer vis ROS damage
Language	English
Publishing date	2023-03-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.29.534596
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Article ; Online: Teledermatology availability post-COVID-19: a cross-sectional secret-shopper study.

Thomas, Kaden M / Wilkowski, Caroline M / Bhatty, Maira A / Rothermel, Luke D / Hoehn, Richard S / Bordeaux, Jeremy S

Archives of dermatological research

2024 Volume 316, Issue 2, Page(s) 82

MeSH term(s)	Humans ; Cross-Sectional Studies ; COVID-19 ; Dermatology ; Skin Diseases/diagnosis ; Telemedicine
Language	English
Publishing date	2024-01-27
Publishing country	Germany
Document type	Letter
ZDB-ID	130131-7
ISSN	1432-069X ; 0340-3696
ISSN (online)	1432-069X
ISSN	0340-3696
DOI	10.1007/s00403-024-02816-5
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Article ; Online: Disparities in the Receipt of Systemic Treatment in Metastatic Melanoma.

Kakish, Hanna / Pawar, Omkar / Bhatty, Maira / Doh, Susan / Mulligan, Kathleen M / Rothermel, Luke D / Bordeaux, Jeremy S / Mangla, Ankit / Hoehn, Richard S

American journal of clinical oncology

2024 Volume 47, Issue 5, Page(s) 239–245

Abstract: Background: In 2011, immunotherapy and targeted therapy revolutionized melanoma treatment. However, inequities in their use may limit the benefits seen by certain patients.: Methods: We performed a retrospective review of patients in the National ... ...

Abstract	Background: In 2011, immunotherapy and targeted therapy revolutionized melanoma treatment. However, inequities in their use may limit the benefits seen by certain patients. Methods: We performed a retrospective review of patients in the National Cancer Database for patients with stage IV melanoma from 2 time periods: 2004-2010 and 2016-2020, distinguishing between those who received systemic therapy and those who did not. We investigated the rates and factors associated with treatment omission. We employed Kaplan-Meier analysis to explore the impact of treatment on overall survival. Results: A total of 19,961 patients met the inclusion criteria: 7621 patients were diagnosed in 2004-2010 and 12,340 patients in 2016-2020, of whom 54.9% and 28.3% did not receive systemic treatment, respectively. The rate of "no treatment" has decreased to a plateau of ∼25% in 2020. Median overall survival was improved with treatment in both time periods (2004-2010: 8.8 vs. 5.6 mo [ P <0.05]; and 2016-2020: 25.9 vs. 4.3 mo [ P <0.05]). Nonmedical factors associated with the omission of treatment in both periods included low socioeconomic status, Medicaid or no health insurance, and treatment at low-volume centers. In the period from 2016 to 2020, patients treated at nonacademic programs were also less likely to receive treatment. Conclusions: Systemic therapies significantly improve survival for patients with metastatic melanoma, but significant disparities exist with their receipt. Local efforts are needed to ensure all patients benefit from these revolutionary treatments.
MeSH term(s)	Humans ; Melanoma/therapy ; Melanoma/mortality ; Melanoma/pathology ; Melanoma/drug therapy ; Retrospective Studies ; Female ; Male ; Middle Aged ; Healthcare Disparities/statistics & numerical data ; Aged ; United States ; Skin Neoplasms/therapy ; Skin Neoplasms/mortality ; Skin Neoplasms/pathology ; Adult ; Survival Rate
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	604536-4
ISSN	1537-453X ; 0277-3732
ISSN (online)	1537-453X
ISSN	0277-3732
DOI	10.1097/COC.0000000000001083
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1557: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Engineered oncolytic viruses to treat melanoma: where are we now and what comes next?

Rothermel, Luke D / Zager, Jonathan S

Expert opinion on biological therapy

2018 Volume 18, Issue 12, Page(s) 1199–1207

Abstract: Introduction: Melanoma treatments have evolved rapidly in the past decade and have included the use of intratumoral injections of engineered oncolytic viruses. One such oncolytic virus is talimogene laherparepvec (T-VEC), which is the first approved ... ...

