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Cancers
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Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology
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Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 6 July 2025 | Viewed by 8124

Special Issue Editors

Dr. Jeong A Park

E-Mail Website
Guest Editor
Pediatric Hematology & Oncology, Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Republic of Korea
Interests: cancer immunotherapy; translational research; childhood cancer; sarcoma; bispecific antibody; T cell immunotherapy; leukemia; neuroblastoma; osteosarcoma
Dr. Jaume Mora

E-Mail Website
Guest Editor
Pediatric Oncologist, Scientific Director of the Pediatric Cancer Center Barcelona (PCCB), Barcelona, Spain
Interests: developmental tumors: neuroblastoma, Ewing sarcoma, Wilm's tumor, brain stem glioma; translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The last decade has seen a revolution in our understanding of the molecular and genetic basis of pediatric cancers. With this advance, molecular and genetic characterization is being integrated into cancer diagnosis, revealing subgroups of pediatric cancers with both prognostic and therapeutic relevance. This enables risk-adoptive therapy, focusing intensive therapy on the most aggressive cancers while refining the treatment for low-risk diseases, resulting in a significant reduction in serious long-term complications.

Cancer immunotherapy changed the prognosis of high-risk malignancies. By targeting cell surface antigens, immunotherapeutic strategies, such as monoclonal antibody, antibody-drug conjugates, T cell engaging bispecific antibody (BsAb), and chimeric antigen receptor (CAR) T cells, shifted the treatment paradigm of high-risk neuroblastoma and relapsed/refractory leukemia and lymphoma in pediatric patients. However, immunotherapy has not lived up to its promise in most pediatric solid tumors. How to define which tumors are more likely to respond to immunotherapy and how to activate the immune system via either cell-based or antibody-based strategies remain major challenges.

This Special Issue will highlight the advances in our understanding of pediatric malignancies and in the development of treatments including small-molecular-targeted therapies, BsAb, CART, transplant, radioisotope or drug conjugates, radiotherapy, and photoimmunotherapy and address current challenges and future prospects for a more personalized therapy for pediatric cancer patients.

Dr. Jeong A Park
Dr. Jaume Mora
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibody-drug conjugate
  • bispecific antibody
  • cancer predisposition
  • CAR T cell
  • immunotherapy
  • leukemia
  • monoclonal antibody
  • neuroblastoma
  • pediatric cancer
  • photoimmunotherapy
  • precision medicine
  • sarcoma
  • translational research
  • tyrosine kinase inhibitor

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Published Papers (6 papers)

