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1. 89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer

Author

Kok, I.C., Hooiveld, J.S., van de Donk, P.P., Giesen, D., van der Veen, E.L., Lub-de Hooge, M.N., Brouwers, A.H., Hiltermann, T.J.N., van der Wekken, A.J., Hijmering-Kappelle, L.B.M., Timens, W., Elias, S.G., Hospers, G.A.P., Groen, H.J.M., Uyterlinde, W., van der Hiel, B., Haanen, J.B., de Groot, D.J.A., Jalving, M., and de Vries, E.G.E.

Published
2022
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5. 89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer

Author

Epi Kanker Team C, Cancer, JC onderzoeksprogramma Cancer, Kok, I C, Hooiveld, J S, van de Donk, P P, Giesen, D, van der Veen, E L, Lub-de Hooge, M N, Brouwers, A H, Hiltermann, T J N, van der Wekken, A J, Hijmering-Kappelle, L B M, Timens, W, Elias, S G, Hospers, G A P, Groen, H J M, Uyterlinde, W, van der Hiel, B, Haanen, J B, de Groot, D J A, Jalving, M, de Vries, E G E, Epi Kanker Team C, Cancer, JC onderzoeksprogramma Cancer, Kok, I C, Hooiveld, J S, van de Donk, P P, Giesen, D, van der Veen, E L, Lub-de Hooge, M N, Brouwers, A H, Hiltermann, T J N, van der Wekken, A J, Hijmering-Kappelle, L B M, Timens, W, Elias, S G, Hospers, G A P, Groen, H J M, Uyterlinde, W, van der Hiel, B, Haanen, J B, de Groot, D J A, Jalving, M, and de Vries, E G E

Published
2022

7. The role of 18F-FDG PET/CT in retroperitoneal sarcomas-A multicenter retrospective study

Author

Subramaniam, S, Callahan, J, Bressel, M, Hofman, MS, Mitchell, C, Hendry, S, Vissers, FL, Van Der Hiel, B, Patel, D, Van Houdt, WJ, Tseng, WW, Gyorki, DE, Subramaniam, S, Callahan, J, Bressel, M, Hofman, MS, Mitchell, C, Hendry, S, Vissers, FL, Van Der Hiel, B, Patel, D, Van Houdt, WJ, Tseng, WW, and Gyorki, DE

Abstract

BACKGROUND: The role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in the evaluation of retroperitoneal sarcomas is poorly defined. We evaluated the correlation of maximum standardized uptake value (SUVmax) with pathologic tumor grade in the surgical specimen of primary retroperitoneal dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS). METHODS: Patients with the above histological subtypes in three participating institutions with preoperative 18 F-FDG PET/CT scan and histopathological specimen available for review were included. The association between SUVmax and pathological grade was assessed. Correlation between SUVmax and relapse-free survival (RFS) and overall survival (OS) were also studied. RESULTS: Of the total 58 patients, final pathological subtype was DDLPS in 44 (75.9%) patients and LMS in 14 (24.1%) patients. The mean SUVmax was 8.7 with a median 7.1 (range, 2.2-33.9). The tumors were graded I, II, III in 6 (10.3%), 35 (60.3%), and 17 (29.3%) patients, respectively. There was an association of higher histological grade with higher SUVmax (rs = 0.40, p = .002). Increasing SUVmax was associated with worse RFS (p = .003) and OS (p = .003). CONCLUSION: There is a correlation between SUVmax and pathologic tumor grade; increasing SUVmax was associated with worse OS and RFS, providing a preoperative noninvasive surrogate marker of tumor grade and biological behavior.

Published
2021

10. 1112P Intralesional therapy with talimogene laherparepvec for stage IIIB-IVM1a melanoma is able to achieve a high rate of complete and durable responses and is associated with tumour load

Author

Stahlie, E., primary, Franke, V., additional, Zuur, L., additional, Klop, M., additional, van de Wiel, B.A., additional, van der Hiel, B., additional, Wouters, M., additional, Schrage, Y., additional, van Houdt, W.J., additional, and van Akkooi, A.C.J., additional

Published
2020
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11. 1098P Neoadjuvant cytoreductive treatment with BRAF/MEK inhibition of prior unresectable regionally advanced melanoma to allow complete surgical resection, REDUCTOR: A prospective single arm phase II trial

Author

Rohaan, M., primary, Blankenstein, S., additional, Klop, M., additional, van der Hiel, B., additional, Lahaye, M.J., additional, Sari, A., additional, Sikorska, K., additional, van de Wiel, B.A., additional, Peeper, D., additional, van Akkooi, A.C.J., additional, and Haanen, J.B.A.G., additional

Published
2020
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17. The value of lymph node ultrasound and whole body 18F-FDG PET/CT in stage IIB/C melanoma patients prior to SLNB.

Author

Stahlie, E.H.A., van der Hiel, B., Bruining, A., van de Wiel, B., Schrage, Y.M., Wouters, M.W.J.M., van Houdt, W.J., and van Akkooi, A.C.J.