Abstract	Introduction: Melanoma treatments have evolved rapidly in the past decade and have included the use of intratumoral injections of engineered oncolytic viruses. One such oncolytic virus is talimogene laherparepvec (T-VEC), which is the first approved therapy of its kind for use in recurrent, unresectable stage IIIB-IVM1a melanoma. Additional oncolytic viruses and their uses in combination with other interventions are currently under investigation. Areas covered: Oncolytic viruses are being evaluated as immunotherapies for a variety of advanced malignancies. In this article, we review T-VEC, the only FDA-approved engineered oncolytic virus, in addition to ongoing research regarding other oncolytic viruses for the treatment of advanced melanomas. Finally, we discuss opportunities to improve these therapies through viral, host, and tumor-related modifications. Expert opinion: Engineered and naturally oncolytic viruses have demonstrable local and systemic efficacy as immunotherapies in cancer. T-VEC leads the way with improved survival outcomes for unresectable, stage IIIB-IVM1a melanoma as a monotherapy, and is demonstrating superior results in combination with systemic checkpoint inhibitors. Additional viral vectors show acceptable safety profiles and varying degrees of efficacy in targeting melanoma. The indications for use of oncolytic viruses will expand as their efficacy and appropriate usage is better understood in coming years.
MeSH term(s)	Animals ; Bioengineering/methods ; Bioengineering/trends ; Genetic Vectors ; Humans ; Immunotherapy/methods ; Immunotherapy/trends ; Melanoma/pathology ; Melanoma/therapy ; Oncolytic Virotherapy/methods ; Oncolytic Virotherapy/trends ; Oncolytic Viruses/genetics ; Oncolytic Viruses/physiology ; Recurrence ; Skin Neoplasms/pathology ; Skin Neoplasms/therapy ; Melanoma, Cutaneous Malignant
Language	English
Publishing date	2018-11-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1080/14712598.2018.1544614
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Zs.A 6094: Show issues

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Article ; Online: Is sentinel lymph node biopsy needed for lentigo maligna melanoma?

Kakish, Hanna / Lal, Trisha / Thuener, Jason E / Bordeaux, Jeremy S / Mangla, Ankit / Rothermel, Luke D / Hoehn, Richard S

Journal of surgical oncology

2023 Volume 129, Issue 4, Page(s) 804–812

Abstract: Background and objectives: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases.: Methods: We ... ...

Abstract	Background and objectives: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases. Methods: We performed a retrospective review of the National Cancer Database (2012-2020) and the Surveillance, Epidemiology, and End Results (2010-2019) database for patients with cutaneous nonmetastatic LMM with Breslow thickness >1.0 mm. Multivariable logistic regression identified factors associated with SLNB performance and sentinel lymph node (SLN) positivity. Univariable and multivariable analyses assessed overall survival (OS) and melanoma-specific survival (MSS) based on SLNB performance and SLN status. Results: Compared to other melanoma subtypes, LMM had lower rates of SLNB (66.6% vs. 80.0%-84.0%) and SLN positivity (11.3% vs. 18.6%-34.2%). Compared to patients who did not undergo SLNB, SLN status was significantly associated with improved OS in patients with SLN positive (HR = 0.64 [0.55-0.76]) and SLN negative (HR = 0.68 [0.49-0.94]), and worse MSS only in patients with positive SLN (HR = 3.93, p < 0.05). Conclusion: The improved OS associated with SLNB likely implies surgical selection bias. Analysis of MSS confirms appropriate patient selection and suggests important prognostic value associated with SLN status. These results support continued SLNB for LMM patients according to standard guidelines.
MeSH term(s)	Humans ; Sentinel Lymph Node Biopsy ; Melanoma/pathology ; Skin Neoplasms/pathology ; Hutchinson's Melanotic Freckle/surgery ; Hutchinson's Melanotic Freckle/pathology ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node/surgery ; Sentinel Lymph Node/pathology ; Lymph Nodes/pathology
Language	English
Publishing date	2023-11-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	82063-5
ISSN	1096-9098 ; 0022-4790
ISSN (online)	1096-9098
ISSN	0022-4790
DOI	10.1002/jso.27543
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Zs.A 706: Show issues

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Article ; Online: Surgical management of 1- to 2-cm neuroendocrine tumors of the appendix: Appendectomy or right hemicolectomy?

Ahmed, Fasih Ali / Wu, Victoria S / Kakish, Hanna / Elshami, Mohamedraed / Ocuin, Lee M / Rothermel, Luke D / Mohamed, Amr / Hoehn, Richard S

Surgery

2023 Volume 175, Issue 2, Page(s) 251–257

Abstract: Background: The surgical management of 1- to 2-cm neuroendocrine tumors of the appendix is an area of debate. We analyzed the clinical outcomes of appendectomy and compared them to right hemicolectomy.: Methods: We queried the National Cancer ... ...