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Research

11 pages, 1976 KiB  
Article
Renal Autotransplantation for Resection of Bilateral Nephroblastoma and High-Risk Neuroblastoma in Children
by Benjamin F. B. Mayer, Matthias C. Schunn, Cristian Urla, Lea Weinpert, Ilias Tsiflikas, Martin Ebinger, Frank Fideler, Felix Neunhoeffer, Marcus Weitz, Silvio Nadalin, Steven W. Warmann and Jörg Fuchs
Cancers 2025, 17(6), 989; https://doi.org/10.3390/cancers17060989 - 15 Mar 2025
Viewed by 237
Abstract
Background/Objectives: In bilateral nephroblastoma and high-risk neuroblastoma in children with extensive tumor involvement of the renal vessels or pedicle, complete tumor resection with preservation of healthy renal tissue is not feasible with in situ nephron-sparing surgery or vascular replacement. The aim of this [...] Read more.
Background/Objectives: In bilateral nephroblastoma and high-risk neuroblastoma in children with extensive tumor involvement of the renal vessels or pedicle, complete tumor resection with preservation of healthy renal tissue is not feasible with in situ nephron-sparing surgery or vascular replacement. The aim of this study was to present our experience with ante situ tumor resection and renal autotransplantation (RATX) in these children. Methods: A retrospective study of children with bilateral nephroblastoma and high-risk neuroblastoma who underwent tumor resection and RATX at an international referral center for pediatric surgical oncology between 2006 and 2024 was performed. RATX was performed by transection of renal vessels, ante situ mobilization, and perfusion of the kidney with Bretschneider’s solution. Tumor resection was performed on a bloodless kidney under hypothermia. Results: Ante situ tumor resection and RATX were performed at a median age of 36 months (range 13–62) in 4 children with bilateral nephroblastoma and 4 children with high-risk neuroblastoma. Complete tumor resection was achieved in all patients. One patient with neuroblastoma died of sepsis after 14 days. The 7 surviving patients showed no evidence of disease and normal to slightly decreased glomerulofiltration rates at a median follow-up of 20 months (range 3–155). Limitations include the retrospective design, small sample size, and heterogeneity of the study population due to very rare indication. Conclusions: Ante situ tumor resection and RATX is a feasible surgical approach for children with multifocal bilateral nephroblastoma or high-risk neuroblastoma who are ineligible for in situ nephron-sparing surgery or vascular reconstruction. Full article
(This article belongs to the Special Issue Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology)
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14 pages, 570 KiB  
Article
Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study
by Tim Flaadt, Jonas Rehm, Thorsten Simon, Barbara Hero, Ruth L. Ladenstein, Holger N. Lode, Desiree Grabow, Sandra Nolte, Roman Crazzolara, Johann Greil, Martin Ebinger, Michael Abele, Ursula Holzer, Michaela Döring, Johannes H. Schulte, Peter Bader, Paul-Gerhardt Schlegel, Matthias Eyrich, Peter Lang, Thomas Klingebiel and Rupert Handgretingeradd Show full author list remove Hide full author list
Cancers 2025, 17(1), 149; https://doi.org/10.3390/cancers17010149 - 5 Jan 2025
Viewed by 1451
Abstract
Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective [...] Read more.
Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these. Patients and Methods: Between 1991 and 2002, 65 children received a multimodal treatment, including ch14.18/SP2/0, for primary HR-NB. All received chemotherapy according to the NB90/NB97 trial, 51 received high-dose chemotherapy, and all received ch14.18/SP2/0 treatment. We analyzed the long-term sequelae and HRQoL (EORTC QLQ-C30), and evaluated overall and event-free survival (OS/EFS). Results: Twenty-five survivors were evaluated for HRQoL and long-term effects. All reported long-term sequelae, including ototoxicity in 16/25 (64%), cardiac toxicity in 6/25 (24%), and endocrine toxicity in 19/25 (76%) patients. Chronic diarrhea was reported in 20% of female patients. Seven patients developed autoimmune diseases. HRQoL scores were better across multiple scales than those of the matched German general population. Twenty-five-year OS and EFS were 50.8% (95% confidence interval: 31–55) and 43% (30.1–55.3), with 33 (50.8%) long-term survivors. Thirty-two patients died: 28 (43.1%) because of progression/relapse and 4 (6.2%) because of secondary neoplasms. Conclusions: Multimodal treatment, including ch14.18/SP2/0, can achieve long-term survival in HR-NB patients, with a substantial proportion of survivors reporting better HRQoL compared to the general population. All patients reported long-term side effects mostly attributable to chemotherapy and radiotherapy. The relatively high prevalence of autoimmune diseases and persistent diarrhea warrants additional longitudinal research on individuals treated with anti-GD2 antibodies. Full article
(This article belongs to the Special Issue Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology)
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18 pages, 4490 KiB  
Article
Is Serum Ferritin a Predictor of Blood Transfusions Outcome and Survival in Childhood Lymphomas and Solid Tumors?
by Małgorzata Sawicka-Żukowska, Anna Krętowska-Grunwald, Magdalena Topczewska, Maryna Krawczuk-Rybak and Kamil Grubczak
Cancers 2024, 16(22), 3742; https://doi.org/10.3390/cancers16223742 - 6 Nov 2024
Cited by 1 | Viewed by 1133
Abstract
Packed red blood cell (PRBC) transfusions are an important part of supportive treatment in oncology; however, when used frequently, they can be a result of transfusion-related iron overload. The aim of the study was to evaluate the role of ferritin as a non-specific [...] Read more.
