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Cancers
Special Issues
Updates on Management and Clinical Trials in Pediatric Oncology
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Updates on Management and Clinical Trials in Pediatric Oncology

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

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 11140

Special Issue Editors

Dr. Atsushi Makimoto

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Guest Editor
Department of Laboratory Medicine, Tokyo Metropolitan Children’s Medical Center, Fuchu, Japan
Interests: pediatric oncology; clinical trial; developmental therapeutics
Dr. Yasuhiro Okamoto

E-Mail Website
Guest Editor
Department of Pediatrics, Kagoshima University School of Medicine, Kagoshima, Japan
Interests: pediatric oncology; pediatric acute lymphoblastic leukemia; stem cell transplantation
Dr. Yuki Yuza

E-Mail Website
Guest Editor
Department of Hematology/Oncology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan
Interests: pediatric oncology; pediatric hematology; stem cell transplantation

Special Issue Information

Dear Colleagues,

Pediatric oncology is one of the most successful fields in oncology on the basis of the following two facts. One is the achievement of excellent survival outcomes in recent decades. Another is the extremely high enrollment ratio in clinical trials, which are systematically designed from phase 1 for testing novel therapeutics in children with refractory cancers to phase 3 for providing “standard” or “modified standard” multidisciplinary treatment for children with newly diagnosed cancers. These two continue actively interacting to develop a cutting-edge treatment strategy with high efficacy and low toxicity in each disease entity.

On the other hand, it is too difficult to define a “standard” treatment” for each specific disease entity because numerous medicines and devices are being invented so fast and efficacy and safety outcome in each disease is continuously improving with a better-designed treatment strategy. Such a condition might cause difficulty to distinguish the best practice from the newest treatment in the trial. A pediatric oncologist should be familiar not only with the newest information of clinical trials but also a series of “standard treatment” for each disease entity of pediatric cancers such as leukemia, lymphoma, neuroblastoma, brain tumor, Wilms tumor, liver tumor, rhabdomyosarcoma, Ewing sarcoma family of tumor, osteosarcoma, and so forth.

In order to know the range of “standard” in treatment, a historical perspective of treatment development for each cancer is inevitable. Based on that perspective, the roles of a novel therapeutic agent or devices can be objectively discussed. In this Special Issue, therefore, the editors would like to gather disease-specific reviews which describes what is “standard” treatment for the specific cancer, preferably with well investigated historical perspective. At the same time, we are pleased to invite original research articles which describes therapeutic development of promising novel medicines or devices which are expected to change the future “standard” therapy for pediatric oncology. Articles describes design or planning of clinical trials for such novel therapeutics are also welcome if they elaborate the basic research data which could rationalize the design of clinical trials.

Dr. Atsushi Makimoto
Dr. Yasuhiro Okamoto
Dr. Yuki Yuza
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

  • standard treatment
  • developmental therapeutics
  • historical perspective
  • pediatric oncology
  • leukemia
  • lymphoma
  • neuroblastoma
  • brain tumor
  • wilms tumor
  • liver tumor
  • rhabdomyosarcoma
  • ewing sarcoma family of tumor
  • osteosarcoma
  • rare cancers in childhood

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Published Papers (5 papers)