Subjects
MELANOMA, SENTINEL lymph node biopsy, WHOLE body imaging, LYMPH nodes, NEEDLE biopsy, CROSS-sectional imaging, LYMPHADENECTOMY
Abstract

Stage IIB/IIC (8th AJCC) melanoma patients are known to have high-risk primary tumors, however they follow the same routine to sentinel lymph node biopsy (SLNB) as more low risk tumors. Guidelines are not conclusive regarding the use of preoperative imaging for these patients. The aim of this pilot study was to assess the value of ultrasound (US) and 18F-FDG PET/CT prior to lymphoscintigraphy (LSG) and SLNB for stage IIB/C melanoma patients. From 2019-04 till 2020–01, all stage IIB/C melanoma patients underwent US of the regional lymph nodes and whole body 18F-FDG PET/CT before their planned LSG and SLNB. Suspected metastases were confirmed with fine needle aspiration (FNA), prior to surgery. In total 23 patients were screened: six had metastases detected by imaging, two by US, one by 18F-FDG PET/CT and three were detected by both imaging modalities. All metastases were nodal and therefore treatment was altered to lymph node dissection and all but one also received adjuvant therapy. Eight (47%) of the 17 patients without macroscopic disease, still had a positive SN. Sensitivity, specificity and false negative rate for US and 18F-FDG PET/CT were 36%, 89%, 64% and 29%, 100% and 71%, respectively. Preoperative negative imaging does not exclude the presence of SN metastases, therefore SLNB cannot be foregone. However, US detected metastases in 22% of patients, altering their treatment, which suggests it is effective in the work-up of stage IIB/C melanoma. Staging with 18F-FDG PET/CT is not of added value prior to LSG and SLNB and should therefore not be used. • Whole body staging with 18F-FDG PET/CT is not of added value (in newly diagnosed stage melanoma IIB or IIC patients) prior to LSG and SLNB and should therefore not be used. • Nodal staging with US is sufficient in the work-up of stage IIB/IIC melanoma. • Despite negative imaging, SLNB cannot be foregone for pT3b-pT4N0 melanoma, as many patients still have an involved SN. • Cross-sectional imaging should be reserved for patients after positive cytology or SN to confirm the absence of distant visceral metastases. [ABSTRACT FROM AUTHOR]

Published
2021
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20. Gamma probe and ultrasound-guided fine needle aspiration cytology of the sentinel node (GULF) trial

Author

Verver, D. (Daniëlle), Oude Ophuis, C.M.C. (Charlotte), Koppert, L.B. (Lisa B.), Monyé, C. (Cécile) de, Deurzen, C.H.M. (Carolien) van, Koljenović, S. (Senada), Bruining, A. (Annemarie), van der Hiel, B., Ter Meulen, S. (Sylvia), Akkooi, A.C.J. (Alexander) van, Verhoef, C. (Kees), Grunhagen, D.J. (Dirk Jan), Verver, D. (Daniëlle), Oude Ophuis, C.M.C. (Charlotte), Koppert, L.B. (Lisa B.), Monyé, C. (Cécile) de, Deurzen, C.H.M. (Carolien) van, Koljenović, S. (Senada), Bruining, A. (Annemarie), van der Hiel, B., Ter Meulen, S. (Sylvia), Akkooi, A.C.J. (Alexander) van, Verhoef, C. (Kees), and Grunhagen, D.J. (Dirk Jan)

Abstract

Purpose: Sentinel lymph node biopsy (SLNB) was introduced as a minimally invasive technique for nodal staging. Since associated morbidity is not negligible, it is highly relevant to pursue a more minimally invasive alternative. The purpose of this study was to prospectively evaluate the sensitivity of fine needle aspiration cytology (FNAC) with combined gamma probe and ultrasound (US) guidance in comparison with the gold standard histology of the sentinel node (SN) after SLNB for detecting metastasis. Methods: The study was designed as a prospective, multicentre, open-label, single-arm trial enrolling patients with newly diagnosed cutaneous melanoma or breast cancer between May 2015 and August 2017. Sample radioactivity was measured using a Mini 900 scintillation monitor. After FNAC, all patients underwent SLNB. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were estimated. Results: Accrual was terminated early following an unplanned interim analysis indicating that a FNAC sensitivity of at least 80% could not be achieved. In total 58 patients of the originally planned 116 patients underwent FNAC with gamma probe and US guidance. There were no true-positive FNAC results, 14 false-negative results and one false-positive result, and thus the sensitivity, specificity, PPV and NPV of FNAC were 0%, 98%, 0% and 75%, respectively. At least 75% of the FNAC samples had a radioactivity signal higher than the background signal. Conclusion: FNAC with gamma probe and US guidance is not able to correctly detect metastases in the SN and is therefore not able to replace SLNB. Gamma probe-guided US is a highly accurate method for correctly identifying the SN, which offers possibilities for future research.

Published
2018
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24. Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma

Author

van der Hiel, B., Haanen, J.B. (John), Stokkel, M. (Marcel), Peeper, D.S. (Daniel S.), Jimenez, C.R. (Connie R.), Beijnen, J.H. (Jos H.), van de Wiel, B., Boellaard, R. (Ronald), Eertwegh, A.J.M. (Fons) van den, Tinteren, H. (Harm) van, Wessels, L. (Lodewyk), Lolkema, M.P. (Martijn), Hoekstra, O.S. (Otto), Hospers, G.A.P. (Geke), Brouwers, A.H. (A.), Koornstra, R.H.T. (Rutger), Arens, A. (Anne), Vos, F.Y.F.L. de, Hobbelink, M.G.G. (M. G.G.), Kapiteijn, H.W. (H. W.), Geus-Oei, L.-F. (Lioe-Fee) de, Kruit, W.H.J. (Wim), Verzijlbergen, J.F. (Fred), Aarts, M.J. (Mieke), Mottaghy, F.M. (F. M.), Groot, J.W.B. (Jan Willem) de, Knollema, S. (S.), Piersma, D. (Djura), Agool, A. (A.), Vreugdenhil, A. (A.), Liem, I.H. (I. H.), Berkmortel, F.W.P.J. (Franchette) van den, Schreurs, W. (W.), van der Hiel, B., Haanen, J.B. (John), Stokkel, M. (Marcel), Peeper, D.S. (Daniel S.), Jimenez, C.R. (Connie R.), Beijnen, J.H. (Jos H.), van de Wiel, B., Boellaard, R. (Ronald), Eertwegh, A.J.M. (Fons) van den, Tinteren, H. (Harm) van, Wessels, L. (Lodewyk), Lolkema, M.P. (Martijn), Hoekstra, O.S. (Otto), Hospers, G.A.P. (Geke), Brouwers, A.H. (A.), Koornstra, R.H.T. (Rutger), Arens, A. (Anne), Vos, F.Y.F.L. de, Hobbelink, M.G.G. (M. G.G.), Kapiteijn, H.W. (H. W.), Geus-Oei, L.-F. (Lioe-Fee) de, Kruit, W.H.J. (Wim), Verzijlbergen, J.F. (Fred), Aarts, M.J. (Mieke), Mottaghy, F.M. (F. M.), Groot, J.W.B. (Jan Willem) de, Knollema, S. (S.), Piersma, D. (Djura), Agool, A. (A.), Vreugdenhil, A. (A.), Liem, I.H. (I. H.), Berkmortel, F.W.P.J. (Franchette) van den, and Schreurs, W. (W.)