Packed red blood cell (PRBC) transfusions are an important part of supportive treatment in oncology; however, when used frequently, they can be a result of transfusion-related iron overload. The aim of the study was to evaluate the role of ferritin as a non-specific marker of neoplastic growth and transfusion-related iron overload in children with lymphomas and solid tumors. We performed a longitudinal analysis of PRBC transfusions and changes in ferritin concentrations during oncological treatment of 88 children with lymphomas and solid tumors. A ferritin concentration above 500 ng/mL was diagnosed in 14.77% of patients at the moment of admission and 18.18% at the end of treatment. No differences were shown in serum ferritin in the context of tumor type-, sex-, and transfusion-related parameters. Those above the age of 10 demonstrated higher ferritin concentrations compared to subjects younger than 5 years of age. In addition, those over than 10 years old or above 30 kg in weight showed a tendency for better survival. All tested patients demonstrated highly significant correlations between ferritin at the 15th month of treatment or after therapy discontinuation and transfusion-related parameters. Interestingly, ferritin levels were found to lower back to the values before therapy shortly after its discontinuation. Transfusion parameters and ferritin levels had no influence on the survival of the studied cancer patients. Full article
(This article belongs to the Special Issue Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology)
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12 pages, 1434 KiB  
Article
Disease Control and Toxicity Outcomes after Stereotactic Ablative Radiation Therapy for Recurrent and/or Metastatic Cancers in Young-Adult and Pediatric Patients
by Rituraj Upadhyay, Brett Klamer, Jennifer Matsui, Vikram B. Chakravarthy, Thomas Scharschmidt, Nicholas Yeager, Bhuvana A. Setty, Timothy P. Cripe, Ryan D. Roberts, Jennifer H. Aldrink, Raj Singh, Raju R. Raval, Joshua D. Palmer and Sujith Baliga
Cancers 2024, 16(11), 2090; https://doi.org/10.3390/cancers16112090 - 30 May 2024
Cited by 2 | Viewed by 1221
Abstract
Background: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. Methods: This [...] Read more.
Background: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. Methods: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan–Meier estimates in R v4.2.3. Results: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14–23 y) and the median follow-up was 18.1 months (IQR: 7.7–29.1). The median SABR dose was 30 Gy (IQR 25–35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). Conclusions: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field. Full article
(This article belongs to the Special Issue Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology)
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13 pages, 1013 KiB  
Article
Prevalence and Treatment Outcomes of Childhood Acute Lymphoblastic Leukemia in Kosovo
by Flaka Pasha, Dunja Urbančič, Rufadie Maxhuni, Shaip Krasniqi, Violeta Grajçevci Uka and Irena Mlinarič-Raščan
Cancers 2024, 16(11), 1988; https://doi.org/10.3390/cancers16111988 - 23 May 2024
Viewed by 1712
Abstract
Advances in research, including novel biomarker identification and patient stratification, have significantly improved the therapy for childhood acute lymphoblastic leukemia (ALL), though access to improved healthcare services varies across geographical regions. In an effort to evaluate the advances in therapeutic approaches, we performed [...] Read more.
Advances in research, including novel biomarker identification and patient stratification, have significantly improved the therapy for childhood acute lymphoblastic leukemia (ALL), though access to improved healthcare services varies across geographical regions. In an effort to evaluate the advances in therapeutic approaches, we performed a retrospective analysis of childhood ALL in Kosovo. Our retrospective analysis included 225 cases diagnosed between 2008 and 2023, representing 52% of 429 diagnosed childhood cancers. The average annual incidence was 14, with a median age diagnosis of seven years, and a male predominance (59.54%). Patients were categorized into risk groups, with the majority (43%) in the standard-risk category. We identified five different treatment protocols for this study period. Over 61% of patients achieved remission after the first chemotherapy cycle and we observed a 20% mortality rate. Survival analysis showed that 55% and 40% of patients achieved 2-year and 5-year event-free survival (EFS), respectively, with significant differences across risk groups. Treatment advancements significantly correlated with improved survival rates, achieving a 5-year overall survival (OS) of 88% in the currently used standardized AIEOP-BFM-2009 protocol. Our study emphasizes the need for continued research and customized care strategies to enhance clinical outcomes. Full article
(This article belongs to the Special Issue Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology)
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13 pages, 578 KiB  
Article
Multilevel Social Determinants of Patient-Reported Outcomes in Young Survivors of Childhood Cancer
by Jin-ah Sim, Madeline R. Horan, Jaesung Choi, Deo Kumar Srivastava, Gregory T. Armstrong, Kirsten K. Ness, Melissa M. Hudson and I-Chan Huang
Cancers 2024, 16(9), 1661; https://doi.org/10.3390/cancers16091661 - 25 Apr 2024
Viewed by 1562
Abstract
In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving [...] Read more.
In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving treatment at St. Jude Children’s Research Hospital who were <18 years of age during follow-up from 2017 to 2018 and their primary caregivers. Social determinants included family factors (caregiver-reported PROs, family dynamics) and county-level deprivation (socioeconomic status, physical environment via the County Health Rankings & Roadmaps). PROMIS measures assessed survivors’ and caregivers’ PROs. General linear regression tested associations of social determinants with survivors’ PROs. We found that caregivers’ higher anxiety was significantly associated with survivors’ poorer depression, stress, fatigue, sleep issues, and reduced positive affect (p < 0.05); caregivers’ sleep disturbances were significantly associated with lower mobility in survivors (p < 0.05). Family conflicts were associated with survivors’ sleep problems (p < 0.05). Residing in socioeconomically deprived areas was significantly associated with survivors’ poorer sleep quality (p < 0.05), while higher physical environment deprivation was associated with survivors’ higher psychological stress and fatigue and lower positive affect and mobility (p < 0.05). Parental, family, and neighborhood factors are critical influences on young survivors’ quality of life and well-being and represent new intervention targets. Full article
(This article belongs to the Special Issue Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology)
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