Abstract	Background: The surgical management of 1- to 2-cm neuroendocrine tumors of the appendix is an area of debate. We analyzed the clinical outcomes of appendectomy and compared them to right hemicolectomy. Methods: We queried the National Cancer Database to identify patients treated for 1- to 2-cm ANETs from 2004 to 2018. Patients were stratified by surgical approach (appendectomy vs. hemicolectomy). Multivariable models were used to identify factors associated with the choice of surgical approach and the association between surgical approach and overall survival. Results: Of the 3,189 patients we included, 1,573 (49.3%) underwent right hemicolectomy and 1,616 (50.7%) appendectomy. The appendectomy rate increased from 37.7% in 2004 to 58.9% in 2018. On multivariable analysis, patients with grade 2 and 3 tumors were less likely to undergo appendectomy alone (odds ratio = 0.41, 95% confidence interval = 0.26-0.66). Longer travel distance was associated with a higher likelihood of undergoing appendectomy (odds ratio = 2.52, 95% confidence interval = 1.15-5.51). After adjusting for tumor grade, appendectomy alone had similar survival to hemicolectomy (hazard ratio = 1.03, 95% confidence interval = 0.67-1.59). Conclusion: In this updated analysis of the National Cancer Database, right hemicolectomy was not associated with improved overall survival compared to appendectomy alone for 1- to 2-cm neuroendocrine tumors of the appendix. Although patients with grade 2 or 3 tumors are more likely to undergo right hemicolectomy, this procedure may not improve their treatment or overall outcome.
MeSH term(s)	Humans ; Neuroendocrine Tumors ; Appendectomy/methods ; Appendiceal Neoplasms/surgery ; Appendiceal Neoplasms/pathology ; Proportional Hazards Models ; Colectomy/methods ; Retrospective Studies
Language	English
Publishing date	2023-11-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	202467-6
ISSN	1532-7361 ; 0039-6060
ISSN (online)	1532-7361
ISSN	0039-6060
DOI	10.1016/j.surg.2023.09.048
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Article ; Online: The effect of surgical timing in nonmetastatic melanoma.

Kakish, Hanna / Drigotas, Claire / Ahmed, Fasih Ali / Elshami, Mohamedraed / Bordeaux, Jeremy S / Rothermel, Luke D / Hoehn, Richard S

Journal of surgical oncology

2023 Volume 129, Issue 3, Page(s) 509–516

Abstract: Background and objectives: There is no consensus guidelines on the best timing to perform Sentinel lymph node biopsy (SLNB) in high-risk melanoma patients. We aimed to understand the impact of surgical timing on nodal upstaging in patients with ... ...

Abstract	Background and objectives: There is no consensus guidelines on the best timing to perform Sentinel lymph node biopsy (SLNB) in high-risk melanoma patients. We aimed to understand the impact of surgical timing on nodal upstaging in patients with cutaneous melanoma. Methods: We queried the National Cancer Database from 2004 to 2018 for patients with T2-T4, N0, M0 melanomas, who underwent melanoma excision and nodal surgery. We included patients who underwent surgery within 2-19 weeks postdiagnosis. We aimed to determine the association of surgical delay (weeks) with nodal positivity. Results: A total of 53 355 patients were included, of whom 20.9% had positive lymph nodes. Patients underwent surgery at a median of 5 (4-7) weeks after diagnosis. The rate of positive nodes increased with increased weeks to surgery (line of best-fit slope = 0.38). Multivariable regression analysis identified an association between time to surgery and nodal positivity (2.4% increased risk per week, p < 0.05). Our analysis showed significantly increased likelihood of nodal positivity beginning 9 weeks after diagnosis (odds ratio [OR] = 1.3, p < 0.05). Furthermore, patients with T2-3 tumors had a significant increase in nodal positivity with increased time to surgery (OR = 1.03 per week, p < 0.001). However, no significant trend in nodal positivity was identified for patients with T4 melanomas (OR = 1.01 per week, p = 0.596). Conclusion: Surgery within 9 weeks of melanoma diagnosis was not associated with increased likelihood of nodal positivity. These data can guide clinical conversations regarding the importance of surgical timing for melanoma.
MeSH term(s)	Humans ; Melanoma/pathology ; Skin Neoplasms/surgery ; Skin Neoplasms/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Lymph Node Excision
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	82063-5
ISSN	1096-9098 ; 0022-4790
ISSN (online)	1096-9098
ISSN	0022-4790
DOI	10.1002/jso.27507
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