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1. Cognitive and Behavioral Development of 9-Year-Old Children after Maternal Cancer during Pregnancy: A Prospective Multicenter Cohort Study

Author

Van Assche, I, Huis In 'T Veld, E, Van Calsteren, K, Van Gerwen, M, Blommaert, J, Cardonick, E, Halaska, M, Fruscio, R, Fumagalli, M, Lemiere, J, Van Dijk-Lokkart, E, Fontana, C, Van Tinteren, H, De Ridder, J, Van Grotel, M, Van Den Heuvel-Eibrink, M, Lagae, L, Amant, F, Van Assche I. A., Huis In 'T Veld E. A., Van Calsteren K., Van Gerwen M., Blommaert J., Cardonick E., Halaska M. J., Fruscio R., Fumagalli M., Lemiere J., Van Dijk-Lokkart E. M., Fontana C., Van Tinteren H., De Ridder J., Van Grotel M., Van Den Heuvel-Eibrink M. M., Lagae L., Amant F., Van Assche, I, Huis In 'T Veld, E, Van Calsteren, K, Van Gerwen, M, Blommaert, J, Cardonick, E, Halaska, M, Fruscio, R, Fumagalli, M, Lemiere, J, Van Dijk-Lokkart, E, Fontana, C, Van Tinteren, H, De Ridder, J, Van Grotel, M, Van Den Heuvel-Eibrink, M, Lagae, L, Amant, F, Van Assche I. A., Huis In 'T Veld E. A., Van Calsteren K., Van Gerwen M., Blommaert J., Cardonick E., Halaska M. J., Fruscio R., Fumagalli M., Lemiere J., Van Dijk-Lokkart E. M., Fontana C., Van Tinteren H., De Ridder J., Van Grotel M., Van Den Heuvel-Eibrink M. M., Lagae L., and Amant F.

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P <.001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P =.776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education.

Published
2023

4. Ten-year experience of a national multidisciplinary tumour board for cancer and pregnancy in the Netherlands

Author

Heimovaara, Joosje H., primary, Boere, Ingrid A., additional, de Haan, Jorine, additional, van Calsteren, Kristel, additional, Amant, Frédéric, additional, van Zuylen, Lia, additional, Lok, Christine A.R., additional, Lok, C.A.R., additional, van Zuylen, L., additional, Boere, I.A., additional, Amant, F., additional, Beerendonk, C.C.M., additional, Bellido-Casado, M., additional, Beltman, J.J., additional, Bos, M.E.M.M., additional, Duvekot, J.J., additional, Gerestein, C.G.,, additional, Gordijn, S., additional, de Groot, C.J.M., additional, van Grotel, M., additional, Han, S.N., additional, Heeres, B.C., additional, van den Heuvel-Eibrink, M.M., additional, Houwink, A., additional, Huitema, D.R., additional, Koken, PhW., additional, Koppert, L.B., additional, Lugtenburg, P.J., additional, Ottevanger, P.B., additional, Painter, R.C., additional, Poortmans, P.M.P., additional, Roes, E.M., additional, van der Scheer, L., additional, Schröder, C.P., additional, Suelmann, B.B.M., additional, Suijkerbuijk, K.P.M., additional, van Tienhoven, G., additional, van Trommel, N.E., additional, Trum, J.W., additional, van der Velden, J., additional, Vriens, I.J.H., additional, and Witteveen, P.O., additional

Published
2022
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5. Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy

Author

Vandenbroucke, T, Verheecke, M, van Gerwen, M, Van Calsteren, K, Halaska, M, Fumagalli, M, Fruscio, R, Gandhi, A, Veening, M, Lagae, L, Ottevanger, P, Voigt, J, de Haan, J, Gziri, M, Maggen, C, Mertens, L, Naulaers, G, Claes, L, Amant, F, Blommaert, J, Dekrem, J, Goffin, F, Rigo, V, Fontana, C, Mosca, F, Passera, S, Picciolini, O, Scarfone, G, Peccatori, F, Boffi, M, Delle Marchette, M, Nacinovich, R, Lok, C, Wolters, V, Boere, I, Witteveen, E, Schroder, C, de Groot, C, van Grotel, M, van den Heuvel-Eibrink, M, Babkova, A, Drochytek, V, Vandenbroucke T., Verheecke M., van Gerwen M., Van Calsteren K., Halaska M. J., Fumagalli M., Fruscio R., Gandhi A., Veening M., Lagae L., Ottevanger P. B., Voigt J. -U., de Haan J., Gziri M. M., Maggen C., Mertens L., Naulaers G., Claes L., Amant F., Blommaert J., Dekrem J., Goffin F., Rigo V., Fontana C., Mosca F., Passera S., Picciolini O., Scarfone G., Peccatori F. A., Boffi M. L., Delle Marchette M., Nacinovich R., Lok C., Wolters V., Boere I., Witteveen E., Schroder C., de Groot C., van Grotel M., van den Heuvel-Eibrink M., Babkova A., Drochytek V., Vandenbroucke, T, Verheecke, M, van Gerwen, M, Van Calsteren, K, Halaska, M, Fumagalli, M, Fruscio, R, Gandhi, A, Veening, M, Lagae, L, Ottevanger, P, Voigt, J, de Haan, J, Gziri, M, Maggen, C, Mertens, L, Naulaers, G, Claes, L, Amant, F, Blommaert, J, Dekrem, J, Goffin, F, Rigo, V, Fontana, C, Mosca, F, Passera, S, Picciolini, O, Scarfone, G, Peccatori, F, Boffi, M, Delle Marchette, M, Nacinovich, R, Lok, C, Wolters, V, Boere, I, Witteveen, E, Schroder, C, de Groot, C, van Grotel, M, van den Heuvel-Eibrink, M, Babkova, A, Drochytek, V, Vandenbroucke T., Verheecke M., van Gerwen M., Van Calsteren K., Halaska M. J., Fumagalli M., Fruscio R., Gandhi A., Veening M., Lagae L., Ottevanger P. B., Voigt J. -U., de Haan J., Gziri M. M., Maggen C., Mertens L., Naulaers G., Claes L., Amant F., Blommaert J., Dekrem J., Goffin F., Rigo V., Fontana C., Mosca F., Passera S., Picciolini O., Scarfone G., Peccatori F. A., Boffi M. L., Delle Marchette M., Nacinovich R., Lok C., Wolters V., Boere I., Witteveen E., Schroder C., de Groot C., van Grotel M., van den Heuvel-Eibrink M., Babkova A., and Drochytek V.

