A pivotal encounter during medical school inspired my aspiration to pursue pediatric oncology, especially long-term follow-up care. During my residency, I observed a comprehensive long-term follow-up system for childhood cancer survivors in the United States, which motivated me to explore ways to implement a similarly structured approach in Japan. This journey led me through a series of fortunate encounters, from the bedside to the data center.

Thereafter, I have been involved in establishing a long-term follow-up system. Currently, I focus on implementing the system, expanding its applications, and fostering international collaborations. Although it remains a work-in-progress, I recognize that each critical turning point in my career was marked by invaluable encounters with distinguished pioneers in pediatric oncology. These experiences have formed a coherent trajectory that reinforced my belief in the significance of these connections through the will.

Opportunities will present themselves to anyone aware of dreams and act with a commitment to achieve them. It would be essential to be prepared and accept opportunities once they appear. In doing so, making conscious efforts to enhance one’s uniqueness to become “the only one” would be helpful. Above all, cherishing and being thankful to the individuals around you would come first.

Although my career path has been unique, I hope that my experiences and thoughts will be of some use to female and/or young doctors as they proceed with their future careers.

I present a summary of the application of pediatric protocols for the treatment of adult patients with acute lymphoblastic leukemia (ALL) in the Japan Adult Leukemia Study Group (JALSG), including the process leading to collaborative clinical research with the Japanese Pediatric Leukemia Study Group (JPLSG) and the steps taken to initiate collaborative studies. Historically, the 5-year survival rate for adult ALL has remained low at 30–40%. In response, we incorporated high-dose methotrexate into adult-type ALL treatment for patients aged 25 years and older, increasing the 5-year overall survival (OS) rate to 64%. Patients younger than 25 years were treated with a pediatric high-risk ALL regimen, achieving a 5-year OS rate of 73% (ALL202). Subsequently, in the ALL213 study, a pediatric-type protocol was adopted, resulting in a 3-year OS rate of 69.3% among patients with Philadelphia chromosome-negative B-cell ALL. Among patients with T-cell acute lymphoblastic leukemia younger than 25 years, collaborative research with the JPLSG yielded a 3-year OS rate of 93.4% in the 15–24-year age group. Subsequent clinical studies were planned as a fully integrated collaboration between JALSG and JPLSG; the first JPLSG–JALSG Joint ALL meeting was held in June 2017. Despite differences in perspective between pediatric and adult hematologists, both groups prioritized safer and more effective treatment for patients with ALL. This shared commitment has facilitated the progress from protocol development to clinical trial initiation. The ongoing ALL-B19 and ALL-T19 trials have passed the midpoint and remain on track.

Targeted therapies has attracted attention as next-generation treatment strategies for pediatric acute lymphoblastic leukemia (ALL). One of such approach is molecular-targeted therapy, which directly inhibits aberrant molecules derived from genomic alterations that underlie leukemogenesis. For example, the introduction of tyrosine kinase inhibitors (TKIs) has markedly improved the outcomes in Philadelphia chromosome-positive ALL (Ph+ALL), and their application has recently been extended to Ph-like ALL. Additionally, menin inhibitors for KMT2A-rearranged ALL and ALK inhibitors for hematological malignancies harboring ALK fusion genes have been promising. As comprehensive genomic profiling has become increasingly integrated into clinical practice and drug development continues to advance, the selection of appropriate targeted agents may expand. Immunotherapeutic strategies targeting surface antigens have been used to treat relapsed or refractory ALL. Chimeric antigen receptor T-cells and antibody-drug conjugates reshape the therapeutic landscape. Furthermore, the bispecific T-cell engager blinatumomab has demonstrated efficacy in relapsed or refractory disease and is being evaluated in clinical trials for use in frontline treatment. In Ph+ALL, strategies incorporating TKIs and immunotherapies, such as blinatumomab, may offer an alternative to conventional chemotherapy. Although challenges remain, including the identification of risk stratification factors in targeted therapy and elucidation of the tumor immune microenvironment, the continued integration of these approaches may drive substantial progress in the treatment of pediatric ALL.

In 2009, Hill et al. reported that familial pleuropulmonary blastoma was associated with DICER1 abnormalities. In addition to pleuropulmonary blastomas, various benign and malignant tumors associated with DICER1 pathogenic variants have been recognized, predominantly affecting children and young adults, including thyroid cancer, pediatric cystic nephroma, anaplastic sarcoma of the kidney (ASK), and nasal chondromesenchymal hamartoma. Although DICER1-related tumors can arise in multiple organs and display diverse histological features, they often share several characteristic patterns: (1) a component of poorly differentiated tumor cells that resemble the histology of fetal developmental stages, (2) variously differentiated components such as rhabdomyoblasts, immature cartilage, and neuroectodermal components, (3) tumors composed of cystic components or a mixture of cystic and solid components, and (4) histopathological and molecular biological evidence of a hyperplasia or precancerous stage to an invasive sarcoma. The term “DICER1-associated sarcomas” has been proposed for tumors associated with DICER1 pathogenic variants. The diagnosis of DICER1-associated tumors based on characteristic histological findings led to appropriate genetic testing and patient counseling.