Abstract

Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. D

Published
2017
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31. Risk Factors for Positive Deep Pelvic Nodal Involvement in Patients with Palpable Groin Melanoma Metastases: Can the Extent of Surgery be Safely Minimized?: A Retrospective, Multicenter Cohort Study

Author

Oude Ophuis, C.M.C. (Charlotte), Akkooi, A.C.J. (Alexander) van, Hoekstra, H.J. (Harald), Bonenkamp, J.J. (Han), van Wissen, J., Niebling, M.G., Wilt, J.H.W. (Johannes) de, van der Hiel, B., van de Wiel, B., Koljenović, S. (Senada), Grunhagen, D.J. (Dirk Jan), Verhoef, C. (Kees), Oude Ophuis, C.M.C. (Charlotte), Akkooi, A.C.J. (Alexander) van, Hoekstra, H.J. (Harald), Bonenkamp, J.J. (Han), van Wissen, J., Niebling, M.G., Wilt, J.H.W. (Johannes) de, van der Hiel, B., van de Wiel, B., Koljenović, S. (Senada), Grunhagen, D.J. (Dirk Jan), and Verhoef, C. (Kees)

Abstract

Background: Patients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient. Aim: The aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future. Methods: This study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992–2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT] ± positron emission tomography [PET], or PET − low-dose CT). Results: Median age was 57 years, 54 % of patients were female, and median follow-up was 21 months (interquartile range [IQR] 11–46 months). Median Breslow thickness was 2.10 mm (IQR 1.4

Published
2015
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32. Risk Factors for Positive Deep Pelvic Nodal Involvement in Patients with Palpable Groin Melanoma Metastases:Can the Extent of Surgery be Safely Minimized? : A Retrospective, Multicenter Cohort Study

Author

Oude Ophuis, C M C, van Akkooi, A C J, Hoekstra, H J, Bonenkamp, J J, van Wissen, J, Niebling, M G, de Wilt, J H W, van der Hiel, B, van de Wiel, B, Koljenović, S, Grünhagen, D J, Verhoef, C, Oude Ophuis, C M C, van Akkooi, A C J, Hoekstra, H J, Bonenkamp, J J, van Wissen, J, Niebling, M G, de Wilt, J H W, van der Hiel, B, van de Wiel, B, Koljenović, S, Grünhagen, D J, and Verhoef, C

Abstract

BACKGROUND: Patients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient.AIM: The aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future.METHODS: This study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992-2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT] ± positron emission tomography [PET], or PET - low-dose CT).RESULTS: Median age was 57 years, 54 % of patients were female, and median follow-up was 21 months (interquartile range [IQR] 11-46 months). Median Breslow thickness was 2.10 mm (IQR 1.40-3.40 mm), and 26 % of all primary melanomas were ulcerated. Positive deep pelvic nodes occurred in 35 % of CGDs. Significantly fewer inguinal nodes were positive in case of negative deep pelvic nodes (median 1 [IQR 1-2] vs. 3 [IQR 1-4] for positive deep pelvic nodes; p < 0.001), and LNR was significantly lower for negative versus positive deep pelvic nodes [median 0.15 (IQR 0.10-0.25) vs. 0.33 (IQR 0.14-0.54); p < 0.001]. A combination of negative imaging, low LNR, low number of positive inguinal nodes, and no extracapsular extension (ECE) could accurately predict the absence of pelvic nodal involvement in 84 % of patients.CONCLUSIONS: Patients with negative imaging, few positive inguinal nodes, no ECE, and low LNR have a low risk of positive deep pelvic nodes and may safely undergo SGD alone.

Published
2015

36. Is there a role for radioguided surgery with iodine-labeled metaiodobenzylguanidine in resection of neuroendocrine tumors?

Author

van Hulsteijn, L.T., Corssmit, E.P., van der Hiel, B., Smit, J.W.A., Stokkel, M.P., van Hulsteijn, L.T., Corssmit, E.P., van der Hiel, B., Smit, J.W.A., and Stokkel, M.P.

Abstract

Item does not contain fulltext, PURPOSE: The aim of this study was to systematically review literature, exploring the role of radioguided surgery with iodine-labeled metaiodobenzylguanidine (MIBG) in resection of neuroendocrine tumors. METHODS: PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, Academic Search Premier, ScienceDirect, Wiley, and references of key articles were searched to identify potentially relevant studies. RESULTS: Twenty studies were included. A total of 130 procedures in 120 patients were performed. Ninety percent of included studies concerned case reports or case series. It is described that radioguided surgery with iodine-labeled MIBG can improve the quality of macroscopic resection of neuroendocrine tumors in selected cases, ie, in cases where the tumor is small, nonpalpable, difficult to visualize on conventional imaging studies, or located in an area with adhesional scar tissue from previous surgery. However, in a substantial number of cases the gamma probe failed due to technical problems. CONCLUSIONS: Since there is limited evidence that radioguided surgery contributes substantially in resection of neuroendocrine tumors, we cannot advocate its use in general. However, we can conclude that it can seemingly improve the quality of resection in selected cases. When radioguided surgery is performed in neuroendocrine tumors, we advocate the use of I to label MIBG.

