Motohiro Matsui

Background/Objectives: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a valuable imaging modality for detecting malignancies and diagnosing fever of unknown origin (FUO). However, data regarding FDG accumulation in bone marrow among pediatric acute leukemia (AL) cases are limited. In this study, we aimed to compare FDG-PET/CT findings between children with AL and those with inflammatory diseases (IDs), including FUO, and develop a scoring system for differential diagnoses. Methods: We retrospectively analyzed FDG-PET/CT findings in six children with AL and 22 with IDs. The maximum standardized uptake value (SUV max), visual score (VS), and spread score (SS) were evaluated across various bone marrow sites, including vertebrae, pelvic bone, humerus, forearm, and femur. Statistical analysis consisted of Mann–Whitney U test for group comparisons and receiver operating characteristic curve (ROC)/area under the curve (AUC) analyses to assess diagnostic performance. Results: SUV max, VS, and SS were significantly higher in children with AL across all evaluated sites. The combined VS + SS scoring system yielded the highest diagnostic accuracy. A simplified version using only the VS of the middle humerus and femur plus the SS showed comparable effectiveness. Conclusions: FDG-PET/CT in children with AL showed high FDG accumulation in bone marrow areas in the whole body. The simple scoring system, which comprises FDG accumulation in the middle portion of the extremities and the whole body, appears to be helpful in distinguishing AL from IDs in children. FDG-PET/CT-based visual scoring may provide supportive information alongside conventional diagnostics in pediatric acute leukemia.

BackgroundThe efficacy of a combination therapy consisting of venetoclax (VEN) and azacytidine (AZA) for newly diagnosed acute myeloid leukemia (AML) has been confirmed in elderly patients. However, the clinical data on VEN for pediatric AML are limited. A combination therapy consisting of crushed VEN tablets and AZA (VEN/AZA) was administered to two children with recurrent AML. The pharmacokinetics of VEN were then analysed.Case presentation[Patient 1] A 1-year-old, male patient who experienced an AML relapse following an allogeneic hematopoietic stem cell transplantation received three courses of VEN/AZA. At the initial dosage of VEN (8 mg/kg), the minimum plasma concentration (Cmin) was only 0.44 mu g/ml, which was far less than the optimal Cmin of 1.2 mu g/ml. Subsequent dose-escalation to 10 mg/kg only achieved Cmin 0.42 mu g/ml. [Patient 2] A 3-year-old, female patient in whom infantile acute lymphoblastic leukemia was originally diagnosed experienced a recurrence in the form of AML after lineage-switching. Three courses of VEN/AZA were administered with the same therapeutic drug monitoring as in Case 1. The Cmin of VEN was 0.15 mu g/ml at 8 mg/kg. Afterwards, voriconazole 16 mg/kg/day was begun for a concomitant fungal infection together with VEN 2 mg/kg. This combination finally achieved Cmin 1.14 mu g/ml probably through CYP3A4 inhibition by voriconazole. In terms of safety, only grade 4 hematological adverse events were observed in both patients. In terms of efficacy, patient 1 and patient 2 achieved stable disease status for two months and six months, respectively.ConclusionPediatric patients may scarcely achieve effective plasma concentration of VEN when crushed tablets are used at the same dosage as in adults.

Background The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. Methods The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. Results Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. Conclusions The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. Trial registration JRCT (https://jrct.niph.go.jp/) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR (http://www.umin.ac.jp/icdr/index.html) Identifier UMIN000029215.

Background: Although positron emission tomography combined with computed tomography (PET-CT) plays an important role in detecting various types of childhood malignancy, it has low positive predictive value, owing to the nonspecific uptake of 18F-fluorodeoxyglucose (FDG) by normal tissue in various benign conditions. Case summary: A 5-year-old male patient with a malignant rhabdoid tumor originating in the left neck underwent primary tumor resection concurrently with ipsilateral lymph node dissection after receiving neoadjuvant chemotherapy consisting of cyclophosphamide, carboplatin, etoposide, vincristine, and doxorubicin. He later received the same adjuvant chemotherapy as well as proton therapy for the primary tumor. Sixteen months after completing the initial therapy, follow-up PET-CT revealed a novel area of glucose hypermetabolism in the right side of the tongue, which was suspected of being a recurrence. However, a physical examination and magnetic resonance imaging (MRI) demonstrated no evidence of tumor recurrence. The patient had a significant leftward deviation of the tongue, suggesting left hypoglossal nerve paralysis. Denervation of the ipsilateral intrinsic tongue muscles secondary to the treatment had caused atrophy in the ipsilateral muscles and compensatory hypertrophy in the contralateral muscles, which increased FDG uptake. Physicians should carefully confirm any diagnosis of a locally recurrent tumor because PET-CT often produces ambiguous findings.

