Publications by authors named "W Martin C Klop"

90 Publications

Single agent Talimogene Laherparepvec for stage IIIB-IVM1c melanoma patients: a systematic review and meta-analysis.

Crit Rev Oncol Hematol 2022 May 12:103705. Epub 2022 May 12.

Melanoma Institute Australia, The University of Sydney, NSW, Australia. Electronic address:

Single-agent Talimogene Laherparepvec(T-VEC) was developed for treatment of unresectable and injectable stage III-IV melanoma. Since its approval and reimbursement, studies have reported varying response rates. The purpose of this systematic review and meta-analysis was to investigate the efficacy and safety of T-VEC. Of 341 publications that were identified, eight studies with a total of 642 patients were included. In patients with stage IIIB-IVM1a, the pooled complete- and overall response rate(CRR and ORR) were 41% and 64%, respectively. In patients with stage IIIB-IVM1c, the pooled CRR and ORR were 30% and 44%, respectively. In patients with stage IVM1b and IVM1c, the pooled CRR and ORR were 4% and 9%, respectively. Adverse events(AEs) were seen in 41 - 100% of all patients and 0 - 11% of AEs were severe. In conclusion, single agent T-VEC achieves the highest response rates in patients with early metastatic melanoma and is well-tolerated with generally only mild toxicities.
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http://dx.doi.org/10.1016/j.critrevonc.2022.103705DOI Listing
May 2022

18F-FDG PET/CT During Neoadjuvant Targeted Therapy in Prior Unresectable Stage III Melanoma Patients: Can (Early) Metabolic Imaging Predict Histopathologic Response or Recurrence?

Clin Nucl Med 2022 Apr 22. Epub 2022 Apr 22.

Medical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands.

Purpose: The aim of this study was to investigate whether 18F-FDG PET/CT can predict histopathological response or recurrence in BRAF-mutated unresectable locally advanced stage III melanoma treated with neoadjuvant BRAF/MEK inhibition followed by resection and the value of PET in detecting early recurrence after resection.

Patients And Methods: Twenty BRAF-mutated, unresectable stage III melanoma patients received BRAF/MEK inhibitors before surgery. 18F-FDG PET/CT was performed at baseline and 2 and 8 weeks after initiation of therapy. After resection, PET/CT was performed at specific time points during 5 years of follow-up. Pathological response was assessed on the dissection specimen. Response monitoring was measured with SUVmax, SUVpeak, MATV, and TLG and according to EORTC and PERCIST criteria.

Results: Pathological response was assessed in 18 patients. Nine patients (50%) had a pathologic complete or near-complete response, and 9 (50%) had a pathologic partial or no response. EORTC or PERCIST response measurements did not correspond with pathologic outcome. SUVmax, SUVpeak, MATV, and TLG at all time points and absolute or percentage change among the 3 initial time points did not differ between the groups.During follow-up, 8 of 17 patients with R0 resection developed a recurrence, 6 recurrences were detected with imaging only, 4 of which with PET/CT in less than 6 months after surgery. PET parameters before surgery did not predict recurrence.

Conclusions: Baseline 18F-FDG PET or PET response in previous unresectable stage III melanoma patients seems not useful to predict pathologic response after neoadjuvant BRAF/MEK inhibitors treatment. However, PET/CT seems valuable in detecting recurrence early after R0 resection.
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http://dx.doi.org/10.1097/RLU.0000000000004217DOI Listing
April 2022

Representativeness of the Index Lymph Node for Total Nodal Basin in Pathologic Response Assessment After Neoadjuvant Checkpoint Inhibitor Therapy in Patients With Stage III Melanoma.

JAMA Surg 2022 04;157(4):335-342

Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.

Importance: Neoadjuvant checkpoint inhibition in patients with high-risk stage III melanoma shows high pathologic response rates associated with a durable relapse-free survival. Whether a therapeutic lymph node dissection (TLND) can be safely omitted when a major pathologic response in the largest lymph node metastasis at baseline (index lymph node; ILN) is obtained is currently being investigated. A previous small pilot study (nā€‰=ā€‰12) showed that the response in the ILN may be representative of the pathologic response in the entire TLND specimen.

Objective: To assess the concordance of response between the ILN and the total lymph node bed in a larger clinical trial population.

Design, Setting, And Participants: Retrospective pathologic response analysis of a multicenter clinical trial population of patients from the randomized Study to Identify the Optimal Adjuvant Combination Scheme of Ipilimumab and Nivolumab in Melanoma Patients (OpACIN) and Optimal Neo-Adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) trials. Included patients were treated with 6 weeks neoadjuvant ipilimumab plus nivolumab. Patient inclusion into the trials was conducted from August 12, 2015, to October 24, 2016 (OpACIN), and November 24, 2016, and June 28, 2018 (OpACIN-neo). Data were analyzed from April 1, 2020, to August 31, 2021.

Main Outcomes And Measures: Concordance of the pathologic response between the ILN and the TLND tumor bed. The pathologic response of the ILN was retrospectively assessed according to the International Neoadjuvant Melanoma Consortium criteria and compared with the pathologic response of the entire TLND specimen.

Results: A total of 82 patients treated with neoadjuvant ipilimumab and nivolumab followed by TLND (48 [59%] were male; median age, 58.5 [range, 18-80] years) were included. The pathologic response in the ILN was concordant with the entire TLND specimen response in 81 of 82 patients (99%) and in 79 of 82 patients (96%) concordant when comparing the ILN response with the response in every individual lymph node. In the single patient with a discordant response, the ILN response (20% viable tumor, partial pathologic response) underestimated the entire TLND specimen response (5% viable, near-complete pathologic response). Two other patients each had 1 small nonindex node that contained 80% viable tumor (pathologic nonresponse) whereas all other lymph nodes (including the ILN) showed a partial pathologic response. In these 2 patients, the risk of regional relapse might potentially have been increased if TLND had been omitted.

Conclusions And Relevance: The results of this study suggest that the pathologic response of the ILN may be considered a reliable indicator of the entire TLND specimen response and may support the ILN response-directed omission of TLND in a prospective trial.
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http://dx.doi.org/10.1001/jamasurg.2021.7554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829746PMC
April 2022

Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).

Ann Surg Oncol 2022 Jun 28;29(6):3694-3708. Epub 2022 Jan 28.

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.
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http://dx.doi.org/10.1245/s10434-021-11236-yDOI Listing
June 2022
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