Published
2012

37. 167. Intraoperative sentinel lymph node detection in breast cancer patients using a multimodal near-infrared fluorescence and radioactive tracer

Author

Schaafsma, B.E., primary, van der Vorst, J.R., additional, VerbeeK, F.P.R., additional, Tummers, Q.R.J.G., additional, Liefers, G.J., additional, van der Hiel, B., additional, Rietbergen, D.D.D., additional, Frangioni, J.V., additional, van de Velde, C.J.H., additional, and Vahrmeijer, A.L., additional

Published
2012
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38. Abstracts

Author

Dunet, V., primary, Dabiri, A., additional, Allenbach, G., additional, Goyeneche Achigar, A., additional, Waeber, B., additional, Feihl, F., additional, Heinzer, R., additional, Prior, J. O., additional, Van Velzen, J. E., additional, Schuijf, J. D., additional, De Graaf, F. R., additional, De Graaf, M. A., additional, Schalij, M. J., additional, Kroft, L. J., additional, De Roos, A., additional, Jukema, J. W., additional, Van Der Wall, E. E., additional, Bax, J. J., additional, Lankinen, E., additional, Saraste, A., additional, Noponen, T., additional, Klen, R., additional, Teras, M., additional, Kokki, T., additional, Kajander, S., additional, Pietila, M., additional, Ukkonen, H., additional, Knuuti, J., additional, Pazhenkottil, A. P., additional, Nkoulou, R. N., additional, Ghadri, J. R., additional, Herzog, B. A., additional, Buechel, R. R., additional, Kuest, S. M., additional, Wolfrum, M., additional, Gaemperli, O., additional, Husmann, L., additional, Kaufmann, P. A., additional, Andreini, D., additional, Pontone, G., additional, Mushtaq, S., additional, Antonioli, L., additional, Bertella, E., additional, Formenti, A., additional, Cortinovis, S., additional, Ballerini, G., additional, Fiorentini, C., additional, Pepi, M., additional, Koh, A. S., additional, Flores, J. S., additional, Keng, F. Y. J., additional, Tan, R. S., additional, Chua, T. S. J., additional, Annoni, A. D., additional, Tamborini, G., additional, Fusari, M., additional, Bartorelli, A. L., additional, Ewe, S. H., additional, Ng, A. C. T., additional, Delgado, V., additional, Schuijf, J., additional, Van Der Kley, F., additional, Colli, A., additional, De Weger, A., additional, Marsan, N. A., additional, Yiu, K. H., additional, Ng, A. C., additional, Timmer, S. A. J., additional, Knaapen, P., additional, Germans, T., additional, Dijkmans, P. A., additional, Lubberink, M., additional, Ten Berg, J. M., additional, Ten Cate, F. J., additional, Russel, I. K., additional, Lammertsma, A. A., additional, Van Rossum, A. C., additional, Wong, Y. Y., additional, Ruiter, G., additional, Raijmakers, P., additional, Van Der Laarse, W. J., additional, Westerhof, N., additional, Vonk-Noordegraaf, A., additional, Youssef, G., additional, Leung, E., additional, Wisenberg, G., additional, Marriot, C., additional, Williams, K., additional, Etele, J., additional, Dekemp, R. A., additional, Dasilva, J., additional, Birnie, D., additional, Beanlands, R. S. B., additional, Thompson, R. C., additional, Allam, A. H., additional, Wann, L. S., additional, Nureldin, A. H., additional, Adelmaksoub, G., additional, Badr, I., additional, Sutherland, M. L., additional, Sutherland, J. D., additional, Miyamoto, M. I., additional, Thomas, G. S., additional, Harms, H. J., additional, De Haan, S., additional, Huisman, M. C., additional, Schuit, R. C., additional, Windhorst, A. D., additional, Allaart, C., additional, Einstein, A. J., additional, Khawaja, T., additional, Greer, C., additional, Chokshi, A., additional, Jones, M., additional, Schaefle, K., additional, Bhatia, K., additional, Shimbo, D., additional, Schulze, P. C., additional, Srivastava, A., additional, Chettiar, R., additional, Moody, J., additional, Weyman, C., additional, Natale, D., additional, Bruni, W., additional, Liu, Y., additional, Ficaro, E., additional, Sinusas, A. J., additional, Peix, A., additional, Batista, E., additional, Cabrera, L. O., additional, Padron, K., additional, Rodriguez, L., additional, Sainz, B., additional, Mendoza, V., additional, Carrillo, R., additional, Fernandez, Y., additional, Mena, E., additional, Naum, A., additional, Bach-Gansmo, T., additional, Kleven-Madsen, N., additional, Biermann, M., additional, Johnsen, B., additional, Aase Husby, J., additional, Rotevatn, S., additional, Nordrehaug, J. E., additional, Schaap, J., additional, Kauling, R. M., additional, Post, M. C., additional, Rensing, B. J. W. M., additional, Verzijlbergen, J. F., additional, Sanchez, J., additional, Giamouzis, G., additional, Tziolas, N., additional, Georgoulias, P., additional, Karayannis, G., additional, Chamaidi, A., additional, Zavos, N., additional, Koutrakis, K., additional, Sitafidis, G., additional, Skoularigis, J., additional, Triposkiadis, F., additional, Radovanovic, S., additional, Djokovic, A., additional, Simic, D. V., additional, Krotin, M., additional, Savic-Radojevic, A., additional, Pljesa-Ercegovac, M., additional, Zdravkovic, M., additional, Saponjski, J., additional, Jelic, S., additional, Simic, T., additional, Eckardt, R., additional, Kjeldsen, B. J., additional, Andersen, L. I., additional, Haghfelt, T., additional, Grupe, P., additional, Johansen, A., additional, Hesse, B., additional, Pena, H., additional, Cantinho, G., additional, Wilk, M., additional, Srour, Y., additional, Godinho, F., additional, Zafrir, N., additional, Gutstein, A., additional, Mats, I., additional, Battler, A., additional, Solodky, A., additional, Sari, E., additional, Singh, N., additional, Vara, A., additional, Peters, A. M., additional, De Belder, A., additional, Nair, S., additional, Ryan, N., additional, James, R., additional, Dizdarevic, S., additional, Depuey, G., additional, Friedman, M., additional, Wray, R., additional, Old, R., additional, Babla, H., additional, Chuanyong, B., additional, Maddahi, J., additional, Tragardh Johansson, E., additional, Sjostrand, K., additional, Edenbrandt, L., additional, Aguade-Bruix, S., additional, Cuberas-Borros, G., additional, Pizzi, M. N., additional, Sabate-Fernandez, M., additional, De Leon, G., additional, Garcia-Dorado, D., additional, Castell-Conesa, J., additional, Candell-Riera, J., additional, Casset-Senon, D., additional, Edjlali-Goujon, M., additional, Alison, D., additional, Delhommais, A., additional, Cosnay, P., additional, Low, C. S., additional, Notghi, A., additional, O'brien, J., additional, Tweddel, A. 