Abstract

Background: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6–4.3, versus 4.5, 95% CI: 4.1–4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). Conclusions: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. Clinical trial registration: The study is registered at ClinicalTrials.gov, NCT00330447.

Published
2020

8. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

Author

Meijer, A, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garrè, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Falck-Winther, J, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LC, Kruseova, J, Pluijm, SMF, Kuehni, CF, van der Pal, H, Parfitt, R, Spix, C, Hesping, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drögemöller, BI, Ross, CJD, Bhavsar, AP, am Zehnhoff-Dinnesen, A, Carleton, BC, Zolk, O, van den Heuvel-Eibrink, M, Meijer, A, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garrè, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Falck-Winther, J, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LC, Kruseova, J, Pluijm, SMF, Kuehni, CF, van der Pal, H, Parfitt, R, Spix, C, Hesping, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drögemöller, BI, Ross, CJD, Bhavsar, AP, am Zehnhoff-Dinnesen, A, Carleton, BC, Zolk, O, and van den Heuvel-Eibrink, M

Abstract

Background: Ototoxicity (hearing loss, tinnitus and/or vertigo) is a serious adverse event of cisplatin treatment in children with cancer. The heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. This study investigated the association between carriership of novel single nucleotide polymorphisms (SNPs) and cisplatin-induced hearing loss (CIHL) in childhood cancer patients.Material and methods: The discovery cohort included cisplatin treated, non-cranial irradiated pediatric cancer patients within the European PanCareLIFE (PCL) study (N=390). CIHL at end of cancer treatment was defined as Muenster grade >=2b, assessed by pure tone audiometry. DNA was genotyped using the Infinium© Global Screening Array. Logistic regression models were applied including age at diagnosis, sex, cisplatin total cumulative dose and principal components 1-4, assuming an additive effect of the minor allele. Replication of the findings was performed in two independent, similarly treated cohorts (N=192 and N=188). Functional validation experiments in cultured human HeLa cell lines were performed to determine the effect of knockdown of the SNPs nearest identified gene on cisplatin-induced toxicity.Results: In the PCL discovery cohort, 8 SNPs reached a suggestive significance of P<1.0x10-5. One variant (rs893507) within the TCERG1L gene showed evidence of replication (P=0.01) in the Canadian first replication cohort. Analysis in the PCL second replication cohort confirmed this finding (P=1.0x10-4). The combined analysis showed that carriership of the C-allele of this newly discovered variant increases the odds of CIHL with 3.11-fold (P=5.3x10-10, 95% CI 2.2-4.5). Modulating TCERG1L expression significantly altered cell viability in response to cisplatin treatment, where TCERG1L overexpression and silencing protected and sensitized cells to cisplatin toxicity, respectively.Discussion: Children with cancer who carry a variant in the TCERG1L g

Published
2021

9. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

Author

Meijer, A. J.M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C.H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., Winther, J. F., Rechnitzer, C., Hasle, H., Kepak, T., Kepakova, K., Tissing, W. J.E., van der Kooi, A. L.F., Kremer, L. C.M., Kruseova, J., Pluijm, S. M.F., Kuehni, C. E., van der Pal, H. J.H., Parfitt, R., Spix, C., Tillmanns, A., Deuster, D., Matulat, P., Calaminus, G., Hoetink, A. E., Elsner, S., Gebauer, J., Haupt, R., Lackner, H., Blattmann, C., Neggers, S. J.C.M.M., Rassekh, S. R., Wright, G. E.B., Brooks, B., Nagtegaal, A. P., Drögemöller, B. I., Ross, C. J.D., Meijer, A. J.M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C.H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., Winther, J. F., Rechnitzer, C., Hasle, H., Kepak, T., Kepakova, K., Tissing, W. J.E., van der Kooi, A. L.F., Kremer, L. C.M., Kruseova, J., Pluijm, S. M.F., Kuehni, C. E., van der Pal, H. J.H., Parfitt, R., Spix, C., Tillmanns, A., Deuster, D., Matulat, P., Calaminus, G., Hoetink, A. E., Elsner, S., Gebauer, J., Haupt, R., Lackner, H., Blattmann, C., Neggers, S. J.C.M.M., Rassekh, S. R., Wright, G. E.B., Brooks, B., Nagtegaal, A. P., Drögemöller, B. I., and Ross, C. J.D.

Abstract

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

Published
2021

10. Long-term neurodevelopmental outcome after prenatal exposure to maternal hematological malignancies with or without cytotoxic treatment

Author

van Gerwen, M, Huis In 't Veld, E, van Grotel, M, van den Heuvel-Eibrink, M, Van Calsteren, K, Maggen, C, Drochytek, V, Scarfone, G, Fontana, C, Fruscio, R, Cardonick, E, van Dijk-Lokkart, E, Amant, F, van Gerwen, Mathilde, Huis In 't Veld, Evangeline, van Grotel, Martine, van den Heuvel-Eibrink, Marry M, Van Calsteren, Kristel, Maggen, Charlotte, Drochytek, Vit, Scarfone, Giovanna, Fontana, Camilla, Fruscio, Robert, Cardonick, Elyce, van Dijk-Lokkart, Elisabeth M, Amant, Frédéric, van Gerwen, M, Huis In 't Veld, E, van Grotel, M, van den Heuvel-Eibrink, M, Van Calsteren, K, Maggen, C, Drochytek, V, Scarfone, G, Fontana, C, Fruscio, R, Cardonick, E, van Dijk-Lokkart, E, Amant, F, van Gerwen, Mathilde, Huis In 't Veld, Evangeline, van Grotel, Martine, van den Heuvel-Eibrink, Marry M, Van Calsteren, Kristel, Maggen, Charlotte, Drochytek, Vit, Scarfone, Giovanna, Fontana, Camilla, Fruscio, Robert, Cardonick, Elyce, van Dijk-Lokkart, Elisabeth M, and Amant, Frédéric