Purpose: Adolescents and young adults (AYA) who undergo cancer treatment sometimes report posttraumatic growth (PTG). Although the importance of peer support has been suggested, its association with PTG, especially its five distinct domains, needs to be investigated further in AYA cancer survivors. The present study examined the role of demographics and peer support in PTG among AYA cancer patients and survivors. Methods: The present, multicenter, cross-sectional, web-based study enrolled AYA cancer patients and survivors (median age: 28 years). Of 549 AYA patients recruited, 212 from 11 cancer centers and 12 cancer patient communities agreed to participate by completing a self-reported measure of PTG (Extended Version of the Posttraumatic Growth Inventory-Japanese) and providing information about their diagnosis, treatment, peer support (affiliation with an AYA patient community or friendship with other AYA patients), and social status. Multiple regression analysis was used to identify significant correlations overall and in the five PTG domains. Results: PTG was positively associated with male sex, having a confidant, and friendship with other AYA patients, and negatively associated with cranial radiation. Friendship with other AYA patients was positively associated with four of the five PTG subscales. For the five subscale scores, “cranial radiation” was negatively associated with “relating to others”; “belonging to a religion” was positively associated with “spiritual change”; and “having a confidant” was positively associated with “relating to others” and “new possibility.” Conclusion: “Having a confidant” and “friendship with other AYA patients” were positively associated with PTG. Psychosocial interventions mobilizing peer support may contribute to promoting PTG in AYA patients. UMIN000035439.

Purpose: Several studies have investigated good communication practices with adult patients receiving bad news about cancer. However, while communication preferences may differ between adults and adolescent and young adult (AYA) patients, these preferences have not been determined for AYA patients. The primary endpoint of this study was to describe the communication preferred by AYA patients with cancer. Methods: The study cohort consisted of 15 patients who received a cancer diagnosis at the age of 15–29 years. Patients were recruited at the National Cancer Center Hospital or through “STAND UP!!,” an association of AYA patients with cancer. Semistructured interviews were conducted, and content analysis was performed to analyze the data. Results: For the preferred communication of AYA patients, 80 categories were extracted in the following five domains: (1) “Supportive setting,” (2) “Method of disclosure of bad news,” (3) “Information given,” (4) “Emotional support,” and (5) “Support for the patient's decision making.” Although more than half of the categories extracted were identical to the preferred communication of adult patients, some categories specific to AYA patients were identified that physicians should consider. Preferences specific to AYA patients included mentioning generation-specific social factors, not showing excessive empathy, and communicating in a manner considering their age and cognitive development that supports their decision making. Conclusion: Although physicians should be mindful of the specific preferences of AYA patients, the basic attitude and communication preferences are similar to those of patients of other generations.

Background: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. Methods: The present phase II, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevating serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. Results: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in elevated serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465), nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than in group A. No adverse events related to magnesium administration were observed. Conclusions: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. Trial registration JRCT (https://jrct.niph.go.jp/) Identifier UMIN000029215 jRCTs031180251.

Background : The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. Methods: The present phase II, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevating serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. Results: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in elevated serum creatinine between the groups (group A: 10% vs. group B: 6%; P=0.465), nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than in group A. No adverse events related to magnesium administration were observed. Conclusions: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients.

Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation and is sometimes fatal. Observations: A 4-year-old, male patient with stage M neuroblastoma (NBL) who had received an allogeneic bone marrow transplantation (BMT) from his sibling five months previously presented with rapidly progressive posterior reversible encephalopathy (PRES) complicated with TA-TMA. Although the patient was transferred to the pediatric intensive care unit, he died within one week after the onset of the latest symptoms. Conclusions: This is the first description of a fatal case of NBL complicated by PRES with rapidly evolving TA-TMA after an allogenic BMT.