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U., additional, Savenkova, G., additional, Lebedev, D., additional, Alexandridis, E., additional, Rovithis, D., additional, Parisis, C., additional, Sazonova, I., additional, Saushkin, V., additional, Chernov, V., additional, Zaabar, L., additional, Bahri, H., additional, Hadj Ali, S., additional, Sellem, A., additional, Slim, I., additional, El Kadri, N., additional, Slimen, H., additional, Hammami, H., additional, Lucic, S., additional, Peter, A., additional, Tadic, S., additional, Nikoletic, K., additional, Jung, R., additional, Lucic, M., additional, Tagil, K., additional, Jakobsson, D., additional, Svensson, S.- E., additional, Wollmer, P., additional, Leccisotti, L., additional, Indovina, L., additional, Paraggio, L., additional, Calcagni, M. 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W., additional, Gama, V., additional, Ciarka, A., additional, Neefjes, L. A., additional, Mollet, N. R., additional, Sijbrands, E. J., additional, Wilczek, J., additional, Llibre Pallares, C., additional, Abdul-Jawad Altisent, O., additional, Cuellar Calabria, H., additional, Mahia Casado, P., additional, Gonzalez-Alujas, M. T., additional, Evangelista Masip, A., additional, Garcia-Dorado Garcia, D., additional, Tekabe, Y., additional, Shen, X., additional, Li, Q., additional, Luma, J., additional, Weisenberger, D., additional, Schmidt, A. M., additional, Haubner, R., additional, Johnson, L., additional, Sleiman, L., additional, Thorn, S., additional, Hasu, M., additional, Thabet, M., additional, Dasilva, J. N., additional, Whitman, S. C., additional, Genovesi, D., additional, Giorgetti, A., additional, Gimelli, A., additional, Cannizzaro, G., additional, Bertagna, F., additional, Fagioli, G., additional, Rossi, M., additional, Bonini, R., additional, Marzullo, P., additional, Paterson, C. A., additional, Smith, S. A., additional, Small, A. D., additional, Goodfield, N. E. R., additional, Martin, W., additional, Nekolla, S., additional, Sherif, H., additional, Reder, S., additional, Yu, M., additional, Kusch, A., additional, Li, D., additional, Zou, J., additional, Lloyd, M. S., additional, Cao, K., additional, Motherwell, D. W., additional, Rice, A., additional, Mccurrach, G. M., additional, Cobbe, S. M., additional, Petrie, M. C., additional, Al Younis, I., additional, Van Der Wall, E., additional, Mirza, T., additional, Raza, M., additional, Hashemizadeh, H., additional, Santos, L., additional, Krishna, B. A., additional, Perna, F., additional, Lago, M., additional, Leo, M., additional, Pelargonio, G., additional, Bencardino, G., additional, Narducci, M. L., additional, Casella, M., additional, Bellocci, F., additional, Kirac, S., additional, Yaylali, O., additional, Serteser, M., additional, Yaylali, T., additional, Okizaki, A., additional, Urano, Y., additional, Nakayama, M., additional, Ishitoya, S., additional, Sato, J., additional, Ishikawa, Y., additional, Sakaguchi, M., additional, Nakagami, N., additional, Aburano, T., additional, Solav, S. V., additional, Bhandari, R., additional, Burrell, S., additional, Dorbala, S., additional, Bruno, I., additional, Caldarella, C., additional, Collarino, A., additional, Mattoli, M. V., additional, Stefanelli, A., additional, Cannarile, A., additional, Maggi, F., additional, Soukhov, V., additional, Bondarev, S., additional, Yalfimov, A., additional, Khan, M., additional, Priyadharshan, P. 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S., additional, Sattar, A., additional, Swadia, T., additional, Chattahi, J., additional, Qureshi, W., additional, Khalid, F., additional, Gonzalez, A., additional, Hechavarria, S., additional, Takamura, K., additional, Fujimoto, S., additional, Nakanishi, R., additional, Yamashina, S., additional, Namiki, A., additional, Yamazaki, J., additional, Koshino, K., additional, Hashikawa, Y., additional, Teramoto, N., additional, Hikake, M., additional, Ishikane, S., additional, Ikeda, T., additional, Iida, H., additional, Takahashi, Y., additional, Oriuchi, N., additional, Higashino, H., additional, Endo, K., additional, Mochizuki, T., additional, Murase, K., additional, Baali, A., additional, Moreno, R., additional, Chau, M., additional, Rousseau, H., additional, Nicoud, F., additional, Dolliner, P., additional, Brammen, L., additional, Steurer, G., additional, Traub-Weidinger, T., additional, Ubl, P., additional, Schaffarich, P., additional, Dobrozemsky, G., additional, Staudenherz, A., additional, Ozgen Kiratli, M., additional, Temelli, B., additional, Kanat, N. 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A., additional, Luotolahti, M., additional, Wendelin-Saarenhovi, M., additional, Sundell, J., additional, Raitakari, O., additional, Huidu, S., additional, Gadiraju, R., additional, Ghesani, M., additional, Uddin, Q., additional, Wosnitzer, B., additional, Takahashi, N., additional, Alhaj, E., additional, Legasto, A., additional, Abiri, B., additional, Elsaban, K., additional, El Khouly, T., additional, El Kammash, T., additional, Al Ghamdi, A., additional, Kyung Deok, B., additional, Bon Seung, K., additional, Sang Geun, Y., additional, Chang Min, D., additional, and Gwan Hong, M., additional