Abstract

Data on the long-term neurodevelopmental outcomes of children exposed to hematological maternal cancer with or without treatment during pregnancy are lacking. A total of 57 children, of whom 33 males and 24 females, prenatally exposed to hematological malignancies and its treatment, were invited for neuropsychological and physical examinations at 18months, 36months, 6, 9, 12, 15 and 18years of age. Oncological, obstetrical, neonatal and follow-up data of these children were collected. Parents were asked to complete questionnaires on their child's general health, school performances, social situation, behavioral development, executive functioning, and if their child receives supportive care. Non-Hodgkin lymphoma was diagnosed in 35.1%, Hodgkin lymphoma in 28.1%, acute myeloid leukemia in 15.8%, chronic myeloid leukemia in 12.3%, and acute lymphoblastic leukemia in 8.8%. Cognitive development at a median age of 10.7years was within the normal range. In subgroup analyses of children in early childhood, the gestational age at birth was correlated with the cognitive outcome at a median age of 1.7years. Scores for language development, intelligence, attention, memory and behavior, as well as clinical neurological and general pediatric examinations were within normal ranges. In subgroup analyses, the need for supportive care in the child was associated with the loss of the mother. Prenatal exposure to hematological maternal malignancies with or without treatment did not affect the neurodevelopment of the child in the long term. Yet, caution is indicated and surveillance of the emotional development of the child is needed, especially when the mother is deceased to cancer.

Published
2021

11. Locoregional Control Using Highly Conformal Flank Target Volumes and Volumetric-Modulated Arc Therapy in Pediatric Renal Tumors: Results from the Dutch National Cohort

Author

Hubrecht Institute with UMC, PMC Medisch specialisten, Klinische Fysica RT, Cancer, MS Radiotherapie, Onderzoek Beeld, NEMI, Zorgeenheid Kinderchirurgie Medisch, Pathologie Pathologen staf, MS Radiologie, Speerpunt, Zorg en O&O, Child Health, Mul, J., Van Grotel, M., Seravalli, E., Bosman, M., Van Tinteren, H., Roy, P., Fajardo, R. Davila, Tytgat, L., Mavinkurve-Groothuis, A., Van De Ven, C., Wijnen, M., De Krijger, R., Littooij, A., Van den Heuvel-Eibrink, M., Janssens, G., Hubrecht Institute with UMC, PMC Medisch specialisten, Klinische Fysica RT, Cancer, MS Radiotherapie, Onderzoek Beeld, NEMI, Zorgeenheid Kinderchirurgie Medisch, Pathologie Pathologen staf, MS Radiologie, Speerpunt, Zorg en O&O, Child Health, Mul, J., Van Grotel, M., Seravalli, E., Bosman, M., Van Tinteren, H., Roy, P., Fajardo, R. Davila, Tytgat, L., Mavinkurve-Groothuis, A., Van De Ven, C., Wijnen, M., De Krijger, R., Littooij, A., Van den Heuvel-Eibrink, M., and Janssens, G.

Published
2021

12. Characteristics and Outcome of Children with Renal Tumors in the Netherlands: First Five Year Single National Center Experience

Author

Hubrecht Institute with UMC, PMC Medisch specialisten, NEMI, MS Radiotherapie, Pathologie Pathologen staf, Genetica Klinische Genetica, Child Health, Cancer, MS Radiologie, Zorgeenheid Kinderchirurgie Medisch, Onderzoek Beeld, Speerpunt, Zorg en O&O, Roy, P., Witte, M., Van Peer, S., Karim-Kos, H., Van Grotel, M., Van De Ven, C., Mavinkurve-Groothuis, A., Merks, J., Janssens, G., De Krijger, R., Jongmans, M., Drost, J., Littooij, A., Wijnen, M., Van der Steeg, A., Tytgat, L., Van Tinteren, H., Van den Heuvel-Eibrink, M., Hubrecht Institute with UMC, PMC Medisch specialisten, NEMI, MS Radiotherapie, Pathologie Pathologen staf, Genetica Klinische Genetica, Child Health, Cancer, MS Radiologie, Zorgeenheid Kinderchirurgie Medisch, Onderzoek Beeld, Speerpunt, Zorg en O&O, Roy, P., Witte, M., Van Peer, S., Karim-Kos, H., Van Grotel, M., Van De Ven, C., Mavinkurve-Groothuis, A., Merks, J., Janssens, G., De Krijger, R., Jongmans, M., Drost, J., Littooij, A., Wijnen, M., Van der Steeg, A., Tytgat, L., Van Tinteren, H., and Van den Heuvel-Eibrink, M.

Published
2021

13. Inter-Clinician Delineation Variation for a New Highly-Conformal Flank Target Volume in Children with Renal Tumors: A Siop-Renal Tumor Study Group International Multicenter Exercise

Author

Hubrecht Institute with UMC, Klinische Fysica RT, Cancer, MS Radiotherapie, Arts-assistenten Radiotherapie, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, Mul, J., Melchior, P., Seravalli, E., Saunders, D., Bolle, S., Cameron, A., Gurtner, K., Harrabi, S., Lassen-Ramshad, Y., Lavan, N., Magelssen, H., Mandeville, H., Boterberg, T., Kroon, P., Kotte, A., Hoeben, B., Van Rossum, P., Van Grotel, M., Graf, N., Van den Heuvel-Eibrink, M., Rube, C., Janssens, G., Hubrecht Institute with UMC, Klinische Fysica RT, Cancer, MS Radiotherapie, Arts-assistenten Radiotherapie, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, Mul, J., Melchior, P., Seravalli, E., Saunders, D., Bolle, S., Cameron, A., Gurtner, K., Harrabi, S., Lassen-Ramshad, Y., Lavan, N., Magelssen, H., Mandeville, H., Boterberg, T., Kroon, P., Kotte, A., Hoeben, B., Van Rossum, P., Van Grotel, M., Graf, N., Van den Heuvel-Eibrink, M., Rube, C., and Janssens, G.