Various cancers develop during childhood, and hematological malignancies, brain tumors, malignant bone tumors, and soft tissue sarcomas are common. Malignant epithelial neoplasms (adult-type carcinomas) are most common during adulthood and extremely rare in childhood. However, some adult-type carcinomas can occur during childhood. This study included patients aged < 15 years with adult-type carcinomas. We identified papillary thyroid carcinoma, medullary thyroid carcinoma, adrenocortical carcinoma, colorectal carcinoma, fibrolamellar variant of hepatocellular carcinoma (FLHCC), pancreatic acinar cell carcinoma, and mucoepidermoid carcinoma of the lungs. Medullary thyroid carcinoma was detected during surveillance for multiple endocrine neoplasia type 2. Li-Fraumeni syndrome manifests with the development of adrenocortical carcinoma. A case of colorectal carcinoma was detected during surveillance for constitutional mismatch repair deficiency syndrome. Children may develop tumors with the same histology as adults. However, the background of such tumors is often different from that of adults; for instance, in relation to hereditary tumors. Notably, several rare adult-type carcinomas, including FLHCC, acinar cell carcinoma, and mucoepidermoid carcinoma, are more common in children. This article presents actual cases of adult-type carcinomas in children and outlines their characteristics and differences from adult-onset carcinomas.

Total body irradiation (TBI) and total lymphoid/thoraco-abdominal irradiation (TLI/TAI) are standard treatments performed before hematopoietic cell transplantation. At our institution, TBI at 200 MU/min was initiated in January 2019, and the outcomes of pediatric patients treated with TBI or TLI/TAI were retrospectively analyzed. Twenty-nine patients aged ≤ 19 years who underwent TBI or TLI/TAI as a pretreatment for allogeneic hematopoietic cell transplantation at our institution between January 2019 and April 2024 were included. The patients’ median age during irradiation was 109 months. Thirteen patients underwent myeloablative conditioning with TBI of 12 Gy/6 fr, and 16 patients underwent reduced-intensity conditioning with TBI in 12 cases (2–6 Gy/1–3 fr) and TLI/TAI in four cases (3 Gy/1 fr). The median follow-up period was 24.0 months. Three patients died (two died from worsening respiratory status), two patients recovered autologous hematopoiesis, and one patient experienced relapse of the primary disease. We observed 14 cases of grade 2–4 acute graft-versus-host disease (GVHD) and three cases of chronic GVHD. Additionally, one case each of nephrotic syndrome, hyperuricemia, and treatment-related secondary malignant disease were found to be late effects of CTCAE ver.5 grade ≥ 3. Although the follow-up period was short and backgrounds and treatments varied, the results were considered acceptable. Strategies to reduce the impact on the organs at risk while maintaining tumor control and viability, are warranted.

Total-body irradiation varies according to the irradiation method, irradiation dose, dose fractionation, and dose rate at each facility. In 2015, a nationwide survey of total-body irradiation was conducted by the Japanese Radiation Oncology Study Group. A questionnaire survey was conducted with 82 body irradiation facilities that responded to a structural survey of the Japanese Society of Radiation Oncology. For myeloablative transplantation, the most common irradiation method was the long source-to-skin distance method at 64 facilities (82.9%) and the moving couch method at eight facilities (17.1%); none of the facilities responded that they used the sweeping beam method or helical tomotherapy. The most common fractionation dose was 12 Gy/six fractions/three days at 52 facilities (63.4%). Regarding shielding, the most common practice was shielding the lungs and lenses in 47 facilities (57.3%). For non-myeloablative transplantation, the most common dose fractions were 4 Gy/two fractions/1–2 days (57.7%) and 2 Gy/fraction/day (28.2%). Besides the lungs (43.6%) and eyes (50.0%), the ovaries (14.1%), thyroid gland (6.4%), and testicles (16.7%) were shielded.

Recently, several guidelines for total-body irradiation have been published overseas, and high-precision total-body irradiation treatments have been applied clinically. There are plans to create clinical guidelines in Japan, and total-body irradiation methods may become more standardized eventually; hence, further development is expected.

Individuals with pathogenic DICER1 germline variants are predisposed to developing tumors in various organs, including pleuropulmonary blastoma, as part of DICER1 syndrome. A 6-month-old girl was referred to our hospital with an abdominal mass and feeding difficulties. Physical examination revealed a firm mass on the left side of the abdomen. Imaging demonstrated a multifocal, septated tumor in the left kidney. The patient underwent a total left nephrectomy, and histopathological analysis confirmed the diagnosis of cystic nephroma. Additionally, imaging at the time of diagnosis detected a nodule in the left lobe of the thyroid gland. Genetic testing identified a pathogenic DICER1 germline variant, confirming the diagnosis of DICER1 syndrome. No additional DICER1-associated tumors were detected during the 3 years of postoperative follow-up. It is noteworthy that thyroid tumors in individuals with DICER1 syndrome typically manifest after the age of 10, making the concurrent presence of a cystic nephroma and a thyroid nodule in infancy an uncommon finding. Close monitoring is essential to assess thyroid nodule growth and the potential development of new tumors.