Published
2011
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44. Baseline and on Treatment Biodistribution Variability of 18 F-FLT Uptake in Patients With Advanced Melanoma: Brief Communication.

Author

van der Hiel B, Aalbersberg EA, van den Eertwegh AJM, Fischer J, Boellaard R, de Vos FYFL, Boers-Sonderen MJ, Stokkel MPM, de Wit-van der Veen LJ, and Haanen JBAG

Subjects
Humans, Tissue Distribution, Middle Aged, Male, Female, Aged, Adult, Neoplasm Staging, Biological Transport, Melanoma diagnostic imaging, Melanoma drug therapy, Melanoma metabolism, Positron Emission Tomography Computed Tomography, Dideoxynucleosides pharmacokinetics
Abstract

Purpose: This prospective study evaluates the biodistribution of 18 F-FLT PET in patients with advanced melanoma before and after treatment with BRAF/MEK inhibitors., Patients and Methods: Eighteen BRAF-positive unresectable stage IIIc or IV melanoma patients referred for 18 F-FLT PET/CT before (BL) and during (D14) BRAF/MEK inhibition were included. 18 F-FLT accumulation in the liver, bone marrow, blood, and muscle was quantified., Results: Baseline interpatient 18 F-FLT uptake had a coefficient-of-variation between 17.5% and 21.5%. During treatment, liver uptake increased (SUV meanBL = 4.86 ± 0.98, SUV meanD14 = 6.31 ± 1.36, P < 0.001) and bone marrow uptake decreased (SUV meanBL = 7.67 ± 1.65, SUV meanD14 = 6.78 ± 1.19, P < 0.025). Both changes were unrelated to baseline metabolic tumor volume or tumor response., Conclusions: To assess 18 F-FLT PET, both liver and bone marrow uptake may be used as normal tissue references at baseline, but 18 F-FLT biodistribution significantly changes in longitudinal response studies when treated with BRAF/MEK inhibitors., Competing Interests: Conflicts of interest and sources of funding: A.J.M.v.d.E. received study grant from Sanofi, Roche, Bristol Myers Squibb, TEVA, and Idera; received travel expenses coverage from MSD Oncology, Roche, Pfizer, and Sanofi; received speaker honoraria from Bristol Myers Squibb and Novartis; and is part of the advisory board of Bristol Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, and Merck, Pierre Fabre. E.K. has consultancy/advisory relationships with Bristol Myers Squibb, Novartis, Merck, Pierre Fabre, Lilly, and Bayer, all paid to institute, as well as received research grants not related to this paper from Bristol Myers Squibb, Delcath, Novartis, and Pierre Fabre. F.Y.F.L.d.V. received research grant from Foundation STOPBraintumors.org , Bristol Myers Squibb, Novartis, Servier, CureVac, and EORTC, all paid to institute. J.B.A.G.H. has advisory roles for Bristol Myers Squibb, CureVac, GSK, Ipsen, Iovance Biotherapeutics, Imcyse, Merck Serono, Molecular Partners, MSD, Novartis, Pfizer, Roche, Sanofi, and Third Rock Ventures; is a member of SAB of Achilles Tx, BioNTech, Gadeta, Immunocore, Instil Bio, PokeAcell, Scenic, T-Knife, and Neogene Tx, all paid to institute except Neogene Tx and Scenic; and received grant support from Amgen, Asher Bio, BioNTech, Bristol Myers Squibb, MSD, Novartis, and Sastra Cell Therapy, all paid to institute. The other authors declare no conflicts of interest. This work was supported by an unrestricted grant by Roche Medical B.V. The company has approved the design of the study and provided cobimetinib free of charge. The company has no role in collection, analysis, and interpretation of data or in writing the manuscript., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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45. The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF -Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression?

Author

van der Hiel B, Aalbersberg EA, van den Eertwegh AJM, de Wit-van der Veen LJ, Stokkel MPM, Lopez-Yurda M, Boellaard R, Kapiteijn EW, Hospers GAP, Aarts MJB, de Vos FYFL, Boers-Sonderen MJ, van der Veldt AAM, de Groot JWB, and Haanen JBAG

Subjects
Humans, Positron Emission Tomography Computed Tomography, Fluorodeoxyglucose F18, Proto-Oncogene Proteins B-raf genetics, Progression-Free Survival, Prospective Studies, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Melanoma diagnostic imaging, Melanoma drug therapy, Melanoma genetics, Skin Neoplasms pathology
Abstract