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Research

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13 pages, 1126 KiB  
Article
Late Changes in Renal Volume and Function after Proton Beam Therapy in Pediatric and Adult Patients: Children Show Significant Renal Atrophy but Deterioration of Renal Function Is Minimal in the Long-Term in Both Groups
by Yinuo Li, Masashi Mizumoto, Hazuki Nitta, Hiroko Fukushima, Ryoko Suzuki, Sho Hosaka, Yuni Yamaki, Motohiro Murakami, Keiichiro Baba, Masatoshi Nakamura, Toshiki Ishida, Hirokazu Makishima, Takashi Iizumi, Takashi Saito, Haruko Numajiri, Kei Nakai, Satoshi Kamizawa, Chie Kawano, Yoshiko Oshiro and Hideyuki Sakurai
Cancers 2024, 16(9), 1634; https://doi.org/10.3390/cancers16091634 - 24 Apr 2024
Cited by 2 | Viewed by 979
Abstract
To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1–14 years old) and 12 [...] Read more.
To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1–14 years old) and 12 adults (51–80 years old). Kidney volumes were measured from CT or MRI images during follow-up. Dose-volume histograms were calculated using a treatment planning system. In children, the median volume changes for the irradiated and control kidneys were −5.58 (−94.95 to +4.79) and +14.92 (−19.45 to +53.89) mL, respectively, with a relative volume change of −28.38 (−119.45 to −3.87) mL for the irradiated kidneys. For adults, these volume changes were −22.43 (−68.7 to −3.48) and −21.56 (−57.26 to −0.16) mL, respectively, with a relative volume change of −5.83 (−28.85 to +30.92) mL. Control kidneys in children exhibited a marked increase in size, while those in adults showed slight volumetric loss. The percentage of irradiated volume receiving 10 Gy (RBE) (V10) and 20 Gy (RBE) (V20) were significantly negatively associated with the relative volume change per year, especially in children. The CKD stage based on eGFR for all patients ranged from 1 to 3 and no cases with severe renal dysfunction were found before or after PBT. Late effects on the kidneys after PBT vary among age groups. Children are more susceptible than adults to significant renal atrophy after PBT. V10 and V20 might serve as predictors of the degree of renal atrophy after PBT, especially in children. PBT has a minimal impact on deterioration of renal function in both children and adults. Full article
(This article belongs to the Special Issue Updates on Management and Clinical Trials in Pediatric Oncology)
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16 pages, 4342 KiB  
Article
Impact of Time to Surgery on Outcome in Wilms Tumor Treated with Preoperative Chemotherapy
by Clemens-Magnus Meier, Rhoikos Furtwängler, Marvin Mergen, Nils Welter, Patrick Melchior, Jens-Peter Schenk, Christian Vokuhl, Leo Kager, Sabine Kroiss-Benninger, Stefan Wagenpfeil and Norbert Graf
Cancers 2023, 15(5), 1494; https://doi.org/10.3390/cancers15051494 - 27 Feb 2023
Cited by 1 | Viewed by 1901
Abstract
(1) Background: Wilms tumor (WT) treated preoperatively is cured in over 90% of cases. However, how long preoperative chemotherapy can be given is unknown. (2) Methods: 2561/3030 patients with WT (age < 18 years) treated between 1989 and 2022 according to SIOP-9/GPOH, SIOP-93-01/GPOH, [...] Read more.
(1) Background: Wilms tumor (WT) treated preoperatively is cured in over 90% of cases. However, how long preoperative chemotherapy can be given is unknown. (2) Methods: 2561/3030 patients with WT (age < 18 years) treated between 1989 and 2022 according to SIOP-9/GPOH, SIOP-93-01/GPOH, and SIOP-2001/GPOH are retrospectively analyzed to assess the risk of time to surgery (TTS) for relapse-free survival (RFS) and overall survival (OS). (3) Results: TTS was calculated for all surgeries, with the mean being 39 days (38.5 ± 12.5) for unilateral tumors (UWT) and 70 days (69.9 ± 32.7) for bilateral disease (BWT). Relapse occurred in 347 patients, of which 63 (2.5%) were local, 199 (7.8%) were metastatic, and 85 (3.3%) were combined. Moreover, 184 patients (7.2%) died, 152 (5.9%) due to tumor progression. In UWT, recurrences and mortality are independent of TTS. For BWT without metastases at diagnosis, the incidence of recurrence is less than 18% up to 120 days and increases to 29% after 120 days, and to 60% after 150 days. The risk of relapse (Hazard Ratio) adjusted for age, local stage, and histological risk group increases to 2.87 after 120 days (CI 1.19–7.95, p = 0.022) and to 4.62 after 150 days (CI 1.17–18.26, p = 0.029). In metastatic BWT, no influence of TTS is detected. (4) Conclusions: The length of preoperative chemotherapy has no negative impact on RFS or OS in UWT. In BWT without metastatic disease, surgery should be performed before day 120, as the risk of recurrence increases significantly thereafter. Full article
(This article belongs to the Special Issue Updates on Management and Clinical Trials in Pediatric Oncology)
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Review