Published
2021

14. Aminoglycoside- and glycopeptide-induced ototoxicity in children: a systematic review

Author

Functiecentrum KNO, Zorgeenheid KNO Medisch, AIOS Anesthesiologie, PMC Medisch specialisten, Apotheek O&O&O, Cancer, Brain, Speerpunt, Zorg en O&O, Child Health, Sportgeneeskunde Onderwijs, Diepstraten, F. A., Hoetink, A. E., Van Grotel, M., Huitema, A. D.R., Stokroos, R. J., Van Den Heuvel-Eibrink, M. M., Meijer, A. J.M., Functiecentrum KNO, Zorgeenheid KNO Medisch, AIOS Anesthesiologie, PMC Medisch specialisten, Apotheek O&O&O, Cancer, Brain, Speerpunt, Zorg en O&O, Child Health, Sportgeneeskunde Onderwijs, Diepstraten, F. A., Hoetink, A. E., Van Grotel, M., Huitema, A. D.R., Stokroos, R. J., Van Den Heuvel-Eibrink, M. M., and Meijer, A. J.M.

Published
2021

17. Design Strategies for Promoting Young Children’s Physical Activity: A Playscapes Perspective

Author

Boon, Boudewijn, Rozendaal, M.C., Van den Heuvel-Eibrink, Marry M., van der Net, J.J., van Grotel, M., and Stappers, P.J.

Subjects
Exergames, Research through design, Childhood Cancer, Open-Ended Play, Pediatric Healthcare, Intermediate-Level Knowledge
Abstract

This paper develops a set of design strategies for promoting young children’s physical activity. These strategies are developed by taking the design perspective of Playscapes as a starting point. Playscapes suggests that three play qualities are key in promoting young children’s physical activity: free, bodily, and dispersed play. We present two field studies in a pediatric oncology center, in which we observed how these play qualities were reflected in children’s interactions with two Playscape designs: Stickz, a collection of branch-shaped objects, were placed in a semi-public waiting area; Fizzy, a self-propelled robotic ball, was introduced to patient rooms. Free play was analyzed according to the diversity of play activities, bodily play according to the diversity and exertion level of bodily movements, and dispersed play according to the floor area covered. Based on the findings, we discuss how Fizzy and Stickz contributed to each play quality, and derive a set of design strategies that can be applied in different contexts to stimulate young children’s physical activity. With these strategies, Playscapes offers a concrete alternative to existing approaches, supporting designers in directing interactions towards physical activity while leaving room for children’s unstructured and spontaneous play.

Published
2020

18. Neuroblastoma between 1990 and 2014 in the Netherlands : Increased incidence and improved survival of high-risk neuroblastoma

Author

Tas, M. L., Reedijk, A. M.J., Karim-Kos, H. E., Kremer, L. C.M., van de Ven, C. P., Dierselhuis, M. P., van Eijkelenburg, N. K.A., van Grotel, M., Kraal, K. C.J.M., Peek, A. M.L., Coebergh, J. W.W., Janssens, G. O.R., de Keizer, B., de Krijger, R. R., Pieters, R., Tygtat, G. A.M., van Noesel, M. M., Tas, M. L., Reedijk, A. M.J., Karim-Kos, H. E., Kremer, L. C.M., van de Ven, C. P., Dierselhuis, M. P., van Eijkelenburg, N. K.A., van Grotel, M., Kraal, K. C.J.M., Peek, A. M.L., Coebergh, J. W.W., Janssens, G. O.R., de Keizer, B., de Krijger, R. R., Pieters, R., Tygtat, G. A.M., and van Noesel, M. M.

Published
2020

19. Design Strategies for Promoting Young Children’s Physical Activity: A Playscapes Perspective

Author

Boon, Boudewijn (author), Rozendaal, M.C. (author), Van den Heuvel-Eibrink, Marry M. (author), van der Net, J.J. (author), van Grotel, M. (author), Stappers, P.J. (author), Boon, Boudewijn (author), Rozendaal, M.C. (author), Van den Heuvel-Eibrink, Marry M. (author), van der Net, J.J. (author), van Grotel, M. (author), and Stappers, P.J. (author)

Abstract

This paper develops a set of design strategies for promoting young children’s physical activity. These strategies are developed by taking the design perspective of Playscapes as a starting point. Playscapes suggests that three play qualities are key in promoting young children’s physical activity: free, bodily, and dispersed play. We present two field studies in a pediatric oncology center, in which we observed how these play qualities were reflected in children’s interactions with two Playscape designs: Stickz, a collection of branch-shaped objects, were placed in a semi-public waiting area; Fizzy, a self-propelled robotic ball, was introduced to patient rooms. Free play was analyzed according to the diversity of play activities, bodily play according to the diversity and exertion level of bodily movements, and dispersed play according to the floor area covered. Based on the findings, we discuss how Fizzy and Stickz contributed to each play quality, and derive a set of design strategies that can be applied in different contexts to stimulate young children’s physical activity. With these strategies, Playscapes offers a concrete alternative to existing approaches, supporting designers in directing interactions towards physical activity while leaving room for children’s unstructured and spontaneous play., Design Aesthetics, Human Information Communication Design, Design Conceptualization and Communication

Published
2020

20. Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma

Author

MS Radiotherapie, Cancer, MS Radiologie, Pathologie patiënten zorg, Pathologie Pathologen staf, Tas, M. L., Reedijk, A. M.J., Karim-Kos, H. E., Kremer, L. C.M., van de Ven, C. P., Dierselhuis, M. P., van Eijkelenburg, N. K.A., van Grotel, M., Kraal, K. C.J.M., Peek, A. M.L., Coebergh, J. W.W., Janssens, G. O.R., de Keizer, B., de Krijger, R. R., Pieters, R., Tygtat, G. A.M., van Noesel, M. M., MS Radiotherapie, Cancer, MS Radiologie, Pathologie patiënten zorg, Pathologie Pathologen staf, Tas, M. L., Reedijk, A. M.J., Karim-Kos, H. E., Kremer, L. C.M., van de Ven, C. P., Dierselhuis, M. P., van Eijkelenburg, N. K.A., van Grotel, M., Kraal, K. C.J.M., Peek, A. M.L., Coebergh, J. W.W., Janssens, G. O.R., de Keizer, B., de Krijger, R. R., Pieters, R., Tygtat, G. A.M., and van Noesel, M. M.