Purpose: The aims of this study were to investigate whether (early) PERCIST response monitoring with 18 F-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of 18 F-FDG PET/CT during BRAF/MEKi., Patients and Methods: This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF -mutated melanoma who underwent contrast-enhanced CT and 18 F-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.1 and PERCIST. Follow-up PET/CT scans were visually compared with baseline to assess dissemination patterns., Results: Using RECIST1.1, PFS was not significantly different between the response groups ( P = 0.26). At 2 weeks, PERCIST median PFS was 15.7 months for patients with complete metabolic response (CMR) versus 8.3 months for non-CMR ( P = 0.035). The hazards ratio (HR) for progression/death in non-CMR versus CMR was 1.99 (95% confidence interval [CI], 1.03-3.84; P = 0.040) and 1.77 (95% CI, 0.91-3.43; P = 0.0935) when adjusting for lactate dehydrogenase (LDH). At 7 weeks, median PFS for PERCIST CMR was 16.7 months versus 8.5 months for non-CMR ( P = 0.0003). The HR for progression/death in the non-CMR group was significantly increased (HR, 2.94; 95% CI, 1.60-5.40; P = 0.0005), even when adjusting for LDH (HR, 2.65; 95% CI, 1.43-4.91; P = 0.0020). At week 7, 18 F-FDG PET/CT was false-positive in all 4 (6%) patients with new FDG-avid lesions but CMR of known metastases. When 18 F-FDG PET/CT was performed at progressive disease, 18/22 (82%) patients had progression of known metastases with or without new 18 F-FDG-avid lesions., Conclusions: This study shows that PERCIST response assessment at week 7 is predictive for PFS, regardless of LDH. At 2 weeks, patients with CMR have longer PFS than patients with non-CMR, but different PET parameters should be investigated to further evaluate the added value of early 18 F-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new 18 F-FDG-avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease., Competing Interests: Conflicts of interest and sources of funding: The REPOSIT study is supported by an unrestricted grant by Roche Medical B.V. The company has approved the design of the study and provided cobimetinib free of charge. The company has no role in collection, analysis, and interpretation of data or in writing the article. A.J.M.v.d.E. received study grant from Sanofi, Roche, Bristol Myers Squibb, TEVA, and Idera; received travel expenses coverage from MSD Oncology, Roche, Pfizer, and Sanofi; received speaker honoraria from Bristol Myers Squibb and Novartis; and is part of the advisory board of Bristol Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck, and Pierre Fabre. E.W.K. has consultancy/advisory relationships with Bristol Myers Squibb, Novartis, Merck, Pierre Fabre, Lilly, and Bayer, all paid to the institute; and received research grants not related to this article from Bristol Myers Squibb, Delcath, Novartis, and Pierre Fabre. G.A.P.H. has consultancy/advisory relationships with Amgen, Bristol Myers Squibb, Roche, MSD, Pfizer, Novartis, Sanofi, and Pierre Fabre, all paid to the institute; and received research grants from Bristol Myers Squibb and Seerave, all paid to the institute. M.J.B.A. has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, and Bayer, and research grants from Merck-Pfizer, all paid to the institute and not related to current work. F.Y.F.L.d.V. received research grant from Foundation STOPBraintumors.org , Bristol Myers Squibb, Novartis, Servier, CureVac, and EORTC, all paid to the institute. A.A.M.v.d.V. has consultancy roles (all paid to the institute) for Bristol Myers Squibb, MSD, Roche, Sanofi, Novartis, Pierre Fabre, Merck, Ipsen, Eisai, and Pfizer, all paid to the institute. J.B.A.G.H. has advisory roles for Bristol Myers Squibb, CureVac, GSK, Ipsen, Iovance Biotherapeutics, Imcyse, Merck Serono, Molecular Partners, MSD, Novartis, Pfizer, Roche, Sanofi, and Third Rock Ventures; is a member of SAB of Achilles Tx, BioNTech, Gadeta, Immunocore, Instil Bio, PokeAcell, Scenic, T-Knife, and Neogene Tx, all paid to the institute except Neogene Tx and Scenic; and received grant support from Amgen, Asher Bio, BioNTech, Bristol Myers Squibb, MSD, Novartis, and Sastra Cell Therapy, all paid to the institute. The other authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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46. Baseline ultrasound and FDG-PET/CT imaging in Merkel cell carcinoma.

Author

Zijlker LP, Bakker M, van der Hiel B, Bruining A, Klop WMC, Zuur CL, Wouters MWJM, and van Akkooi ACJ

Subjects
Humans, Positron Emission Tomography Computed Tomography, Fluorodeoxyglucose F18, Retrospective Studies, Lymph Nodes pathology, Sentinel Lymph Node Biopsy, Radiopharmaceuticals, Carcinoma, Merkel Cell diagnostic imaging, Carcinoma, Merkel Cell pathology, Skin Neoplasms diagnostic imaging, Skin Neoplasms pathology
Abstract

Background: Merkel cell carcinoma (MCC) is a cutaneous tumor with a high tendency to metastasize, and a significant proportion of patients have metastases at first presentation. This study aims to determine the value of baseline ultrasound (US) and  18 fluorodeoxyglucose-positron emission tomography/computed tomography ( 18 FDG-PET/CT) imaging in both patients with clinically localized MCC (Stage I/II) and patients who present with palpable lymph nodes (Stage III)., Methods: This retrospective cohort included 135 MCC patients who underwent baseline US (with fine needle aspiration cytology (FNAC)) and/or FDG-PET/CT imaging between 2015 and 2021., Results: Of the 104 patients with clinically localized disease, 48% were upstaged to Stage III and 3% to Stage IV by imaging or sentinel lymph node biopsy (SLNB). FDG-PET/CT imaging identified regional metastases in 23%, while US with FNAC identified regional metastases in 19%. SLNB was performed in 56 patients, of whom 57% were upstaged to Stage III. Of the 31 patients who presented with palpable lymph nodes, 16% were upstaged to Stage IV by FDG-PET/CT imaging., Conclusion: Baseline imaging frequently upstages Stage I/II MCC patients to Stage III, both by US and FDG-PET/CT, Stage IV disease is rarely identified. Patients who present with palpable nodes are frequently upstaged to Stage IV by FDG-PET/CT imaging., (© 2022 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Published
2023
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47. Talimogene laherparepvec monotherapy for head and neck melanoma patients.