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14 pages, 696 KiB  
Review
Human Leukocyte Antigen–Haploidentical Haematopoietic Stem Cell Transplantation Using Post-Transplant Cyclophosphamide for Paediatric Haematological Malignancies
by Takuro Nishikawa
Cancers 2024, 16(3), 600; https://doi.org/10.3390/cancers16030600 - 31 Jan 2024
Cited by 2 | Viewed by 1365
Abstract
The use of human leukocyte antigen (HLA)–haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCY), which markedly reduces the risk of graft-versus-host disease, has rapidly increased worldwide, even in children. It was initially developed for post-transplant relapse or non-remission at transplant for [...] Read more.
The use of human leukocyte antigen (HLA)–haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCY), which markedly reduces the risk of graft-versus-host disease, has rapidly increased worldwide, even in children. It was initially developed for post-transplant relapse or non-remission at transplant for patients with high-risk haematologic malignancies. However, this strategy is currently used more frequently for standard-risk, transplant-eligible paediatric haematological malignancies. It has recently been recognised in adults that the transplant outcomes after PTCY-based HLA–haploidentical HSCT are comparable with those achieved after HLA-matched HSCT. Therefore, even in children, parental donors who are HLA–haploidentical donors and cord blood are currently considered the next donor candidates when an HLA-matched related or unrelated donor is unavailable. This review addresses the current status of the use of haplo-HSCT with PTCY for paediatric haematologic malignancies and future directions for donor selection (sex, age, ABO blood type, and HLA disparity), donor source, the dose of infused CD34+ cells, optimal conditioning, the concomitant graft-versus-host disease prophylaxis other than PTCY, and the pharmacokinetic study of CY and CY metabolites. These aspects present key solutions for further improvements in the outcomes of haplo-HSCT with PTCY for paediatric haematological malignancies. Full article
(This article belongs to the Special Issue Updates on Management and Clinical Trials in Pediatric Oncology)
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16 pages, 1467 KiB  
Review
Retinoid Therapy for Neuroblastoma: Historical Overview, Regulatory Challenges, and Prospects
by Atsushi Makimoto, Hiroyuki Fujisaki, Kimikazu Matsumoto, Yoshiyuki Takahashi, Yuko Cho, Yoshihiko Morikawa, Yuki Yuza, Tatsuro Tajiri and Tomoko Iehara
Cancers 2024, 16(3), 544; https://doi.org/10.3390/cancers16030544 - 26 Jan 2024
Cited by 5 | Viewed by 2802
Abstract
Retinoids are vitamin A derivatives and include trans-retinoic acid, isotretinoin, tamibarotene, and bexarotene, all of which are currently available for clinical use. The clinical development of retinoid therapy for neuroblastoma has a history spanning more than four decades. The most promising agent is [...] Read more.
Retinoids are vitamin A derivatives and include trans-retinoic acid, isotretinoin, tamibarotene, and bexarotene, all of which are currently available for clinical use. The clinical development of retinoid therapy for neuroblastoma has a history spanning more than four decades. The most promising agent is isotretinoin, which can contribute to improving event-free survival in patients with high-risk neuroblastoma by approximately 10% when administered over six months as maintenance therapy. Although isotretinoin is regarded as an essential component in the standard clinical management of high-risk neuroblastoma, its use for this purpose in the US and EU is off-label. To promote isotretinoin use in Japan as a treatment for neuroblastoma, our clinical research team is planning to launch an investigator-initiated, registration-directed clinical trial. The present review article discusses the basic science behind retinoid therapy, pre-clinical/clinical evidence on neuroblastoma, the concept of the proposed clinical trial, and prospects for this therapy. Full article
(This article belongs to the Special Issue Updates on Management and Clinical Trials in Pediatric Oncology)
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21 pages, 1328 KiB  
Review
Risk-Stratified Therapy for Pediatric Acute Myeloid Leukemia
by Daisuke Tomizawa and Shin-Ichi Tsujimoto
Cancers 2023, 15(16), 4171; https://doi.org/10.3390/cancers15164171 - 18 Aug 2023
Cited by 6 | Viewed by 2886
Abstract
Acute Myeloid Leukemia (AML) is the second most common type of leukemia in children. Recent advances in high-resolution genomic profiling techniques have uncovered the mutational landscape of pediatric AML as distinct from adult AML. Overall survival rates of children with AML have dramatically [...] Read more.
Acute Myeloid Leukemia (AML) is the second most common type of leukemia in children. Recent advances in high-resolution genomic profiling techniques have uncovered the mutational landscape of pediatric AML as distinct from adult AML. Overall survival rates of children with AML have dramatically improved in the past 40 years, currently reaching 70% to 80% in developed countries. This was accomplished by the intensification of conventional chemotherapy, improvement in risk stratification using leukemia-specific cytogenetics/molecular genetics and measurable residual disease, appropriate use of allogeneic hematopoietic stem cell transplantation, and improvement in supportive care. However, the principle therapeutic approach for pediatric AML has not changed substantially for decades and improvement in event-free survival is rather modest. Further refinements in risk stratification and the introduction of emerging novel therapies to contemporary therapy, through international collaboration, would be key solutions for further improvements in outcomes. Full article
(This article belongs to the Special Issue Updates on Management and Clinical Trials in Pediatric Oncology)
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