Published
2020

21. Renal cell carcinoma in young FH mutation carriers: case series and review of the literature

Author

Genetica Klinische Genetica, MS Neonatologie, MS Radiologie, Cancer, Pathologie Pathologen staf, Child Health, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Hol, J A, Jongmans, M C J, Littooij, A S, de Krijger, R R, Kuiper, R P, van Harssel, J J T, Mensenkamp, A, Simons, M, Tytgat, G A M, van den Heuvel-Eibrink, M M, van Grotel, M, Genetica Klinische Genetica, MS Neonatologie, MS Radiologie, Cancer, Pathologie Pathologen staf, Child Health, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Hol, J A, Jongmans, M C J, Littooij, A S, de Krijger, R R, Kuiper, R P, van Harssel, J J T, Mensenkamp, A, Simons, M, Tytgat, G A M, van den Heuvel-Eibrink, M M, and van Grotel, M

Published
2020

22. Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma

Author

Tas, M.L., primary, Reedijk, A.M.J., additional, Karim-Kos, H.E., additional, Kremer, L.C.M., additional, van de Ven, C.P., additional, Dierselhuis, M.P., additional, van Eijkelenburg, N.K.A., additional, van Grotel, M., additional, Kraal, K.C.J.M., additional, Peek, A.M.L., additional, Coebergh, J.W.W., additional, Janssens, G.O.R., additional, de Keizer, B., additional, de Krijger, R.R., additional, Pieters, R., additional, Tytgat, G.A.M., additional, and van Noesel, M.M., additional

Published
2020
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27. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

Author

Meijer, A. J. M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C. H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., and Winther, J. F.

Subjects
DEAFNESS, CHILDHOOD cancer, CISPLATIN, HUMAN cell culture, PATHOLOGICAL physiology
Abstract

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity. [ABSTRACT FROM AUTHOR]

Published
2021
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29. Prognostic significance of age in 5631 patients with Wilms tumour prospectively registered in International Society of Paediatric Oncology (SIOP) 93-01 and 2001

Author

Hol, J. A., primary, Lopez-Yurda, M. I., additional, Van Tinteren, H., additional, Van Grotel, M., additional, Godzinski, J., additional, Vujanic, G., additional, Oldenburger, F., additional, De Camargo, B., additional, Ramírez-Villar, G. L., additional, Bergeron, C., additional, Pritchard-Jones, K., additional, Graf, N., additional, and Van den Heuvel-Eibrink, M. M., additional

Published
2019
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31. The unique characteristics of intussusception after renal tumor surgery in children

Author

van Peer, S. E., van de Ven, C. P., Terwisscha van Scheltinga, C. E.J., Hol, J. A., Wijnen, M. H.W.A., Littooij, A. S., van Grotel, M., van den Heuvel-Eibrink, M. M., van Peer, S. E., van de Ven, C. P., Terwisscha van Scheltinga, C. E.J., Hol, J. A., Wijnen, M. H.W.A., Littooij, A. S., van Grotel, M., and van den Heuvel-Eibrink, M. M.

Published
2018

32. The unique characteristics of intussusception after renal tumor surgery in children

Author

PMC Medisch specialisten, MS Radiologie, Cancer, Zorg en O&O, Child Health, van Peer, S. E., van de Ven, C. P., Terwisscha van Scheltinga, C. E.J., Hol, J. A., Wijnen, M. H.W.A., Littooij, A. S., van Grotel, M., van den Heuvel-Eibrink, M. M., PMC Medisch specialisten, MS Radiologie, Cancer, Zorg en O&O, Child Health, van Peer, S. E., van de Ven, C. P., Terwisscha van Scheltinga, C. E.J., Hol, J. A., Wijnen, M. H.W.A., Littooij, A. S., van Grotel, M., and van den Heuvel-Eibrink, M. M.

Published
2018

33. Hearing loss after platinum treatment is irreversible in noncranial irradiated childhood cancer survivors

Author

Clemens, Eva, de Vries, A.C.H., Zehnhoff-Dinnesen, AA, Tissing, WJE, Loonen, JJ, Pluijm, Saskia, van Dulmen-den Broeder, E, Bresters, D, Versluys, B, Kremer, LCM (Leontien), van der Pal, HJ, Neggers, S.J.C.M.M., van Grotel, M, Van den Heuvel - Eibrink, Marry, Clemens, Eva, de Vries, A.C.H., Zehnhoff-Dinnesen, AA, Tissing, WJE, Loonen, JJ, Pluijm, Saskia, van Dulmen-den Broeder, E, Bresters, D, Versluys, B, Kremer, LCM (Leontien), van der Pal, HJ, Neggers, S.J.C.M.M., van Grotel, M, and Van den Heuvel - Eibrink, Marry

Published
2017

38. Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences

Author

van Grotel, M, primary, Meijerink, J P P, additional, van Wering, E R, additional, Langerak, A W, additional, Beverloo, H B, additional, Buijs-Gladdines, J G C A M, additional, Burger, N B, additional, Passier, M, additional, van Lieshout, E M, additional, Kamps, W A, additional, Veerman, A J P, additional, van Noesel, M M, additional, and Pieters, R, additional

Published
2007
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39. The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia

Author

Van Vlierberghe, P., primary, van Grotel, M., additional, Beverloo, H. B., additional, Lee, C., additional, Helgason, T., additional, Buijs-Gladdines, J., additional, Passier, M., additional, van Wering, E. R., additional, Veerman, A. J. P., additional, Kamps, W. A., additional, Meijerink, J. P. P., additional, and Pieters, R., additional

Published
2006
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42. Cognitive and Behavioral Development of 9-Year-Old Children After Maternal Cancer During Pregnancy: A Prospective Multicenter Cohort Study