Author

Franke V, Stahlie EHA, Klop WMC, Zuur CL, Berger DMS, van der Hiel B, van de Wiel BA, Wouters MWJM, van Houdt WJ, and van Akkooi ACJ

Subjects
Humans, Aged, Aged, 80 and over, Positron Emission Tomography Computed Tomography, Immunotherapy methods, Melanoma pathology, Skin Neoplasms pathology, Oncolytic Virotherapy adverse effects
Abstract

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1, intralesionally administered in patients with stage IIIB/C-IVM1a unresectable melanoma. When surgery is not a treatment option in the head and neck region, T-VEC can be an elegant alternative to systemic immunotherapy. Ten patients with metastatic melanoma in the head and neck region started treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We collected data on response, adverse events (AEs), and baseline characteristics. For response evaluation, we used clinical evaluation with photography, 3-monthly PET/computed tomography (PET/CT) using 18F-fluoro-2-D-deoxyglucose, and histological biopsies. Median age at baseline was 78.2 (35-97) years with a median follow-up of 11.6months. Of these 10 patients, 5 had a complete response (CR), 3 had a partial response, 1 had stable disease and 1 showed progressive disease (PD) as their best response. Best overall response rate (ORR) was 80%. Median progression-free survival was 10.8 months (95% confidence interval, 2.2-19.4). Grade 1 AEs occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms, and injection site pain. PET-CT and histological biopsies proved to be clinically useful tools to evaluate treatment response for T-VEC monotherapy, confirming pCR or PD to stage IV disease requiring systemic treatment. ORR for T-VEC monotherapy for melanoma in the head and neck region at our institute was 80% with 50% achieving a CR. This realworld data demonstrates promising results and suggests T-VEC can be an alternative to systemic therapy in this select, mostly elderly patient population., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2023
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48. Single agent Talimogene Laherparepvec for stage IIIB-IVM1c melanoma patients: A systematic review and meta-analysis.

Author

Stahlie EHA, Mulder EEAP, Reijers S, Balduzzi S, Zuur CL, Klop WMC, van der Hiel B, Van de Wiel BA, Wouters MWJM, Schrage YM, van Houdt WJ, Grunhagen DJ, and van Akkooi ACJ

Subjects
Herpesvirus 1, Human, Humans, Immunotherapy, Melanoma, Cutaneous Malignant, Biological Products therapeutic use, Melanoma drug therapy, Melanoma etiology, Oncolytic Virotherapy adverse effects, Skin Neoplasms pathology
Abstract

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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Published
2022
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49. Re-introduction of T-VEC Monotherapy in Recurrent Melanoma is Effective.

Author

Franke V, Stahlie EHA, van der Hiel B, van de Wiel BA, Wouters MWJM, van Houdt WJ, and van Akkooi ACJ

Subjects
Biological Products, Chronic Disease, Humans, Immunotherapy methods, Melanoma, Cutaneous Malignant, Herpesvirus 1, Human, Melanoma drug therapy, Melanoma pathology, Oncolytic Virotherapy adverse effects, Oncolytic Virotherapy methods, Skin Neoplasms drug therapy, Skin Neoplasms pathology
Abstract

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus type 1, which can be administered intralesionally in patients with stage IIIB/C-IVM1a (American Joint Committee of Cancer; AJCC 7th edition) unresectable melanoma. In the case of disease recurrence, T-VEC can be re-introduced for the same category of patients. Five patients with recurrent disease after a prior achieved complete response (CR) recommenced treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We collected data on response, adverse events and baseline characteristics. All 5 patients that were re-treated with T-VEC presented with in-transit metastases on the lower limb. Median age at baseline was 72.1 years with a median follow-up time of 30.4 months. Histologically proven CR was achieved after a median of 8 T-VEC courses on the initial exposure. Duration of response (time between first CR and recurrence) varied between 3.8 and 14.2 months. All 5 patients achieved a histologically and/or positron emission tomography/computed tomography proven CR again after re-introduction of T-VEC with a median of 5 courses. One patient (20%) developed a second recurrence and is currently still on treatment with T-VEC. No patients developed distant metastases. Grade 1 adverse events occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms and injection site pain. Response to re-introduction of T-VEC monotherapy in this select patient population is promising. This real world data on re-introduction of T-VEC monotherapy in stage IIIB/C-IVM1a melanoma suggests T-VEC could be a treatment option for chronic disease control., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2022
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50. 18F-FDG PET/CT During Neoadjuvant Targeted Therapy in Prior Unresectable Stage III Melanoma Patients: Can (Early) Metabolic Imaging Predict Histopathologic Response or Recurrence?

Author

van der Hiel B, Blankenstein SA, Aalbersberg EA, Wondergem M, Stokkel MPM, van de Wiel BA, Klop WMC, van Akkooi ACJ, and Haanen JB

Subjects
Humans, Mitogen-Activated Protein Kinase Kinases, Neoadjuvant Therapy, Positron Emission Tomography Computed Tomography methods, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, Radiopharmaceuticals, Skin Neoplasms, Melanoma, Cutaneous Malignant, Fluorodeoxyglucose F18, Melanoma diagnostic imaging, Melanoma drug therapy
Abstract

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., Competing Interests: Conflicts of interest and sources of funding: AvA advisory board and consultancy honoraria for Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, and 4SC; and research grant from Amgen and Merck-Pfizer, all unrelated and paid to institute. J.B.H. has advisory roles for Bristol-Myers Squibb, Ipsen, Iovance Biotherapeutics, Merck Serono, Molecular Partners, MSD, Novartis, Pfizer, Roche, Sanofi, Seattle Genetics, and Third Rock Ventures, all paid to institute; member of SAB of Achilles Tx, BioNTech, Gadeta, Immunocore, Instil Bio, PokeAcel, T-Knife, and Neogene Tx; received grant support from Amgen, Asher Bio, BioNTech, Bristol-Myers Squibb, MSD, Novartis, and Neogene Tx, all paid to institute; and has stock options in Neogene Tx., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2022
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