Author

Indra A. Van Assche, Evangeline A. Huis in 't Veld, Kristel Van Calsteren, Mathilde van Gerwen, Jeroen Blommaert, Elyce Cardonick, Michael J. Halaska, Robert Fruscio, Monica Fumagalli, Jurgen Lemiere, Elisabeth M. van Dijk-Lokkart, Camilla Fontana, Harm van Tinteren, Jessie De Ridder, Martine van Grotel, Marry M. van den Heuvel-Eibrink, Lieven Lagae, Frédéric Amant, Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, CCA - Cancer biology and immunology, Amsterdam Reproduction & Development (AR&D), Van Assche, I, Huis In 'T Veld, E, Van Calsteren, K, Van Gerwen, M, Blommaert, J, Cardonick, E, Halaska, M, Fruscio, R, Fumagalli, M, Lemiere, J, Van Dijk-Lokkart, E, Fontana, C, Van Tinteren, H, De Ridder, J, Van Grotel, M, Van Den Heuvel-Eibrink, M, Lagae, L, and Amant, F

Subjects
Cancer Research, Oncology, Cancer in pregnancy
Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education. ispartof: JOURNAL OF CLINICAL ONCOLOGY vol:41 issue:8 pages:1527-+ ispartof: location:United States status: published

Published
2023

43. Long-term neurodevelopmental outcome after prenatal exposure to maternal hematological malignancies with or without cytotoxic treatment

Author

Elyce Cardonick, Martine van Grotel, Elisabeth M. van Dijk-Lokkart, Evangeline Huis in ‘t Veld, Mathilde van Gerwen, Robert Fruscio, Camilla Fontana, Charlotte Maggen, Frédéric Amant, Marry M. van den Heuvel-Eibrink, Vit Drochytek, Giovanna Scarfone, Kristel Van Calsteren, Obstetrics, van Gerwen, M, Huis In 't Veld, E, van Grotel, M, van den Heuvel-Eibrink, M, Van Calsteren, K, Maggen, C, Drochytek, V, Scarfone, G, Fontana, C, Fruscio, R, Cardonick, E, van Dijk-Lokkart, E, Amant, F, Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, Amsterdam Reproduction & Development (AR&D), Obstetrics and gynaecology, and CCA - Cancer Treatment and quality of life

Subjects
Male, Pediatrics, 0302 clinical medicine, hemic and lymphatic diseases, Developmental and Educational Psychology, Cognitive development, Early childhood, Child, Child development, 05 social sciences, Neuropsychology, Myeloid leukemia, Gestational age, cancer in pregnancy, intelligence, follow-up studies, 3. Good health, Neuropsychology and Physiological Psychology, Prenatal Exposure Delayed Effects, prenatal exposure delayed effect, Female, pregnancy, Psychology, Life Sciences & Biomedicine, 050104 developmental & child psychology, medicine.medical_specialty, Child, preschool, Clinical Neurology, follow-up studie, Mothers, Antineoplastic Agents, hematologic malignancie, Hematologic Neoplasms/complications, 03 medical and health sciences, prenatal exposure delayed effects, medicine, Humans, 0501 psychology and cognitive sciences, Pregnancy, Science & Technology, Infant, Newborn, Infant, Cancer, hematologic malignancies, medicine.disease, Lymphoma, Pediatrics, Perinatology and Child Health, Neurosciences & Neurology, 030217 neurology & neurosurgery
Abstract

Data on the long-term neurodevelopmental outcomes of children exposed to hematological maternal cancer with or without treatment during pregnancy are lacking. A total of 57 children, of whom 33 males and 24 females, prenatally exposed to hematological malignancies and its treatment, were invited for neuropsychological and physical examinations at 18 months, 36 months, 6, 9, 12, 15 and 18 years of age. Oncological, obstetrical, neonatal and follow-up data of these children were collected. Parents were asked to complete questionnaires on their child's general health, school performances, social situation, behavioral development, executive functioning, and if their child receives supportive care. Non-Hodgkin lymphoma was diagnosed in 35.1%, Hodgkin lymphoma in 28.1%, acute myeloid leukemia in 15.8%, chronic myeloid leukemia in 12.3%, and acute lymphoblastic leukemia in 8.8%. Cognitive development at a median age of 10.7 years was within the normal range. In subgroup analyses of children in early childhood, the gestational age at birth was correlated with the cognitive outcome at a median age of 1.7 years. Scores for language development, intelligence, attention, memory and behavior, as well as clinical neurological and general pediatric examinations were within normal ranges. In subgroup analyses, the need for supportive care in the child was associated with the loss of the mother. Prenatal exposure to hematological maternal malignancies with or without treatment did not affect the neurodevelopment of the child in the long term. Yet, caution is indicated and surveillance of the emotional development of the child is needed, especially when the mother is deceased to cancer. ispartof: CHILD NEUROPSYCHOLOGY vol:27 issue:6 pages:822-833 ispartof: location:England status: published

Published
2021

44. Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy

Author

Fedro A. Peccatori, Anna Babkova, Monica Fumagalli, Amarendra Gandhi, Michael J. Halaska, Charlotte Maggen, Ingrid A. Boere, Sofia Passera, Christianne A. R. Lok, Giovanna Scarfone, Magali Verheecke, Laurence Claes, Vít Drochýtek, Mathilde van Gerwen, Vincent Rigo, Martine van Grotel, Jorine de Haan, Martina Delle Marchette, Marry M. van den Heuvel-Eibrink, Gunnar Naulaers, Robert Fruscio, Tineke Vandenbroucke, Maria Lucia Boffi, Lieven Lagae, Mina Mhallem Gziri, Fabio Mosca, Margreet A. Veening, Jens-Uwe Voigt, Jana Dekrem, Luc Mertens, Kristel Van Calsteren, Christianne J.M. de Groot, Frédéric Amant, Vera E. R. A. Wolters, Els Witteveen, Odoardo Picciolini, Camilla Fontana, Jeroen Blommaert, Petronella B. Ottevanger, Renata Nacinovich, Frédéric Goffin, Carolina P. Schröder, Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, ARD - Amsterdam Reproduction and Development, Obstetrics, Vandenbroucke, T, Verheecke, M, van Gerwen, M, Van Calsteren, K, Halaska, M, Fumagalli, M, Fruscio, R, Gandhi, A, Veening, M, Lagae, L, Ottevanger, P, Voigt, J, de Haan, J, Gziri, M, Maggen, C, Mertens, L, Naulaers, G, Claes, L, Amant, F, Blommaert, J, Dekrem, J, Goffin, F, Rigo, V, Fontana, C, Mosca, F, Passera, S, Picciolini, O, Scarfone, G, Peccatori, F, Boffi, M, Delle Marchette, M, Nacinovich, R, Lok, C, Wolters, V, Boere, I, Witteveen, E, Schroder, C, de Groot, C, van Grotel, M, van den Heuvel-Eibrink, M, Babkova, A, Drochytek, V, Obstetrics and gynaecology, Pediatric surgery, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Erasmus MC other, Medical Oncology, and Pathology

Subjects
0301 basic medicine, Male, Pediatrics, Cancer Research, Memory/drug effects, Intelligence, Pregnancy Complications, Neoplastic/drug therapy, 0302 clinical medicine, Diastole, Pregnancy, Antineoplastic agents, Medicine, Childbirth, Fertility preservation, Prospective Studies, Child, Child development, Original Research, media_common, Cervical cancer, 0303 health sciences, Prenatal exposure delayed effect, Intelligence quotient, Obstetrics, High risk, Hematology, Prenatal exposure delayed effects, Chemotherapy regimen, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, Antineoplastic agent, Oncology, 030220 oncology & carcinogenesis, Female, Pregnancy Complications, Neoplastic, Cohort study, Adult, medicine.medical_specialty, Child, preschool, media_common.quotation_subject, Fertility, Follow-up studies, 03 medical and health sciences, Intelligence/drug effects, Breast cancer, SDG 3 - Good Health and Well-being, Memory, media_common.cataloged_instance, Humans, European union, Child Development/drug effects, 030304 developmental biology, Diastole/drug effects, Follow-up studie, business.industry, Cancer, Infant, Antineoplastic Agents/adverse effects, medicine.disease, Clinical trial, 030104 developmental biology, business
Abstract

Background Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q, Highlights • Cancer treatment including chemotherapy is possible during pregnancy. • Children are at risk for lower verbal IQ and visuospatial long-term memory scores. • Other cognitive functions and cardiac outcomes were normal at the age of 6 years. • We documented ototoxicity in three children exposed to cisplatin. • Follow-up until adulthood is recommended.

Published
2020

45. Prevalence of fungal DNAemia mediated by putatively non-pathogenic fungi in immunocompromised patients with febrile neutropenia: a prospective cohort study.

Author

Lucini C, Obrová K, Krickl I, Nogueira F, Kocmanová I, Herndlhofer S, Gleixner KV, Sperr WR, Frank T, Andrade N, Peters C, Engstler G, Dworzak M, Attarbaschi A, van Grotel M, van den Heuvel-Eibrink MM, Moiseev IS, Rogacheva Y, Zubarovskaya L, Zubarovskaya N, Pichler H, Lawitschka A, Koller E, Keil F, Mayer J, Weinbergerová B, Valent P, and Lion T

Subjects
Humans, Prospective Studies, Adult, Female, Male, Child, Adolescent, Middle Aged, Prevalence, Young Adult, Aged, Fungi isolation & purification, Fungi genetics, Hematologic Neoplasms complications, Child, Preschool, Hematopoietic Stem Cell Transplantation adverse effects, Invasive Fungal Infections epidemiology, Invasive Fungal Infections prevention & control, Invasive Fungal Infections etiology, Invasive Fungal Infections microbiology, Antifungal Agents therapeutic use, Immunocompromised Host, Febrile Neutropenia microbiology, DNA, Fungal analysis
Abstract

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies., (© 2024. The Author(s).)

Published
2024
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46. Long-term neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy: a multicentre cohort study of the International Network on Cancer, Infertility, and Pregnancy.

Author

Van Assche IA, Van Calsteren K, Lemiere J, Hohmann J, Blommaert J, Huis In 't Veld EA, Cardonick E, LeJeune C, Ottevanger NPB, Witteveen EPO, van Grotel M, van den Heuvel-Eibrink MM, Lagae L, Lambrecht M, and Amant F

Subjects
Humans, Female, Pregnancy, Adult, Adolescent, Child, Male, Child, Preschool, Young Adult, Infant, Retrospective Studies, Prospective Studies, Middle Aged, Radiotherapy adverse effects, Netherlands, United States epidemiology, Belgium epidemiology, Prenatal Exposure Delayed Effects, Neoplasms radiotherapy, Neoplasms psychology
Abstract

Background: The main data available on the safety of radiation during pregnancy originate from animal studies and from studies of survivors of atomic or nuclear disasters. The effect of radiotherapy to treat maternal cancer on fetal development is uncertain. This report presents a unique cohort and aims to determine the long-term neurocognitive, psychosocial and physical outcomes of offspring of mothers treated with radiotherapy during pregnancy., Methods: In this international, multicentre, mixed retrospective-prospective cohort study, we recruited participants between Aug 5, 2006, and Aug 24, 2023, aged between 1·5 and 46 years, at three referral centres in Belgium, the Netherlands, and the USA. Participants were eligible if they were born from mothers treated with radiotherapy during pregnancy. Fetal radiation doses were obtained from medical records and participants were followed up at predefined ages (1·5, 3, 6, 9, 12, 15, and 18 years) and 5-yearly in adulthood, based on age at enrolment, using a neurocognitive test battery (measuring intelligence, attention, and memory), parent-reported executive function and psychosocial questionnaires, and a medical assessment. Results were compared with test-specific normative data. Linear regression models investigated associations between radiotherapy factors (fetal radiation dose, gestational age at the start and end of radiotherapy, and radiotherapy duration) and outcomes., Findings: 68 maternal cases of radiotherapy during pregnancy were registered by the three participating centres, of which 61 resulted in a livebirth and were therefore eligible to participate in the child follow-up study. After excluding those who did not give consent, 43 participants born from 42 mothers treated with radiotherapy during pregnancy were included in the study (median age at first assessment 3 years [IQR 2-11]; median age at last assessment 12 years [9-18]; median number of assessments two [1-4]). 18 (42%) of the included participants were female and 25 (58%) male, and 37 (86%) were of White ethnicity. Mean neurocognitive outcomes of the entire cohort were within normal ranges. No associations were found with fetal radiation dose or timing of radiotherapy during pregnancy. Six (16%) of 38 participants with neurocognitive outcomes scored lower than one SD on at least one neurocognitive outcome, three (7%) reported chronic medical conditions (spasmophilia, spastic diplegia, and IgG deficiency), and three (7%) were diagnosed with attention-deficit hyperactivity disorder (of whom two scored lower on attention). Of ten (23%) participants with lower neurocognitive score(s), a chronic medical condition, or attention-deficit hyperactivity disorder, eight were born preterm. The remaining 33 (77%) participants showed no neurocognitive, psychosocial, or chronic physical problems., Interpretation: We show on average normal neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy. Differences in outcomes could not be explained by exposure to radiotherapy during pregnancy. These results suggest that extra-abdomino-pelvic radiotherapy exposure during pregnancy in general does not adversely affect outcomes of liveborn children. Further research with a larger sample is necessary to confirm these findings., Funding: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Research Foundation Flanders., Competing Interests: Declaration of interests FA is on the MiMARK advisory board for early detection of endometrial cancer and is Chair of the International Network on Cancer, Infertility, and Pregnancy of the European Society of Gynecologic Oncology, and of the Advisory Board on Cancer, Infertility and Pregnancy. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Published
2024
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47. Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab.

Author

Baarslag MA, Heimovaara JH, Borgers JSW, van Aerde KJ, Koenen HJPM, Smeets RL, Buitelaar PLM, Pluim D, Vos S, Henriet SSV, de Groot JWB, van Grotel M, Rosing H, Beijnen JH, Huitema ADR, Haanen JBAG, Amant F, and Gierenz N

Subjects
Humans, Infant, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Enteritis chemically induced, Enteritis diagnosis, Enteritis drug therapy, Enteritis immunology, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Antineoplastic Agents, Immunological therapeutic use, Failure to Thrive chemically induced, Failure to Thrive immunology, Diarrhea, Infantile chemically induced, Diarrhea, Infantile immunology, Enterocolitis chemically induced, Enterocolitis diagnosis, Enterocolitis drug therapy, Enterocolitis immunology, Programmed Cell Death 1 Receptor immunology, Neoplasms drug therapy, Immune Checkpoint Inhibitors administration & dosage, Immune Checkpoint Inhibitors adverse effects, Immune Checkpoint Inhibitors therapeutic use, Gastroenteritis chemically induced, Gastroenteritis diagnosis, Gastroenteritis drug therapy, Gastroenteritis immunology
Abstract

Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab., (Copyright © 2023 Massachusetts Medical Society.)

Published
2023
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48. Long-term nephrotoxicity in irradiated pediatric kidney tumor survivors: A systematic review.

Author

Dávila Fajardo R, Raymakers-Janssen P, van Grotel M, van Wösten-van Asperen RM, Terhaard CH, Lilien MR, van den Heuvel-Eibrink MM, and Janssens GO

Subjects
Humans, Child, Adult, Survivors, Glomerular Filtration Rate, Kidney, Kidney Neoplasms therapy
Abstract

Objective: Nephrotoxicity can occur as a side effect after treatment for kidney tumor in childhood. The use of radiotherapy (RT) has a potential additional effect., Methods: A systematic electronic literature search that combined childhood kidney cancer with different treatments and nephrotoxicity terms was performed in EMBASE. Studies were included based on the reporting of nephrotoxicity occurrence after treatment for kidney tumor during pediatric age, with 75% of participants being under the age of 25 years at the time of diagnosis, and having been treated with any type of kidney surgery, chemotherapy, and/or RT., Results: A pooled analysis did not show significant difference in estimated glomerular filtration rate between the group of patients who received RT compared with the group treated without RT (SMD -0.11 [95% CI -1.07-0.84] p = .733)., Conclusion: The current literature suggests that the use of RT does not have a significant impact on the decline of kidney function as independent factor., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Published
2023
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49. Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring.

Author

Gelineau NU, van Barneveld A, Samim A, Van Zogchel L, Lak N, Tas ML, Matser Y, Mavinkurve-Groothuis AMC, van Grotel M, Zsiros J, van Eijkelenburg NKA, Knops RRG, van Ewijk R, Langenberg KPS, Krijger R, Hiemcke-Jiwa LS, Van Paemel R, Cornelli L, De Preter K, De Wilde B, Van Der Schoot E, and Tytgat G

Abstract

Background and Aims: Solid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making., Methods: We performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Máxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring., Results: In three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making., Conclusion: This case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gelineau, van Barneveld, Samim, Van Zogchel, Lak, Tas, Matser, Mavinkurve-Groothuis, van Grotel, Zsiros, van Eijkelenburg, Knops, van Ewijk, Langenberg, Krijger, Hiemcke-Jiwa, Van Paemel, Cornelli, De Preter, De Wilde, Van Der Schoot and Tytgat.)

Published
2023
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50. Cognitive and Behavioral Development of 9-Year-Old Children After Maternal Cancer During Pregnancy: A Prospective Multicenter Cohort Study.

Author

Van Assche IA, Huis In 't Veld EA, Van Calsteren K, van Gerwen M, Blommaert J, Cardonick E, Halaska MJ, Fruscio R, Fumagalli M, Lemiere J, van Dijk-Lokkart EM, Fontana C, van Tinteren H, De Ridder J, van Grotel M, van den Heuvel-Eibrink MM, Lagae L, and Amant F

Subjects
Pregnancy, Female, Child, Humans, Infant, Newborn, Cohort Studies, Prospective Studies, Cognition, Prenatal Exposure Delayed Effects, Premature Birth, Neoplasms drug therapy
Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education.

Published
2023
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